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Sample records for attenuated aids virus

  1. An effective AIDS vaccine based on live attenuated vesicular stomatitis virus recombinants.

    Science.gov (United States)

    Rose, N F; Marx, P A; Luckay, A; Nixon, D F; Moretto, W J; Donahoe, S M; Montefiori, D; Roberts, A; Buonocore, L; Rose, J K

    2001-09-07

    We developed an AIDS vaccine based on attenuated VSV vectors expressing env and gag genes and tested it in rhesus monkeys. Boosting was accomplished using vectors with glycoproteins from different VSV serotypes. Animals were challenged with a pathogenic AIDS virus (SHIV89.6P). Control monkeys showed a severe loss of CD4+ T cells and high viral loads, and 7/8 progressed to AIDS with an average time of 148 days. All seven vaccinees were initially infected with SHIV89.6P but have remained healthy for up to 14 months after challenge with low or undetectable viral loads. Protection from AIDS was highly significant (p = 0.001). VSV vectors are promising candidates for human AIDS vaccine trials because they propagate to high titers and can be delivered without injection.

  2. Induction of Mucosal Homing Virus-Specific CD8+ T Lymphocytes by Attenuated Simian Immunodeficiency Virus

    OpenAIRE

    Cromwell, Mandy A.; Veazey, Ronald S.; Altman, John D.; Mansfield, Keith G.; Glickman, Rhona; Allen, Todd M.; Watkins, David I.; Lackner, Andrew A.; Johnson, R. Paul

    2000-01-01

    Induction of virus-specific T-cell responses in mucosal as well as systemic compartments of the immune system is likely to be a critical feature of an effective AIDS vaccine. We investigated whether virus-specific CD8+ lymphocytes induced in rhesus macaques by immunization with attenuated simian immunodeficiency virus (SIV), an approach that is highly effective in eliciting protection against mucosal challenge, express the mucosa-homing receptor α4β7 and traffic to the intestinal mucosa. SIV-...

  3. MicroRNA-Based Attenuation of Influenza Virus across Susceptible Hosts.

    Science.gov (United States)

    Waring, Barbara M; Sjaastad, Louisa E; Fiege, Jessica K; Fay, Elizabeth J; Reyes, Ismarc; Moriarity, Branden; Langlois, Ryan A

    2018-01-15

    Influenza A virus drives significant morbidity and mortality in humans and livestock. Annual circulation of the virus in livestock and waterfowl contributes to severe economic disruption and increases the risk of zoonotic transmission of novel strains into the human population, where there is no preexisting immunity. Seasonal vaccinations in humans help prevent infection and can reduce symptoms when infection does occur. However, current vaccination regimens available for livestock are limited in part due to safety concerns regarding reassortment/recombination with circulating strains. Therefore, inactivated vaccines are used instead of the more immunostimulatory live attenuated vaccines. MicroRNAs (miRNAs) have been used previously to generate attenuated influenza A viruses for use as a vaccine. Here, we systematically targeted individual influenza gene mRNAs using the same miRNA to determine the segment(s) that yields maximal attenuation potential. This analysis demonstrated that targeting of NP mRNA most efficiently ablates replication. We further increased the plasticity of miRNA-mediated attenuation of influenza A virus by exploiting a miRNA, miR-21, that is ubiquitously expressed across influenza-susceptible hosts. In order to construct this targeted virus, we used CRISPR/Cas9 to eliminate the universally expressed miR-21 from MDCK cells. miR-21-targeted viruses were attenuated in human, mouse, canine, and avian cells and drove protective immunity in mice. This strategy has the potential to enhance the safety of live attenuated vaccines in humans and zoonotic reservoirs. IMPORTANCE Influenza A virus circulates annually in both avian and human populations, causing significant morbidity, mortality, and economic burden. High incidence of zoonotic infections greatly increases the potential for transmission to humans, where no preexisting immunity or vaccine exists. There is a critical need for new vaccine strategies to combat emerging influenza outbreaks. Micro

  4. Mechanism of attenuation of a chimeric influenza A/B transfectant virus.

    Science.gov (United States)

    Luo, G; Bergmann, M; Garcia-Sastre, A; Palese, P

    1992-08-01

    The ribonucleoprotein transfection system for influenza virus allowed us to construct an influenza A virus containing a chimeric neuraminidase (NA) gene in which the noncoding sequence is derived from the NS gene of influenza B virus (T. Muster, E. K. Subbarao, M. Enami, B. P. Murphy, and P. Palese, Proc. Natl. Acad. Sci. USA 88:5177-5181, 1991). This transfectant virus is attenuated in mice and grows to lower titers in tissue culture than wild-type virus. Since such a virus has characteristics desirable for a live attenuated vaccine strain, attempts were made to characterize this virus at the molecular level. Our analysis suggests that the attenuation of the virus is due to changes in the cis signal sequences, which resulted in a reduction of transcription and replication of the chimeric NA gene. The major finding concerns a sixfold reduction in NA-specific viral RNA in the virion, causing a reduction in the ratio of infectious particles to physical particles compared with the ratio in wild-type virus. Although the NA-specific mRNA level is also reduced in transfectant virus-infected cells, it does not appear to contribute to the attenuation characteristics of the virus. The levels of the other RNAs and their expression appear to be unchanged for the transfectant virus. It is suggested that downregulation of the synthesis of one viral RNA segment leads to the generation of defective viruses during each replication cycle. We believe that this represents a general principle for attenuation which may be applied to other segmented viruses containing either single-stranded or double-stranded RNA.

  5. AIDS and Cancer Virus Program (ACVP)

    Data.gov (United States)

    Federal Laboratory Consortium — Researchers from the AIDS and Cancer Virus Program (ACVP) work to improve the diagnosis, prevention, and treatment of HIV infection, AIDS, and AIDS-related tumors,...

  6. A replication-deficient rabies virus vaccine expressing Ebola virus glycoprotein is highly attenuated for neurovirulence

    International Nuclear Information System (INIS)

    Papaneri, Amy B.; Wirblich, Christoph; Cann, Jennifer A.; Cooper, Kurt; Jahrling, Peter B.; Schnell, Matthias J.; Blaney, Joseph E.

    2012-01-01

    We are developing inactivated and live-attenuated rabies virus (RABV) vaccines expressing Ebola virus (EBOV) glycoprotein for use in humans and endangered wildlife, respectively. Here, we further characterize the pathogenesis of the live-attenuated RABV/EBOV vaccine candidates in mice in an effort to define their growth properties and potential for safety. RABV vaccines expressing GP (RV-GP) or a replication-deficient derivative with a deletion of the RABV G gene (RVΔG-GP) are both avirulent after intracerebral inoculation of adult mice. Furthermore, RVΔG-GP is completely avirulent upon intracerebral inoculation of suckling mice unlike parental RABV vaccine or RV-GP. Analysis of RVΔG-GP in the brain by quantitative PCR, determination of virus titer, and immunohistochemistry indicated greatly restricted virus replication. In summary, our findings indicate that RV-GP retains the attenuation phenotype of the live-attenuated RABV vaccine, and RVΔG-GP would appear to be an even safer alternative for use in wildlife or consideration for human use.

  7. Wild type measles virus attenuation independent of type I IFN

    Directory of Open Access Journals (Sweden)

    Horvat Branka

    2008-02-01

    Full Text Available Abstract Background Measles virus attenuation has been historically performed by adaptation to cell culture. The current dogma is that attenuated virus strains induce more type I IFN and are more resistant to IFN-induced protection than wild type (wt. Results The adaptation of a measles virus isolate (G954-PBL by 13 passages in Vero cells induced a strong attenuation of this strain in vivo. The adapted virus (G954-V13 differs from its parental strain by only 5 amino acids (4 in P/V/C and 1 in the M gene. While a vaccine strain, Edmonston Zagreb, could replicate equally well in various primate cells, both G954 strains exhibited restriction to the specific cell type used initially for their propagation. Surprisingly, we observed that both G954 strains induced type I IFN, the wt strain inducing even more than the attenuated ones, particularly in human plasmacytoid Dendritic Cells. Type I IFN-induced protection from the infection of both G954 strains depended on the cell type analyzed, being less efficient in the cells used to grow the viral strain. Conclusion Thus, mutations in M and P/V/C proteins can critically affect MV pathogenicity, cellular tropism and lead to virus attenuation without interfering with the α/β IFN system.

  8. A replication-deficient rabies virus vaccine expressing Ebola virus glycoprotein is highly attenuated for neurovirulence

    Energy Technology Data Exchange (ETDEWEB)

    Papaneri, Amy B. [Emerging Viral Pathogens Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, MD 21702 (United States); Wirblich, Christoph [Department of Microbiology and Immunology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA 19107 (United States); Cann, Jennifer A.; Cooper, Kurt [Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick MD, 21702 (United States); Jahrling, Peter B. [Emerging Viral Pathogens Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, MD 21702 (United States); Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick MD, 21702 (United States); Schnell, Matthias J., E-mail: matthias.schnell@jefferson.edu [Department of Microbiology and Immunology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA 19107 (United States); Jefferson Vaccine Center, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA 19107 (United States); Blaney, Joseph E., E-mail: jblaney@niaid.nih.gov [Emerging Viral Pathogens Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, MD 21702 (United States)

    2012-12-05

    We are developing inactivated and live-attenuated rabies virus (RABV) vaccines expressing Ebola virus (EBOV) glycoprotein for use in humans and endangered wildlife, respectively. Here, we further characterize the pathogenesis of the live-attenuated RABV/EBOV vaccine candidates in mice in an effort to define their growth properties and potential for safety. RABV vaccines expressing GP (RV-GP) or a replication-deficient derivative with a deletion of the RABV G gene (RV{Delta}G-GP) are both avirulent after intracerebral inoculation of adult mice. Furthermore, RV{Delta}G-GP is completely avirulent upon intracerebral inoculation of suckling mice unlike parental RABV vaccine or RV-GP. Analysis of RV{Delta}G-GP in the brain by quantitative PCR, determination of virus titer, and immunohistochemistry indicated greatly restricted virus replication. In summary, our findings indicate that RV-GP retains the attenuation phenotype of the live-attenuated RABV vaccine, and RV{Delta}G-GP would appear to be an even safer alternative for use in wildlife or consideration for human use.

  9. Exploratory re-encoding of Yellow Fever Virus genome: new insights for the design of live-attenuated viruses

    OpenAIRE

    Klitting, Raphaelle; Riziki, Toilhata; Moureau, Gregory; De Lamballerie, Xavier; Piorkowski, Geraldine

    2018-01-01

    Virus attenuation by genome re-encoding is a pioneering approach for generating live-attenuated vaccine candidates. Its core principle is to introduce a large number of slightly deleterious synonymous mutations into the viral genome to produce a stable attenuation of the targeted virus. The large number of mutations introduced is supposed to guarantee the stability of the attenuated phenotype by lowering the risks of reversion and recombination for re-encoded sequences. In this prospect, iden...

  10. Comparison of the nucleotide sequence of wild-type hepatitis - A virus and its attenuated candidate vaccine derivative

    International Nuclear Information System (INIS)

    Cohen, J.I.; Rosenblum, B.; Ticehurst, J.R.; Daemer, R.; Feinstone, S.; Purcell, R.H.

    1987-01-01

    Development of attenuated mutants for use as vaccines is in progress for other viruses, including influenza, rotavirus, varicella-zoster, cytomegalovirus, and hepatitis-A virus (HAV). Attenuated viruses may be derived from naturally occurring mutants that infect human or nonhuman hosts. Alternatively, attenuated mutants may be generated by passage of wild-type virus in cell culture. Production of attenuated viruses in cell culture is a laborious and empiric process. Despite previous empiric successes, understanding the molecular basis for attenuation of vaccine viruses could facilitate future development and use of live-virus vaccines. Comparison of the complete nucleotide sequences of wild-type (virulent) and vaccine (attenuated) viruses has been reported for polioviruses and yellow fever virus. Here, the authors compare the nucleotide sequence of wild-type HAV HM-175 with that of a candidate vaccine derivative

  11. Factors Influencing Virulence and Plaque Properties of Attenuated Venezuelan Equine Encephalomyelitis Virus Populations

    Science.gov (United States)

    Hearn, Henry J.; Seliokas, Zenonas V.; Andersen, Arthur A.

    1969-01-01

    A minority of stable large-plaque virus increased proportionally in stored unstable attenuated (9t) Venezuelan equine encephalomyelitis virus populations. L-cell-grown progeny (9t2) of stored 9t showed large amounts of large-plaque virus and increased virulence. Small-plaque virus inhibited large-plaque virus but not the reverse. Serial passage of small-plaque virus from 9t2 yielded a strain (20t) that was more attenuated than 9t. PMID:5823235

  12. Evolutionary characteristics of morbilliviruses during serial passages in vitro: Gradual attenuation of virus virulence.

    Science.gov (United States)

    Liu, Fuxiao; Wu, Xiaodong; Li, Lin; Zou, Yanli; Liu, Shan; Wang, Zhiliang

    2016-08-01

    The genus Morbillivirus is classified into the family Paramyxoviridae, and is composed of 6 members, namely measles virus (MV), rinderpest virus (RPV), peste-des-petits-ruminants virus (PPRV), canine distemper virus (CDV), phocine distemper virus (PDV) and cetacean morbillivirus (CeMV). The MV, RPV, PPRV and CDV have been successfully attenuated through their serial passages in vitro for the production of live vaccines. It has been demonstrated that the morbilliviral virulence in animals was progressively attenuated with their consecutive passages in vitro. However, only a few reports were involved in explanation of an attenuation-related mechanism on them until many years after the establishment of a quasispecies theory. RNA virus quasispecies arise from rapid evolution of viruses with high mutation rate during genomic replication, and play an important role in gradual loss of viral virulence by serial passages. Here, we overviewed the development of live-attenuated vaccine strains against morbilliviruses by consecutive passages in vitro, and further discussed a related mechanism concerning the relationship between virulence attenuation and viral evolution. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Molecularly engineered live-attenuated chimeric West Nile/dengue virus vaccines protect rhesus monkeys from West Nile virus

    International Nuclear Information System (INIS)

    Pletnev, Alexander G.; St Claire, Marisa; Elkins, Randy; Speicher, Jim; Murphy, Brian R.; Chanock, Robert M.

    2003-01-01

    Two molecularly engineered, live-attenuated West Nile virus (WN) vaccine candidates were highly attenuated and protective in rhesus monkeys. The vaccine candidates are chimeric viruses (designated WN/DEN4) bearing the membrane precursor and envelope protein genes of WN on a backbone of dengue 4 virus (DEN4) with or without a deletion of 30 nucleotides (Δ30) in the 3' noncoding region of DEN4. Viremia in WN/DEN4- infected monkeys was reduced 100-fold compared to that in WN- or DEN4-infected monkeys. WN/DEN4-3'Δ30 did not cause detectable viremia, indicating that it is even more attenuated for monkeys. These findings indicate that chimerization itself and the presence of the Δ30 mutation independently contribute to the attenuation phenotype for nonhuman primates. Despite their high level of attenuation in monkeys, the chimeras induced a moderate-to-high titer of neutralizing antibodies and prevented viremia in monkeys challenged with WN. The more attenuated vaccine candidate, WN/DEN4-3'Δ30, will be evaluated first in our initial clinical studies

  14. Pathogenesis of virulent and attenuated foot-and-mouth disease virus in cattle.

    Science.gov (United States)

    Arzt, Jonathan; Pacheco, Juan M; Stenfeldt, Carolina; Rodriguez, Luis L

    2017-05-02

    Understanding the mechanisms of attenuation and virulence of foot-and-mouth disease virus (FMDV) in the natural host species is critical for development of next-generation countermeasures such as live-attenuated vaccines. Functional genomics analyses of FMDV have identified few virulence factors of which the leader proteinase (L pro ) is the most thoroughly investigated. Previous work from our laboratory has characterized host factors in cattle inoculated with virulent FMDV and attenuated mutant strains with transposon insertions within L pro . In the current study, the characteristics defining virulence of FMDV in cattle were further investigated by comparing the pathogenesis of a mutant, attenuated strain (FMDV-Mut) to the parental, virulent virus from which the mutant was derived (FMDV-WT). The only difference between the two viruses was an insertion mutation in the inter-AUG region of the leader proteinase of FMDV-Mut. All cattle were infected by simulated-natural, aerosol inoculation. Both viruses were demonstrated to establish primary infection in the nasopharyngeal mucosa with subsequent dissemination to the lungs. Immunomicroscopic localization of FMDV antigens indicated that both viruses infected superficial epithelial cells of the nasopharynx and lungs. The critical differences between the two viruses were a more rapid establishment of infection by FMDV-WT and quantitatively greater virus loads in secretions and infected tissues compared to FMDV-Mut. The slower replicating FMDV-Mut established a subclinical infection that was limited to respiratory epithelial sites, whereas the faster replication of FMDV-WT facilitated establishment of viremia, systemic dissemination of infection, and clinical disease. The mutant FMDV was capable of achieving all the same early pathogenesis landmarks as FMDV-WT, but was unable to establish systemic infection. The precise mechanism of attenuation remains undetermined; but current data suggests that the impaired replication

  15. No evidence of murine leukemia virus-related viruses in live attenuated human vaccines.

    Directory of Open Access Journals (Sweden)

    William M Switzer

    Full Text Available The association of xenotropic murine leukemia virus (MLV-related virus (XMRV in prostate cancer and chronic fatigue syndrome reported in previous studies remains controversial as these results have been questioned by recent data. Nonetheless, concerns have been raised regarding contamination of human vaccines as a possible source of introduction of XMRV and MLV into human populations. To address this possibility, we tested eight live attenuated human vaccines using generic PCR for XMRV and MLV sequences. Viral metagenomics using deep sequencing was also done to identify the possibility of other adventitious agents.All eight live attenuated vaccines, including Japanese encephalitis virus (JEV (SA-14-14-2, varicella (Varivax, measles, mumps, and rubella (MMR-II, measles (Attenuvax, rubella (Meruvax-II, rotavirus (Rotateq and Rotarix, and yellow fever virus were negative for XMRV and highly related MLV sequences. However, residual hamster DNA, but not RNA, containing novel endogenous gammaretrovirus sequences was detected in the JEV vaccine using PCR. Metagenomics analysis did not detect any adventitious viral sequences of public health concern. Intracisternal A particle sequences closest to those present in Syrian hamsters and not mice were also detected in the JEV SA-14-14-2 vaccine. Combined, these results are consistent with the production of the JEV vaccine in Syrian hamster cells.We found no evidence of XMRV and MLV in eight live attenuated human vaccines further supporting the safety of these vaccines. Our findings suggest that vaccines are an unlikely source of XMRV and MLV exposure in humans and are consistent with the mounting evidence on the absence of these viruses in humans.

  16. A polymerase chain reaction assay for detection of virulent and attenuated strains of duck plague virus.

    Science.gov (United States)

    Xie, Liji; Xie, Zhixun; Huang, Li; Wang, Sheng; Huang, Jiaoling; Zhang, Yanfang; Zeng, Tingting; Luo, Sisi

    2017-11-01

    Sequence analysis of duck plague virus (DPV) revealed that there was a 528bp (B fragment) deletion within the UL2 gene of DPV attenuated vaccine strain in comparison with field virulent strains. The finding of gene deletion provides a potential differentiation test between DPV virulent strain and attenuated strain based on their UL2 gene sizes. Thus we developed a polymerase chain reaction (PCR) assay targeting to the DPV UL2 gene for simultaneous detection of DPV virulent strain and attenuated strain, 827bp for virulent strain and 299bp for attenuated strain. This newly developed PCR for DPV was highly sensitive and specific. It detected as low as 100fg of DNA on both DPV virulent and attenuated strains, no same size bands were amplified from other duck viruses including duck paramyxovirus, duck tembusu virus, duck circovirus, Muscovy duck parvovirus, duck hepatitis virus type I, avian influenza virus and gosling plague virus. Therefore, this PCR assay can be used for the rapid, sensitive and specific detection of DPV virulent and attenuated strains affecting ducks. Copyright © 2017. Published by Elsevier B.V.

  17. Attenuation of Recombinant Yellow Fever 17D Viruses Expressing Foreign Protein Epitopes at the Surface

    Science.gov (United States)

    Bonaldo, Myrna C.; Garratt, Richard C.; Marchevsky, Renato S.; Coutinho, Evandro S. F.; Jabor, Alfredo V.; Almeida, Luís F. C.; Yamamura, Anna M. Y.; Duarte, Adriana S.; Oliveira, Prisciliana J.; Lizeu, Jackeline O. P.; Camacho, Luiz A. B.; Freire, Marcos S.; Galler, Ricardo

    2005-01-01

    The yellow fever (YF) 17D vaccine is a live attenuated virus. Three-dimensional (3D) homology modeling of the E protein structure from YF 17D virus and its comparison with that from tick-borne encephalitis virus revealed that it is possible to accommodate inserts of different sizes and amino acid compositions in the flavivirus E protein fg loop. This is consistent with the 3D structures of both the dimeric and trimeric forms in which the fg loop lies exposed to solvents. We demonstrate here that YF 17D viruses bearing foreign humoral (17D/8) and T-cell (17D/13) epitopes, which vary in sequence and length, displayed growth restriction. It is hypothesized that interference with the dimer-trimer transition and with the formation of a ring of such trimers in order to allow fusion compromises the capability of the E protein to induce fusion of viral and endosomal membranes, and a slower rate of fusion may delay the extent of virus production. This would account for the lower levels of replication in cultured cells and of viremia in monkeys, as well as for the more attenuated phenotype of the recombinant viruses in monkeys. Testing of both recombinant viruses (17D/8 and 17D/13) for monkey neurovirulence also suggests that insertion at the 17D E protein fg loop does not compromise the attenuated phenotype of YF 17D virus, further confirming the potential use of this site for the development of new live attenuated 17D virus-based vaccines. PMID:15956601

  18. Failure of attenuated canine distemper virus (Rockborn strain) to suppress lymphocyte blastogenesis in dogs.

    Science.gov (United States)

    Schultz, R D

    1976-01-01

    The attenuated Rockborn strain of canine distemper virus is commonly used in commercial vaccines. Since immunosuppression is a common feature of virulent (Snyder Hill) distemper virus infection of the dog, an evaluation of the cellular immune functions of dogs given inoculums of the less virulent Rockborn strain was done using lymphocyte blastogenesis responses to various mitogens. Unlike the viruslent Snyder Hill strain, the attenuated distemper virus did not alter lymphocyte blastogenesis responses to phytohemaglutinin (PHA) and pokeweed mitogen (PWM) which are considered in vitro correlates of T and B cell immunity.

  19. Attenuation of Foot-and-Mouth Disease Virus by Engineered Viral Polymerase Fidelity.

    Science.gov (United States)

    Rai, Devendra K; Diaz-San Segundo, Fayna; Campagnola, Grace; Keith, Anna; Schafer, Elizabeth A; Kloc, Anna; de Los Santos, Teresa; Peersen, Olve; Rieder, Elizabeth

    2017-08-01

    Foot-and-mouth disease virus (FMDV) RNA-dependent RNA polymerase (RdRp) (3D pol ) catalyzes viral RNA synthesis. Its characteristic low fidelity and absence of proofreading activity allow FMDV to rapidly mutate and adapt to dynamic environments. In this study, we used the structure of FMDV 3D pol in combination with previously reported results from similar picornaviral polymerases to design point mutations that would alter replication fidelity. In particular, we targeted Trp237 within conserved polymerase motif A because of the low reversion potential inherent in the single UGG codon. Using biochemical and genetic tools, we show that the replacement of tryptophan 237 with phenylalanine imparts higher fidelity, but replacements with isoleucine and leucine resulted in lower-fidelity phenotypes. Viruses containing these W237 substitutions show in vitro growth kinetics and plaque morphologies similar to those of the wild-type (WT) A 24 Cruzeiro strain in BHK cells, and both high- and low-fidelity variants retained fitness during coinfection with the wild-type virus. The higher-fidelity W237F (W237F HF ) mutant virus was more resistant to the mutagenic nucleoside analogs ribavirin and 5-fluorouracil than the WT virus, whereas the lower-fidelity W237I (W237I LF ) and W237L LF mutant viruses exhibited lower ribavirin resistance. Interestingly, the variant viruses showed heterogeneous and slightly delayed growth kinetics in primary porcine kidney cells, and they were significantly attenuated in mouse infection experiments. These data demonstrate, for a single virus, that either increased or decreased RdRp fidelity attenuates virus growth in animals, which is a desirable feature for the development of safer and genetically more stable vaccine candidates. IMPORTANCE Foot-and-mouth disease (FMD) is the most devastating disease affecting livestock worldwide. Here, using structural and biochemical analyses, we have identified FMDV 3D pol mutations that affect polymerase

  20. Hepatitis B and C virus infections and liver function in AIDS patients ...

    African Journals Online (AJOL)

    Background: Impaired liver function tests and co-infection with hepatitis viruses in AIDS patients are common in western countries. Objective: To assess liver function and prevalence of co-infection with hepatitis B and hepatitis C viruses in AIDS patients at Chris Hani Baragwanath Hospital. Design: A prospective study.

  1. Mapping of the mutations present in the genome of the Rift Valley fever virus attenuated MP12 strain and their putative role in attenuation.

    Science.gov (United States)

    Vialat, P; Muller, R; Vu, T H; Prehaud, C; Bouloy, M

    1997-11-01

    The MP12 attenuated strain of Rift Valley fever virus was obtained by 12 serial passages of a virulent isolate ZH548 in the presence of 5-fluorouracil (Caplen et al., 1985. Mutagen-directed attenuation of Rift Valley fever virus as a method for vaccine development. J. Gen. Virol., 66, 2271-2277). The comparison of the M segment of the two strains has already been reported by Takehara et al. (Takehara et al., 1989. Identification of mutations in the M RNA of a candidate vaccine strain of Rift Valley fever virus. Virology 169, 452-457). We have completed the comparison and found that altogether a total of nine, 12 and four nucleotides were changed in the L, M and S segments of the two strains, respectively. Three mutations induced amino acid changes in the L protein but none of them was located in the recognized motifs conserved among RNA dependent polymerases. In the S segment, a single change modified an amino acid in the NSs protein and in the M segment, seven of the mutations resulted in amino acid changes in each of the four encoded G1, G2, 14 kDa and 78 kDa proteins. Characterization of the MP12 virus indicated that determinants for attenuation were present in each segment and that they were introduced progressively during the 12 passages in the presence of the mutagen (Saluzzo and Smith, 1990. Use of reassortant viruses to map attenuating and temperature-sensitive mutations of the Rift Valley fever virus MP-12 vaccine. Vaccine 8, 369-375). Passages 4 and 7-9 were found to be essential for introduction of temperature-sensitive lesions and attenuation. In an attempt to correlate some of the mutations with the attenuated or temperature-sensitive phenotypes, we determined by sequencing the passage level at which the different mutations appeared. This work should help to address the question of the role of the viral gene products in Rift Valley fever pathogenesis.

  2. DNA vaccines encoding proteins from wild-type and attenuated canine distemper virus protect equally well against wild-type virus challenge.

    Science.gov (United States)

    Nielsen, Line; Jensen, Trine Hammer; Kristensen, Birte; Jensen, Tove Dannemann; Karlskov-Mortensen, Peter; Lund, Morten; Aasted, Bent; Blixenkrone-Møller, Merete

    2012-10-01

    Immunity induced by DNA vaccines containing the hemagglutinin (H) and nucleoprotein (N) genes of wild-type and attenuated canine distemper virus (CDV) was investigated in mink (Mustela vison), a highly susceptible natural host of CDV. All DNA-immunized mink seroconverted, and significant levels of virus-neutralizing (VN) antibodies were present on the day of challenge with wild-type CDV. The DNA vaccines also primed the cell-mediated memory responses, as indicated by an early increase in the number of interferon-gamma (IFN-γ)-producing lymphocytes after challenge. Importantly, the wild-type and attenuated CDV DNA vaccines had a long-term protective effect against wild-type CDV challenge. The vaccine-induced immunity induced by the H and N genes from wild-type CDV and those from attenuated CDV was comparable. Because these two DNA vaccines were shown to protect equally well against wild-type virus challenge, it is suggested that the genetic/antigenic heterogeneity between vaccine strains and contemporary wild-type strains are unlikely to cause vaccine failure.

  3. [The growth of attenuated strains of canine parvovirus, mink enteritis virus, feline panleukopenia virus, and rabies virus on various types of cell cultures].

    Science.gov (United States)

    Zuffa, T

    1987-10-01

    The growth characteristics were studied in the attenuated strains of canine parvovirus CPVA-BN 80/82, mink enteritis virus MEVA-BN 63/82 and feline panleucopenia virus FPVA-BN 110/83 on the stable feline kidney cell line FE, and in the attenuated canine distemper virus CDV-F-BN 10/83 on chicken embryo cell cultures (KEB) and cultures of the stable cell line VERO. When the FE cultures were infected with different parvoviruses in cell suspension at MOI 2-4 TKID50 per cell, the first multiplication of the intracellular virus was recorded 20 hours p. i. In the canine parvovirus, the content of intracellular and extracellular virus continued increasing parallelly until the fourth day; then, from the fourth to the sixth day, the content of extracellular virus still increased whereas that of intracellular virus fell rapidly. In the case of the mink enteritis virus the release of the virus into the culture medium continued parallelly with the production of the cellular virus until the sixth day. In the case of the feline panleucopenia virus the values concerning free virus and virus bound to cells were lower, starting from the second day p. i. When KEB or VERO cultures were infected in cell suspension with the canine distemper virus at MOI about 0.004 per 1 cell, the replicated intracellular virus was first recorded in the KEB cultures five hours after infection but in the VERO cultures only 20 hours after infection, with a timely release of the virus into the culture medium in both kinds of tissue. In the KEB and VERO cultures the highest values of infection titres were recorded on the fourth day p. i., the course of virus multiplication on the cells being parallel with its release into the culture medium.

  4. Conditional live virus as a novel approach towards a safe live attenuated HIV vaccine

    NARCIS (Netherlands)

    Das, Atze T.; Zhou, Xue; Vink, Monique; Klaver, Bep; Berkhout, Ben

    2002-01-01

    To control the worldwide spread of HIV, a safe and effective prophylactic vaccine is urgently needed. Studies with the simian immunodeficiency virus demonstrated that a live attenuated virus can be effective as a vaccine, but serious concerns about the safety of such a vaccine virus have arisen. We

  5. Generation and Characterization of Live Attenuated Influenza A(H7N9 Candidate Vaccine Virus Based on Russian Donor of Attenuation.

    Directory of Open Access Journals (Sweden)

    Svetlana Shcherbik

    Full Text Available Avian influenza A (H7N9 virus has emerged recently and continues to cause severe disease with a high mortality rate in humans prompting the development of candidate vaccine viruses. Live attenuated influenza vaccines (LAIV are 6:2 reassortant viruses containing the HA and NA gene segments from wild type influenza viruses to induce protective immune responses and the six internal genes from Master Donor Viruses (MDV to provide temperature sensitive, cold-adapted and attenuated phenotypes.LAIV candidate A/Anhui/1/2013(H7N9-CDC-LV7A (abbreviated as CDC-LV7A, based on the Russian MDV, A/Leningrad/134/17/57 (H2N2, was generated by classical reassortment in eggs and retained MDV temperature-sensitive and cold-adapted phenotypes. CDC-LV7A had two amino acid substitutions N123D and N149D (H7 numbering in HA and one substitution T10I in NA. To evaluate the role of these mutations on the replication capacity of the reassortants in eggs, the recombinant viruses A(H7N9RG-LV1 and A(H7N9RG-LV2 were generated by reverse genetics. These changes did not alter virus antigenicity as ferret antiserum to CDC-LV7A vaccine candidate inhibited hemagglutination by homologous A(H7N9 virus efficiently. Safety studies in ferrets confirmed that CDC-LV7A was attenuated compared to wild-type A/Anhui/1/2013. In addition, the genetic stability of this vaccine candidate was examined in eggs and ferrets by monitoring sequence changes acquired during virus replication in the two host models. No changes in the viral genome were detected after five passages in eggs. However, after ten passages additional mutations were detected in the HA gene. The vaccine candidate was shown to be stable in the ferret model; post-vaccination sequence data analysis showed no changes in viruses collected in nasal washes present at day 5 or day 7.Our data indicate that the A/Anhui/1/2013(H7N9-CDC-LV7A reassortant virus is a safe and genetically stable candidate vaccine virus that is now available for

  6. Attenuated Human Parainfluenza Virus Type 1 Expressing Ebola Virus Glycoprotein GP Administered Intranasally Is Immunogenic in African Green Monkeys.

    Science.gov (United States)

    Lingemann, Matthias; Liu, Xueqiao; Surman, Sonja; Liang, Bo; Herbert, Richard; Hackenberg, Ashley D; Buchholz, Ursula J; Collins, Peter L; Munir, Shirin

    2017-05-15

    The recent 2014-2016 Ebola virus (EBOV) outbreak prompted increased efforts to develop vaccines against EBOV disease. We describe the development and preclinical evaluation of an attenuated recombinant human parainfluenza virus type 1 (rHPIV1) expressing the membrane-anchored form of EBOV glycoprotein GP, as an intranasal (i.n.) EBOV vaccine. GP was codon optimized and expressed either as a full-length protein or as an engineered chimeric form in which its transmembrane and cytoplasmic tail (TMCT) domains were replaced with those of the HPIV1 F protein in an effort to enhance packaging into the vector particle and immunogenicity. GP was inserted either preceding the N gene (pre-N) or between the N and P genes (N-P) of rHPIV1 bearing a stabilized attenuating mutation in the P/C gene (C Δ170 ). The constructs grew to high titers and efficiently and stably expressed GP. Viruses were attenuated, replicating at low titers over several days, in the respiratory tract of African green monkeys (AGMs). Two doses of candidates expressing GP from the pre-N position elicited higher GP neutralizing serum antibody titers than the N-P viruses, and unmodified GP induced higher levels than its TMCT counterpart. Unmodified EBOV GP was packaged into the HPIV1 particle, and the TMCT modification did not increase packaging or immunogenicity but rather reduced the stability of GP expression during in vivo replication. In conclusion, we identified an attenuated and immunogenic i.n. vaccine candidate expressing GP from the pre-N position. It is expected to be well tolerated in humans and is available for clinical evaluation. IMPORTANCE EBOV hemorrhagic fever is one of the most lethal viral infections and lacks a licensed vaccine. Contact of fluids from infected individuals, including droplets or aerosols, with mucosal surfaces is an important route of EBOV spread during a natural outbreak, and aerosols also might be exploited for intentional virus spread. Therefore, vaccines that protect

  7. Attenuation and immunogenicity of recombinant yellow fever 17D-dengue type 2 virus for rhesus monkeys

    Directory of Open Access Journals (Sweden)

    Galler R.

    2005-01-01

    Full Text Available A chimeric yellow fever (YF-dengue serotype 2 (dengue 2 virus was constructed by replacing the premembrane and envelope genes of the YF 17D virus with those from dengue 2 virus strains of Southeast Asian genotype. The virus grew to high titers in Vero cells and, after passage 2, was used for immunogenicity and attenuation studies in rhesus monkeys. Subcutaneous immunization of naive rhesus monkeys with the 17D-D2 chimeric virus induced a neutralizing antibody response associated with the protection of 6 of 7 monkeys against viremia by wild-type dengue 2 virus. Neutralizing antibody titers to dengue 2 were significantly lower in YF-immune animals than in YF-naive monkeys and protection against challenge with wild-type dengue 2 virus was observed in only 2 of 11 YF-immune monkeys. An anamnestic response to dengue 2, indicated by a sharp increase of neutralizing antibody titers, was observed in the majority of the monkeys after challenge with wild-type virus. Virus attenuation was demonstrated using the standard monkey neurovirulence test. The 17D-D2 chimera caused significantly fewer histological lesions than the YF 17DD virus. The attenuated phenotype could also be inferred from the limited viremias compared to the YF 17DD vaccine. Overall, these results provide further support for the use of chimeric viruses for the development of a new live tetravalent dengue vaccine.

  8. A live attenuated cold-adapted influenza A H7N3 virus vaccine provides protection against homologous and heterologous H7 viruses in mice and ferrets

    International Nuclear Information System (INIS)

    Joseph, Tomy; McAuliffe, Josephine; Lu, Bin; Vogel, Leatrice; Swayne, David; Jin, Hong; Kemble, George; Subbarao, Kanta

    2008-01-01

    The appearance of human infections caused by avian influenza A H7 subtype viruses underscores their pandemic potential and the need to develop vaccines to protect humans from viruses of this subtype. A live attenuated H7N3 virus vaccine was generated by reverse genetics using the HA and NA genes of a low pathogenicity A/chicken/BC/CN-6/04 (H7N3) virus and the six internal protein genes of the cold-adapted A/Ann Arbor/6/60 ca (H2N2) virus. The reassortant H7N3 BC 04 ca vaccine virus was temperature sensitive and showed attenuation in mice and ferrets. Intranasal immunization with one dose of the vaccine protected mice and ferrets when challenged with homologous and heterologous H7 viruses. The reassortant H7N3 BC 04 ca vaccine virus showed comparable levels of attenuation, immunogenicity and efficacy in mice and ferret models. The safety, immunogenicity, and efficacy of this vaccine in mice and ferrets support the evaluation of this vaccine in clinical trials

  9. Utilisation of ISA Reverse Genetics and Large-Scale Random Codon Re-Encoding to Produce Attenuated Strains of Tick-Borne Encephalitis Virus within Days.

    Science.gov (United States)

    de Fabritus, Lauriane; Nougairède, Antoine; Aubry, Fabien; Gould, Ernest A; de Lamballerie, Xavier

    2016-01-01

    Large-scale codon re-encoding is a new method of attenuating RNA viruses. However, the use of infectious clones to generate attenuated viruses has inherent technical problems. We previously developed a bacterium-free reverse genetics protocol, designated ISA, and now combined it with large-scale random codon-re-encoding method to produce attenuated tick-borne encephalitis virus (TBEV), a pathogenic flavivirus which causes febrile illness and encephalitis in humans. We produced wild-type (WT) and two re-encoded TBEVs, containing 273 or 273+284 synonymous mutations in the NS5 and NS5+NS3 coding regions respectively. Both re-encoded viruses were attenuated when compared with WT virus using a laboratory mouse model and the relative level of attenuation increased with the degree of re-encoding. Moreover, all infected animals produced neutralizing antibodies. This novel, rapid and efficient approach to engineering attenuated viruses could potentially expedite the development of safe and effective new-generation live attenuated vaccines.

  10. Vaccinia virus recombinants expressing chimeric proteins of human immunodeficiency virus and gamma interferon are attenuated for nude mice.

    OpenAIRE

    Giavedoni, L D; Jones, L; Gardner, M B; Gibson, H L; Ng, C T; Barr, P J; Yilma, T

    1992-01-01

    We have developed a method for attenuating vaccinia virus recombinants by expressing a fusion protein of a lymphokine and an immunogen. Chimeric genes were constructed that coded for gamma interferon (IFN-gamma) and structural proteins of the human immunodeficiency virus type 1 (HIV-1). In this study, we describe the biological and immunological properties of vaccinia virus recombinants expressing chimeric genes of murine or human IFN-gamma with glycoprotein gp120, gag, and a fragment of gp41...

  11. Live Attenuated Recombinant Vaccine Protects Nonhuman Primates Against Ebola and Marburg Viruses

    National Research Council Canada - National Science Library

    Jones, Steven M; Feldmann, Heinz; Stroher, Ute; Geisbert, Joan B; Fernando, Lisa; Grolla, Allen; Klenk, Hans-Dieter; Sullivan, Nancy J; Volchkov, Viktor E; Fritz, Elizabeth A; Daddario, Kathleen M; Hensley, Lisa E; Jahrling, Peter B; Geisbert, Thomas W

    2005-01-01

    ...). Here, we developed replication-competent vaccines against EBOV and MARV based on attenuated recombinant vesicular stomatitis virus vectors expressing either the EBOV glycoprotein or MARV glycoprotein...

  12. Recoding structural glycoprotein E2 in classical swine fever virus (CSFV) produces complete virus attenuation in swine and protects infected animals against disease.

    Science.gov (United States)

    Velazquez-Salinas, Lauro; Risatti, Guillermo R; Holinka, Lauren G; O'Donnell, Vivian; Carlson, Jolene; Alfano, Marialexia; Rodriguez, Luis L; Carrillo, Consuelo; Gladue, Douglas P; Borca, Manuel V

    2016-07-01

    Controlling classical swine fever (CSF) mainly involves vaccination with live attenuated vaccines (LAV). Experimental CSFV LAVs has been lately developed through reverse genetics using several different approaches. Here we present that codon de-optimization in the major CSFV structural glycoprotein E2 coding region, causes virus attenuation in swine. Four different mutated constructs (pCSFm1-pCSFm4) were designed using various mutational approaches based on the genetic background of the highly virulent strain Brescia (BICv). Three of these constructs produced infectious viruses (CSFm2v, CSFm3v, and CSFm4v). Animals infected with CSFm2v presented a reduced and extended viremia but did not display any CSF-related clinical signs. Animals that were infected with CSFm2v were protected against challenge with virulent parental BICv. This is the first report describing the development of an attenuated CSFV experimental vaccine by codon usage de-optimization, and one of the few examples of virus attenuation using this methodology that is assessed in a natural host. Published by Elsevier Inc.

  13. Temperature-sensitive mutations for live-attenuated Rift Valley fever vaccines: Implications from other RNA viruses

    Directory of Open Access Journals (Sweden)

    Shoko eNishiyama

    2015-08-01

    Full Text Available Rift Valley fever (RVF is a mosquito-borne zoonotic disease endemic to the African continent. RVF is characterized by high rate of abortions in ruminants and hemorrhagic fever, encephalitis or blindness in humans. RVF is caused by the Rift Valley fever virus (RVFV: genus Phlebovirus, family Bunyaviridae. Vaccination is the only known effective strategy to prevent the disease, but there are no licensed RVF vaccines available for humans. A live-attenuated vaccine candidate derived from the wild-type pathogenic Egyptian ZH548 strain, MP-12, has been conditionally licensed for veterinary use in the United States. MP-12 displays a temperature-sensitive (ts phenotype and does not replicate at 41oC. The ts mutation limits viral replication at a specific body temperature and may lead to an attenuation of the virus. Here we will review well-characterized ts mutations for RNA viruses, and further discuss the potential in designing novel live-attenuated vaccines for RVF.

  14. Premature emphysema in AIDS

    International Nuclear Information System (INIS)

    Kuhlman, J.E.; Fishman, E.K.; Zerhouni, E.A.; Knowles, M.

    1988-01-01

    The CT scans of 55 patients with acquired immunodeficiency syndrome (AIDS) were reviewed for evidence of pulmonary emphysema. While the average age of patients in this series was 38 years, 25 of the 55 patients, or 45%, demonstrated CT evidence of emphysema. CT findings suggestive of emphysema included areas of low-attenuation, blebs and/or vascular disruption. The authors conclude there is an increased incidence of CT-detectable pulmonary emphysema that is premature for age in patients with AIDS. Destruction of pulmonary parenchyma may represent the response of the lung to repeated pulmonary infections or may be a direct result of the human immunodeficiency virus

  15. A single-dose live-attenuated vaccine prevents Zika virus pregnancy transmission and testis damage.

    Science.gov (United States)

    Shan, Chao; Muruato, Antonio E; Jagger, Brett W; Richner, Justin; Nunes, Bruno T D; Medeiros, Daniele B A; Xie, Xuping; Nunes, Jannyce G C; Morabito, Kaitlyn M; Kong, Wing-Pui; Pierson, Theodore C; Barrett, Alan D; Weaver, Scott C; Rossi, Shannan L; Vasconcelos, Pedro F C; Graham, Barney S; Diamond, Michael S; Shi, Pei-Yong

    2017-09-22

    Zika virus infection during pregnancy can cause congenital abnormities or fetal demise. The persistence of Zika virus in the male reproductive system poses a risk of sexual transmission. Here we demonstrate that live-attenuated Zika virus vaccine candidates containing deletions in the 3' untranslated region of the Zika virus genome (ZIKV-3'UTR-LAV) prevent viral transmission during pregnancy and testis damage in mice, as well as infection of nonhuman primates. After a single-dose vaccination, pregnant mice challenged with Zika virus at embryonic day 6 and evaluated at embryonic day 13 show markedly diminished levels of viral RNA in maternal, placental, and fetal tissues. Vaccinated male mice challenged with Zika virus were protected against testis infection, injury, and oligospermia. A single immunization of rhesus macaques elicited a rapid and robust antibody response, conferring complete protection upon challenge. Furthermore, the ZIKV-3'UTR-LAV vaccine candidates have a desirable safety profile. These results suggest that further development of ZIKV-3'UTR-LAV is warranted for humans.Zika virus infection can result in congenital disorders and cause disease in adults, and there is currently no approved vaccine. Here Shan et al. show that a single dose of a live-attenuated Zika vaccine prevents infection, testis damage and transmission to the fetus during pregnancy in different animal models.

  16. Cross-Protection against Marburg Virus Strains by Using a Live, Attenuated Recombinant Vaccine

    National Research Council Canada - National Science Library

    Daddario-DiCaprio, Kathleen M; Geisbert, Thomas W; Geisbert, Joan B; Stroeher, Ute; Hensley, Lisa E; Grolla, Allen; Fritz, Elizabeth A; Feldmann, Friederike; Feldmann, Heinz; Jones, Steven M

    2006-01-01

    .... MARV is also considered to have potential as a biological weapon. Recently, we reported the development of a promising attenuated, replication-competent vaccine against MARV based on recombinant vesicular stomatitis virus (VSV...

  17. Rapid strategy for screening by pyrosequencing of influenza virus reassortants--candidates for live attenuated vaccines.

    Science.gov (United States)

    Shcherbik, Svetlana V; Pearce, Nicholas C; Levine, Marnie L; Klimov, Alexander I; Villanueva, Julie M; Bousse, Tatiana L

    2014-01-01

    Live attenuated influenza vaccine viruses (LAIVs) can be generated by classical reassortment of gene segments between a cold adapted, temperature sensitive and attenuated Master Donor Virus (MDV) and a seasonal wild-type (wt) virus. The vaccine candidates contain hemagglutinin (HA) and neuraminidase (NA) genes derived from the circulating wt viruses and the remaining six genes derived from the MDV strains. Rapid, efficient selection of the viruses with 6∶2 genome compositions from the large number of genetically different viruses generated during reassortment is essential for the biannual production schedule of vaccine viruses. This manuscript describes a new approach for the genotypic analysis of LAIV reassortant virus clones based on pyrosequencing. LAIV candidate viruses were created by classical reassortment of seasonal influenza A (H3N2) (A/Victoria/361/2011, A/Ohio/02/2012, A/Texas/50/2012) or influenza A (H7N9) (A/Anhui/1/2013) wt viruses with the MDV A/Leningrad/134/17/57(H2N2). Using strain-specific pyrosequencing assays, mixed gene variations were detected in the allantoic progenies during the cloning procedure. The pyrosequencing analysis also allowed for estimation of the relative abundance of segment variants in mixed populations. This semi-quantitative approach was used for selecting specific clones for the subsequent cloning procedures. The present study demonstrates that pyrosequencing analysis is a useful technique for rapid and reliable genotyping of reassortants and intermediate clones during the preparation of LAIV candidates, and can expedite the selection of vaccine virus candidates.

  18. Rapid strategy for screening by pyrosequencing of influenza virus reassortants--candidates for live attenuated vaccines.

    Directory of Open Access Journals (Sweden)

    Svetlana V Shcherbik

    Full Text Available BACKGROUND: Live attenuated influenza vaccine viruses (LAIVs can be generated by classical reassortment of gene segments between a cold adapted, temperature sensitive and attenuated Master Donor Virus (MDV and a seasonal wild-type (wt virus. The vaccine candidates contain hemagglutinin (HA and neuraminidase (NA genes derived from the circulating wt viruses and the remaining six genes derived from the MDV strains. Rapid, efficient selection of the viruses with 6∶2 genome compositions from the large number of genetically different viruses generated during reassortment is essential for the biannual production schedule of vaccine viruses. METHODOLOGY/PRINCIPAL FINDINGS: This manuscript describes a new approach for the genotypic analysis of LAIV reassortant virus clones based on pyrosequencing. LAIV candidate viruses were created by classical reassortment of seasonal influenza A (H3N2 (A/Victoria/361/2011, A/Ohio/02/2012, A/Texas/50/2012 or influenza A (H7N9 (A/Anhui/1/2013 wt viruses with the MDV A/Leningrad/134/17/57(H2N2. Using strain-specific pyrosequencing assays, mixed gene variations were detected in the allantoic progenies during the cloning procedure. The pyrosequencing analysis also allowed for estimation of the relative abundance of segment variants in mixed populations. This semi-quantitative approach was used for selecting specific clones for the subsequent cloning procedures. CONCLUSIONS/SIGNIFICANCE: The present study demonstrates that pyrosequencing analysis is a useful technique for rapid and reliable genotyping of reassortants and intermediate clones during the preparation of LAIV candidates, and can expedite the selection of vaccine virus candidates.

  19. Mechanism of Cytotoxicity of the AIDS Virus, HTLV-III/LAV

    Science.gov (United States)

    1990-06-25

    AIDS) and associated diseases . Studies of related viruses , simian inmunodeficiency virus (SIV) and HIV-1, complement these studies and allow additional...envelope alterations in inmune evasion and tissue tropism. 20 DISTRIBUTIONIAVAILASILITY OF ABSTRACT j21 ABSTRACT SECURITY CLASSIFICATION O- UNCLASSIFMI...the pathogenesis of HIV-1 infections in vivo, and to the development of vaccines for this disease . It is clear that HIV-l’s are a heterogeneous

  20. Identification of an attenuated barley stripe mosaic virus for the virus-induced gene silencing of pathogenesis-related wheat genes.

    Science.gov (United States)

    Buhrow, Leann M; Clark, Shawn M; Loewen, Michele C

    2016-01-01

    Virus-induced gene silencing (VIGS) has become an emerging technology for the rapid, efficient functional genomic screening of monocot and dicot species. The barley stripe mosaic virus (BSMV) has been described as an effective VIGS vehicle for the evaluation of genes involved in wheat and barley phytopathogenesis; however, these studies have been obscured by BSMV-induced phenotypes and defense responses. The utility of BSMV VIGS may be improved using a BSMV genetic background which is more tolerable to the host plant especially upon secondary infection of highly aggressive, necrotrophic pathogens such as Fusarium graminearum. BSMV-induced VIGS in Triticum aestivum (bread wheat) cv. 'Fielder' was assessed for the study of wheat genes putatively related to Fusarium Head Blight (FHB), the necrotrophism of wheat and other cereals by F. graminearum. Due to the lack of 'Fielder' spike viability and increased accumulation of Fusarium-derived deoxynivalenol contamination upon co-infection of BSMV and FHB, an attenuated BSMV construct was generated by the addition of a glycine-rich, C-terminal peptide to the BSMV γ b protein. This attenuated BSMV effectively silenced target wheat genes while limiting disease severity, deoxynivalenol contamination, and yield loss upon Fusarium co-infection compared to the original BSMV construct. The attenuated BSMV-infected tissue exhibited reduced abscisic, jasmonic, and salicylic acid defense phytohormone accumulation upon secondary Fusarium infection. Finally, the attenuated BSMV was used to investigate the role of the salicylic acid-responsive pathogenesis-related 1 in response to FHB. The use of an attenuated BSMV may be advantageous in characterizing wheat genes involved in phytopathogenesis, including Fusarium necrotrophism, where minimal viral background effects on defense are required. Additionally, the attenuated BSMV elicits reduced defense hormone accumulation, suggesting that this genotype may have applications for the

  1. Role of the ubiquitin system and tumor viruses in AIDS-related cancer

    Directory of Open Access Journals (Sweden)

    Pagano Joseph S

    2007-11-01

    Full Text Available Abstract Tumor viruses are linked to approximately 20% of human malignancies worldwide. This review focuses on examples of human oncogenic viruses that manipulate the ubiquitin system in a subset of viral malignancies; those associated with AIDS. The viruses include Kaposi's sarcoma herpesvirus, Epstein-Barr virus and human papilloma virus, which are causally linked to Kaposi's sarcoma, certain B-cell lymphomas and cervical cancer, respectively. We discuss the molecular mechanisms by which these viruses subvert the ubiquitin system and potential viral targets for anti-cancer therapy from the perspective of this system. Publication history: Republished from Current BioData's Targeted Proteins database (TPdb; http://www.targetedproteinsdb.com.

  2. Attenuation of virus production at high multiplicities of infection in Aureococcus anophagefferens

    Energy Technology Data Exchange (ETDEWEB)

    Brown, Christopher M.; Bidle, Kay D., E-mail: bidle@marine.rutgers.edu

    2014-10-15

    Infection dynamics (saturation kinetics, infection efficiency, adsorption and burst size) for the Aureococcus anophagefferens-Brown Tide virus (AaV) system were investigated using susceptible and resistant strains. Adsorption assays revealed that virus affinity to the cell surface is a key determinant of infectivity. Saturation of infection occurred at a multiplicity of infection (MOI) of 8 viruses per host and resulted in ∼90–95% of infected cells, with burst sizes ranging from 164 to 191. Insight from the AaV genome implicates recycling of host nucleotides rather than de novo synthesis as a constraint on viral replication. Viral yields and mean burst sizes were significantly diminished with increasing MOI. This phenomenon, which was reminiscent of phage-induced ‘lysis from without’, appeared to be caused by viral contact and was unrelated to bacteria, signaling/toxic compounds, or defective interfering viruses. We posit that high-MOI effects attenuate viral proliferation in natural systems providing a negative feedback on virus-induced bloom collapse.

  3. Expression of the Surface Glycoproteins of Human Parainfluenza Virus Type 3 by Bovine Parainfluenza Virus Type 3, a Novel Attenuated Virus Vaccine Vector

    OpenAIRE

    Haller, Aurelia A.; Miller, Tessa; Mitiku, Misrach; Coelingh, Kathleen

    2000-01-01

    Bovine parainfluenza virus type 3 (bPIV3) is being evaluated as an intranasal vaccine for protection against human PIV3 (hPIV3). In young infants, the bPIV3 vaccine appears to be infectious, attenuated, immunogenic, and genetically stable, which are desirable characteristics for an RNA virus vector. To test the potential of the bPIV3 vaccine strain as a vector, an infectious DNA clone of bPIV3 was assembled and recombinant bPIV3 (r-bPIV3) was rescued. r-bPIV3 displayed a temperature-sensitive...

  4. Association between biological properties of human immunodeficiency virus variants and risk for AIDS and AIDS mortality

    NARCIS (Netherlands)

    Tersmette, M.; Lange, J. M.; de Goede, R. E.; de Wolf, F.; Eeftink-Schattenkerk, J. K.; Schellekens, P. T.; Coutinho, R. A.; Huisman, J. G.; Goudsmit, J.; Miedema, F.

    1989-01-01

    49 individuals seropositive for human immunodeficiency virus (HIV) antibody were studied longitudinally for the relation between in-vitro properties of their sequential HIV isolates and clinical course before and after the development of AIDS. They were classified into three groups according to the

  5. Detection of polyomavirus simian virus 40 tumor antigen DNA in AIDS-related systemic non-Hodgkin lymphoma

    Science.gov (United States)

    Vilchez, Regis A.; Lednicky, John A.; Halvorson, Steven J.; White, Zoe S.; Kozinetz, Claudia A.; Butel, Janet S.

    2002-01-01

    Systemic non-Hodgkin lymphoma (S-NHL) is a common malignancy during HIV infection, and it is hypothesized that infectious agents may be involved in the etiology. Epstein-Barr virus DNA is found in <40% of patients with AIDS-related S-NHL, suggesting that other oncogenic viruses, such as polyomaviruses, may play a role in pathogenesis. We analyzed AIDS-related S-NHL samples, NHL samples from HIV-negative patients, peripheral blood leukocytes from HIV-infected and -uninfected patients without NHL, and lymph nodes without tumors from HIV-infected patients. Specimens were examined by polymerase chain reaction analysis with use of primers specific for an N-terminal region of the oncoprotein large tumor antigen ( T-ag ) gene conserved among all three polyomaviruses (simian virus 40 [SV40], JC virus, and BK virus). Polyomavirus T-ag DNA sequences, proven to be SV40-specific, were detected more frequently in AIDS-related S-NHL samples (6 of 26) than in peripheral blood leukocytes from HIV-infected patients (6 of 26 vs. 0 of 69; p =.0001), NHL samples from HIV-negative patients (6 of 26 vs. 0 of 10; p =.09), or lymph nodes (6 of 26 vs. 0 of 7; p =.16). Sequences of C-terminal T-ag DNA from SV40 were amplified from two AIDS-related S-NHL samples. Epstein-Barr virus DNA sequences were detected in 38% (10 of 26) AIDS-related S-NHL samples, 50% (5 of 10) HIV-negative S-NHL samples, and 57% (4 of 7) lymph nodes. None of the S-NHL samples were positive for both Epstein-Barr virus DNA and SV40 DNA. Further studies of the possible role of SV40 in the pathogenesis of S-NHL are warranted.

  6. In vitro reassortment between endemic H1N2 and 2009 H1N1 pandemic swine influenza viruses generates attenuated viruses.

    Directory of Open Access Journals (Sweden)

    Ben M Hause

    Full Text Available The pandemic H1N1 (pH1N1 influenza virus was first reported in humans in the spring of 2009 and soon thereafter was identified in numerous species, including swine. Reassortant viruses, presumably arising from the co-infection of pH1N1 and endemic swine influenza virus (SIV, were subsequently identified from diagnostic samples collected from swine. In this study, co-infection of swine testicle (ST cells with swine-derived endemic H1N2 (MN745 and pH1N1 (MN432 yielded two reassortant H1N2 viruses (R1 and R2, both possessing a matrix gene derived from pH1N1. In ST cells, the reassortant viruses had growth kinetics similar to the parental H1N2 virus and reached titers approximately 2 log(10 TCID(50/mL higher than the pH1N1 virus, while in A549 cells these viruses had similar growth kinetics. Intranasal challenge of pigs with H1N2, pH1N1, R1 or R2 found that all viruses were capable of infecting and transmitting between direct contact pigs as measured by real time reverse transcription PCR of nasal swabs. Lung samples were also PCR-positive for all challenge groups and influenza-associated microscopic lesions were detected by histology. Interestingly, infectious virus was detected in lung samples for pigs challenged with the parental H1N2 and pH1N1 at levels significantly higher than either reassortant virus despite similar levels of viral RNA. Results of our experiment suggested that the reassortant viruses generated through in vitro cell culture system were attenuated without gaining any selective growth advantage in pigs over the parental lineages. Thus, reassortant influenza viruses described in this study may provide a good system to study genetic basis of the attenuation and its mechanism.

  7. Attenuation of monkeypox virus by deletion of genomic regions

    Science.gov (United States)

    Lopera, Juan G.; Falendysz, Elizabeth A.; Rocke, Tonie E.; Osorio, Jorge E.

    2015-01-01

    Monkeypox virus (MPXV) is an emerging pathogen from Africa that causes disease similar to smallpox. Two clades with different geographic distributions and virulence have been described. Here, we utilized bioinformatic tools to identify genomic regions in MPXV containing multiple virulence genes and explored their roles in pathogenicity; two selected regions were then deleted singularly or in combination. In vitro and in vivostudies indicated that these regions play a significant role in MPXV replication, tissue spread, and mortality in mice. Interestingly, while deletion of either region led to decreased virulence in mice, one region had no effect on in vitro replication. Deletion of both regions simultaneously also reduced cell culture replication and significantly increased the attenuation in vivo over either single deletion. Attenuated MPXV with genomic deletions present a safe and efficacious tool in the study of MPX pathogenesis and in the identification of genetic factors associated with virulence.

  8. Foot-and-mouth disease virus type O specific mutations determine RNA-dependent RNA polymerase fidelity and virus attenuation.

    Science.gov (United States)

    Li, Chen; Wang, Haiwei; Yuan, Tiangang; Woodman, Andrew; Yang, Decheng; Zhou, Guohui; Cameron, Craig E; Yu, Li

    2018-05-01

    Previous studies have shown that the FMDV Asia1/YS/CHA/05 high-fidelity mutagen-resistant variants are attenuated (Zeng et al., 2014). Here, we introduced the same single or multiple-amino-acid substitutions responsible for increased 3D pol fidelity of type Asia1 FMDV into the type O FMDV O/YS/CHA/05 infectious clone. The rescued viruses O-DA and O-DAMM are lower replication fidelity mutants and showed an attenuated phenotype. These results demonstrated that the same amino acid substitution of 3D pol in different serotypes of FMDV strains had different effects on viral fidelity. In addition, nucleoside analogues were used to select high-fidelity mutagen-resistant type O FMDV variants. The rescued mutagen-resistant type O FMDV high-fidelity variants exhibited significantly attenuated fitness and a reduced virulence phenotype. These results have important implications for understanding the molecular mechanism of FMDV evolution and pathogenicity, especially in developing a safer modified live-attenuated vaccine against FMDV. Copyright © 2018 Elsevier Inc. All rights reserved.

  9. Association of the Host Immune Response with Protection Using a Live Attenuated African Swine Fever Virus Model.

    Science.gov (United States)

    Carlson, Jolene; O'Donnell, Vivian; Alfano, Marialexia; Velazquez Salinas, Lauro; Holinka, Lauren G; Krug, Peter W; Gladue, Douglas P; Higgs, Stephen; Borca, Manuel V

    2016-10-22

    African swine fever (ASF) is a lethal hemorrhagic disease of swine caused by a double-stranded DNA virus, ASF virus (ASFV). There is no vaccine to prevent the disease and current control measures are limited to culling and restricting animal movement. Swine infected with attenuated strains are protected against challenge with a homologous virulent virus, but there is limited knowledge of the host immune mechanisms generating that protection. Swine infected with Pretoriuskop/96/4 (Pret4) virus develop a fatal severe disease, while a derivative strain lacking virulence-associated gene 9GL (Pret4Δ9GL virus) is completely attenuated. Swine infected with Pret4Δ9GL virus and challenged with the virulent parental virus at 7, 10, 14, 21, and 28 days post infection (dpi) showed a progressive acquisition of protection (from 40% at 7 dpi to 80% at 21 and 28 dpi). This animal model was used to associate the presence of host immune response (ASFV-specific antibody and interferon (IFN)-γ responses, or specific cytokine profiles) and protection against challenge. With the exception of ASFV-specific antibodies in survivors challenged at 21 and 28 dpi, no association between the parameters assessed and protection could be established. These results, encompassing data from 65 immunized swine, underscore the complexity of the system under study, suggesting that protection relies on the concurrence of different host immune mechanisms.

  10. Newcastle disease virus-attenuated vaccine co-contaminated with fowl adenovirus and chicken infectious anemia virus results in inclusion body hepatitis-hydropericardium syndrome in poultry.

    Science.gov (United States)

    Su, Qi; Li, Yang; Meng, Fanfeng; Cui, Zhizhong; Chang, Shuang; Zhao, Peng

    2018-05-01

    Inclusion body hepatitis-hydropericardium syndrome (IBH-HPS) induced by fowl adenovirus type 4 (FAdV-4) has caused huge economic losses to the poultry industry of China, but the source of infection for different flocks, especially flocks with high biological safety conditions, has remained unclear. This study tested the pathogenicity of Newcastle disease virus (NDV)-attenuated vaccine from a large-scale poultry farm in China where IBH-HPS had appeared with high mortality. Analysis revealed that the NDV-attenuated vaccine in use from the abovementioned poultry farm was simultaneously contaminated with FAdV-4 and chicken infectious anemia virus (CIAV). The FAdV and CIAV isolated from the vaccine were purified for the artificial preparation of an NDV-attenuated vaccine singly contaminated with FAdV or CIAV, or simultaneously contaminated with both of them. Seven-day-old specific pathogen-free chicks were inoculated with the artificially prepared contaminated vaccines and tested for corresponding indices. The experiments showed that no hydropericardium syndrome (HPS) and corresponding death occurred after administering the NDV-attenuated vaccine singly contaminated with FAdV or CIAV, but a mortality of 75% with IBH-HPS was commonly found in birds after administering the NDV-attenuated vaccine co-contaminated with FAdV and CIAV. In conclusion, this study found the co-contamination of FAdV-4 and CIAV in the same attenuated vaccine and confirmed that such a contaminated attenuated vaccine was a significant source of infection for outbreaks of IBH-HPS in some flocks. Copyright © 2018 Elsevier B.V. All rights reserved.

  11. MALT1 Controls Attenuated Rabies Virus by Inducing Early Inflammation and T Cell Activation in the Brain.

    Science.gov (United States)

    Kip, E; Staal, J; Verstrepen, L; Tima, H G; Terryn, S; Romano, M; Lemeire, K; Suin, V; Hamouda, A; Kalai, M; Beyaert, R; Van Gucht, S

    2018-04-15

    MALT1 is involved in the activation of immune responses, as well as in the proliferation and survival of certain cancer cells. MALT1 acts as a scaffold protein for NF-κB signaling and a cysteine protease that cleaves substrates, further promoting the expression of immunoregulatory genes. Deregulated MALT1 activity has been associated with autoimmunity and cancer, implicating MALT1 as a new therapeutic target. Although MALT1 deficiency has been shown to protect against experimental autoimmune encephalomyelitis, nothing is known about the impact of MALT1 on virus infection in the central nervous system. Here, we studied infection with an attenuated rabies virus, Evelyn-Rotnycki-Abelseth (ERA) virus, and observed increased susceptibility with ERA virus in MALT1 -/- mice. Indeed, after intranasal infection with ERA virus, wild-type mice developed mild transient clinical signs with recovery at 35 days postinoculation (dpi). Interestingly, MALT1 -/- mice developed severe disease requiring euthanasia at around 17 dpi. A decreased induction of inflammatory gene expression and cell infiltration and activation was observed in MALT1 -/- mice at 10 dpi compared to MALT1 +/+ infected mice. At 17 dpi, however, the level of inflammatory cell activation was comparable to that observed in MALT1 +/+ mice. Moreover, MALT1 -/- mice failed to produce virus-neutralizing antibodies. Similar results were obtained with specific inactivation of MALT1 in T cells. Finally, treatment of wild-type mice with mepazine, a MALT1 protease inhibitor, also led to mortality upon ERA virus infection. These data emphasize the importance of early inflammation and activation of T cells through MALT1 for controlling the virulence of an attenuated rabies virus in the brain. IMPORTANCE Rabies virus is a neurotropic virus which can infect any mammal. Annually, 59,000 people die from rabies. Effective therapy is lacking and hampered by gaps in the understanding of virus pathogenicity. MALT1 is an intracellular

  12. AIDS

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/000594.htm HIV/AIDS To use the sharing features on this page, ... immunodeficiency virus (HIV) is the virus that causes AIDS. When a person becomes infected with HIV, the ...

  13. Live Zika virus chimeric vaccine candidate based on a yellow fever 17-D attenuated backbone

    OpenAIRE

    Nougairede, Antoine; Klitting, Raphaelle; Aubry, Fabien; Gilles, Magali; Touret, Franck; De Lamballerie, Xavier

    2018-01-01

    Zika virus (ZIKV) recently dispersed throughout the tropics and sub-tropics causing epidemics associated with congenital disease and neurological complications. There is currently no commercial vaccine for ZIKV. Here we describe the initial development of a chimeric virus containing the prM/E proteins of a ZIKV epidemic strain incorporated into a yellow fever 17-D attenuated backbone. Using the versatile and rapid ISA (Infectious Subgenomic Amplicons) reverse genetics method, we compared diff...

  14. The supposedly attenuated Hy-HK variant of highly virulent Hypr strain of Tick-borne encephalitis virus is obviously a strain of Langat virus

    Czech Academy of Sciences Publication Activity Database

    Růžek, Daniel; Štěrba, Ján; Kopecký, Jan; Grubhoffer, Libor

    2006-01-01

    Roč. 50, č. 4 (2006), s. 277-278 ISSN 0001-723X R&D Projects: GA ČR(CZ) GA524/06/1479 Grant - others:Grant Agency of the University of South Bohemia(CZ) 35/2005/P-BF Institutional research plan: CEZ:AV0Z60220518 Keywords : TBE virus * Langat virus * Hy-HK attenuated variant Subject RIV: GJ - Animal Vermins ; Diseases, Veterinary Medicine Impact factor: 0.788, year: 2006

  15. The temperature-sensitive and attenuation phenotypes conferred by mutations in the influenza virus PB2, PB1, and NP genes are influenced by the species of origin of the PB2 gene in reassortant viruses derived from influenza A/California/07/2009 and A/WSN/33 viruses.

    Science.gov (United States)

    Broadbent, Andrew J; Santos, Celia P; Godbout, Rachel A; Subbarao, Kanta

    2014-11-01

    Live attenuated influenza vaccines in the United States are derived from a human virus that is temperature sensitive (ts), characterized by restricted (≥ 100-fold) replication at 39 °C. The ts genetic signature (ts sig) has been mapped to 5 loci in 3 genes: PB1 (391 E, 581 G, and 661 T), PB2 (265 S), and NP (34 G). However, when transferred into avian and swine influenza viruses, only partial ts and attenuation phenotypes occur. To investigate the reason for this, we introduced the ts sig into the human origin virus A/WSN/33 (WSN), the avian-origin virus A/Vietnam/1203/04 (VN04), and the swine origin triple-reassortant 2009 pandemic H1N1 virus A/California/07/2009 (CA07), which contains gene segments from human, avian, and swine viruses. The VN04(ts sig) and CA07(ts sig) viruses replicated efficiently in Madin-Darby canine kidney (MDCK) cells at 39 °C, but the replication of WSN(ts sig) was restricted ≥ 100-fold compared to that at 33 °C. Reassortant CA07(ts sig) viruses were generated with individual polymerase gene segments from WSN, and vice versa. Only ts sig viruses with a PB2 gene segment derived from WSN were restricted in replication ≥ 100-fold at 39 °C. In ferrets, the CA07(ts sig) virus replicated in the upper and lower respiratory tract, but the replication of a reassortant CA07(ts sig) virus with a WSN PB2 gene was severely restricted in the lungs. Taken together, these data suggest that the origin of the PB2 gene segment influences the ts phenotype in vitro and attenuation in vivo. This could have implications for the design of novel live vaccines against animal origin influenza viruses. Live attenuated influenza vaccines (LAIVs) on temperature-sensitive (ts) backbones derived from animal origin influenza viruses are being sought for use in the poultry and swine industries and to protect people against animal origin influenza. However, inserting the ts genetic signature from a licensed LAIV backbone fails to fully attenuate these viruses. Our

  16. Association of the Host Immune Response with Protection Using a Live Attenuated African Swine Fever Virus Model

    Directory of Open Access Journals (Sweden)

    Jolene Carlson

    2016-10-01

    Full Text Available African swine fever (ASF is a lethal hemorrhagic disease of swine caused by a double-stranded DNA virus, ASF virus (ASFV. There is no vaccine to prevent the disease and current control measures are limited to culling and restricting animal movement. Swine infected with attenuated strains are protected against challenge with a homologous virulent virus, but there is limited knowledge of the host immune mechanisms generating that protection. Swine infected with Pretoriuskop/96/4 (Pret4 virus develop a fatal severe disease, while a derivative strain lacking virulence-associated gene 9GL (Pret4Δ9GL virus is completely attenuated. Swine infected with Pret4Δ9GL virus and challenged with the virulent parental virus at 7, 10, 14, 21, and 28 days post infection (dpi showed a progressive acquisition of protection (from 40% at 7 dpi to 80% at 21 and 28 dpi. This animal model was used to associate the presence of host immune response (ASFV-specific antibody and interferon (IFN-γ responses, or specific cytokine profiles and protection against challenge. With the exception of ASFV-specific antibodies in survivors challenged at 21 and 28 dpi, no association between the parameters assessed and protection could be established. These results, encompassing data from 65 immunized swine, underscore the complexity of the system under study, suggesting that protection relies on the concurrence of different host immune mechanisms.

  17. Pre- and post-exposure safety and efficacy of attenuated rabies virus vaccines are enhanced by their expression of IFNγ

    Energy Technology Data Exchange (ETDEWEB)

    Barkhouse, Darryll A. [Department of Cancer Biology, 1020 Locust St., Jefferson Alumni Hall, Room 454, Philadelphia, PA 19107 (United States); Center for Neurovirology 1020 Locust St., Jefferson Alumni Hall, Room 454, Philadelphia, PA 19107 (United States); Faber, Milosz [Center for Neurovirology 1020 Locust St., Jefferson Alumni Hall, Room 454, Philadelphia, PA 19107 (United States); Department of Microbiology and Immunology 1020 Locust St., Jefferson Alumni Hall, Room 465, Philadelphia, PA 19107 (United States); Hooper, D. Craig, E-mail: douglas.hooper@jefferson.edu [Department of Cancer Biology, 1020 Locust St., Jefferson Alumni Hall, Room 454, Philadelphia, PA 19107 (United States); Department of Neurological Surgery, 1020 Locust St., Jefferson Alumni Hall, Room 454, Philadelphia, PA 19107 (United States); Center for Neurovirology 1020 Locust St., Jefferson Alumni Hall, Room 454, Philadelphia, PA 19107 (United States)

    2015-01-01

    Consistent with evidence of a strong correlation between interferon gamma (IFNγ) production and rabies virus (RABV) clearance from the CNS, we recently demonstrated that engineering a pathogenic RABV to express IFNγ highly attenuates the virus. Reasoning that IFNγ expression by RABV vaccines would enhance their safety and efficacy, we reverse-engineered two proven vaccine vectors, GAS and GASGAS, to express murine IFNγ. Mortality and morbidity were monitored during suckling mice infection, immunize/challenge experiments and mixed intracranial infections. We demonstrate that GASγ and GASγGAS are significantly attenuated in suckling mice compared to the GASGAS vaccine. GASγ better protects mice from lethal DRV4 RABV infection in both pre- and post-exposure experiments compared to GASGAS. Finally, GASγGAS reduces post-infection neurological sequelae, compared to control, during mixed intracranial infection with DRV4. These data show IFNγ expression by a vaccine vector can enhance its safety while increasing its efficacy as pre- and post-exposure treatment. - Highlights: • IFNγ expression improves attenuated rabies virus safety and immunogenicity. • IFNγ expression is safer and more immunogenic than doubling glycoprotein expression. • Co-infection with IFNγ-expressing RABV prevents wild-type rabies virus lethality. • Vaccine safety and efficacy is additive for IFNγ and double glycoprotein expression.

  18. Pre- and post-exposure safety and efficacy of attenuated rabies virus vaccines are enhanced by their expression of IFNγ

    International Nuclear Information System (INIS)

    Barkhouse, Darryll A.; Faber, Milosz; Hooper, D. Craig

    2015-01-01

    Consistent with evidence of a strong correlation between interferon gamma (IFNγ) production and rabies virus (RABV) clearance from the CNS, we recently demonstrated that engineering a pathogenic RABV to express IFNγ highly attenuates the virus. Reasoning that IFNγ expression by RABV vaccines would enhance their safety and efficacy, we reverse-engineered two proven vaccine vectors, GAS and GASGAS, to express murine IFNγ. Mortality and morbidity were monitored during suckling mice infection, immunize/challenge experiments and mixed intracranial infections. We demonstrate that GASγ and GASγGAS are significantly attenuated in suckling mice compared to the GASGAS vaccine. GASγ better protects mice from lethal DRV4 RABV infection in both pre- and post-exposure experiments compared to GASGAS. Finally, GASγGAS reduces post-infection neurological sequelae, compared to control, during mixed intracranial infection with DRV4. These data show IFNγ expression by a vaccine vector can enhance its safety while increasing its efficacy as pre- and post-exposure treatment. - Highlights: • IFNγ expression improves attenuated rabies virus safety and immunogenicity. • IFNγ expression is safer and more immunogenic than doubling glycoprotein expression. • Co-infection with IFNγ-expressing RABV prevents wild-type rabies virus lethality. • Vaccine safety and efficacy is additive for IFNγ and double glycoprotein expression

  19. Capsid proteins from field strains of foot-and-mouth disease virus confer a pathogenic phenotype in cattle on an attenuated, cell-culture-adapted virus

    DEFF Research Database (Denmark)

    Bøtner, Anette; Kakker, Naresh K.; Barbezange, Cyril

    2011-01-01

    Chimeric foot-and-mouth disease viruses (FMDVs) have been generated from plasmids containing full-length FMDV cDNAs and characterized. The parental virus cDNA was derived from the cell-culture-adapted O1Kaufbeuren B64 (O1K B64) strain. Chimeric viruses, containing capsid coding sequences derived...... cells than the rescued parental O1K B64 virus. The two chimeric viruses displayed the expected antigenicity in serotype-specific antigen ELISAs. Following inoculation of each virus into cattle, the rescued O1K B64 strain proved to be attenuated whereas, with each chimeric virus, typical clinical signs...... region within the O1K B64 strain that inhibits replication in cattle. These chimeric infectious cDNA plasmids provide a basis for the analysis of FMDV pathogenicity and characterization of receptor utilization in vivo....

  20. Absolute level of Epstein-Barr virus DNA in human immunodeficiency virus type 1 infection is not predictive of AIDS-related non-Hodgkin lymphoma

    NARCIS (Netherlands)

    van Baarle, Debbie; Wolthers, Katja C.; Hovenkamp, Egbert; Niesters, Hubert G. M.; Osterhaus, Albert D. M. E.; Miedema, Frank; van Oers, Marinus H. J.

    2002-01-01

    To study whether Epstein-Barr virus (EBV) load can be used to predict the occurrence of acquired immunodeficiency syndrome-related non-Hodgkin lymphoma (AIDS-NHL), we determined EBV load longitudinally for individuals infected with human immunodeficiency virus type 1. EBV load in peripheral blood

  1. Evaluation of synthetic infection-enhancing lipopeptides as adjuvants for a live-attenuated canine distemper virus vaccine administered intra-nasally to ferrets.

    Science.gov (United States)

    Nguyen, D Tien; Ludlow, Martin; van Amerongen, Geert; de Vries, Rory D; Yüksel, Selma; Verburgh, R Joyce; Osterhaus, Albert D M E; Duprex, W Paul; de Swart, Rik L

    2012-07-20

    Inactivated paramyxovirus vaccines have been associated with hypersensitivity responses upon challenge infection. For measles and canine distemper virus (CDV) safe and effective live-attenuated virus vaccines are available, but for human respiratory syncytial virus and human metapneumovirus development of such vaccines has proven difficult. We recently identified three synthetic bacterial lipopeptides that enhance paramyxovirus infections in vitro, and hypothesized these could be used as adjuvants to promote immune responses induced by live-attenuated paramyxovirus vaccines. Here, we tested this hypothesis using a CDV vaccination and challenge model in ferrets. Three groups of six animals were intra-nasally vaccinated with recombinant (r) CDV(5804P)L(CCEGFPC) in the presence or absence of the infection-enhancing lipopeptides Pam3CSK4 or PHCSK4. The recombinant CDV vaccine virus had previously been described to be over-attenuated in ferrets. A group of six animals was mock-vaccinated as control. Six weeks after vaccination all animals were challenged with a lethal dose of rCDV strain Snyder-Hill expressing the red fluorescent protein dTomato. Unexpectedly, intra-nasal vaccination of ferrets with rCDV(5804P)L(CCEGFPC) in the absence of lipopeptides resulted in good immune responses and protection against lethal challenge infection. However, in animals vaccinated with lipopeptide-adjuvanted virus significantly higher vaccine virus loads were detected in nasopharyngeal lavages and peripheral blood mononuclear cells. In addition, these animals developed significantly higher CDV neutralizing antibody titers compared to animals vaccinated with non-adjuvanted vaccine. This study demonstrates that the synthetic cationic lipopeptides Pam3CSK4 and PHCSK4 not only enhance paramyxovirus infection in vitro, but also in vivo. Given the observed enhancement of immunogenicity their potential as adjuvants for other live-attenuated paramyxovirus vaccines should be considered

  2. Complete Genome Sequence of the Goatpox Virus Strain Gorgan Obtained Directly from a Commercial Live Attenuated Vaccine

    Science.gov (United States)

    Mathijs, Elisabeth; Vandenbussche, Frank; Haegeman, Andy; Al-Majali, Ahmad; De Clercq, Kris

    2016-01-01

    This is a report of the complete genome sequence of the goatpox virus strain Gorgan, which was obtained directly from a commercial live attenuated vaccine (Caprivac, Jordan Bio-Industries Centre). PMID:27738031

  3. Absolute level of Epstein-Barr Virus (EBV) DNA in human immunodeficiency virus type 1 infection is not predictive of AIDS-related non-Hodgkin lymphoma.

    NARCIS (Netherlands)

    D. van Baarle (Debbie); K.C. Wolthers (Katja); E. Hovenkamp (Egbert); A.D.M.E. Osterhaus (Albert); F. Miedema (Frank); M.H.J. van Oers (Marinus); H.G.M. Niesters (Bert)

    2002-01-01

    textabstractTo study whether Epstein-Barr virus (EBV) load can be used to predict the occurrence of acquired immunodeficiency syndrome-related non-Hodgkin lymphoma (AIDS-NHL), we determined EBV load longitudinally for individuals infected with human immunodeficiency virus type 1. EBV load in

  4. Induction of influenza-specific mucosal immunity by an attenuated recombinant Sendai virus.

    Directory of Open Access Journals (Sweden)

    Thuc-vy L Le

    2011-04-01

    Full Text Available Many pathogens initiate infection at the mucosal surfaces; therefore, induction of mucosal immune responses is a first level of defense against infection and is the most powerful means of protection. Although intramuscular injection is widely used for vaccination and is effective at inducing circulating antibodies, it is less effective at inducing mucosal antibodies.Here we report a novel recombinant, attenuated Sendai virus vector (GP42-H1 in which the hemagglutinin (HA gene of influenza A virus was introduced into the Sendai virus genome as an additional gene. Infection of CV-1 cells by GP42-H1 resulted in cell surface expression of the HA protein. Intranasal immunization of mice with 1,000 plaque forming units (pfu of GP42-H1 induced HA-specific IgG and IgA antibodies in the blood, bronchoalveolar lavage fluid, fecal pellet extracts and saliva. The HA-specific antibody titer induced by GP42-H1 closely resembles the titer induced by sublethal infection by live influenza virus; however, in contrast to infection by influenza virus, immunization with GP42-H1 did not result in disease symptoms or the loss of body weight. In mice that were immunized with GP42-H1 and then challenged with 5LD(50 (1250 pfu of influenza virus, no significant weight loss was observed and other visual signs of morbidity were not detected.These results demonstrate that the GP42-H1 Sendai virus recombinant is able to confer full protection from lethal infection by influenza virus, supporting the conclusion that it is a safe and effective mucosal vaccine vector.

  5. Suppressing active replication of a live attenuated simian immunodeficiency virus vaccine does not abrogate protection from challenge

    Energy Technology Data Exchange (ETDEWEB)

    Gabriel, Benjamin; Fiebig, Uwe; Hohn, Oliver [Robert Koch-Institut, Berlin (Germany); Plesker, Roland; Coulibaly, Cheick; Cichutek, Klaus; Mühlebach, Michael D. [Paul-Ehrlich-Institut, Langen (Germany); Bannert, Norbert; Kurth, Reinhard [Robert Koch-Institut, Berlin (Germany); Norley, Stephen, E-mail: NorleyS@rki.de [Robert Koch-Institut, Berlin (Germany)

    2016-02-15

    Although safety concerns preclude the use of live attenuated HIV vaccines in humans, they provide a useful system for identifying the elusive correlates of protective immunity in the SIV/macaque animal model. However, a number of pieces of evidence suggest that protection may result from prior occupancy of susceptible target cells by the vaccine virus rather than the immune response. To address this, we developed a Nef-deletion variant of an RT-SHIV whose active replication could be shut off by treatment with RT-inhibitors. Groups of macaques were inoculated with the ∆Nef-RT-SHIV and immune responses allowed to develop before antiretroviral treatment and subsequent challenge with wild-type SIVmac239. Vaccinated animals either resisted infection fully or significantly controlled the subsequent viremia. However, there was no difference between animals undergoing replication of the vaccine virus and those without. This strongly suggests that competition for available target cells does not play a role in protection. - Highlights: • A Nef-deleted RT-SHIV was used as a live attenuated vaccine in macaques. • Vaccine virus replication was shut down to investigate its role in protection. • Ongoing vaccine virus replication did not appear to be necessary for protection. • An analysis of T- and B-cell responses failed to identify a correlate of protection.

  6. Suppressing active replication of a live attenuated simian immunodeficiency virus vaccine does not abrogate protection from challenge

    International Nuclear Information System (INIS)

    Gabriel, Benjamin; Fiebig, Uwe; Hohn, Oliver; Plesker, Roland; Coulibaly, Cheick; Cichutek, Klaus; Mühlebach, Michael D.; Bannert, Norbert; Kurth, Reinhard; Norley, Stephen

    2016-01-01

    Although safety concerns preclude the use of live attenuated HIV vaccines in humans, they provide a useful system for identifying the elusive correlates of protective immunity in the SIV/macaque animal model. However, a number of pieces of evidence suggest that protection may result from prior occupancy of susceptible target cells by the vaccine virus rather than the immune response. To address this, we developed a Nef-deletion variant of an RT-SHIV whose active replication could be shut off by treatment with RT-inhibitors. Groups of macaques were inoculated with the ∆Nef-RT-SHIV and immune responses allowed to develop before antiretroviral treatment and subsequent challenge with wild-type SIVmac239. Vaccinated animals either resisted infection fully or significantly controlled the subsequent viremia. However, there was no difference between animals undergoing replication of the vaccine virus and those without. This strongly suggests that competition for available target cells does not play a role in protection. - Highlights: • A Nef-deleted RT-SHIV was used as a live attenuated vaccine in macaques. • Vaccine virus replication was shut down to investigate its role in protection. • Ongoing vaccine virus replication did not appear to be necessary for protection. • An analysis of T- and B-cell responses failed to identify a correlate of protection.

  7. Live attenuated measles vaccine expressing HIV-1 Gag virus like particles covered with gp160ΔV1V2 is strongly immunogenic

    International Nuclear Information System (INIS)

    Guerbois, Mathilde; Moris, Arnaud; Combredet, Chantal; Najburg, Valerie; Ruffie, Claude; Fevrier, Michele; Cayet, Nadege; Brandler, Samantha; Schwartz, Olivier; Tangy, Frederic

    2009-01-01

    Although a live attenuated HIV vaccine is not currently considered for safety reasons, a strategy inducing both T cells and neutralizing antibodies to native assembled HIV-1 particles expressed by a replicating virus might mimic the advantageous characteristics of live attenuated vaccine. To this aim, we generated a live attenuated recombinant measles vaccine expressing HIV-1 Gag virus-like particles (VLPs) covered with gp160ΔV1V2 Env protein. The measles-HIV virus replicated efficiently in cell culture and induced the intense budding of HIV particles covered with Env. In mice sensitive to MV infection, this recombinant vaccine stimulated high levels of cellular and humoral immunity to both MV and HIV with neutralizing activity. The measles-HIV virus infected human professional antigen-presenting cells, such as dendritic cells and B cells, and induced efficient presentation of HIV-1 epitopes and subsequent activation of human HIV-1 Gag-specific T cell clones. This candidate vaccine will be next tested in non-human primates. As a pediatric vaccine, it might protect children and adolescents simultaneously from measles and HIV.

  8. Attenuation of pathogenic Rift Valley fever virus strain through the chimeric S-segment encoding sandfly fever phlebovirus NSs or a dominant-negative PKR.

    Science.gov (United States)

    Nishiyama, Shoko; Slack, Olga A L; Lokugamage, Nandadeva; Hill, Terence E; Juelich, Terry L; Zhang, Lihong; Smith, Jennifer K; Perez, David; Gong, Bin; Freiberg, Alexander N; Ikegami, Tetsuro

    2016-11-16

    Rift Valley fever is a mosquito-borne zoonotic disease affecting ruminants and humans. Rift Valley fever virus (RVFV: family Bunyaviridae, genus Phlebovirus) causes abortions and fetal malformations in ruminants, and hemorrhagic fever, encephalitis, or retinitis in humans. The live-attenuated MP-12 vaccine is conditionally licensed for veterinary use in the US. However, this vaccine lacks a marker for the differentiation of vaccinated from infected animals (DIVA). NSs gene is dispensable for RVFV replication, and thus, rMP-12 strains lacking NSs gene is applicable to monitor vaccinated animals. However, the immunogenicity of MP-12 lacking NSs was not as high as parental MP-12. Thus, chimeric MP-12 strains encoding NSs from either Toscana virus (TOSV), sandfly fever Sicilian virus (SFSV) or Punta Toro virus Adames strain (PTA) were characterized previously. Although chimeric MP-12 strains are highly immunogenic, the attenuation through the S-segment remains unknown. Using pathogenic ZH501 strain, we aimed to demonstrate the attenuation of ZH501 strain through chimeric S-segment encoding either the NSs of TOSV, SFSV, PTA, or Punta Toro virus Balliet strain (PTB). In addition, we characterized rZH501 encoding a human dominant-negative PKR (PKRΔE7), which also enhances the immunogenicity of MP-12. Study done on mice revealed that attenuation of rZH501 occurred through the S-segment encoding either PKRΔE7 or SFSV NSs. However, rZH501 encoding either TOSV, PTA, or PTB NSs in the S-segment uniformly caused lethal encephalitis. Our results indicated that the S-segments encoding PKRΔE7 or SFSV NSs are attenuated and thus applicable toward next generation MP-12 vaccine candidates that encode a DIVA marker.

  9. Development of a dual-protective live attenuated vaccine against H5N1 and H9N2 avian influenza viruses by modifying the NS1 gene.

    Science.gov (United States)

    Choi, Eun-hye; Song, Min-Suk; Park, Su-Jin; Pascua, Philippe Noriel Q; Baek, Yun Hee; Kwon, Hyeok-il; Kim, Eun-Ha; Kim, Semi; Jang, Hyung-Kwan; Poo, Haryoung; Kim, Chul-Joong; Choi, Young Ki

    2015-07-01

    An increasing number of outbreaks of avian influenza H5N1 and H9N2 viruses in poultry have caused serious economic losses and raised concerns for human health due to the risk of zoonotic transmission. However, licensed H5N1 and H9N2 vaccines for animals and humans have not been developed. Thus, to develop a dual H5N1 and H9N2 live-attenuated influenza vaccine (LAIV), the HA and NA genes from a virulent mouse-adapted avian H5N2 (A/WB/Korea/ma81/06) virus and a recently isolated chicken H9N2 (A/CK/Korea/116/06) virus, respectively, were introduced into the A/Puerto Rico/8/34 backbone expressing truncated NS1 proteins (NS1-73, NS1-86, NS1-101, NS1-122) but still possessing a full-length NS gene. Two H5N2/NS1-LAIV viruses (H5N2/NS1-86 and H5N2/NS1-101) were highly attenuated compared with the full-length and remaining H5N2/NS-LAIV viruses in a mouse model. Furthermore, viruses containing NS1 modifications were found to induce more IFN-β activation than viruses with full-length NS1 proteins and were correspondingly attenuated in mice. Intranasal vaccination with a single dose (10(4.0) PFU/ml) of these viruses completely protected mice from a lethal challenge with the homologous A/WB/Korea/ma81/06 (H5N2), heterologous highly pathogenic A/EM/Korea/W149/06 (H5N1), and heterosubtypic highly virulent mouse-adapted H9N2 viruses. This study clearly demonstrates that the modified H5N2/NS1-LAIV viruses attenuated through the introduction of mutations in the NS1 coding region display characteristics that are desirable for live attenuated vaccines and hold potential as vaccine candidates for mammalian hosts.

  10. The yellow fever 17D virus as a platform for new live attenuated vaccines.

    Science.gov (United States)

    Bonaldo, Myrna C; Sequeira, Patrícia C; Galler, Ricardo

    2014-01-01

    The live-attenuated yellow fever 17D virus is one of the most outstanding human vaccines ever developed. It induces efficacious immune responses at a low production cost with a well-established manufacture process. These advantages make the YF17D virus attractive as a vector for the development of new vaccines. At the beginning of vector development studies, YF17D was genetically manipulated to express other flavivirus prM and E proteins, components of the viral envelope. While these 17D recombinants are based on the substitution of equivalent YF17D genes, other antigens from unrelated pathogens have also been successfully expressed and delivered by recombinant YF17D viruses employing alternative strategies for genetic manipulation of the YF17D genome. Herein, we discuss these strategies in terms of possibilities of single epitope or larger sequence expression and the main properties of these replication-competent viral platforms.

  11. Feline immunodeficiency virus model for designing HIV/AIDS vaccines.

    Science.gov (United States)

    Yamamoto, Janet K; Sanou, Missa P; Abbott, Jeffrey R; Coleman, James K

    2010-01-01

    Feline immunodeficiency virus (FIV) discovered in 1986 is a lentivirus that causes AIDS in domestic cats. FIV is classified into five subtypes (A-E), and all subtypes and circulating intersubtype recombinants have been identified throughout the world. A commercial FIV vaccine, consisting of inactivated subtype-A and -D viruses (Fel-O-Vax FIV, Fort Dodge Animal Health), was released in the United States in 2002. The United States Department of Agriculture approved the commercial release of Fel-O-Vax FIV based on two efficacy trials using 105 laboratory cats and a major safety trial performed on 689 pet cats. The prototype and commercial FIV vaccines had broad prophylactic efficacy against global FIV subtypes and circulating intersubtype recombinants. The mechanisms of cross-subtype efficacy are attributed to FIV-specific T-cell immunity. Findings from these studies are being used to define the prophylactic epitopes needed for an HIV-1 vaccine for humans.

  12. Mommy, Daddy--What's AIDS?

    Science.gov (United States)

    National Association of Pediatric Nurse Associates and Practitioners, Cherry Hill, NJ.

    This brochure is designed to help parents answer the questions that their children may ask them about Acquired Immune Deficiency Syndrome (AIDS) and the Human Immuno Deficiency Virus (HIV), the virus that causes AIDS. It provides basic information about AIDS and HIV, as well as sources for further information, such as the National AIDS Hotline. It…

  13. Development of a human live attenuated West Nile infectious DNA vaccine: Suitability of attenuating mutations found in SA14-14-2 for WN vaccine design

    Energy Technology Data Exchange (ETDEWEB)

    Yamshchikov, Vladimir, E-mail: yaximik@gmail.com; Manuvakhova, Marina; Rodriguez, Efrain

    2016-01-15

    Direct attenuation of West Nile (WN) virus strain NY99 for the purpose of vaccine development is not feasible due to its high virulence and pathogenicity. Instead, we created highly attenuated chimeric virus W1806 with the serological identity of NY99. To further attenuate W1806, we investigated effects of mutations found in Japanese encephalitis virus vaccine SA14-14-2. WN viruses carrying all attenuating mutations lost infectivity in mammalian, but not in mosquito cells. No single reversion restored infectivity in mammalian cells, although increased infectivity in mosquito cells was observed. To identify a subset of mutations suitable for further attenuation of W1806, we analyzed effects of E{sub 138}K and K{sub 279}M changes on virulence, growth properties, and immunogenicity of derivatized W956, from which chimeric W1806 inherited its biological properties and attenuation profile. Despite strong dominant attenuating effect, introduction of only two mutations was not sufficient for attenuating W1806 to the safety level acceptable for human use. - Highlights: • Further attenuation of a WN vaccine precursor is outlined. • Effect of SA14-14-2 attenuating mutations is tested. • Mechanism of attenuation is proposed and illustrated. • The need for additional attenuating mutations is justified.

  14. AIDS: the frightening facts.

    Science.gov (United States)

    Ryan, M

    1986-01-01

    Aquired Immune Deficiency Syndrome (AIDS) has succeeded in creating an unprecedented wave of panic among the Western public and some sections of the medical profession. Research clearly shows that the AIDS virus is transmissible in a number of ways: from man to woman and vice versa during sexual intercourse, through semen and possibly vaginal fluids; from mothers to their children through breast milk; through exchange of saliva (but not through just a casual kiss); and through blood and blood products. Far from being exclusive to homosexuals, studies in Europe have shown that female virus carriers can transmit AIDS to healthy men through sexual intercourse--the predominant means by which transmission appears to occur in Central Africa. Although cases of AIDS began being diagnosed in a few Central African countries at the beginning of the 1980s, at the same time as they were first being observed in Europe and North America, many commentators assumed that the virus originated in Africa. Yet, it is safe to say that the nature of the virus, let alone its origins, remains controversial among scientists and virologists. 1 supporter of the theory that the AIDS virus has African origins is Robert Gall of the US National Institute of Health (NIH). He is one of the co-discoverers of the virus, which he named HTLV3 (Human T-cell Lymphotropic Virus 3). The virus also was discovered at France's Pasteur Institute by Luc Montaigner, who called it LAV (Lymphadenpathy Associated Virus). Gallo named the virus as he did because he believes it to be related to a pair of other viruses, HTLV1 and HTLV2, which like the AIDS virus attack the body's immunity system. Unlike AIDS, these 2 viruses, do not destroy the T-cells but cause them to replicate into cancer tumors. In Gallo's view, HTLV1 has long been endemic to some parts of Africa, from where he believes it spread via the slave trade to other parts of the world. Montaigner does not agree. He denies that the AIDS virus is related to

  15. Safety and efficacy of an attenuated Chinese QX-like infectious bronchitis virus strain as a candidate vaccine.

    Science.gov (United States)

    Zhao, Ye; Cheng, Jin-long; Liu, Xiao-yu; Zhao, Jing; Hu, Yan-xin; Zhang, Guo-zhong

    2015-10-22

    Infectious bronchitis (IB) is a highly contagious respiratory and urogenital disease of chickens caused by infectious bronchitis virus (IBV). This disease is of considerable economic importance and is primarily controlled through biosecurity and immunization with live attenuated and inactivated IB vaccines of various serotypes. In the present study, we tested the safety and efficacy of an attenuated predominant Chinese QX-like IBV strain. The results revealed that the attenuated strain has a clear decrease in pathogenicity for specific-pathogen-free (SPF) chickens compared with the parent strain. Strain YN-inoculated birds had clinical signs of varying severity with 30% mortality, while the attenuated group appeared healthy, with less tissue damage. The attenuated strain also had relatively low tissue replication rates and higher antibody levels. The superior protective efficacy of the attenuated strain was observed when vaccinated birds were challenged with a homologous or heterologous field IBV strain, indicating the potential of the attenuated YN (aYN) as a vaccine. Producing a vaccine targeting the abundant serotype in China is essential to reducing the economic impact of IB on the poultry industry. Copyright © 2015 Elsevier B.V. All rights reserved.

  16. Establishment of a nanoparticle-assisted RT-PCR assay to distinguish field strains and attenuated strains of porcine epidemic diarrhea virus.

    Science.gov (United States)

    Zhu, Yu; Wang, Gui-Hua; Cui, Yu-Dong; Cui, Shang-Jin

    2016-09-01

    Porcine epidemic diarrhea virus (PEDV) can cause serious disease and even death in neonatal piglets, resulting in serious damage to the swine industry worldwide. Open reading frame 3 (ORF3) is the only accessory gene in the PEDV genome. Previous studies have indicated that PEDV vaccine strains have a partial deletion in ORF3. In this study, a nanoparticle-assisted polymerase chain reaction (nanoparticle-assisted RT-PCR) assay targeting the ORF3 of PEDV was developed to distinguish PEDV field strains from attenuated strains by using a specific pair of primers. The PCR products of field strains and attenuated strains were 264 bp and 215 bp in length, respectively. The sensitivity and specificity of this assay were also assessed. The nanoparticle-assisted RT-PCR assay was 10-100 times more sensitive than the conventional RT-PCR assay, with no cross-reactions when amplifying porcine pseudorabies virus (PRV), porcine circovirus type 2 (PCV2), classical swine fever virus (CSFV), porcine parvovirus (PPV), porcine reproductive and respiratory syndrome virus (PRRSV), porcine rotavirus (RV), and porcine transmissible gastroenteritis virus (TGEV). The nanoparticle-assisted RT-PCR assay we describe here can be used to distinguish field strains from vaccine strains of PEDV, and it shows promise for reducing economic loss due to PEDV infection.

  17. Safety and immunogenicity of a live attenuated Japanese encephalitis chimeric virus vaccine (IMOJEV®) in children.

    Science.gov (United States)

    Chokephaibulkit, K; Houillon, G; Feroldi, E; Bouckenooghe, A

    2016-01-01

    JE-CV (IMOJEV®, Sanofi Pasteur, France) is a live attenuated virus vaccine constructed by inserting coding sequences of the prM and E structural proteins of the Japanese encephalitis SA14-14-2 virus into the genome of yellow fever 17D virus. Primary immunization with JE-CV requires a single dose of the vaccine. This article reviews clinical trials of JE-CV in children aged up to 6 years conducted in countries across South-East Asia. Strong and persistent antibody responses were observed after single primary and booster doses, with 97% of children seroprotected up to five years after booster vaccination. Models of long-term antibody persistence predict a median duration of protection of approximately 30 years after a booster dose. The safety and reactogenicity profiles of JE-CV primary and booster doses are comparable to other widely used childhood vaccines.

  18. Characterization of field isolates of Suid herpesvirus 1 (Aujeszky's disease virus) as derivatives of attenuated vaccine strains

    DEFF Research Database (Denmark)

    Christensen, Laurids Siig; Medveczky, I.; Strandbygaard, Bertel

    1992-01-01

    Field isolates of suid herpesvirus 1 (Aujeszky's disease virus) from Poland and Hungary were identified by restriction fragment pattern analysis as derivatives of attenuated vaccine strains. The Polish isolates were found to be related to the BUK-TK-900 strain (Suivac A) which is widely used...

  19. PREDICTING ATTENUATION OF VIRUSES DURING PERCOLATION IN SOILS: 2. USER'S GUIDE TO THE VIRULO 1.0 COMPUTER MODEL

    Science.gov (United States)

    In the EPA document Predicting Attenuation of Viruses During Percolation in Soils 1. Probabilistic Model the conceptual, theoretical, and mathematical foundations for a predictive screening model were presented. In this current volume we present a User's Guide for the computer mo...

  20. Rift valley fever virus lacking the NSs and NSm genes is highly attenuated, confers protective immunity from virulent virus challenge, and allows for differential identification of infected and vaccinated animals.

    Science.gov (United States)

    Bird, Brian H; Albariño, César G; Hartman, Amy L; Erickson, Bobbie Rae; Ksiazek, Thomas G; Nichol, Stuart T

    2008-03-01

    Rift Valley fever (RVF) virus is a mosquito-borne human and veterinary pathogen associated with large outbreaks of severe disease throughout Africa and more recently the Arabian peninsula. Infection of livestock can result in sweeping "abortion storms" and high mortality among young animals. Human infection results in self-limiting febrile disease that in approximately 1 to 2% of patients progresses to more serious complications including hepatitis, encephalitis, and retinitis or a hemorrhagic syndrome with high fatality. The virus S segment-encoded NSs and the M segment-encoded NSm proteins are important virulence factors. The development of safe, effective vaccines and tools to screen and evaluate antiviral compounds is critical for future control strategies. Here, we report the successful reverse genetics generation of multiple recombinant enhanced green fluorescent protein-tagged RVF viruses containing either the full-length, complete virus genome or precise deletions of the NSs gene alone or the NSs/NSm genes in combination, thus creating attenuating deletions on multiple virus genome segments. These viruses were highly attenuated, with no detectable viremia or clinical illness observed with high challenge dosages (1.0 x 10(4) PFU) in the rat lethal disease model. A single-dose immunization regimen induced robust anti-RVF virus immunoglobulin G antibodies (titer, approximately 1:6,400) by day 26 postvaccination. All vaccinated animals that were subsequently challenged with a high dose of virulent RVF virus survived infection and could be serologically differentiated from naïve, experimentally infected animals by the lack of NSs antibodies. These rationally designed marker RVF vaccine viruses will be useful tools for in vitro screening of therapeutic compounds and will provide a basis for further development of RVF virus marker vaccines for use in endemic regions or following the natural or intentional introduction of the virus into previously unaffected areas.

  1. A modified live canine parvovirus strain with novel plaque characteristics. I. Viral attenuation and dog response.

    Science.gov (United States)

    Carmichael, L E; Joubert, J C; Pollock, R V

    1981-10-01

    A canine parvovirus (CPV) strain (C-780916) was found attenuated for pups at 80, but not after 51 serial passages in dog kidney cell (DKC) cultures. A variant viral population ('large plaque') emerged after prolonged cultivation in DKC cultures that may be associated with reduced native virulence. Dogs vaccinated with modified CPV developed high hemagglutination-inhibiting (HI) antibody titers within 4 days of incoluation and antibody persisted. Vaccinated animals shed small amounts of virus in the feces that spread to contact dogs. After five back-passages in dogs the modified strain was not pathogenic for pups and the plaque characteristics of the virus isolated from the feces were typical of the attenuated strain. The modified live CPV did not cause infection of the fetus when inoculated parenterally into pregnant bitches at various stages of gestation. It was not pathogenic for neonatal pups. These results suggest that a safe and effective live homologous (CPV) vaccine has been developed which should aid substantially in controlling CPV infection.

  2. Field Efficacy of an Attenuated Infectious Bronchitis Variant 2 Virus Vaccine in Commercial Broiler Chickens

    Directory of Open Access Journals (Sweden)

    Mohamed A. Elhady

    2018-05-01

    Full Text Available Egyptian poultry suffer from frequent respiratory disease outbreaks associated with Infectious Bronchitis Virus (IBV variant 2 strains (Egy/VarII. Different vaccination programs using imported vaccines have failed to protect the flocks from field challenge. Recent studies confirmed a successful protection using homologous strains as live attenuated vaccines. In this study, a newly developed live attenuated IB-VAR2 vaccine representing the GI-23 Middle East IBV lineage was evaluated in day-old commercial broilers in an IBV-endemic area. A commercial broiler flock was vaccinated with the IB-VAR2 vaccine at day-old age followed by IB-H120 at day 16. The vaccinated flock was monitored on a weekly basis till the slaughter age. The health status and growth performance were monitored, and selected viral pathogen real-time RT-PCR (rRT-PCR detection was conducted on a weekly basis. Finally, the flock was compared to a nearby farm with only the classical IB-H120 vaccination program. Results showed that the IB-VAR2 vaccine was tolerable in day-old broiler chicks. The IBV virus rRT-PCR detection was limited to the trachea as compared to its nephropathogenic parent virus. Respiratory disease problems and high mortalities were reported in the IB-H120-only vaccinated flock. An exposure to a wild-type Egy/VarII strain was confirmed in both flocks as indicated by partial IBV S1 gene sequence. Even though the IB-VAR2-vaccinated flock performance was better than the flock that received only IB-H120, the IBV ELISA (enzyme-linked immunosorbent assay and log2 Haemagglutination inhibition (HI antibody mean titers remained high (3128 ± 2713 and ≥9 log2, respectively until the 28th day of age. The current study demonstrates the safety and effectiveness of IB-VAR2 as a live attenuated vaccine in day-old commercial broilers. Also, the combination of IB-VAR2 and classical IBV vaccines confers a broader protective immune response against IBV in endemic areas.

  3. The yellow fever 17D vaccine virus: molecular basis of viral attenuation and its use as an expression vector

    Directory of Open Access Journals (Sweden)

    Galler R.

    1997-01-01

    Full Text Available The yellow fever (YF virus is the prototype flavivirus. The use of molecular techniques has unraveled the basic mechanisms of viral genome structure and expression. Recent trends in flavivirus research include the use of infectious clone technology with which it is possible to recover virus from cloned cDNA. Using this technique, mutations can be introduced at any point of the viral genome and their resulting effect on virus phenotype can be assessed. This approach has opened new possibilities to study several biological viral features with special emphasis on the issue of virulence/attenuation of the YF virus. The feasibility of using YF virus 17D vaccine strain, for which infectious cDNA is available, as a vector for the expression of heterologous antigens is reviewed

  4. The progressive adaptation of a georgian isolate of African swine fever virus to vero cells leads to a gradual attenuation of virulence in swine corresponding to major modifications of the viral genome.

    Science.gov (United States)

    Krug, Peter W; Holinka, Lauren G; O'Donnell, Vivian; Reese, Bo; Sanford, Brenton; Fernandez-Sainz, Ignacio; Gladue, Douglas P; Arzt, Jonathan; Rodriguez, Luis; Risatti, Guillermo R; Borca, Manuel V

    2015-02-01

    African swine fever virus (ASFV) causes a contagious and often lethal disease of feral and domestic swine. Experimental vaccines derived from naturally occurring, genetically modified, or cell culture-adapted ASFV have been evaluated, but no commercial vaccine is available to control African swine fever (ASF). We report here the genotypic and phenotypic analysis of viruses obtained at different passages during the process of adaptation of a virulent ASFV field isolate from the Republic of Georgia (ASFV-G) to grow in cultured cell lines. ASFV-G was successively passaged 110 times in Vero cells. Viruses obtained at passages 30, 60, 80, and 110 were evaluated in vitro for the ability to replicate in Vero cells and primary swine macrophages cultures and in vivo for assessing virulence in swine. Replication of ASFV-G in Vero cells increased with successive passages, corresponding to a decreased replication in primary swine macrophages cultures. In vivo, progressive loss of virus virulence was observed with increased passages in Vero cells, and complete attenuation of ASFV-G was observed at passage 110. Infection of swine with the fully attenuated virus did not confer protection against challenge with virulent parental ASFV-G. Full-length sequence analysis of each of these viruses revealed significant deletions that gradually accumulated in specific areas at the right and left variable ends of the genome. Mutations that result in amino acid substitutions and frameshift mutations were also observed, though in a rather limited number of genes. The potential importance of these genetic changes in virus adaptation/attenuation is discussed. The main problem in controlling ASF is the lack of vaccines. Attempts to produce vaccines by adaptation of ASFV to cultured cell lines have been made. These attempts led to the production of attenuated viruses that conferred only homologous protection. Specifics regarding adaptation of these isolates to cell cultures have been

  5. Deletion of the thymidine kinase gene induces complete attenuation of the Georgia isolate of African swine fever virus

    Science.gov (United States)

    African swine fever virus (ASFV) is the etiological agent of a contagious and often lethal viral disease of domestic pigs. There are no vaccines to control Africa swine fever (ASF). Experimental vaccines have been developed using genetically modified live attenuated ASFVs obtained by specifically de...

  6. Mutations within ICP4 acquired during in vitro attenuation do not alter virulence of recombinant Marek's disease viruses in vivo

    Directory of Open Access Journals (Sweden)

    Evin Hildebrandt

    2015-12-01

    Full Text Available Marek's disease (MD is a T-cell lymphoma of chickens caused by the oncogenic Marek's disease virus (MDV. MD is primarily controlled by live-attenuated vaccines generated by repeated in vitro serial passage. Previous efforts to characterize attenuated MDVs identified numerous mutations, particularly a convergence of high-frequency mutations around amino acids 60–63 within ICP4 (RS1, therefore, ICP4 was considered a candidate gene deserving further characterization. Recombinant MDVs were generated containing a single Q63H mutation or double Q63H + S1630P mutations. Despite the repetitive nature of mutations within ICP4, neither recombinant virus decreased virulence, although one mutant reduced in vivo replication and failed to transmit horizontally. Our results indicate that these mutations are insufficient to reduce disease incidence in infected birds, and suggest that variants in ICP4 do not directly alter virulence, but rather may enhance MDV replication rates in vitro, offering an explanation for the widespread occurrence of ICP4 mutations in a variety of attenuated herpesviruses.

  7. Effective preexposure and postexposure prophylaxis of rabies with a highly attenuated recombinant rabies virus

    OpenAIRE

    Faber, Milosz; Li, Jianwei; Kean, Rhonda B.; Hooper, D. Craig; Alugupalli, Kishore R.; Dietzschold, Bernhard

    2009-01-01

    Rabies remains an important public health problem with more than 95% of all human rabies cases caused by exposure to rabid dogs in areas where effective, inexpensive vaccines are unavailable. Because of their ability to induce strong innate and adaptive immune responses capable of clearing the infection from the CNS after a single immunization, live-attenuated rabies virus (RV) vaccines could be particularly useful not only for the global eradication of canine rabies but also for late-stage r...

  8. Live Cell Analysis and Mathematical Modeling Identify Determinants of Attenuation of Dengue Virus 2'-O-Methylation Mutant.

    Directory of Open Access Journals (Sweden)

    Bianca Schmid

    2015-12-01

    Full Text Available Dengue virus (DENV is the most common mosquito-transmitted virus infecting ~390 million people worldwide. In spite of this high medical relevance, neither a vaccine nor antiviral therapy is currently available. DENV elicits a strong interferon (IFN response in infected cells, but at the same time actively counteracts IFN production and signaling. Although the kinetics of activation of this innate antiviral defense and the timing of viral counteraction critically determine the magnitude of infection and thus disease, quantitative and kinetic analyses are lacking and it remains poorly understood how DENV spreads in IFN-competent cell systems. To dissect the dynamics of replication versus antiviral defense at the single cell level, we generated a fully viable reporter DENV and host cells with authentic reporters for IFN-stimulated antiviral genes. We find that IFN controls DENV infection in a kinetically determined manner that at the single cell level is highly heterogeneous and stochastic. Even at high-dose, IFN does not fully protect all cells in the culture and, therefore, viral spread occurs even in the face of antiviral protection of naïve cells by IFN. By contrast, a vaccine candidate DENV mutant, which lacks 2'-O-methylation of viral RNA is profoundly attenuated in IFN-competent cells. Through mathematical modeling of time-resolved data and validation experiments we show that the primary determinant for attenuation is the accelerated kinetics of IFN production. This rapid induction triggered by mutant DENV precedes establishment of IFN-resistance in infected cells, thus causing a massive reduction of virus production rate. In contrast, accelerated protection of naïve cells by paracrine IFN action has negligible impact. In conclusion, these results show that attenuation of the 2'-O-methylation DENV mutant is primarily determined by kinetics of autocrine IFN action on infected cells.

  9. Gastroenteritis: First Aid

    Science.gov (United States)

    First aid Gastroenteritis: First aid Gastroenteritis: First aid By Mayo Clinic Staff Gastroenteritis is an inflammation of your stomach and intestines. Common causes are: Viruses. Food or water contaminated by ...

  10. Human immunodeficiency virus (HIV) is highly associated with giant idiopathic esophageal ulcers in acquired immunodeficiency syndrome (AIDS) patients.

    Science.gov (United States)

    Lv, Bei; Cheng, Xin; Gao, Jackson; Zhao, Hong; Chen, Liping; Wang, Liwei; Huang, Shaoping; Fan, Zhenyu; Zhang, Renfang; Shen, Yinzhong; Li, Lei; Liu, Baochi; Qi, Tangkai; Wang, Jing; Cheng, Jilin

    2016-01-01

    This study aimed to determine whether the human immunodeficiency virus (HIV) exists in giant idiopathic esophageal ulcers in the patients with acquired immune deficiency syndrome (AIDS). 16 AIDS patients with a primary complaint of epigastric discomfort were examined by gastroscopy. Multiple and giant esophageal ulcers were biopsied and analyzed with pathology staining and reverse transcription-polymerase chain reaction (RT-PCR) to determine the potential pathogenic microorganisms, including HIV, cytomegalovirus (CMV) and herpes simplex viruses (HSV). HIV was detected in ulcer samples from 12 out of these 16 patients. Ulcers in 2 patients were infected with CMV and ulcers in another 2 patients were found HSV positive. No obvious cancerous pathological changes were found in these multiple giant esophageal ulcer specimens. HIV may be one of the major causative agents of multiple benign giant esophageal ulcers in AIDS patients.

  11. Comparison of egg and high yielding MDCK cell-derived live attenuated influenza virus for commercial production of trivalent influenza vaccine: in vitro cell susceptibility and influenza virus replication kinetics in permissive and semi-permissive cells.

    Science.gov (United States)

    Hussain, Althaf I; Cordeiro, Melissa; Sevilla, Elizabeth; Liu, Jonathan

    2010-05-14

    Currently MedImmune manufactures cold-adapted (ca) live, attenuated influenza vaccine (LAIV) from specific-pathogen free (SPF) chicken eggs. Difficulties in production scale-up and potential exposure of chicken flocks to avian influenza viruses especially in the event of a pandemic influenza outbreak have prompted evaluation and development of alternative non-egg based influenza vaccine manufacturing technologies. As part of MedImmune's effort to develop the live attenuated influenza vaccine (LAIV) using cell culture production technologies we have investigated the use of high yielding, cloned MDCK cells as a substrate for vaccine production by assessing host range and virus replication of influenza virus produced from both SPF egg and MDCK cell production technologies. In addition to cloned MDCK cells the indicator cell lines used to evaluate the impact of producing LAIV in cells on host range and replication included two human cell lines: human lung carcinoma (A549) cells and human muco-epidermoid bronchiolar carcinoma (NCI H292) cells. The influenza viruses used to infect the indicators cell lines represented both the egg and cell culture manufacturing processes and included virus strains that composed the 2006-2007 influenza seasonal trivalent vaccine (A/New Caledonia/20/99 (H1N1), A/Wisconsin/67/05 (H3N2) and B/Malaysia/2506/04). Results from this study demonstrate remarkable similarity between influenza viruses representing the current commercial egg produced and developmental MDCK cell produced vaccine production platforms. MedImmune's high yielding cloned MDCK cells used for the cell culture based vaccine production were highly permissive to both egg and cell produced ca attenuated influenza viruses. Both the A549 and NCI H292 cells regardless of production system were less permissive to influenza A and B viruses than the MDCK cells. Irrespective of the indicator cell line used the replication properties were similar between egg and the cell produced

  12. Effective preexposure and postexposure prophylaxis of rabies with a highly attenuated recombinant rabies virus.

    Science.gov (United States)

    Faber, Milosz; Li, Jianwei; Kean, Rhonda B; Hooper, D Craig; Alugupalli, Kishore R; Dietzschold, Bernhard

    2009-07-07

    Rabies remains an important public health problem with more than 95% of all human rabies cases caused by exposure to rabid dogs in areas where effective, inexpensive vaccines are unavailable. Because of their ability to induce strong innate and adaptive immune responses capable of clearing the infection from the CNS after a single immunization, live-attenuated rabies virus (RV) vaccines could be particularly useful not only for the global eradication of canine rabies but also for late-stage rabies postexposure prophylaxis of humans. To overcome concerns regarding the safety of live-attenuated RV vaccines, we developed the highly attenuated triple RV G variant, SPBAANGAS-GAS-GAS. In contrast to most attenuated recombinant RVs generated thus far, SPBAANGAS-GAS-GAS is completely nonpathogenic after intracranial infection of mice that are either developmentally immunocompromised (e.g., 5-day-old mice) or have inherited deficits in immune function (e.g., antibody production or type I IFN signaling), as well as normal adult animals. In addition, SPBAANGAS-GAS-GAS induces immune mechanisms capable of containing a CNS infection with pathogenic RV, thereby preventing lethal rabies encephalopathy. The lack of pathogenicity together with excellent immunogenicity and the capacity to deliver immune effectors to CNS tissues makes SPBAANGAS-GAS-GAS a promising vaccine candidate for both the preexposure and postexposure prophylaxis of rabies.

  13. The PB2-K627E mutation attenuates H3N2 swine influenza virus in cultured cells and in mice.

    Science.gov (United States)

    Gong, Xiao-Qian; Ruan, Bao-Yang; Liu, Xiao-Min; Zhang, Peng; Wang, Xiu-Hui; Wang, Qi; Shan, Tong-Ling; Tong, Wu; Zhou, Yan-Jun; Li, Guo-Xin; Zheng, Hao; Tong, Guang-Zhi; Yu, Hai

    2018-04-01

    PB2-627K is an important amino acid that determines the virulence of some influenza A viruses. However, it has not been experimentally investigated in the H3N2 swine influenza virus. To explore the potential role of PB2-K627E substitution in H3N2 swine influenza virus, the growth properties and pathogenicity between H3N2 swine influenza virus and its PB2-K627E mutant were compared. For the first time, our results showed that PB2-K627E mutation attenuates H3N2 swine influenza virus in mammalian cells and in mice, suggesting that PB2-627K is required for viral replication and pathogenicity of H3N2 swine influenza virus. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. A live attenuated H7N7 candidate vaccine virus induces neutralizing antibody that confers protection from challenge in mice, ferrets and monkeys

    Science.gov (United States)

    A live attenuated H7N7 candidate vaccine virus was generated by reverse genetics using the modified hemagglutinin (HA) and neuraminidase (NA) genes of HP A/Netherlands/219/03 (NL/03) (H7N7) wild-type (wt) virus and the six internal protein genes of the cold-adapted (ca) A/Ann Arbor/6/60 ca (AA ca) (...

  15. Attenuation and immunogenicity of host-range extended modified vaccinia virus Ankara recombinants.

    Science.gov (United States)

    Melamed, Sharon; Wyatt, Linda S; Kastenmayer, Robin J; Moss, Bernard

    2013-09-23

    Modified vaccinia virus Ankara (MVA) is being widely investigated as a safe smallpox vaccine and as an expression vector to produce vaccines against other infectious diseases and cancer. MVA was isolated following more than 500 passages in chick embryo fibroblasts and suffered several major deletions and numerous small mutations resulting in replication defects in human and most other mammalian cells as well as severe attenuation of pathogenicity. Due to the host range restriction, primary chick embryo fibroblasts are routinely used for production of MVA-based vaccines. While a replication defect undoubtedly contributes to safety of MVA, it is worth considering whether host range and attenuation are partially separable properties. Marker rescue transfection experiments resulted in the creation of recombinant MVAs with extended mammalian cell host range. Here, we characterize two host-range extended rMVAs and show that they (i) have acquired the ability to stably replicate in Vero cells, which are frequently used as a cell substrate for vaccine manufacture, (ii) are severely attenuated in immunocompetent and immunodeficient mouse strains following intranasal infection, (iii) are more pathogenic than MVA but less pathogenic than the ACAM2000 vaccine strain at high intracranial doses, (iv) do not form lesions upon tail scratch in mice in contrast to ACAM2000 and (v) induce protective humoral and cell-mediated immune responses similar to MVA. The extended host range of rMVAs may be useful for vaccine production. Published by Elsevier Ltd.

  16. Genotyping assay for differentiation of wild-type and vaccine viruses in subjects immunized with live attenuated influenza vaccine.

    Directory of Open Access Journals (Sweden)

    Victoria Matyushenko

    Full Text Available Live attenuated influenza vaccines (LAIVs are considered as safe and effective tool to control influenza in different age groups, especially in young children. An important part of the LAIV safety evaluation is the detection of vaccine virus replication in the nasopharynx of the vaccinees, with special attention to a potential virus transmission to the unvaccinated close contacts. Conducting LAIV clinical trials in some geographical regions with year-round circulation of influenza viruses warrants the development of robust and reliable tools for differentiating vaccine viruses from wild-type influenza viruses in nasal pharyngeal wash (NPW specimens of vaccinated subjects. Here we report the development of genotyping assay for the detection of wild-type and vaccine-type influenza virus genes in NPW specimens of young children immunized with Russian-backbone seasonal trivalent LAIV using Sanger sequencing from newly designed universal primers. The new primer set allowed amplification and sequencing of short fragments of viral genes in NPW specimens and appeared to be more sensitive than conventional real-time RT-PCR protocols routinely used for the detection and typing/subtyping of influenza virus in humans. Furthermore, the new assay is capable of defining the origin of wild-type influenza virus through BLAST search with the generated sequences of viral genes fragments.

  17. HIV and AIDS

    Science.gov (United States)

    ... Staying Safe Videos for Educators Search English Español HIV and AIDS KidsHealth / For Kids / HIV and AIDS ... actually the virus that causes the disease AIDS. HIV Hurts the Immune System People who are HIV ...

  18. AIDS (image)

    Science.gov (United States)

    AIDS (acquired immune deficiency syndrome) is caused by HIV (human immunodeficiency virus), and is a syndrome that ... life-threatening illnesses. There is no cure for AIDS, but treatment with antiviral medicine can suppress symptoms. ...

  19. Envelope exchange for the generation of live-attenuated arenavirus vaccines.

    Directory of Open Access Journals (Sweden)

    Andreas Bergthaler

    2006-06-01

    Full Text Available Arenaviruses such as Lassa fever virus cause significant mortality in endemic areas and represent potential bioterrorist weapons. The occurrence of arenaviral hemorrhagic fevers is largely confined to Third World countries with a limited medical infrastructure, and therefore live-attenuated vaccines have long been sought as a method of choice for prevention. Yet their rational design and engineering have been thwarted by technical limitations. In addition, viral genes had not been identified that are needed to cause disease but can be deleted or substituted to generate live-attenuated vaccine strains. Lymphocytic choriomeningitis virus, the prototype arenavirus, induces cell-mediated immunity against Lassa fever virus, but its safety for humans is unclear and untested. Using this virus model, we have developed the necessary methodology to efficiently modify arenavirus genomes and have exploited these techniques to identify an arenaviral Achilles' heel suitable for targeting in vaccine design. Reverse genetic exchange of the viral glycoprotein for foreign glycoproteins created attenuated vaccine strains that remained viable although unable to cause disease in infected mice. This phenotype remained stable even after extensive propagation in immunodeficient hosts. Nevertheless, the engineered viruses induced T cell-mediated immunity protecting against overwhelming systemic infection and severe liver disease upon wild-type virus challenge. Protection was established within 3 to 7 d after immunization and lasted for approximately 300 d. The identification of an arenaviral Achilles' heel demonstrates that the reverse genetic engineering of live-attenuated arenavirus vaccines is feasible. Moreover, our findings offer lymphocytic choriomeningitis virus or other arenaviruses expressing foreign glycoproteins as promising live-attenuated arenavirus vaccine candidates.

  20. Envelope Exchange for the Generation of Live-Attenuated Arenavirus Vaccines.

    Directory of Open Access Journals (Sweden)

    2006-06-01

    Full Text Available Arenaviruses such as Lassa fever virus cause significant mortality in endemic areas and represent potential bioterrorist weapons. The occurrence of arenaviral hemorrhagic fevers is largely confined to Third World countries with a limited medical infrastructure, and therefore live-attenuated vaccines have long been sought as a method of choice for prevention. Yet their rational design and engineering have been thwarted by technical limitations. In addition, viral genes had not been identified that are needed to cause disease but can be deleted or substituted to generate live-attenuated vaccine strains. Lymphocytic choriomeningitis virus, the prototype arenavirus, induces cell-mediated immunity against Lassa fever virus, but its safety for humans is unclear and untested. Using this virus model, we have developed the necessary methodology to efficiently modify arenavirus genomes and have exploited these techniques to identify an arenaviral Achilles' heel suitable for targeting in vaccine design. Reverse genetic exchange of the viral glycoprotein for foreign glycoproteins created attenuated vaccine strains that remained viable although unable to cause disease in infected mice. This phenotype remained stable even after extensive propagation in immunodeficient hosts. Nevertheless, the engineered viruses induced T cell-mediated immunity protecting against overwhelming systemic infection and severe liver disease upon wild-type virus challenge. Protection was established within 3 to 7 d after immunization and lasted for approximately 300 d. The identification of an arenaviral Achilles' heel demonstrates that the reverse genetic engineering of live-attenuated arenavirus vaccines is feasible. Moreover, our findings offer lymphocytic choriomeningitis virus or other arenaviruses expressing foreign glycoproteins as promising live-attenuated arenavirus vaccine candidates.

  1. Mutations within the nuclear localization signal of the porcine reproductive and respiratory syndrome virus nucleocapsid protein attenuate virus replication

    International Nuclear Information System (INIS)

    Lee, Changhee; Hodgins, Douglas; Calvert, Jay G.; Welch, Siao-Kun W.; Jolie, Rika; Yoo, Dongwan

    2006-01-01

    Porcine reproductive and respiratory syndrome virus (PRRSV) is an RNA virus replicating in the cytoplasm, but the nucleocapsid (N) protein is specifically localized to the nucleus and nucleolus in virus-infected cells. A 'pat7' motif of 41-PGKK(N/S)KK has previously been identified in the N protein as the functional nuclear localization signal (NLS); however, the biological consequences of N protein nuclear localization are unknown. In the present study, the role of N protein nuclear localization during infection was investigated in pigs using an NLS-null mutant virus. When two lysines at 43 and 44 at the NLS locus were substituted to glycines, the modified NLS with 41-PGGGNKK restricted the N protein to the cytoplasm. This NLS-null mutation was introduced into a full-length infectious cDNA clone of PRRSV. Upon transfection of cells, the NLS-null full-length clone induced cytopathic effects and produced infectious progeny. The NLS-null virus grew to a titer 100-fold lower than that of wild-type virus. To examine the response to NLS-null PRRSV in the natural host, three groups of pigs, consisting of seven animals per group, were intranasally inoculated with wild-type, placebo, or NLS-null virus, and the animals were maintained for 4 weeks. The NLS-null-infected pigs had a significantly shorter mean duration of viremia than wild-type-infected pigs but developed significantly higher titers of neutralizing antibodies. Mutations occurred at the NLS locus in one pig during viremia, and four types of mutations were identified: 41-PGRGNKK, 41-PGGRNKK, and 41-PGRRNKK, and 41-PGKKSKK. Both wild-type and NLS-null viruses persisted in the tonsils for at least 4 weeks, and the NLS-null virus persisting in the tonsils was found to be mutated to either 41-PGRGNKK or 41-PGGRNKK in all pigs. No other mutation was found in the N gene. All types of reversions which occurred during viremia and persistence were able to translocate the mutated N proteins to the nucleus, indicating a

  2. Transcriptome Analysis of Human Peripheral Blood Mononuclear Cells Exposed to Lassa Virus and to the Attenuated Mopeia/Lassa Reassortant 29 (ML29), a Vaccine Candidate

    Science.gov (United States)

    Zapata, Juan Carlos; Carrion, Ricardo; Patterson, Jean L.; Crasta, Oswald; Zhang, Yan; Mani, Sachin; Jett, Marti; Poonia, Bhawna; Djavani, Mahmoud; White, David M.; Lukashevich, Igor S.; Salvato, Maria S.

    2013-01-01

    Lassa virus (LASV) is the causative agent of Lassa Fever and is responsible for several hundred thousand infections and thousands of deaths annually in West Africa. LASV and the non-pathogenic Mopeia virus (MOPV) are both rodent-borne African arenaviruses. A live attenuated reassortant of MOPV and LASV, designated ML29, protects rodents and primates from LASV challenge and appears to be more attenuated than MOPV. To gain better insight into LASV-induced pathology and mechanism of attenuation we performed gene expression profiling in human peripheral blood mononuclear cells (PBMC) exposed to LASV and the vaccine candidate ML29. PBMC from healthy human subjects were exposed to either LASV or ML29. Although most PBMC are non-permissive for virus replication, they remain susceptible to signal transduction by virus particles. Total RNA was extracted and global gene expression was evaluated during the first 24 hours using high-density microarrays. Results were validated using RT-PCR, flow cytometry and ELISA. LASV and ML29 elicited differential expression of interferon-stimulated genes (ISG), as well as genes involved in apoptosis, NF-kB signaling and the coagulation pathways. These genes could eventually serve as biomarkers to predict disease outcomes. The remarkable differential expression of thrombomodulin, a key regulator of inflammation and coagulation, suggests its involvement with vascular abnormalities and mortality in Lassa fever disease. PMID:24069471

  3. Transcriptome analysis of human peripheral blood mononuclear cells exposed to Lassa virus and to the attenuated Mopeia/Lassa reassortant 29 (ML29, a vaccine candidate.

    Directory of Open Access Journals (Sweden)

    Juan Carlos Zapata

    Full Text Available Lassa virus (LASV is the causative agent of Lassa Fever and is responsible for several hundred thousand infections and thousands of deaths annually in West Africa. LASV and the non-pathogenic Mopeia virus (MOPV are both rodent-borne African arenaviruses. A live attenuated reassortant of MOPV and LASV, designated ML29, protects rodents and primates from LASV challenge and appears to be more attenuated than MOPV. To gain better insight into LASV-induced pathology and mechanism of attenuation we performed gene expression profiling in human peripheral blood mononuclear cells (PBMC exposed to LASV and the vaccine candidate ML29. PBMC from healthy human subjects were exposed to either LASV or ML29. Although most PBMC are non-permissive for virus replication, they remain susceptible to signal transduction by virus particles. Total RNA was extracted and global gene expression was evaluated during the first 24 hours using high-density microarrays. Results were validated using RT-PCR, flow cytometry and ELISA. LASV and ML29 elicited differential expression of interferon-stimulated genes (ISG, as well as genes involved in apoptosis, NF-kB signaling and the coagulation pathways. These genes could eventually serve as biomarkers to predict disease outcomes. The remarkable differential expression of thrombomodulin, a key regulator of inflammation and coagulation, suggests its involvement with vascular abnormalities and mortality in Lassa fever disease.

  4. Genomic Changes in an Attenuated ZB Strain of Foot-and-Mouth Disease Virus Serotype Asia1 and Comparison with Its Virulent Parental Strain

    Directory of Open Access Journals (Sweden)

    Aiguo Xin

    2014-01-01

    Full Text Available The molecular basis of attenuation of foot-and-mouth disease virus (FMDV serotype Asia1 ZB strain remains unknown. To understand the genetic changes of attenuation, we compared the entire genomes of three different rabbit-passaged attenuated ZB strains (ZB/CHA/58(att, ZBRF168, and ZBRF188 and their virulent parental strains (ZBCF22 and YNBS/58. The results showed that attenuation may be brought about by 28 common amino acid substitutions in the coding region, with one nucleotide point mutation in the 5′-untranslated region (5′-UTR and another one in the 3′-UTR. In addition, a total of 21 nucleotides silent mutations had been found after attenuation. These substitutions, alone or in combination, may be responsible for the attenuated phenotype of the ZB strain in cattle. This will contribute to elucidation of attenuating molecular basis of the FMDV ZB strain.

  5. AIDS: just the facts from specialists at Johns Hopkins.

    Science.gov (United States)

    Finkbeiner, A

    1985-12-01

    This article, based on information from specialists at Johns Hopkins, poses and then answers 3 broad questions about the acquired immunodeficiency syndrome (AIDS). 1st, it is asked, "What is AIDS and how serious is it?" It is noted that AIDS is only 1 of several forms taken by infection with the human T-lymphotropic virus type III/lymphadenopathy-associated virus (HTLV-III/LAV). The earliest form of infection is believed to occur within a few weeks of exposure to the virus, and some patients develop an acute syndrome that resembles infectious mononucleosis. These symptoms disappear after 4-6 weeks, by which time the patient has developed antibodies to the virus. About 2-4%/year of asymptomatic carriers go on to develop AIDS-related complex (ARC), and 15-30% of ARC patients develop AIDS within 5 years. The 2nd question posed is, "How do you catch AIDS?" To cause infection, the virus must go directly into the blood, although the virus alone may not be enough to cause sickness. Previous viral infections such as hepatitis B, herpes, cytomegalovirus, and intestinal parasites have been suggested as co-factors of AIDS. Promiscuity increases the chances of contracting AIDS. Observations of the families of AIDS patients and health care personnel who work with AIDS patients suggest that AIDS cannot be caught by casual contact. Finally, it is asked, "What is being done about AIDS?" 4 strategies are outlined: 1) as a result of donor screening for antibodies to HTLV-III/LAV, AIDS has been completely removed from the blood banks; 2) virologists are attempting to understand the virus so that it can be attacked, and understanding has been advanced by the theory that HTLV-III might be what is called a "slow virus;" 3) education about AIDS is changing the sexual practices that transmit AIDS; and 4) epidemiologists are carefully following those who are at risk, have been exposed, or are already sick.

  6. Recombinant human parainfluenza virus type 2 with mutations in V that permit cellular interferon signaling are not attenuated in non-human primates

    Science.gov (United States)

    Schaap-Nutt, Anne; D’Angelo, Christopher; Amaro-Carambot, Emerito; Nolan, Sheila M.; Davis, Stephanie; Wise, Shenelle-Marie; Higgins, Caraline; Bradley, Konrad; Kim, Olivia; Mayor, Reina; Skiadopoulos, Mario H.; Collins, Peter L.; Murphy, Brian R.; Schmidt, Alexander C.

    2010-01-01

    The HPIV2 V protein inhibits type I interferon (IFN) induction and signaling. To manipulate the V protein, whose coding sequence overlaps that of the polymerase-associated phosphoprotein (P), without altering the P protein, we generated an HPIV2 virus in which P and V are expressed from separate genes (rHPIV2-P+V). rHPIV2-P+V replicated like HPIV2-WT in vitro and in non-human primates. HPIV2-P+V was modified by introducing two separate mutations into the V protein to create rHPIV2-L101E/L102E and rHPIV2-Δ122–127. In contrast to HPIV2-WT, both mutant viruses were unable to degrade STAT2, leaving virus-infected cells susceptible to IFN. Neither mutant, nor HPIV2-WT, induced significant amounts of IFN-β in infected cells. Surprisingly, neither rHPIV2-L101E/L102E nor rHPIV2-Δ122–127 was attenuated in two species of non-human primates. This indicates that loss of HPIV2's ability to inhibit IFN signaling is insufficient to attenuate virus replication in vivo as long as IFN induction is still inhibited. PMID:20667570

  7. The degree of attenuation of tick-borne encephalitis virus depends on the cumulative effects of point mutations.

    Science.gov (United States)

    Gritsun, T S; Desai, A; Gould, E A

    2001-07-01

    An infectious clone (pGGVs) of the tick-borne encephalitis complex virus Vasilchenko (Vs) was constructed previously. Virus recovered from pGGVs produced slightly smaller plaques than the Vs parental virus. Sequence analysis demonstrated five nucleotide differences between the original Vs virus and pGGVs; four of these mutations resulted in amino acid substitutions, while the fifth mutation was located in the 3' untranslated region (3'UTR). Two mutations were located in conserved regions and three mutations were located in variable regions of the virus genome. Reverse substitutions from the conserved regions of the genome, R(496)-->H in the envelope (E) gene and C(10884)-->T in the 3'UTR, were introduced both separately and together into the infectious clone and their biological effect on virus phenotype was evaluated. The engineered viruses with R(496) in the E protein produced plaques of smaller size than viruses with H(496) at this position. This mutation also affected the growth and neuroinvasiveness of the virus. In contrast, the consequence of a T(10884)-->C substitution within the 3'UTR was noticeable only in cytotoxicity and neuroinvasiveness tests. However, all virus mutants engineered by modification of the infectious clone, including one with two wild-type mutations, H(496) and T(10884), showed reduced neuroinvasiveness in comparison with the Vs parental virus. Therefore, although the H(496)-->R and T(10884)-->C substitutions clearly reduce virus virulence, the other mutations within the variable regions of the capsid (I(45)-->F) and the NS5 (T(2688)-->A and M(3385)-->I) genes also contribute to the process of attenuation. In terms of developing flavivirus vaccines, the impact of accumulating apparently minor mutations should be assessed in detail.

  8. Efficacy of Live-Attenuated H9N2 Influenza Vaccine Candidates Containing NS1 Truncations against H9N2 Avian Influenza Viruses

    Directory of Open Access Journals (Sweden)

    Sujuan Chen

    2017-06-01

    Full Text Available H9N2 avian influenza virus is a zoonotic agent with a broad host range that can contribute genetic information to H5 or H7N9 subtype viruses, which are significant threats to both humans and birds. Thus, there is a great need for a vaccine to control H9N2 avian influenza. Three mutant viruses of an H9N2 virus A/chicken/Taixing/10/2010 (rTX-NS1-73, rTX-NS1-100, and rTX-NS1-128 were constructed with different NS1 gene truncations and confirmed by western blot analysis. The genetic stability, pathogenicity, transmissibility, and host immune responses toward these mutants were evaluated. The mutant virus rTX-NS1-128 exhibited the most attenuated phenotype and lost transmissibility. The expression levels of interleukin 12 in the nasal and tracheal tissues from chickens immunized with rTX-NS1-128 were significantly upregulated on day 3 post-immunization and the IgA and IgG antibody levels were significantly increased on days 7, 14, and 21 post-immunization when compared to chickens that received an inactivated vaccine. rTX-NS1-128 also protected chickens from challenge by homologous and heterologous H9N2 avian influenza viruses. The results indicate that rTX-NS1-128 can be used as a potential live-attenuated vaccine against H9N2 avian influenza.

  9. CANINE DISTEMPER VIRUS ANTIBODY TITERS IN DOMESTIC CATS AFTER DELIVERY OF A LIVE ATTENUATED VIRUS VACCINE.

    Science.gov (United States)

    Ramsay, Edward; Sadler, Ryan; Rush, Robert; Seimon, Tracie; Tomaszewicz, Ania; Fleetwood, Ellen A; McAloose, Denise; Wilkes, Rebecca P

    2016-06-01

    Three methods for delivering a live attenuated canine distemper virus (CDV) vaccine to domestic cats ( Felis catus ) were investigated, as models for developing vaccination protocols for tigers (Panthera tigris). Twenty domestic cats were randomly divided into four treatment groups: saline injection (negative controls); and oral, intranasal, and subcutaneous vaccinates. Cats were injected with saline or a CDV vaccine (Nobivac DP, Merck) at wk 0 and 4. Blood and nasal swabs were collected at wk 0 (prior to the initial vaccination) and weekly thereafter for 9 wk. Urine samples were collected on wk 1 to 9 after initial vaccination. Forty-nine weeks following the initial vaccination series, three cats from the subcutaneous group and three cats from the intranasal group were revaccinated. Blood was collected immediately prior, and 7 and 21 days subsequent to revaccination. Nasal swabs and urine samples were collected from each cat prior to wk 49 revaccination and daily for 7 days thereafter. Nasal swabs and urine were analyzed by quantitative PCR for vaccine virus presence. Sera were tested for CDV antibodies by virus neutralization. All cats were sero-negative for CDV antibodies at the beginning of the study, and saline-injected cats remained sero-negative throughout the study. A dramatic anamnestic response was seen following wk 4 subcutaneous vaccinations, with titers peaking at wk 6 (geometric mean = 2,435.5). Following wk 49 revaccination, subcutaneous vaccinates again mounted impressive titers (wk 52 geometric mean = 2,048). Revaccination of the intranasal group cats at wk 49 produced a small increase in titers (wk 52 geometric mean = 203). CDV viral RNA was detected in six nasal swabs but no urine samples, demonstrating low viral shedding postvaccination. The strong antibody response to subcutaneous vaccination and the lack of adverse effects suggest this vaccine is safe and potentially protective against CDV infection in domestic cats.

  10. Evaluation of live attenuated H7N3 and H7N7 vaccine viruses for their receptor binding preferences, immunogenicity in ferrets and cross reactivity to the novel H7N9 virus.

    Directory of Open Access Journals (Sweden)

    Qi Xu

    Full Text Available Live attenuated influenza vaccine (LAIV candidates of the H7 subtype, A/Netherlands/219/03 (H7N7, NL03 ca and A/chicken/British Columbia/CN-6/2004 (H7N3, BC04 ca, were evaluated for their receptor binding specificity and immunogenicity in ferrets. The BC04 ca virus exhibited α2,3-SA and α2,6-SA dual receptor binding preference while the NL03 ca virus preferentially bound to α2,3-SA. Substitution of the Q226 and G228 (Q-G by the L226 and S228 (L-S residues in the HA improved binding to α2,6-SA for NL03 ca. The vaccine viruses with L-S retained the attenuation phenotype. NL03 L-S ca replicated more efficiently than the original NL03 ca virus in the upper respiratory tract of ferrets, and induced higher levels of humoral and cellular immune responses. Prior vaccination with seasonal LAIV reduced H7-specific antibody responses, but did not reduce the H7N7 vaccine mediated protection against a heterologous H7N3 BC04 wt virus infection in ferrets. In addition, the H7N3 and H7N7 vaccine immunized ferret sera cross reacted with the newly emerged H7N9 virus. These data, in combination with the safety data from previously conducted Phase 1 studies, suggest that these vaccines may have a role in responding to the threat posed by the H7N9 virus.

  11. Internal Gene Cassette from a Genotype S H9N2 Avian Influenza Virus Attenuates the Pathogenicity of H5 Viruses in Chickens and Mice

    Directory of Open Access Journals (Sweden)

    Xiaoli Hao

    2017-10-01

    Full Text Available H9N2 avian influenza virus (AIV of genotype S frequently donate internal genes to facilitate the generation of novel reassortants such as H7N9, H10N8, H5N2 and H5N6 AIVs, posing an enormous threat to both human health and poultry industry. However, the pathogenicity and transmission of reassortant H5 viruses with internal gene cassette of genotype S H9N2-origin in chickens and mice remain unknown. In this study, four H5 reassortants carrying the HA and NA genes from different clades of H5 viruses and the remaining internal genes from an H9N2 virus of the predominant genotype S were generated by reverse genetics. We found that all four H5 reassortant viruses showed attenuated virulence in both chickens and mice, thus leading to increased the mean death times compared to the corresponding parental viruses. Consistently, the polymerase activity and replication ability in mammalian and avian cells, and the cytokine responses in the lungs of chickens and mice were also decreased when compared to their respective parental viruses. Moreover, these reassortants transmitted from birds to birds by direct contact but not by an airborne route. Our data indicate that the internal genes as a whole cassette from genotype S H9N2 viruses play important roles in reducing the pathogenicity of the H5 recombinants in chickens and mice, and might contribute to the circulation in avian or mammalian hosts.

  12. Intrathecal synthesis of antibodies to HTLV-III in patients without AIDS or AIDS related complex

    NARCIS (Netherlands)

    Goudsmit, J.; Wolters, E. C.; Bakker, M.; Smit, L.; van der Noordaa, J.; Hische, E. A.; Tutuarima, J. A.; van der Helm, H. J.

    1986-01-01

    De novo synthesis in the central nervous system of IgG antibodies to human T cell lymphotropic virus type III (HTLV-III) (lymphadenopathy associated virus) was shown in seven of 10 seropositive men who had syphilis but not the acquired immune deficiency syndrome (AIDS) or AIDS related complex. None

  13. HIV/AIDS and Alcohol

    Science.gov (United States)

    ... Psychiatric Disorders Other Substance Abuse HIV/AIDS HIV/AIDS Human immunodeficiency virus (HIV) targets the body’s immune ... and often leads to acquired immune deficiency syndrome (AIDS). The U.S. CDC reported that in 2015, 39, ...

  14. Experimental oral immunization of ferret badgers (Melogale moschata) with a recombinant canine adenovirus vaccine CAV-2-E3Δ-RGP and an attenuated rabies virus SRV9.

    Science.gov (United States)

    Zhao, Jinghui; Liu, Ye; Zhang, Shoufeng; Fang, Lijun; Zhang, Fei; Hu, Rongliang

    2014-04-01

    Ferret badgers (Melogale moschata) are a major reservoir of rabies virus in southeastern China. Oral immunization has been shown to be a practical method for wildlife rabies management in Europe and North America. Two groups of 20 ferret badgers were given a single oral dose of a recombinant canine adenovirus-rabies vaccine, CAV-2-E3Δ-RGP, or an experimental attenuated rabies virus vaccine, SRV9. At 21 days, all ferret badgers had seroconverted, with serum virus-neutralizing antibodies ranging from 0.1 to 4.5 IU/mL. Titers were >0.50 IU/mL (an acceptable level) in 17/20 and 16/20 animals receiving CAV-2-E3Δ-RGP or SRV9, respectively. The serologic results indicate that the recombinant CAV-2-E3Δ-RGP is at least as effective as the attenuated rabies virus vaccine. Both may be considered for additional research as oral rabies vaccine candidates for ferret badgers.

  15. Attenuated, oncolytic, but not wild-type measles virus infection has pleiotropic effects on human neutrophil function.

    Science.gov (United States)

    Zhang, Yu; Patel, Bella; Dey, Aditi; Ghorani, Ehsan; Rai, Lena; Elham, Mohammed; Castleton, Anna Z; Fielding, Adele K

    2012-02-01

    We previously showed that neutrophils play a role in regression of human tumor xenografts in immunodeficient mice following oncolytic vaccine measles virus (MV-Vac) treatment. In this study, we sought, using normal human neutrophils, to identify potential neutrophil-mediated mechanisms for the attenuated MV-Vac induced effects seen in vivo, by comparison with those consequent on wild-type (WT-MV) infection. Both MV-Vac and WT-MV infected and replicated within neutrophils, despite lack of SLAM expression. In both cases, neutrophils survived longer ex vivo postinfection. Furthermore, MV-Vac (but not WT-MV) infection activated neutrophils and stimulated secretion of several specific antitumor cytokines (IL-8, TNF-α, MCP-1, and IFN-α) via induction of de novo RNA and protein synthesis. In addition, MV-Vac (but not WT-MV) infection caused TRAIL secretion in the absence of de novo synthesis by triggering release of prefabricated TRAIL, via a direct effect upon degranulation. The differences between the outcome of infection by MV-Vac and WT-MV were not entirely explained by differential infection and replication of the viruses within neutrophils. To our knowledge, this is the first demonstration of potential mechanisms of oncolytic activity of an attenuated MV as compared with its WT parent. Furthermore, our study suggests that neutrophils have an important role to play in the antitumor effects of oncolytic MV.

  16. Human herpes virus-8 DNA in bronchoalveolar lavage samples from patients with AIDS-associated pulmonary Kaposi's sarcoma

    DEFF Research Database (Denmark)

    Benfield, T L; Dodt, K K; Lundgren, Jens Dilling

    1997-01-01

    Kaposi's sarcoma (KS) is the most frequent AIDS-associated neoplasm, and often disseminates to visceral organs, including the lungs. An ante-mortem diagnosis of pulmonary KS is difficult. Recently, DNA sequences resembling a new human herpes virus (HHV-8), have been identified in various forms...

  17. Hepatopulmonary syndrome in a patient with AIDS and virus C cirrhosis (viral cirrhosis type C)

    International Nuclear Information System (INIS)

    Ferreira, Maria Angelica; Gazzana, Marcelo Basso; Barreto, Sergio Saldanha Menna; Knorst, Marli Maria

    2001-01-01

    Hepatopulmonary syndrome is characterized by a triad consisting of liver disorder, pulmonary vascular dilatation, and hypoxaemia. No case of hepatopulmonary syndrome associated with AIDS has been reported so far. In this study, the authors report the case of a 43-year woman with AIDS and virus C cirrhosis taking prophylactic cotrimoxazole for pneumocystosis and retroviral therapy. Upon admission, the patient presented dyspnoea, cyanosis, digital clubbing, vascular spiders, and normal chest examination. Chest X-ray revealed bilateral interstitial infiltration and evidenced increased alveolar-arterial gradient and liver function impairment. Intrapulmonary shunt was evidenced by contrast-enhanced echocardiography and radionuclide perfusion scanning, thus confirming hepatopulmonary syndrome. (author)

  18. Longitudinal study to assess the safety and efficacy of a live-attenuated SHIV vaccine in long term immunized rhesus macaques

    International Nuclear Information System (INIS)

    Yankee, Thomas M.; Sheffer, Darlene; Liu Zhengian; Dhillon, Sukhbir; Jia Fenglan; Chebloune, Yahia; Stephens, Edward B.; Narayan, Opendra

    2009-01-01

    Live-attenuated viruses derived from SIV and SHIV have provided the most consistent protection against challenge with pathogenic viruses, but concerns regarding their long-term safety and efficacy have hampered their clinical usefulness. We report a longitudinal study in which we evaluated the long-term safety and efficacy of ΔvpuSHIV PPC , a live virus vaccine derived from SHIV PPC . Macaques were administered two inoculations of ΔvpuSHIV PPC , three years apart, and followed for eight years. None of the five vaccinated macaques developed an AIDS-like disease from the vaccine. At eight years, macaques were challenged with pathogenic SIV and SHIV. None of the four macaques with detectable cellular-mediated immunity prior to challenge had detectable viral RNA in the plasma. This study demonstrates that multiple inoculations of a live vaccine virus can be used safely and can significantly extend the efficacy of the vaccine, as compared to a single inoculation, which is efficacious for approximately three years

  19. A Cultural Approach to Conducting HIV/AIDS and Hepatitis C Virus Education among Native American Adolescents

    Science.gov (United States)

    Lowe, John

    2008-01-01

    This pilot study tests the feasibility of using a Talking Circle approach and measures cultural values and beliefs within a HIV/AIDS and hepatitis C virus (HCV) prevention program conducted among a Native American (Cherokee) youth population. A descriptive correlation design was used to examine the relationship between Cherokee self-reliance and…

  20. Enhancement of the safety of live influenza vaccine by attenuating mutations from cold-adapted hemagglutinin

    International Nuclear Information System (INIS)

    Lee, Yoon Jae; Jang, Yo Han; Kim, Paul; Lee, Yun Ha; Lee, Young Jae; Byun, Young Ho; Lee, Kwang-Hee; Kim, Kyusik; Seong, Baik Lin

    2016-01-01

    In our previous study, X-31ca-based H5N1 LAIVs, in particular, became more virulent in mice than the X-31ca MDV, possibly by the introduction of the surface antigens of highly pathogenic H5N1 influenza virus, implying that additional attenuation is needed in this cases to increase the safety level of the vaccine. In this report we suggest an approach to further increase the safety of LAIV through additional cold-adapted mutations in the hemagglutinin. The cold-adaptation of X-31 virus resulted in four amino acid mutations in the HA. We generated a panel of 7:1 reassortant viruses each carrying the hemagglutinins with individual single amino acid mutations. We examined their phenotypes and found a major attenuating mutation, N81K. This attenuation marker conferred additional temperature-sensitive and attenuation phenotype to the LAIV. Our data indicate that the cold-adapted mutation in the HA confers additional attenuation to the LAIV strain, without compromising its productivity and immune response. - Highlights: • Cold-adaptation process induced four amino acid mutations in the HA of X-31 virus. • The four mutations in the HA also contributed to attenuation of the X-31ca virus • N81K mutation was the most significant marker for the attenuation of X-31ca virus. • Introduction of N81K mutation into H3N2 LAIV further attenuated the vaccine. • This approach provides a useful guideline for enhancing the safety of the LAIVs.

  1. Enhancement of the safety of live influenza vaccine by attenuating mutations from cold-adapted hemagglutinin

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Yoon Jae [Graduate Program in Biomaterials Science and Engineering, College of Life Science and Biotechnology, Yonsei University, Seoul (Korea, Republic of); Laboratory of Molecular Medicine, Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul (Korea, Republic of); Vaccine Translational Research Center, Yonsei University, Seoul (Korea, Republic of); Jang, Yo Han [Laboratory of Molecular Medicine, Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul (Korea, Republic of); Kim, Paul; Lee, Yun Ha; Lee, Young Jae [Laboratory of Molecular Medicine, Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul (Korea, Republic of); Vaccine Translational Research Center, Yonsei University, Seoul (Korea, Republic of); Byun, Young Ho; Lee, Kwang-Hee; Kim, Kyusik [Laboratory of Molecular Medicine, Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul (Korea, Republic of); Seong, Baik Lin, E-mail: blseong@yonsei.ac.kr [Graduate Program in Biomaterials Science and Engineering, College of Life Science and Biotechnology, Yonsei University, Seoul (Korea, Republic of); Laboratory of Molecular Medicine, Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul (Korea, Republic of); Vaccine Translational Research Center, Yonsei University, Seoul (Korea, Republic of)

    2016-04-15

    In our previous study, X-31ca-based H5N1 LAIVs, in particular, became more virulent in mice than the X-31ca MDV, possibly by the introduction of the surface antigens of highly pathogenic H5N1 influenza virus, implying that additional attenuation is needed in this cases to increase the safety level of the vaccine. In this report we suggest an approach to further increase the safety of LAIV through additional cold-adapted mutations in the hemagglutinin. The cold-adaptation of X-31 virus resulted in four amino acid mutations in the HA. We generated a panel of 7:1 reassortant viruses each carrying the hemagglutinins with individual single amino acid mutations. We examined their phenotypes and found a major attenuating mutation, N81K. This attenuation marker conferred additional temperature-sensitive and attenuation phenotype to the LAIV. Our data indicate that the cold-adapted mutation in the HA confers additional attenuation to the LAIV strain, without compromising its productivity and immune response. - Highlights: • Cold-adaptation process induced four amino acid mutations in the HA of X-31 virus. • The four mutations in the HA also contributed to attenuation of the X-31ca virus • N81K mutation was the most significant marker for the attenuation of X-31ca virus. • Introduction of N81K mutation into H3N2 LAIV further attenuated the vaccine. • This approach provides a useful guideline for enhancing the safety of the LAIVs.

  2. The humoral immune response to recombinant nucleocapsid antigen of canine distemper virus in dogs vaccinated with attenuated distemper virus or DNA encoding the nucleocapsid of wild-type virus.

    Science.gov (United States)

    Griot-Wenk, M E; Cherpillod, P; Koch, A; Zurbriggen, R; Bruckner, L; Wittek, R; Zurbriggen, A

    2001-06-01

    This study compared the humoral immune response against the nucleocapsid-(N) protein of canine distemper virus (CDV) of dogs vaccinated with a multivalent vaccine against parvo-, adeno-, and parainfluenza virus and leptospira combined with either the attenuated CDV Onderstepoort strain (n = 15) or an expression plasmid containing the N-gene of CDV (n = 30). The vaccinations were applied intramuscularly three times at 2-week intervals beginning at the age of 6 weeks. None of the pre-immune sera recognized the recombinant N-protein, confirming the lack of maternal antibodies at this age. Immunization with DNA vaccine for CDV resulted in positive serum N-specific IgG response. However, their IgG (and IgA) titres were lower than those of CDV-vaccinated dogs. Likewise, DNA-vaccinated dogs did not show an IgM peak. There was no increase in N-specific serum IgE titres in either group. Serum titres to the other multivalent vaccine components were similar in both groups.

  3. Type III Interferon-Mediated Signaling Is Critical for Controlling Live Attenuated Yellow Fever Virus Infection In Vivo.

    Science.gov (United States)

    Douam, Florian; Soto Albrecht, Yentli E; Hrebikova, Gabriela; Sadimin, Evita; Davidson, Christian; Kotenko, Sergei V; Ploss, Alexander

    2017-08-15

    Yellow fever virus (YFV) is an arthropod-borne flavivirus, infecting ~200,000 people worldwide annually and causing about 30,000 deaths. The live attenuated vaccine strain, YFV-17D, has significantly contributed in controlling the global burden of yellow fever worldwide. However, the viral and host contributions to YFV-17D attenuation remain elusive. Type I interferon (IFN-α/β) signaling and type II interferon (IFN-γ) signaling have been shown to be mutually supportive in controlling YFV-17D infection despite distinct mechanisms of action in viral infection. However, it remains unclear how type III IFN (IFN-λ) integrates into this antiviral system. Here, we report that while wild-type (WT) and IFN-λ receptor knockout (λR -/- ) mice were largely resistant to YFV-17D, deficiency in type I IFN signaling resulted in robust infection. Although IFN-α/β receptor knockout (α/βR -/- ) mice survived the infection, mice with combined deficiencies in both type I signaling and type III IFN signaling were hypersusceptible to YFV-17D and succumbed to the infection. Mortality was associated with viral neuroinvasion and increased permeability of the blood-brain barrier (BBB). α/βR -/- λR -/- mice also exhibited distinct changes in the frequencies of multiple immune cell lineages, impaired T-cell activation, and severe perturbation of the proinflammatory cytokine balance. Taken together, our data highlight that type III IFN has critical immunomodulatory and neuroprotective functions that prevent viral neuroinvasion during active YFV-17D replication. Type III IFN thus likely represents a safeguard mechanism crucial for controlling YFV-17D infection and contributing to shaping vaccine immunogenicity. IMPORTANCE YFV-17D is a live attenuated flavivirus vaccine strain recognized as one of the most effective vaccines ever developed. However, the host and viral determinants governing YFV-17D attenuation and its potent immunogenicity are still unknown. Here, we analyzed the

  4. Human immunodeficiency virus, AIDS, and drug consumption in South America and the Caribbean: epidemiological evidence and initiatives to curb the epidemic.

    Science.gov (United States)

    Hacker, Mariana A; Malta, Monica; Enriquez, Melissa; Bastos, Francisco I

    2005-01-01

    The paper reviews data on drug use in relation to the spread of human immunodeficiency virus and AIDS in South America and the Caribbean. Information was gathered by thoroughly reviewing major bibliographic databanks, web sites of international institutions and regional networks working with substance misuse or human immunodeficiency virus and AIDS, and abstracts from conferences and meetings. Although some gaps remain, a growing body of evidence documents the significant role of injected cocaine in the Brazilian and Southern Cone epidemics. The Caribbean and the Andean areas have thus far been spared in large part from the spread of injection drug use and its consequences, but the situation has been changing in Southern Cone countries towards a higher prevalence of harmful injection habits. Additional challenges have been posed by the increasing availability of heroin in the Andean Area and the abuse of crack cocaine and its impact on the sexual transmission of human immunodeficiency virus in many cities. Harm reduction strategies have been established in most areas of Brazil and are gaining momentum in Argentina. Other countries in the Region still face serious limitations due to restrictive legislation and lack of broader support. Greater participation of Latin American and Caribbean countries in research protocols and continued debate on both successful and failed experiences should be encouraged in order to minimize existing barriers to the full adoption of effective measures to curb the human immunodeficiency virus and AIDS epidemic in this Region.

  5. Extracts from rabbit skin inflamed by the vaccinia virus attenuate bupivacaine-induced spinal neurotoxicity in pregnant rats

    Institute of Scientific and Technical Information of China (English)

    Rui Cui; Shiyuan Xu; Liang Wang; Hongyi Lei; Qingxiang Cai; Hongfei Zhang; Dongmei Wang

    2013-01-01

    Extracts from rabbit skin inflamed by the vaccinia virus can relieve pain and promote repair of nerve injury. The present study intraperitoneally injected extracts from rabbit skin inflamed by the vaccinia virus for 3 and 4 days prior to and following intrathecal injection of bupivacaine into pregnant rats. The pain threshold test after bupivacaine injection showed that the maximum possible effect of tail-flick latency peaked 1 day after intrathecal injection of bupivacaine in the extract-pretreatment group, and gradually decreased, while the maximum possible effect in the bupivacaine group continued to increase after intrathecal injection of bupivacaine. Histological observation showed that after 4 days of intrathecal injection of bupivacaine, the number of shrunken, vacuolated, apoptotic and caspase-9-positive cells in the dorsal root ganglion in the extract-pretreatment group was significantly reduced compared with the bupivacaine group. These findings indicate that extracts from rabbit skin inflamed by the vaccinia virus can attenuate neurotoxicity induced by intrathecal injection of bupivacaine in pregnant rats, possibly by inhibiting caspase-9 protein expression and suppressing nerve cell apoptosis.

  6. Use of etanercept in human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS) patients.

    Science.gov (United States)

    Ting, Patricia T; Koo, John Y

    2006-06-01

    Etanercept (Enbrel, Amgen, Thousand Oaks, CA), a soluble p75 tumor necrosis factor receptor:FC (TNFR:FC) fusion protein for plasma cytokines, specifically tumor necrosis factor-alpha (TNF-alpha), is used in the treatment of immune-mediated rheumatic diseases. To our knowledge, the use of etanercept in patients with human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS) is relatively uncommon. The main purpose of this short review is to examine the safety of etanercept in patients with HIV/AIDS. A Medline search was conducted using the keywords etanercept and HIV and/or AIDS for any published articles between 1966 to the present (September 2004). A case report, one case series, and one clinical trial pertained to the use of etanercept in HIV patients. No reports were found on the use of etanercept in AIDS. In addition, two case reports were found documenting the use of infliximab in HIV patients. Preliminary reports indicate that the administration of etanercept does not appear to increase the morbidity or mortality rates in HIV. The inhibition of TNF-alpha may actually improve the symptoms of HIV/AIDS-associated aphthous ulcers, cachexia, dementia, fatigue, and fever, as well as help manage concomitant rheumatic diseases and psoriasis. The use of etanercept shows promise for applications in disease management in patients with HIV/AIDS. Continued research efforts are necessary to establish the long-term safety and efficacy of etanercept and other biologic agents in this patient population.

  7. Heat-accelerated radioinactivation of attenuated poliovirus

    International Nuclear Information System (INIS)

    Dugan, V.L.; Trujillo, R.

    1975-01-01

    Attenuated poliovirus is inactivated in a synergistic manner when exposed simultaneously to heat and ionizing radiation. The synergistic response is observed in both the thermally labile and stable forms of the virus. A three-term kinetic model may be used to describe the inactivation response of the virus in a thermal and/or ionizing radiation environment. (orig.) [de

  8. Improved survival in rhesus macaques immunized with modified vaccinia virus Ankara recombinants expressing simian immunodeficiency virus envelope correlates with reduction in memory CD4+ T-cell loss and higher titers of neutralizing antibody.

    Science.gov (United States)

    Ourmanov, Ilnour; Kuwata, Takeo; Goeken, Robert; Goldstein, Simoy; Iyengar, Ranjani; Buckler-White, Alicia; Lafont, Bernard; Hirsch, Vanessa M

    2009-06-01

    Previous studies demonstrated that immunization of macaques with simian immunodeficiency virus (SIV) Gag-Pol and Env recombinants of the attenuated poxvirus modified vaccinia virus Ankara (MVA) provided protection from high viremia and AIDS following challenge with a pathogenic strain of SIV. Although all animals became infected, plasma viremia was significantly reduced in animals that received the MVA-SIV recombinant vaccines compared with animals that received nonrecombinant MVA. Most importantly, the reduction in viremia resulted in a significant increase in median and cumulative survival. Continued analysis of these animals over the subsequent 9 years has shown that they maintain a survival advantage, although all but two of the macaques have progressed to AIDS. Importantly, improved survival correlated with preservation of memory CD4(+) T cells in the peripheral blood. The greatest survival advantage was observed in macaques immunized with regimens containing SIV Env, and the titer of neutralizing antibodies to the challenge virus prior to or shortly following challenge correlated with preservation of CD4(+) T cells. These data are consistent with a role for neutralizing antibodies in nonsterilizing protection from high viremia and associated memory CD4(+) T-cell loss.

  9. Preliminary development of a live attenuated canine parvovirus vaccine from an isolate of British origin.

    Science.gov (United States)

    Churchill, A E

    1987-04-04

    Canine parvovirus isolated from a case of haemorrhagic enteritis in a breeding kennel in England was passaged and cloned in cultured feline and canine cells. No significant evidence of pathogenicity was found during six serial passages of the modified virus back through young dogs. The attenuated virus was excreted by inoculated animals and spread rapidly to uninoculated animals held in contact. When high titre attenuated virus was given to the six-week-old offspring of a seropositive dam a prompt seroconversion was observed. When the attenuated virus was used as an experimental vaccine in 108 pups in an infected breeding colony a highly significant improvement was obtained in the accumulated morbidity and mortality compared with a parallel group vaccinated with modified live feline panleucopenia virus.

  10. [AIDS: "We will win"].

    Science.gov (United States)

    Chabrier, H

    1989-11-13

    An international colloquium on AIDS held near Paris from October 26-28, 1989, unlike the World Conference on AIDS in Montreal the year before, was able to find reasons for optimism. Significant progress was reported in immunotherapy and in chemotherapy. Successful experiments in vaccinating monkeys against the AIDS virus were reported from the US, France, and Zaire. Time is needed to prove the efficacy of the vaccines because of the slow development in AIDS. A vaccine is being tested by Jonas Salk and collaborators in 75 seropositive volunteers who do not yet show full blown disease but who have very low levels of T4 lymphocytes. Plans are underway for a larger test on 500 seropositive patients at different stages of infection. According to Salk, the new chemical and logical approach toward AIDS will allow combinations of immunotherapy and chemotherapy to destroy the virus. R. Gallo of France listed as accomplishments of the past year a better understanding of the virus, improved case management techniques, increased ability to control Kaposi's sarcoma, considerable progress in the search for a vaccine, and detection of immune proteins that affect the virus. New biological markers permit establishment of correlations between cellular modifications and the progress of the disease as well as the precise effects of treatment. The new immune system drugs immuthiol and DDI are expected to reach the market soon. Patients very soon will be able to receive less toxic alternative treatments, which can be combined for greater efficacy once their toxic interactions are understood.

  11. A live-attenuated HSV-2 ICP0 virus elicits 10 to 100 times greater protection against genital herpes than a glycoprotein D subunit vaccine.

    Directory of Open Access Journals (Sweden)

    William P Halford

    2011-03-01

    Full Text Available Glycoprotein D (gD-2 is the entry receptor of herpes simplex virus 2 (HSV-2, and is the immunogen in the pharmaceutical industry's lead HSV-2 vaccine candidate. Efforts to prevent genital herpes using gD-2 subunit vaccines have been ongoing for 20 years at a cost in excess of $100 million. To date, gD-2 vaccines have yielded equivocal protection in clinical trials. Therefore, using a small animal model, we sought to determine if a live-attenuated HSV-2 ICP0⁻ virus would elicit better protection against genital herpes than a gD-2 subunit vaccine. Mice immunized with gD-2 and a potent adjuvant (alum+monophosphoryl lipid A produced high titers of gD-2 antibody. While gD-2-immunized mice possessed significant resistance to HSV-2, only 3 of 45 gD-2-immunized mice survived an overwhelming challenge of the vagina or eyes with wild-type HSV-2 (MS strain. In contrast, 114 of 115 mice immunized with a live HSV-2 ICP0⁻ virus, 0ΔNLS, survived the same HSV-2 MS challenges. Likewise, 0ΔNLS-immunized mice shed an average 125-fold less HSV-2 MS challenge virus per vagina relative to gD-2-immunized mice. In vivo imaging demonstrated that a luciferase-expressing HSV-2 challenge virus failed to establish a detectable infection in 0ΔNLS-immunized mice, whereas the same virus readily infected naïve and gD-2-immunized mice. Collectively, these results suggest that a HSV-2 vaccine might be more likely to prevent genital herpes if it contained a live-attenuated HSV-2 virus rather than a single HSV-2 protein.

  12. A mutation in the envelope protein fusion loop attenuates mouse neuroinvasiveness of the NY99 strain of West Nile virus

    International Nuclear Information System (INIS)

    Zhang Shuliu; Li Li; Woodson, Sara E.; Huang, Claire Y.-H.; Kinney, Richard M.; Barrett, Alan D.T.; Beasley, David W.C.

    2006-01-01

    Substitutions were engineered individually and in combinations at the fusion loop, receptor-binding domain and a stem-helix structure of the envelope protein of a West Nile virus strain, NY99, and their effects on mouse virulence and presentation of epitopes recognized by monoclonal antibodies (MAbs) were assessed. A single substitution within the fusion loop (L107F) attenuated mouse neuroinvasiveness of NY99. No substitutions attenuated NY99 neurovirulence. The L107F mutation also abolished binding of a non-neutralizing MAb, 3D9, whose epitope had not been previously identified. MAb 3D9 was subsequently shown to be broadly cross-reactive with other flaviviruses, consistent with binding near the highly conserved fusion loop

  13. Immunity to infection with porcine parvovirus in pigs inoculated with the attenuated HT- strain.

    Science.gov (United States)

    Fujisaki, Y; Murakami, Y

    1982-01-01

    Swine were inoculated once with the attenuated HT- strain of porcine parvovirus. Several months later they were challenged by oral inoculation with a field strain of the virus to examine an ability to prevent infection. After challenge inoculation unimmunized control swine exhibited an increase in antibody titer, viremia, and virus discharge. The virus was recovered from many organs. The swine preinoculated with the attenuated HT- strain, however, manifested none of these symptoms and were negative for virus recovery from any organ.

  14. Abdominal imaging in AIDS patients

    International Nuclear Information System (INIS)

    Zhao Dawei; Wang Wei; Yuan Chunwang; Jia Cuiyu; Zhao Xuan; Zhang Tong; Ma Daqing

    2007-01-01

    Objective: To evaluate abdominal imaging in AIDS. Methods: The imaging examinations (including US, CT and MR) of 6 patients with AIDS associated abdominal foci were analysed retrospectively. All the cases were performed US, and CT scan, of which 4 performed enhanced CT scan and 1 with MR. Results: Abdominal tuberculosis were found in 4 patients, including abdominal lymph nodes tuberculosis (3 cases) and pancreatic tuberculosis (1 case). The imaging of lymph nodes tuberculosis typically showed enlarged peripheral tim enhancement with central low-attenuation on contrast-enhanced CT. Pancreatic tuberculosis demonstrated low-attenuation area in pancreatic head and slightly peripheral enhancement. Disseminated Kaposi's sarcoma was seen in 1 case: CT and MRI scan demonstrated tumour infiltrated along hepatic portal vein and bronchovascular bundles. Pelvic tumor was observed in 1 case: CT scan showed large mass with thick and irregular wall and central low attenuation liquefacient necrotic area in the pelvic cavity. Conclusion: The imaging findings of AIDS with abdominal foci is extraordinarily helpful to the diagnosis of such disease. Tissue biopsy is needed to confirm the diagnosis. (authors)

  15. The neurovirulence and neuroinvasiveness of chimeric tick-borne encephalitis/dengue virus can be attenuated by introducing defined mutations into the envelope and NS5 protein genes and the 3' non-coding region of the genome

    International Nuclear Information System (INIS)

    Engel, Amber R.; Rumyantsev, Alexander A.; Maximova, Olga A.; Speicher, James M.; Heiss, Brian; Murphy, Brian R.; Pletnev, Alexander G.

    2010-01-01

    Tick-borne encephalitis (TBE) is a severe disease affecting thousands of people throughout Eurasia. Despite the use of formalin-inactivated vaccines in endemic areas, an increasing incidence of TBE emphasizes the need for an alternative vaccine that will induce a more durable immunity against TBE virus (TBEV). The chimeric attenuated virus vaccine candidate containing the structural protein genes of TBEV on a dengue virus genetic background (TBEV/DEN4) retains a high level of neurovirulence in both mice and monkeys. Therefore, attenuating mutations were introduced into the envelope (E 315 ) and NS5 (NS5 654,655 ) proteins, and into the 3' non-coding region (Δ30) of TBEV/DEN4. The variant that contained all three mutations (vΔ30/E 315 /NS5 654,655 ) was significantly attenuated for neuroinvasiveness and neurovirulence and displayed a reduced level of replication and virus-induced histopathology in the brains of mice. The high level of safety in the central nervous system indicates that vΔ30/E 315 /NS5 654,655 should be further evaluated as a TBEV vaccine.

  16. Live attenuated measles virus vaccine therapy for locally established malignant glioblastoma tumor cells

    Directory of Open Access Journals (Sweden)

    Al-Shammari AM

    2014-05-01

    Full Text Available Ahmed M Al-Shammari,1 Farah E Ismaeel,2 Shahlaa M Salih,2 Nahi Y Yaseen11Experimental Therapy Department, Iraqi Center for Cancer and Medical Genetic Researches, Mustansiriya University, 2Departments of Biotechnology, College of Science, Al-Nahrain University, Baghdad, IraqAbstract: Glioblastoma multiforme is the most aggressive malignant primary brain tumor in humans, with poor prognosis. A new glioblastoma cell line (ANGM5 was established from a cerebral glioblastoma multiforme in a 72-year-old Iraqi man who underwent surgery for an intracranial tumor. This study was carried out to evaluate the antitumor effect of live attenuated measles virus (MV Schwarz vaccine strain on glioblastoma multiforme tumor cell lines in vitro. Live attenuated MV Schwarz strain was propagated on Vero, human rhabdomyosarcoma, and human glioblastoma-multiform (ANGM5 cell lines. The infected confluent monolayer appeared to be covered with syncytia with granulation and vacuolation, as well as cell rounding, shrinkage, and large empty space with cell debris as a result of cell lysis and death. Cell lines infected with virus have the ability for hemadsorption to human red blood cells after 72 hours of infection, whereas no hemadsorption of uninfected cells is seen. Detection of MV hemagglutinin protein by monoclonal antibodies in infected cells of all cell lines by immunocytochemistry assay gave positive results (brown color in the cytoplasm of infected cells. Cell viability was measured after 72 hours of infection by 3-(4,5-Dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide assay. Results showed a significant cytotoxic effect for MV (P≤0.05 on growth of ANGM5 and rhabdomyosarcoma cell lines after 72 hours of infection. Induction of apoptosis by MV was assessed by measuring mitochondrial membrane potentials in tumor cells after 48, 72, and 120 hours of infection. Apoptotic cells were counted, and the mean percentage of dead cells was significantly higher after 48, 72

  17. Optimization of the doxycycline-dependent simian immunodeficiency virus through in vitro evolution

    Directory of Open Access Journals (Sweden)

    Piatak Mike

    2008-06-01

    Full Text Available Abstract Background Vaccination of macaques with live attenuated simian immunodeficiency virus (SIV provides significant protection against the wild-type virus. The use of a live attenuated human immunodeficiency virus (HIV as AIDS vaccine in humans is however considered unsafe because of the risk that the attenuated virus may accumulate genetic changes during persistence and evolve to a pathogenic variant. We earlier presented a conditionally live HIV-1 variant that replicates exclusively in the presence of doxycycline (dox. Replication of this vaccine strain can be limited to the time that is needed to provide full protection through transient dox administration. Since the effectiveness and safety of such a conditionally live virus vaccine should be tested in macaques, we constructed a similar dox-dependent SIV variant. The Tat-TAR transcription control mechanism in this virus was inactivated through mutation and functionally replaced by the dox-inducible Tet-On regulatory system. This SIV-rtTA variant replicated in a dox-dependent manner in T cell lines, but not as efficiently as the parental SIVmac239 strain. Since macaque studies will likely require an efficiently replicating variant, we set out to optimize SIV-rtTA through in vitro viral evolution. Results Upon long-term culturing of SIV-rtTA, additional nucleotide substitutions were observed in TAR that affect the structure of this RNA element but that do not restore Tat binding. We demonstrate that the bulge and loop mutations that we had introduced in the TAR element of SIV-rtTA to inactivate the Tat-TAR mechanism, shifted the equilibrium between two alternative conformations of TAR. The additional TAR mutations observed in the evolved variants partially or completely restored this equilibrium, which suggests that the balance between the two TAR conformations is important for efficient viral replication. Moreover, SIV-rtTA acquired mutations in the U3 promoter region. We demonstrate

  18. Seroprevalence of hepatitis C virus among people living with HIV/AIDS in Latin America and the Caribbean: a systematic review

    Directory of Open Access Journals (Sweden)

    Fatima Mitiko Tengan

    2016-11-01

    Full Text Available Abstract Background Studies have shown that the immunosuppression induced by the human immunodeficiency virus (HIV accelerates the natural history of liver disease associated with hepatitis C virus (HCV, with 3- to 5-fold higher odds of coinfected individuals developing cirrhosis. However, estimates of the seroprevalence of hepatitis C among people living with HIV/acquired immune deficiency syndrome (AIDS (PLHA in Latin America and the Caribbean (LAC are widely variable. Methods We performed a systematic review to estimate the seroprevalence of HCV among PLHA. We searched studies on HIV and HCV infections in LAC included in the PubMed, LILACS and Embase databases in December of 2014 with no time or language restrictions. The following combinations of search terms were used in the PubMed and Embase databases: (HIV OR Acquired Immunodeficiency Syndrome Virus OR AIDS OR HTLV OR Human Immunodeficiency Virus OR Human T Cell AND (HCV OR HEPATITIS C OR HEPATITIS C VIRUS OR HEPACIVIRUS AND (name of an individual country or territory in LAC. The following search terms were used in the LILACS database: (HIV OR AIDS OR Virus da Imunodeficiencia Humana AND (HCV OR Hepatite C OR Hepacivirus. An additional 11 studies were identified through manual searches. A total of 2,380 publications were located, including 617 duplicates; the remaining articles were reviewed to select studies for inclusion in this study. Results A total of 37 studies were selected for systematic review, including 23 from Brazil, 5 from Argentina, 3 from Cuba, 1 from Puerto Rico, 1 from Chile, 1 from Colombia, 1 from Mexico, 1 from Peru and 1 from Venezuela. The estimated seroprevalence of HCV infection varied from 0.8 to 58.5 % (mean 17.37; median 10.91, with the highest in Argentina and Brazil and the lowest in Venezuela and Colombia. Conclusions Investigation of HCV infection among PLHA and of HIV infection among people living with HCV is highly recommended because it allows for better

  19. Resistance to Two Heterologous Neurotropic Oncolytic Viruses, Semliki Forest Virus and Vaccinia Virus, in Experimental Glioma

    Science.gov (United States)

    Le Boeuf, Fabrice; Lemay, Chantal; De Silva, Naomi; Diallo, Jean-Simon; Cox, Julie; Becker, Michelle; Choi, Youngmin; Ananth, Abhirami; Sellers, Clara; Breton, Sophie; Roy, Dominic; Falls, Theresa; Brun, Jan; Hemminki, Akseli; Hinkkanen, Ari; Bell, John C.

    2013-01-01

    Attenuated Semliki Forest virus (SFV) may be suitable for targeting malignant glioma due to its natural neurotropism, but its replication in brain tumor cells may be restricted by innate antiviral defenses. We attempted to facilitate SFV replication in glioma cells by combining it with vaccinia virus, which is capable of antagonizing such defenses. Surprisingly, we found parenchymal mouse brain tumors to be refractory to both viruses. Also, vaccinia virus appears to be sensitive to SFV-induced antiviral interference. PMID:23221568

  20. A novel role for APOBEC3: Susceptibility to sexual transmission of murine acquired immunodeficiency virus (mAIDS) is aggravated in APOBEC3 deficient mice

    Science.gov (United States)

    2012-01-01

    Background APOBEC3 proteins are host factors that restrict infection by retroviruses like HIV, MMTV, and MLV and are variably expressed in hematopoietic and non-hematopoietic cells, such as macrophages, lymphocytes, dendritic, and epithelia cells. Previously, we showed that APOBEC3 expressed in mammary epithelia cells function to limit milk-borne transmission of the beta-retrovirus, mouse mammary tumor virus. In this present study, we used APOBEC3 knockout mice and their wild type counterpart to query the role of APOBEC3 in sexual transmission of LP-BM5 MLV – the etiological agent of murine AIDs (mAIDs). Results We show that mouse APOBEC3 is expressed in murine genital tract tissues and gametes and that genital tract tissue of APOBEC3-deficient mice are more susceptible to infection by LP-BM5 virus. APOBEC3 expressed in genital tract tissues most likely plays a role in decreasing virus transmission via the sexual route, since mice deficient in APOBEC3 gene have higher genitalia and seminal plasma virus load and sexually transmit the virus more efficiently to their partners compared to APOBEC3+ mice. Moreover, we show that female mice sexually infected with LP-BM5 virus transmit the virus to their off-spring in APOBEC3-dependent manner. Conclusion Our data indicate that genital tissue intrinsic APOBEC3 restricts genital tract infection and limits sexual transmission of LP-BM5 virus. PMID:22691411

  1. AIDS guidelines.

    Science.gov (United States)

    Berger, R

    1986-04-30

    The Sun article, "Employers finding that AIDS in the workplace is a managerial nightmare" (April 3), did not accurately portray the status of AIDS in the workplace. The AIDS virus, HTLV III, is transmitted by body fluids, primarily semen and blood, and there is no known risk of transmitting the virus by casual contact in the workplace. The Center for Disease Control (CDC) released guidelines for child care workers last August. Guidelines on preventing transmission of AIDS in the workplace were issued by CDC in November 1985. These guidelines specifically discussed health care, personal service, and food service workers. The recommendations were against routine screening. Furthermore, employment should not be restricted on the basis of a positive HTLV III antibody test. A person with HTLV III infection should be exempt from the workplace only if there are circumstances interfering with job performance. In Maryland, the Governor's Task Force on AIDS has gone on record as endorsing CDC guidelines related to employment. Furthermore, the task force condemns discrimination based on the disease AIDS, AIDS Related Complex (ARC), or HTLV III infection. Increasingly AIDS patients are being considered legally disabled and therefore are protected by federal and state laws prohibiting discrimination on the basis of a handicap. Marylanders who are subjected to mandatory HTLV III screening in the workplace, or if discriminated against on the basis of HTLV III inefction, should contact the Maryland Commission on Human Relations, the Maryland Department of Health and Mental Hygiene, or the Health Education Resource Organization (HERO). All 3 of these resources guarantee confidentiality. It is only by employees reporting incidents that a nightmare in the workplace can be avoided in Maryland. full text

  2. Myxoma Virus and the Leporipoxviruses: An Evolutionary Paradigm

    Directory of Open Access Journals (Sweden)

    Peter J. Kerr

    2015-03-01

    Full Text Available Myxoma virus (MYXV is the type species of the Leporipoxviruses, a genus of Chordopoxvirinae, double stranded DNA viruses, whose members infect leporids and squirrels, inducing cutaneous fibromas from which virus is mechanically transmitted by biting arthropods. However, in the European rabbit (Oryctolagus cuniculus, MYXV causes the lethal disease myxomatosis. The release of MYXV as a biological control for the wild European rabbit population in Australia, initiated one of the great experiments in evolution. The subsequent coevolution of MYXV and rabbits is a classic example of natural selection acting on virulence as a pathogen adapts to a novel host species. Slightly attenuated mutants of the progenitor virus were more readily transmitted by the mosquito vector because the infected rabbit survived longer, while highly attenuated viruses could be controlled by the rabbit immune response. As a consequence, moderately attenuated viruses came to dominate. This evolution of the virus was accompanied by selection for genetic resistance in the wild rabbit population, which may have created an ongoing co-evolutionary dynamic between resistance and virulence for efficient transmission. This natural experiment was repeated on a continental scale with the release of a separate strain of MYXV in France and its subsequent spread throughout Europe. The selection of attenuated strains of virus and resistant rabbits mirrored the experience in Australia in a very different environment, albeit with somewhat different rates. Genome sequencing of the progenitor virus and the early radiation, as well as those from the 1990s in Australia and Europe, has shown that although MYXV evolved at high rates there was no conserved route to attenuation or back to virulence. In contrast, it seems that these relatively large viral genomes have the flexibility for multiple pathways that converge on a similar phenotype.

  3. Myxoma virus and the Leporipoxviruses: an evolutionary paradigm.

    Science.gov (United States)

    Kerr, Peter J; Liu, June; Cattadori, Isabella; Ghedin, Elodie; Read, Andrew F; Holmes, Edward C

    2015-03-06

    Myxoma virus (MYXV) is the type species of the Leporipoxviruses, a genus of Chordopoxvirinae, double stranded DNA viruses, whose members infect leporids and squirrels, inducing cutaneous fibromas from which virus is mechanically transmitted by biting arthropods. However, in the European rabbit (Oryctolagus cuniculus), MYXV causes the lethal disease myxomatosis. The release of MYXV as a biological control for the wild European rabbit population in Australia, initiated one of the great experiments in evolution. The subsequent coevolution of MYXV and rabbits is a classic example of natural selection acting on virulence as a pathogen adapts to a novel host species. Slightly attenuated mutants of the progenitor virus were more readily transmitted by the mosquito vector because the infected rabbit survived longer, while highly attenuated viruses could be controlled by the rabbit immune response. As a consequence, moderately attenuated viruses came to dominate. This evolution of the virus was accompanied by selection for genetic resistance in the wild rabbit population, which may have created an ongoing co-evolutionary dynamic between resistance and virulence for efficient transmission. This natural experiment was repeated on a continental scale with the release of a separate strain of MYXV in France and its subsequent spread throughout Europe. The selection of attenuated strains of virus and resistant rabbits mirrored the experience in Australia in a very different environment, albeit with somewhat different rates. Genome sequencing of the progenitor virus and the early radiation, as well as those from the 1990s in Australia and Europe, has shown that although MYXV evolved at high rates there was no conserved route to attenuation or back to virulence. In contrast, it seems that these relatively large viral genomes have the flexibility for multiple pathways that converge on a similar phenotype.

  4. Myxoma Virus and the Leporipoxviruses: An Evolutionary Paradigm

    Science.gov (United States)

    Kerr, Peter J.; Liu, June; Cattadori, Isabella; Ghedin, Elodie; Read, Andrew F.; Holmes, Edward C.

    2015-01-01

    Myxoma virus (MYXV) is the type species of the Leporipoxviruses, a genus of Chordopoxvirinae, double stranded DNA viruses, whose members infect leporids and squirrels, inducing cutaneous fibromas from which virus is mechanically transmitted by biting arthropods. However, in the European rabbit (Oryctolagus cuniculus), MYXV causes the lethal disease myxomatosis. The release of MYXV as a biological control for the wild European rabbit population in Australia, initiated one of the great experiments in evolution. The subsequent coevolution of MYXV and rabbits is a classic example of natural selection acting on virulence as a pathogen adapts to a novel host species. Slightly attenuated mutants of the progenitor virus were more readily transmitted by the mosquito vector because the infected rabbit survived longer, while highly attenuated viruses could be controlled by the rabbit immune response. As a consequence, moderately attenuated viruses came to dominate. This evolution of the virus was accompanied by selection for genetic resistance in the wild rabbit population, which may have created an ongoing co-evolutionary dynamic between resistance and virulence for efficient transmission. This natural experiment was repeated on a continental scale with the release of a separate strain of MYXV in France and its subsequent spread throughout Europe. The selection of attenuated strains of virus and resistant rabbits mirrored the experience in Australia in a very different environment, albeit with somewhat different rates. Genome sequencing of the progenitor virus and the early radiation, as well as those from the 1990s in Australia and Europe, has shown that although MYXV evolved at high rates there was no conserved route to attenuation or back to virulence. In contrast, it seems that these relatively large viral genomes have the flexibility for multiple pathways that converge on a similar phenotype. PMID:25757062

  5. Transcription of minute virus of mice, an autonomous parvovirus, may be regulated by attenuation

    International Nuclear Information System (INIS)

    Ben-Asher, E.; Aloni, Y.

    1984-01-01

    To characterize the transcriptional organization and regulation of minute virus of mice, an autonomous parvovirus, viral transcriptional complexes were isolated and cleaved with restriction enzymes. The in vivo preinitiated nascent RNA was elongated in vitro in the presence of [alpha- 32 P]UTP to generate runoff transcripts. The lengths of the runoff transcripts were analyzed by gel electrophoresis under denaturing conditions. On the basis of the map locations of the restriction sites and the lengths of the runoff transcripts, the in vivo initiation sites were determined. Two major initiation sites having similar activities were thus identified at residues 201 +/- 5 and 2005 +/- 5; both of them were preceded by a TATAA sequence. When uncleaved viral transcriptional complexes or isolated nuclei were incubated in vitro in the presence of [alpha- 32 P]UTP or [alpha- 32 P]CTP, they synthesized labeled RNA that, as determined by polyacrylamide gel electrophoresis, contained a major band of 142 nucleotides. The RNA of the major band was mapped between the initiation site at residue 201 +/- 5 and residue 342. We noticed the potential of forming two mutually exclusive stem-and-loop structures in the 142-nucleotide RNA; one of them is followed by a string of uridylic acid residues typical of a procaryotic transcription termination signal. We propose that, as in the transcription of simian virus 40, RNA transcription in minute virus of mice may be regulated by attenuation and may involve eucaryotic polymerase B, which can respond to a transcription termination signal similar to that of the procaryotic polymerase

  6. Attenuation and efficacy of human parainfluenza virus type 1 (HPIV1 vaccine candidates containing stabilized mutations in the P/C and L genes

    Directory of Open Access Journals (Sweden)

    Skiadopoulos Mario H

    2007-07-01

    Full Text Available Abstract Background Two recombinant, live attenuated human parainfluenza virus type 1 (rHPIV1 mutant viruses have been developed, using a reverse genetics system, for evaluation as potential intranasal vaccine candidates. These rHPIV1 vaccine candidates have two non-temperature sensitive (non-ts attenuating (att mutations primarily in the P/C gene, namely CR84GHNT553A (two point mutations used together as a set and CΔ170 (a short deletion mutation, and two ts att mutations in the L gene, namely LY942A (a point mutation, and LΔ1710–11 (a short deletion, the last of which has not been previously described. The latter three mutations were specifically designed for increased genetic and phenotypic stability. These mutations were evaluated on the HPIV1 backbone, both individually and in combination, for attenuation, immunogenicity, and protective efficacy in African green monkeys (AGMs. Results The rHPIV1 mutant bearing the novel LΔ1710–11 mutation was highly ts and attenuated in AGMs and was immunogenic and efficacious against HPIV1 wt challenge. The rHPIV1-CR84G/Δ170HNT553ALY942A and rHPIV1-CR84G/Δ170HNT553ALΔ1710–11 vaccine candidates were highly ts, with shut-off temperatures of 38°C and 35°C, respectively, and were highly attenuated in AGMs. Immunization with rHPIV1-CR84G/Δ170HNT553ALY942A protected against HPIV1 wt challenge in both the upper and lower respiratory tracts. In contrast, rHPIV1-CR84G/Δ170HNT553ALΔ1710–11 was not protective in AGMs due to over-attenuation, but it is expected to replicate more efficiently and be more immunogenic in the natural human host. Conclusion The rHPIV1-CR84G/Δ170HNT553ALY942A and rHPIV1-CR84G/Δ170HNT553ALΔ1710–11 vaccine candidates are clearly highly attenuated in AGMs and clinical trials are planned to address safety and immunogenicity in humans.

  7. A combination in-ovo vaccine for avian influenza virus and Newcastle disease virus.

    Science.gov (United States)

    Steel, John; Burmakina, Svetlana V; Thomas, Colleen; Spackman, Erica; García-Sastre, Adolfo; Swayne, David E; Palese, Peter

    2008-01-24

    The protection of poultry from H5N1 highly pathogenic avian influenza A (HPAI) and Newcastle disease virus (NDV) can be achieved through vaccination, as part of a broader disease control strategy. We have previously generated a recombinant influenza virus expressing, (i) an H5 hemagglutinin protein, modified by the removal of the polybasic cleavage peptide and (ii) the ectodomain of the NDV hemagglutinin-neuraminidase (HN) protein in the place of the ectodomain of influenza neuraminidase (Park MS, et al. Proc Natl Acad Sci USA 2006;103(21):8203-8). Here we show this virus is attenuated in primary normal human bronchial epithelial (NHBE) cell culture, and demonstrate protection of C57BL/6 mice from lethal challenge with an H5 HA-containing influenza virus through immunisation with the recombinant virus. In addition, in-ovo vaccination of 18-day-old embryonated chicken eggs provided 90% and 80% protection against highly stringent lethal challenge by NDV and H5N1 virus, respectively. We propose that this virus has potential as a safe in-ovo live, attenuated, bivalent avian influenza and Newcastle disease virus vaccine.

  8. Hepatopulmonary syndrome in a patient with AIDS and virus C cirrhosis (viral cirrhosis type C); Sindrome hepatopulmonar em paciente com cirrose por virus C e SIDA

    Energy Technology Data Exchange (ETDEWEB)

    Ferreira, Maria Angelica; Gazzana, Marcelo Basso [Hospital de Clinicas de Porto Alegre, RS (Brazil). Servico de Pneumologia; Barreto, Sergio Saldanha Menna; Knorst, Marli Maria [Rio Grande do Sul Univ., Porto Alegre, RS (Brazil). Faculdade de Medicina. Dept. de Medicina Interna

    2001-02-01

    Hepatopulmonary syndrome is characterized by a triad consisting of liver disorder, pulmonary vascular dilatation, and hypoxaemia. No case of hepatopulmonary syndrome associated with AIDS has been reported so far. In this study, the authors report the case of a 43-year woman with AIDS and virus C cirrhosis taking prophylactic cotrimoxazole for pneumocystosis and retroviral therapy. Upon admission, the patient presented dyspnoea, cyanosis, digital clubbing, vascular spiders, and normal chest examination. Chest X-ray revealed bilateral interstitial infiltration and evidenced increased alveolar-arterial gradient and liver function impairment. Intrapulmonary shunt was evidenced by contrast-enhanced echocardiography and radionuclide perfusion scanning, thus confirming hepatopulmonary syndrome. (author)

  9. Disruption of the Opal Stop Codon Attenuates Chikungunya Virus-Induced Arthritis and Pathology.

    Science.gov (United States)

    Jones, Jennifer E; Long, Kristin M; Whitmore, Alan C; Sanders, Wes; Thurlow, Lance R; Brown, Julia A; Morrison, Clayton R; Vincent, Heather; Peck, Kayla M; Browning, Christian; Moorman, Nathaniel; Lim, Jean K; Heise, Mark T

    2017-11-14

    of related alphaviruses in mammalian and mosquito hosts. Here, we report that a clinical isolate of a CHIKV strain from the recent outbreak in the Caribbean islands contains a mixture of viruses encoding either the opal termination codon or an arginine mutation. Mutating the opal stop codon to an arginine residue attenuates CHIKV-induced disease in a mouse model. Compared to infection with the opal-containing parental virus, infection with the arginine mutant causes limited swelling and inflammation, as well as dampened recruitment of immune mediators of pathology, including CD4 + T cells and NK cells. We propose that the opal termination codon plays an essential role in the induction of severe CHIKV disease. Copyright © 2017 Jones et al.

  10. Enhanced replication of attenuated HSV-1 in irradiated human glioma xenografts

    International Nuclear Information System (INIS)

    Advani, Sunil J.; Kataoka, Yasushi; Sibley, Greg S.; Song, Paul Y.; Hallahan, Dennis E.; Roizman, Bernard; Weichselbaum, Ralph R.

    1997-01-01

    Purpose: Previously we had shown that combining ionizing radiation (IR) with attenuated replication competent HSV-1 (R3616) significantly increased glioma xenograft eradication compared to IR or virus alone. One hypothesis is that IR induces cell factors that contribute to augment viral replication thereby increasing the efficacy of attenuated HSV-1. The purpose of this study was to examine if IR altered viral replication of attenuated HSV-1 in glioma xenografts Material and Methods: Human U-87MG glioma cells were grown in the hindlimb of athymic mice and grown to >200 mm 3 . Tumors were infected with 2x10 7 plaque forming units (pfu) of R3616 ( γ1 34.5 - ) or R7020 (multimutated, γ1 34.5 + ) on day 0 and irradiated with 20 Gy on day 1 and 25 Gy on day 2. Tumors were harvested 3, 5, 7, and 14 days after viral injection. Tumors were homogenized and sonnicated. Serial dilutions of tumor extract were overlaid on Vero cells to determine the number of pfu. In addition, in-situ hybridization to HSV-1 DNA was performed on tumors harvested at day 7. Results: In-situ hybridization revealed larger numbers of glial cells infected with HSV along with a greater distribution in the irradiated tumors compared to non-irradiated tumors. We next quantified viral particles in infected tumors +/- IR: Conclusion: Herein we demonstrate radiation enhanced viral replication as one of the interactive effects of combining IR and attenuated HSV in treating glioma xenografts and a potential therapeutic motif in the treatment of gliomas. To reduce normal tissue toxicity of HSV in glioma therapy, viruses must be attenuated. However, attenuating the virus compromises its replication and thus its potential efficacy. Our results indicate that IR augments the amount of virus recovered from human glioma xenografts for up to 3 days post IR. The results do not appear to be related to a specific mutation in the herpes genome but rather to herpes viruses in general. Yields of R7020 were greater than R

  11. AIDS Epidemiological models

    Science.gov (United States)

    Rahmani, Fouad Lazhar

    2010-11-01

    The aim of this paper is to present mathematical modelling of the spread of infection in the context of the transmission of the human immunodeficiency virus (HIV) and the acquired immune deficiency syndrome (AIDS). These models are based in part on the models suggested in the field of th AIDS mathematical modelling as reported by ISHAM [6].

  12. MicroRNA-Attenuated Clone of Virulent Semliki Forest Virus Overcomes Antiviral Type I Interferon in Resistant Mouse CT-2A Glioma.

    Science.gov (United States)

    Martikainen, Miika; Niittykoski, Minna; von und zu Fraunberg, Mikael; Immonen, Arto; Koponen, Susanna; van Geenen, Maartje; Vähä-Koskela, Markus; Ylösmäki, Erkko; Jääskeläinen, Juha E; Saksela, Kalle; Hinkkanen, Ari

    2015-10-01

    Glioblastoma is a terminal disease with no effective treatment currently available. Among the new therapy candidates are oncolytic viruses capable of selectively replicating in cancer cells, causing tumor lysis and inducing adaptive immune responses against the tumor. However, tumor antiviral responses, primarily mediated by type I interferon (IFN-I), remain a key problem that severely restricts viral replication and oncolysis. We show here that the Semliki Forest virus (SFV) strain SFV4, which causes lethal encephalitis in mice, is able to infect and replicate independent of the IFN-I defense in mouse glioblastoma cells and cell lines originating from primary human glioblastoma patient samples. The ability to tolerate IFN-I was retained in SFV4-miRT124 cells, a derivative cell line of strain SFV4 with a restricted capacity to replicate in neurons due to insertion of target sites for neuronal microRNA 124. The IFN-I tolerance was associated with the viral nsp3-nsp4 gene region and distinct from the genetic loci responsible for SFV neurovirulence. In contrast to the naturally attenuated strain SFV A7(74) and its derivatives, SFV4-miRT124 displayed increased oncolytic potency in CT-2A murine astrocytoma cells and in the human glioblastoma cell lines pretreated with IFN-I. Following a single intraperitoneal injection of SFV4-miRT124 into C57BL/6 mice bearing CT-2A orthotopic gliomas, the virus homed to the brain and was amplified in the tumor, resulting in significant tumor growth inhibition and improved survival. Although progress has been made in development of replicative oncolytic viruses, information regarding their overall therapeutic potency in a clinical setting is still lacking. This could be at least partially dependent on the IFN-I sensitivity of the viruses used. Here, we show that the conditionally replicating SFV4-miRT124 virus shares the IFN-I tolerance of the pathogenic wild-type SFV, thereby allowing efficient targeting of a glioma that is refractory

  13. HIV/AIDS

    Science.gov (United States)

    HIV stands for human immunodeficiency virus. It harms your immune system by destroying the white blood cells ... It is the final stage of infection with HIV. Not everyone with HIV develops AIDS. HIV most ...

  14. Human Transcriptome Response to Immunization with Live- Attenuated Venezuelan equine encephalitis Virus Vaccine (TC 83): Analysis of Whole Blood

    Science.gov (United States)

    2016-11-21

    natural killer cell 33 signaling, and B-cell development. Biomarkers were identified that differentiate between 34 vaccinees and control subjects...risk laboratory personnel.8 The first vaccine, 68 TC-83, is a live-attenuated virus developed in 1961 by serial passage of the virulent Trinidad 69...HSP90AA1), the ERK5 Signaling pathway 220 (e.g., IL6ST, NRAS, RRAS2, ATF2), the Natural Killer Cell Signaling pathway (e.g., KLRC2, 221 FYN, PRKC1

  15. THE AIDS HANDBOOK

    Directory of Open Access Journals (Sweden)

    Z Khan

    1997-12-01

    Full Text Available HIV infection and AIDS is increasingly becoming a major public health problem in our country. Currently, the reported cases represent only the 'tip of the iceberg' of the problem. In view of the fact that no cure or vaccine for the disease has yet been found, spreading knowledge and removing misconceptions is about the only way that AIDS can be effectively tackled.This handbook, developed by Prof. Shankar Chowdhury and associates, seeks to address all levels of medical and non-medical AIDS workers, as well as the layman. It deals with topics ranging from biology of the virus, symptoms and transmission of disease, to prevention, counselling for infected persons and action plan for AIDS education.The biology of the virus and the immune system is described in simple terms, as well as methods of testing for HIV, and what these test results mean. The progression of disease in adults and children, development of symptoms, diagnostic criteria for AIDS, treatment and outcome of disease is dealt with. How AIDS spreads between people, and the health risk for health workers and families is examined. The various ways in which transmission of HIV can be prevented is looked at in detail, including public health measures, national and internatonal action, and ethical and human rights issues involved.

  16. Isolation of an attenuated myxoma virus field strain that can confer protection against myxomatosis on contacts of vaccinates.

    Science.gov (United States)

    Bárcena, J; Pagès-Manté, A; March, R; Morales, M; Ramírez, M A; Sánchez-Vizcaíno, J M; Torres, J M

    2000-01-01

    Twenty MV strains obtained from a survey of field strains currently circulating throughout Spain were analyzed for their virulence and horizontal spreading among rabbits by contact transmission. A virus strain with suitable characteristics to be used as a potential vaccine against myxomatosis in wild rabbit populations was selected. Following inoculation, the selected MV strain elicited high levels of MV specific antibodies and induced protection of rabbits against a virulent MV challenge. Furthermore, the attenuated MV was transmitted to 9 out of 16 uninoculated rabbits by contact, inducing protection against myxomatosis.

  17. A recombinant chimeric La Crosse virus expressing the surface glycoproteins of Jamestown Canyon virus is immunogenic and protective against challenge with either parental virus in mice or monkeys.

    Science.gov (United States)

    Bennett, R S; Gresko, A K; Nelson, J T; Murphy, B R; Whitehead, S S

    2012-01-01

    La Crosse virus (LACV) and Jamestown Canyon virus (JCV), family Bunyaviridae, are mosquito-borne viruses that are endemic in North America and recognized as etiologic agents of encephalitis in humans. Both viruses belong to the California encephalitis virus serogroup, which causes 70 to 100 cases of encephalitis a year. As a first step in creating live attenuated viral vaccine candidates for this serogroup, we have generated a recombinant LACV expressing the attachment/fusion glycoproteins of JCV. The JCV/LACV chimeric virus contains full-length S and L segments derived from LACV. For the M segment, the open reading frame (ORF) of LACV is replaced with that derived from JCV and is flanked by the untranslated regions of LACV. The resulting chimeric virus retained the same robust growth kinetics in tissue culture as observed for either parent virus, and the virus remains highly infectious and immunogenic in mice. Although both LACV and JCV are highly neurovirulent in 21 day-old mice, with 50% lethal dose (LD₅₀) values of 0.1 and 0.5 log₁₀ PFU, respectively, chimeric JCV/LACV is highly attenuated and does not cause disease even after intracerebral inoculation of 10³ PFU. Parenteral vaccination of mice with 10¹ or 10³ PFU of JCV/LACV protected against lethal challenge with LACV, JCV, and Tahyna virus (TAHV). The chimeric virus was infectious and immunogenic in rhesus monkeys and induced neutralizing antibodies to JCV, LACV, and TAHV. When vaccinated monkeys were challenged with JCV, they were protected against the development of viremia. Generation of highly attenuated yet immunogenic chimeric bunyaviruses could be an efficient general method for development of vaccines effective against these pathogenic viruses.

  18. Initial characterization of Vaccinia Virus B4 suggests a role in virus spread

    Energy Technology Data Exchange (ETDEWEB)

    Burles, Kristin; Irwin, Chad R.; Burton, Robyn-Lee [Li Ka Shing Institute of Virology, Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, Alberta, Canada T6G 2S2 (Canada); Schriewer, Jill [Department of Molecular Microbiology and Immunology, Saint Louis University School of Medicine, St. Louis, MO (United States); Evans, David H. [Li Ka Shing Institute of Virology, Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, Alberta, Canada T6G 2S2 (Canada); Buller, R. Mark [Department of Molecular Microbiology and Immunology, Saint Louis University School of Medicine, St. Louis, MO (United States); Barry, Michele, E-mail: michele.barry@ualberta.ca [Li Ka Shing Institute of Virology, Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, Alberta, Canada T6G 2S2 (Canada)

    2014-05-15

    Currently, little is known about the ankyrin/F-box protein B4. Here, we report that B4R-null viruses exhibited reduced plaque size in tissue culture, and decreased ability to spread, as assessed by multiple-step growth analysis. Electron microscopy indicated that B4R-null viruses still formed mature and extracellular virions; however, there was a slight decrease of virions released into the media following deletion of B4R. Deletion of B4R did not affect the ability of the virus to rearrange actin; however, VACV811, a large vaccinia virus deletion mutant missing 55 open reading frames, had decreased ability to produce actin tails. Using ectromelia virus, a natural mouse pathogen, we demonstrated that virus devoid of EVM154, the B4R homolog, showed decreased spread to organs and was attenuated during infection. This initial characterization suggests that B4 may play a role in virus spread, and that other unidentified mediators of actin tail formation may exist in vaccinia virus. - Highlights: • B4R-null viruses show reduced plaque size, and decreased ability to spread. • B4R-null viruses formed mature and extracellular virions; and rearranged actin. • Virus devoid of EVM154, the B4R homolog, was attenuated during infection. • Initial characterization suggests that B4 may play a role in virus spread. • Unidentified mediators of actin tail formation may exist in vaccinia virus.

  19. Initial characterization of Vaccinia Virus B4 suggests a role in virus spread

    International Nuclear Information System (INIS)

    Burles, Kristin; Irwin, Chad R.; Burton, Robyn-Lee; Schriewer, Jill; Evans, David H.; Buller, R. Mark; Barry, Michele

    2014-01-01

    Currently, little is known about the ankyrin/F-box protein B4. Here, we report that B4R-null viruses exhibited reduced plaque size in tissue culture, and decreased ability to spread, as assessed by multiple-step growth analysis. Electron microscopy indicated that B4R-null viruses still formed mature and extracellular virions; however, there was a slight decrease of virions released into the media following deletion of B4R. Deletion of B4R did not affect the ability of the virus to rearrange actin; however, VACV811, a large vaccinia virus deletion mutant missing 55 open reading frames, had decreased ability to produce actin tails. Using ectromelia virus, a natural mouse pathogen, we demonstrated that virus devoid of EVM154, the B4R homolog, showed decreased spread to organs and was attenuated during infection. This initial characterization suggests that B4 may play a role in virus spread, and that other unidentified mediators of actin tail formation may exist in vaccinia virus. - Highlights: • B4R-null viruses show reduced plaque size, and decreased ability to spread. • B4R-null viruses formed mature and extracellular virions; and rearranged actin. • Virus devoid of EVM154, the B4R homolog, was attenuated during infection. • Initial characterization suggests that B4 may play a role in virus spread. • Unidentified mediators of actin tail formation may exist in vaccinia virus

  20. Modified vaccinia virus Ankara protects macaques against respiratory challenge with monkeypox virus.

    NARCIS (Netherlands)

    K.J. Stittelaar (Koert); G. van Amerongen (Geert); I. Kondova (Ivanela); R.F. van Lavieren (Rob); F.H. Pistoor (Frank); H.G.M. Niesters (Bert); G.J.J. van Doornum (Gerard); B.A.M. van der Zeijst (Ben); L. Mateo (Luis); P.J. Chaplin (Paul); A.D.M.E. Osterhaus (Albert); T. Kuiken (Thijs)

    2005-01-01

    textabstractThe use of classical smallpox vaccines based on vaccinia virus (VV) is associated with severe complications in both naive and immune individuals. Modified vaccinia virus Ankara (MVA), a highly attenuated replication-deficient strain of VV, has been proven to be safe in humans and

  1. How you get HIV/AIDS

    Science.gov (United States)

    How you get HIV/AIDS Which body fluids contain HIV? HIV is a virus that lives in blood and other fluids in the body. Moving ... answers to any questions you have about HIV/AIDS. Your public health department and health care provider ...

  2. Characterization of uncultivable bat influenza virus using a replicative synthetic virus.

    Directory of Open Access Journals (Sweden)

    Bin Zhou

    2014-10-01

    Full Text Available Bats harbor many viruses, which are periodically transmitted to humans resulting in outbreaks of disease (e.g., Ebola, SARS-CoV. Recently, influenza virus-like sequences were identified in bats; however, the viruses could not be cultured. This discovery aroused great interest in understanding the evolutionary history and pandemic potential of bat-influenza. Using synthetic genomics, we were unable to rescue the wild type bat virus, but could rescue a modified bat-influenza virus that had the HA and NA coding regions replaced with those of A/PR/8/1934 (H1N1. This modified bat-influenza virus replicated efficiently in vitro and in mice, resulting in severe disease. Additional studies using a bat-influenza virus that had the HA and NA of A/swine/Texas/4199-2/1998 (H3N2 showed that the PR8 HA and NA contributed to the pathogenicity in mice. Unlike other influenza viruses, engineering truncations hypothesized to reduce interferon antagonism into the NS1 protein didn't attenuate bat-influenza. In contrast, substitution of a putative virulence mutation from the bat-influenza PB2 significantly attenuated the virus in mice and introduction of a putative virulence mutation increased its pathogenicity. Mini-genome replication studies and virus reassortment experiments demonstrated that bat-influenza has very limited genetic and protein compatibility with Type A or Type B influenza viruses, yet it readily reassorts with another divergent bat-influenza virus, suggesting that the bat-influenza lineage may represent a new Genus/Species within the Orthomyxoviridae family. Collectively, our data indicate that the bat-influenza viruses recently identified are authentic viruses that pose little, if any, pandemic threat to humans; however, they provide new insights into the evolution and basic biology of influenza viruses.

  3. Characterization of uncultivable bat influenza virus using a replicative synthetic virus.

    Science.gov (United States)

    Zhou, Bin; Ma, Jingjiao; Liu, Qinfang; Bawa, Bhupinder; Wang, Wei; Shabman, Reed S; Duff, Michael; Lee, Jinhwa; Lang, Yuekun; Cao, Nan; Nagy, Abdou; Lin, Xudong; Stockwell, Timothy B; Richt, Juergen A; Wentworth, David E; Ma, Wenjun

    2014-10-01

    Bats harbor many viruses, which are periodically transmitted to humans resulting in outbreaks of disease (e.g., Ebola, SARS-CoV). Recently, influenza virus-like sequences were identified in bats; however, the viruses could not be cultured. This discovery aroused great interest in understanding the evolutionary history and pandemic potential of bat-influenza. Using synthetic genomics, we were unable to rescue the wild type bat virus, but could rescue a modified bat-influenza virus that had the HA and NA coding regions replaced with those of A/PR/8/1934 (H1N1). This modified bat-influenza virus replicated efficiently in vitro and in mice, resulting in severe disease. Additional studies using a bat-influenza virus that had the HA and NA of A/swine/Texas/4199-2/1998 (H3N2) showed that the PR8 HA and NA contributed to the pathogenicity in mice. Unlike other influenza viruses, engineering truncations hypothesized to reduce interferon antagonism into the NS1 protein didn't attenuate bat-influenza. In contrast, substitution of a putative virulence mutation from the bat-influenza PB2 significantly attenuated the virus in mice and introduction of a putative virulence mutation increased its pathogenicity. Mini-genome replication studies and virus reassortment experiments demonstrated that bat-influenza has very limited genetic and protein compatibility with Type A or Type B influenza viruses, yet it readily reassorts with another divergent bat-influenza virus, suggesting that the bat-influenza lineage may represent a new Genus/Species within the Orthomyxoviridae family. Collectively, our data indicate that the bat-influenza viruses recently identified are authentic viruses that pose little, if any, pandemic threat to humans; however, they provide new insights into the evolution and basic biology of influenza viruses.

  4. Next generation sequencing of DNA-launched Chikungunya vaccine virus

    Energy Technology Data Exchange (ETDEWEB)

    Hidajat, Rachmat; Nickols, Brian [Medigen, Inc., 8420 Gas House Pike, Suite S, Frederick, MD 21701 (United States); Forrester, Naomi [Institute for Human Infections and Immunity, Sealy Center for Vaccine Development and Department of Pathology, University of Texas Medical Branch, GNL, 301 University Blvd., Galveston, TX 77555 (United States); Tretyakova, Irina [Medigen, Inc., 8420 Gas House Pike, Suite S, Frederick, MD 21701 (United States); Weaver, Scott [Institute for Human Infections and Immunity, Sealy Center for Vaccine Development and Department of Pathology, University of Texas Medical Branch, GNL, 301 University Blvd., Galveston, TX 77555 (United States); Pushko, Peter, E-mail: ppushko@medigen-usa.com [Medigen, Inc., 8420 Gas House Pike, Suite S, Frederick, MD 21701 (United States)

    2016-03-15

    Chikungunya virus (CHIKV) represents a pandemic threat with no approved vaccine available. Recently, we described a novel vaccination strategy based on iDNA® infectious clone designed to launch a live-attenuated CHIKV vaccine from plasmid DNA in vitro or in vivo. As a proof of concept, we prepared iDNA plasmid pCHIKV-7 encoding the full-length cDNA of the 181/25 vaccine. The DNA-launched CHIKV-7 virus was prepared and compared to the 181/25 virus. Illumina HiSeq2000 sequencing revealed that with the exception of the 3′ untranslated region, CHIKV-7 viral RNA consistently showed a lower frequency of single-nucleotide polymorphisms than the 181/25 RNA including at the E2-12 and E2-82 residues previously identified as attenuating mutations. In the CHIKV-7, frequencies of reversions at E2-12 and E2-82 were 0.064% and 0.086%, while in the 181/25, frequencies were 0.179% and 0.133%, respectively. We conclude that the DNA-launched virus has a reduced probability of reversion mutations, thereby enhancing vaccine safety. - Highlights: • Chikungunya virus (CHIKV) is an emerging pandemic threat. • In vivo DNA-launched attenuated CHIKV is a novel vaccine technology. • DNA-launched virus was sequenced using HiSeq2000 and compared to the 181/25 virus. • DNA-launched virus has lower frequency of SNPs at E2-12 and E2-82 attenuation loci.

  5. Next generation sequencing of DNA-launched Chikungunya vaccine virus

    International Nuclear Information System (INIS)

    Hidajat, Rachmat; Nickols, Brian; Forrester, Naomi; Tretyakova, Irina; Weaver, Scott; Pushko, Peter

    2016-01-01

    Chikungunya virus (CHIKV) represents a pandemic threat with no approved vaccine available. Recently, we described a novel vaccination strategy based on iDNA® infectious clone designed to launch a live-attenuated CHIKV vaccine from plasmid DNA in vitro or in vivo. As a proof of concept, we prepared iDNA plasmid pCHIKV-7 encoding the full-length cDNA of the 181/25 vaccine. The DNA-launched CHIKV-7 virus was prepared and compared to the 181/25 virus. Illumina HiSeq2000 sequencing revealed that with the exception of the 3′ untranslated region, CHIKV-7 viral RNA consistently showed a lower frequency of single-nucleotide polymorphisms than the 181/25 RNA including at the E2-12 and E2-82 residues previously identified as attenuating mutations. In the CHIKV-7, frequencies of reversions at E2-12 and E2-82 were 0.064% and 0.086%, while in the 181/25, frequencies were 0.179% and 0.133%, respectively. We conclude that the DNA-launched virus has a reduced probability of reversion mutations, thereby enhancing vaccine safety. - Highlights: • Chikungunya virus (CHIKV) is an emerging pandemic threat. • In vivo DNA-launched attenuated CHIKV is a novel vaccine technology. • DNA-launched virus was sequenced using HiSeq2000 and compared to the 181/25 virus. • DNA-launched virus has lower frequency of SNPs at E2-12 and E2-82 attenuation loci.

  6. Chimeric human parainfluenza virus bearing the Ebola virus glycoprotein as the sole surface protein is immunogenic and highly protective against Ebola virus challenge

    International Nuclear Information System (INIS)

    Bukreyev, Alexander; Marzi, Andrea; Feldmann, Friederike; Zhang Liqun; Yang Lijuan; Ward, Jerrold M.; Dorward, David W.; Pickles, Raymond J.; Murphy, Brian R.; Feldmann, Heinz; Collins, Peter L.

    2009-01-01

    We generated a new live-attenuated vaccine against Ebola virus (EBOV) based on a chimeric virus HPIV3/ΔF-HN/EboGP that contains the EBOV glycoprotein (GP) as the sole transmembrane envelope protein combined with the internal proteins of human parainfluenza virus type 3 (HPIV3). Electron microscopy analysis of the virus particles showed that they have an envelope and surface spikes resembling those of EBOV and a particle size and shape resembling those of HPIV3. When HPIV3/ΔF-HN/EboGP was inoculated via apical surface of an in vitro model of human ciliated airway epithelium, the virus was released from the apical surface; when applied to basolateral surface, the virus infected basolateral cells but did not spread through the tissue. Following intranasal (IN) inoculation of guinea pigs, scattered infected cells were detected in the lungs by immunohistochemistry, but infectious HPIV3/ΔF-HN/EboGP could not be recovered from the lungs, blood, or other tissues. Despite the attenuation, the virus was highly immunogenic, and a single IN dose completely protected the animals against a highly lethal intraperitoneal challenge of guinea pig-adapted EBOV

  7. LIVE ATTENUATED VACCINES FOR THE IMMUNOPROPHYLAXIS

    Directory of Open Access Journals (Sweden)

    O. A. Shamsutdinova

    2017-01-01

    Full Text Available The review focuses on the history of the production of live antiviral vaccines and their use for the prevention of infectious diseases. It was noted that before the beginning of the 20th century, only three live vaccines were developed and put into practice — against smallpox, rabies, plague. The discovery of D. Enders, T.H. Weller and F.Ch. Robins of the ability of the polio virus, and then of a number of other viruses, to reproduce in vitro in cell cultures of various types, greatly expanded the studies on the production of attenuated strains of viruses for live vaccines. The historical stages of obtaining and introducing live vaccines for the prevention of smallpox, poliomyelitis, measles, rubella, and mumps are highlighted. Arguments in favor of the use of associated vaccine preparations for the prevention of viral infections are presented. Various variants of the strategy and tactics of using live vaccines, which are used for specific prevention of viral infections in different countries, are described. The review provides information on technological methods for obtaining antiviral vaccines. The publications testifying to the development of specific reactions in immunized vaccine strains of measles, mumps, poliomyelitis and rubella viruses, such as aseptic meningitis (vaccine strains of mumps virus, acute arthritis (vaccine rubella virus strains, temperature reactions, rash (vaccine strains of the virus Measles, vaccine-associated paralytic poliomyelitis (VAPP vaccine vaccine poliovirus. It is particularly noted that the long experience of vaccine prevention both in Russia and abroad convincingly shows that the risk of developing post-vaccination complications is incommensurably lower than the risk of causing harm to health from the corresponding infections. It is concluded that despite introduction of new third and fourth generation vaccines into practice, live attenuated vaccines do not lose their significance and are used in vaccine

  8. AIDS and Chemical Dependency.

    Science.gov (United States)

    Pohl, Melvin I.

    After defining HIV and the AIDS disease and outlining symptoms and means of infection, this fact sheet lists the ways alcohol and drugs are involved with the AIDS epidemic, noting that needle-sharing transmits the virus; that alcohol or mood-altering drugs like crack cocaine cause disinhibition, increase sex drive, encourage sex for drugs, and…

  9. Radioimmunoassay and enzyme-linked immunoassay of antibodies to the core protein (P24) of human T-lymphotropic virus (HTLV III). [Acquired immunodeficiency syndrome (AIDS)

    Energy Technology Data Exchange (ETDEWEB)

    Neurath, A R; Strick, N; Sproul, P

    1985-05-01

    Human T-cell lymphotropic viruses designated HTLV III or LAV are considered to represent the causative agents of the acquired immunodeficiency syndrome (AIDS). Therefore a simple direct RIA or ELISA method for antibodies to distinct epitopes of HTLV III/LAV structural components would be of great value. The authors describe RIA and ELISA assays which obviate the need for purified virus or virus proteins, do not utilize infected cells and thus do not diminish the source for continuous production of viral antigens and are specific for a major core protein of HTLV III/LAV.

  10. Reversion of a live porcine reproductive and respiratory virus vaccine investigated by parallel mutations

    DEFF Research Database (Denmark)

    Nielsen, Henriette S.; Oleksiewicz, Martin B; Forsberg, R

    2001-01-01

    A live attenuated porcine reproductive and respiratory syndrome (PRRS) vaccine virus has been shown to revert to virulence under field conditions. In order to identify genetic virulence determinants, ORF1 from the attenuated vaccine virus and three Danish vaccine-derived field isolates was sequen......A live attenuated porcine reproductive and respiratory syndrome (PRRS) vaccine virus has been shown to revert to virulence under field conditions. In order to identify genetic virulence determinants, ORF1 from the attenuated vaccine virus and three Danish vaccine-derived field isolates...... in the vaccine virus sequence during cell-culture adaptation. Evaluation of the remaining mutations in the ORF1 sequence revealed stronger selective pressure for amino acid conservation during spread in pigs than during vaccine production. Furthermore, it was found that the selective pressure did not change...

  11. Replacement of the Ectodomains of the Hemagglutinin-Neuraminidase and Fusion Glycoproteins of Recombinant Parainfluenza Virus Type 3 (PIV3) with Their Counterparts from PIV2 Yields Attenuated PIV2 Vaccine Candidates

    OpenAIRE

    Tao, Tao; Skiadopoulos, Mario H.; Davoodi, Fatemeh; Riggs, Jeffrey M.; Collins, Peter L.; Murphy, Brian R.

    2000-01-01

    We sought to develop a live attenuated parainfluenza virus type 2 (PIV2) vaccine strain for use in infants and young children, using reverse genetic techniques that previously were used to rapidly produce a live attenuated PIV1 vaccine candidate. The PIV1 vaccine candidate, designated rPIV3-1cp45, was generated by substituting the full-length HN and F proteins of PIV1 for those of PIV3 in the attenuated cp45 PIV3 vaccine candidate (T. Tao et al., J. Virol. 72:2955–2961, 1998; M. H. Skiadopoul...

  12. Computer-Aided Design of an Epitope-Based Vaccine against Epstein-Barr Virus

    Directory of Open Access Journals (Sweden)

    Julio Alonso-Padilla

    2017-01-01

    Full Text Available Epstein-Barr virus is a very common human virus that infects 90% of human adults. EBV replicates in epithelial and B cells and causes infectious mononucleosis. EBV infection is also linked to various cancers, including Burkitt’s lymphoma and nasopharyngeal carcinomas, and autoimmune diseases such as multiple sclerosis. Currently, there are no effective drugs or vaccines to treat or prevent EBV infection. Herein, we applied a computer-aided strategy to design a prophylactic epitope vaccine ensemble from experimentally defined T and B cell epitopes. Such strategy relies on identifying conserved epitopes in conjunction with predictions of HLA presentation for T cell epitope selection and calculations of accessibility and flexibility for B cell epitope selection. The T cell component includes 14 CD8 T cell epitopes from early antigens and 4 CD4 T cell epitopes, targeted during the course of a natural infection and providing a population protection coverage of over 95% and 81.8%, respectively. The B cell component consists of 3 experimentally defined B cell epitopes from gp350 plus 4 predicted B cell epitopes from other EBV envelope glycoproteins, all mapping in flexible and solvent accessible regions. We discuss the rationale for the formulation and possible deployment of this epitope vaccine ensemble.

  13. African Swine Fever Virus Georgia 2007 with a Deletion of Virulence-Associated Gene 9GL (B119L), when Administered at Low Doses, Leads to Virus Attenuation in Swine and Induces an Effective Protection against Homologous Challenge.

    Science.gov (United States)

    O'Donnell, Vivian; Holinka, Lauren G; Krug, Peter W; Gladue, Douglas P; Carlson, Jolene; Sanford, Brenton; Alfano, Marialexia; Kramer, Edward; Lu, Zhiqiang; Arzt, Jonathan; Reese, Bo; Carrillo, Consuelo; Risatti, Guillermo R; Borca, Manuel V

    2015-08-01

    African swine fever virus (ASFV) is the etiological agent of an often lethal disease of domestic pigs. Disease control strategies have been hampered by the unavailability of vaccines against ASFV. Since its introduction in the Republic of Georgia, a highly virulent virus, ASFV Georgia 2007 (ASFV-G), has caused an epizootic that spread rapidly into Eastern European countries. Currently no vaccines are available or under development to control ASFV-G. In the past, genetically modified ASFVs harboring deletions of virulence-associated genes have proven attenuated in swine, inducing protective immunity against challenge with homologous parental viruses. Deletion of the gene 9GL (open reading frame [ORF] B119L) in highly virulent ASFV Malawi-Lil-20/1 produced an attenuated phenotype even when administered to pigs at 10(6) 50% hemadsorption doses (HAD50). Here we report the construction of a genetically modified ASFV-G strain (ASFV-G-Δ9GLv) harboring a deletion of the 9GL (B119L) gene. Like Malawi-Lil-20/1-Δ9GL, ASFV-G-Δ9GL showed limited replication in primary swine macrophages. However, intramuscular inoculation of swine with 10(4) HAD50 of ASFV-G-Δ9GL produced a virulent phenotype that, unlike Malawi-Lil-20/1-Δ9GL, induced a lethal disease in swine like parental ASFV-G. Interestingly, lower doses (10(2) to 10(3) HAD50) of ASFV-G-Δ9GL did not induce a virulent phenotype in swine and when challenged protected pigs against disease. A dose of 10(2) HAD50 of ASFV-G-Δ9GLv conferred partial protection when pigs were challenged at either 21 or 28 days postinfection (dpi). An ASFV-G-Δ9GL HAD50 of 10(3) conferred partial and complete protection at 21 and 28 dpi, respectively. The information provided here adds to our recent report on the first attempts toward experimental vaccines against ASFV-G. The main problem for controlling ASF is the lack of vaccines. Studies on ASFV virulence lead to the production of genetically modified attenuated viruses that induce protection

  14. Principles underlying rational design of live attenuated influenza vaccines

    Science.gov (United States)

    Jang, Yo Han

    2012-01-01

    Despite recent innovative advances in molecular virology and the developments of vaccines, influenza virus remains a serious burden for human health. Vaccination has been considered a primary countermeasure for prevention of influenza infection. Live attenuated influenza vaccines (LAIVs) are particularly attracting attention as an effective strategy due to several advantages over inactivated vaccines. Cold-adaptation, as a classical means for attenuating viral virulence, has been successfully used for generating safe and effective donor strains of LAIVs against seasonal epidemics and occasional pandemics. Recently, the advent of reverse genetics technique expedited a variety of rational strategies to broaden the pool of LAIVs. Considering the breadth of antigenic diversity of influenza virus, the pool of LAIVs is likely to equip us with better options for controlling influenza pandemics. With a brief reflection on classical attenuating strategies used at the initial stage of development of LAIVs, especially on the principles underlying the development of cold-adapted LAIVs, we further discuss and outline other attenuation strategies especially with respect to the rationales for attenuation, and their practicality for mass production. Finally, we propose important considerations for a rational vaccine design, which will provide us with practical guidelines for improving the safety and effectiveness of LAIVs. PMID:23596576

  15. The cold adapted and temperature sensitive influenza A/Ann Arbor/6/60 virus, the master donor virus for live attenuated influenza vaccines, has multiple defects in replication at the restrictive temperature

    International Nuclear Information System (INIS)

    Chan, Winnie; Zhou, Helen; Kemble, George; Jin Hong

    2008-01-01

    We have previously determined that the temperature sensitive (ts) and attenuated (att) phenotypes of the cold adapted influenza A/Ann Arbor/6/60 strain (MDV-A), the master donor virus for the live attenuated influenza A vaccines (FluMist), are specified by the five amino acids in the PB1, PB2 and NP gene segments. To understand how these loci control the ts phenotype of MDV-A, replication of MDV-A at the non-permissive temperature (39 deg. C) was compared with recombinant wild-type A/Ann Arbor/6/60 (rWt). The mRNA and protein synthesis of MDV-A in the infected MDCK cells were not significantly reduced at 39 deg. C during a single-step replication, however, vRNA synthesis was reduced and the nuclear-cytoplasmic export of viral RNP (vRNP) was blocked. In addition, the virions released from MDV-A infected cells at 39 deg. C exhibited irregular morphology and had a greatly reduced amount of the M1 protein incorporated. The reduced M1 protein incorporation and vRNP export blockage correlated well with the virus ts phenotype because these defects could be partially alleviated by removing the three ts loci from the PB1 gene. The virions and vRNPs isolated from the MDV-A infected cells contained a higher level of heat shock protein 70 (Hsp70) than those of rWt, however, whether Hsp70 is involved in thermal inhibition of MDV-A replication remains to be determined. Our studies demonstrate that restrictive replication of MDV-A at the non-permissive temperature occurs in multiple steps of the virus replication cycle

  16. Productive human immunodeficiency virus infection levels correlate with AIDS-related manifestations in the patient

    International Nuclear Information System (INIS)

    Mathez, D.; Paul, D.; de Belilovsky, C.; Sultan, Y.; Deleuze, J.; Gorin, I.; Saurin, W.; Decker, R.; Leibowitch, J.

    1990-01-01

    Mononuclear cells were obtained from 71 human immunodeficiency virus type 1 (HIV-1) seropositive subjects presenting and first visit either as asymptomatic or with minor symptoms and with CD4 lymphocytes greater than 550 per mm3 (group A, 35 patients) or as patients with AIDS, AIDS-related illnesses, or CD4 lymphocytes less than 400 per mm3 (group B, 36 patients). After 1-5 years of follow-up, 13 patients of group A had essentially retained their initial status (asymptomatics); the 22 others had suffered clinical or immunological deterioration (progressors). Frozen cells were thawed and submitted to lethal gamma-irradiation in vitro (4500 rads; 1 rad = 0.01 Gy) before they were cultured with normal phytohemagglutinin-stimulated lymphocytes to determine radiation-resistant HIV expression ex vivo (R-HEV). HIV antigenemia correlated with R-HEV values in 142 samples (r = 0.92, P less than 0.001) but was a less sensitive predictor of disease than R-HEV. R-HEV was detected in all specimens from patients with major AIDS-related illnesses or HIV-associated CD4 lymphopenia. In 77% of the progressors from group A, R-HEV detection preceded the onset of AIDS-associated disease or CD4 lymphopenia by 1 year (average). Conversely, R-HEV was low or was not detected in 36 sequential specimens from the 13 patients who remained asymptomatic over the following 2-5 years. Thus, persistently low HIV expression in vivo predicted a nondiseased state, whereas higher HIV expression levels seemed necessary for disease to occur. These data indicate that R-HEV is related to productive HIV infection in vivo, the latter acting as a determinant of AIDS-related illnesses. In view of this, measurement of HIV expression levels in the patient should be useful in antiviral efficacy trials

  17. Determinants of attenuation and temperature sensitivity in the type 1 poliovirus Sabin vaccine.

    OpenAIRE

    Bouchard, M J; Lam, D H; Racaniello, V R

    1995-01-01

    To identify determinants of attenuation in the poliovirus type 1 Sabin vaccine strain, a series of recombinant viruses were constructed by using infectious cDNA clones of the virulent type 1 poliovirus P1/Mahoney and the attenuated type 1 vaccine strain P1/Sabin. Intracerebral inoculation of these viruses into transgenic mice which express the human receptor for poliovirus identified regions of the genome that conferred reduced neurovirulence. Exchange of smaller restriction fragments and sit...

  18. Reversion of a live porcine reproductive and respiratory syndrome virus vaccine investigated by parallel mutations

    DEFF Research Database (Denmark)

    Nielsen, Henriette S.; Oleksiewicz, M.B.; Forsberg, R.

    2001-01-01

    A live attenuated porcine reproductive and respiratory syndrome (PRRS) vaccine virus has been shown to revert to virulence under field conditions. In order to identify genetic virulence determinants, ORF1 from the attenuated vaccine virus and three Danish vaccine-derived field isolates was sequen......A live attenuated porcine reproductive and respiratory syndrome (PRRS) vaccine virus has been shown to revert to virulence under field conditions. In order to identify genetic virulence determinants, ORF1 from the attenuated vaccine virus and three Danish vaccine-derived field isolates...... in the vaccine virus sequence during cell-culture adaptation. Evaluation of the remaining mutations in the ORF1 sequence revealed stronger selective pressure for amino acid conservation during spread in pigs than during vaccine production. Furthermore, it was found that the selective pressure did not change...

  19. Human Immunodeficiency Virus (HIV) Research (AIDS)

    Science.gov (United States)

    1991-02-28

    lymphocyte concentration and the Walter Reed Staging System. RV4 Neurobehavioral Consequences of HTLV-III Brain Infection and AIDS Encephalopathy . PI...drug trials and behavioral therapeutic interventions. E. To use the AIDS encephalopathy model to study basic brain structure-function relationships...rCD4) in Infants and Children and in Pregnant Women and Newborns with HIV Infection. O PI: Dr. Gerald Fischer Status: In Review (WRAIR SR then HIVSUBC

  20. Unfocused beam patterns in nonattenuating and attenuating fluids

    International Nuclear Information System (INIS)

    Goldstein, Albert

    2004-01-01

    The most important aspect of an ultrasound measuring system is knowledge of the transducer beam pattern. At all depths accurate single integral equations have been derived for the full beam pattern of steady state unfocused circular flat piston sources radiating into nonattenuating and attenuating fluids. The axial depth of the beginning of the unattenuated beam pattern far field is found to be at 6.41Y 0 . The unattenuated single integral equations are identical to a Jinc function directivity term at this and deeper depths. For attenuating fluids values of α and z are found that permit the attenuated axial pressure to be represented by a plane wave multiplicative exponential attenuation factor. This knowledge will aid in the experimental design of highly accurate attenuation measurements. Accurate single integral equations for the attenuated full beam pattern are derived using complex Bessel functions

  1. Targeting an Oncolytic Influenza A Virus to Tumor Tissue by Elastase

    Directory of Open Access Journals (Sweden)

    Irina Kuznetsova

    2017-12-01

    Full Text Available Oncolytic viruses are currently established as a novel type of immunotherapy. The challenge is to safely target oncolytic viruses to tumors. Previously, we have generated influenza A viruses (IAVs containing deletions in the viral interferon antagonist. Those deletions have attenuated the virus in normal tissue but allowed replication in tumor cells. IAV entry is mediated by hemagglutinin (HA, which needs to be activated by a serine protease, for example, through trypsin. To further target the IAV to tumors, we have changed the trypsin cleavage site to an elastase cleavage site. We chose this cleavage site because elastase is expressed in the tumor microenvironment. Moreover, the exchange of the cleavage site previously has been shown to attenuate viral growth in lungs. Newly generated elastase-activated influenza viruses (AE viruses grew to similar titers in tumor cells as the trypsin-activated counterparts (AT viruses. Intratumoral injection of AE viruses into syngeneic B16f1 melanoma-derived tumors in mice reduced tumor growth similar to AT viruses and had a better therapeutic effect in heterologous human PANC-1-derived tumors. Therefore, the introduction of the attenuation marker “elastase cleavage site” in viral HA allows for safe, effective oncolytic virus therapy.

  2. AIDS and its effects on the advancement of women.

    Science.gov (United States)

    1989-01-01

    This document gives an overview of the worldwide spread of acquired immune deficiency syndrome (AIDS), the means of its prevention, and its effects on women who are not infected. It also explains how the AIDS virus is not spread, and why it is important not to be afraid of those infected with the AIDS virus. It stresses the need for information at a time when a vaccine or cure are not yet available, and education is the only means of prevention. The global mobilization being conducted to fight the AIDS crisis is discussed. Different ways in which women are at risk to infection by the HIV virus are reviewed, especially the subordination of women. This denies them the same education, legal rights, training, health, and independent incomes, all of which reduces their chance for access to information about AIDS. It considers risk of being infected by a partner, from a blood transfusion, increased susceptibility in someone who already has a sexually transmitted disease, increased susceptibility in a woman who has been circumcised, risk of infection from rape, and how women are coerced into prostitution, putting them at risk for AIDS. It also covers HIV infection and contraception, the danger to professional health-care workers, transmission of HIV infection from mother-to-infant, and discrimination that is AIDS-related. Women who are not infected are impacted by AIDS because they suffer stress as caretakers. The document also discusses the social and economic consequences of AIDS.

  3. Acute meningoencephalomyelitis due to varicella-zoster virus in an AIDS patient: report of a case and review of the literature

    Directory of Open Access Journals (Sweden)

    Marcelo Corti

    2011-12-01

    Full Text Available Varicella-zoster virus (VZV meningoencephalomyelitis is a rare but severe neurological complication of VZV reactivation in immunocompromised patients. We report the case of an HIV-infected individual who developed an acute and severe meningoencephalomyelitis accompanied by a disseminated cutaneous eruption due to VZV. The presence of VZV DNA in cerebrospinal fluid was confirmed by polymerase chain reaction (PCR technique. The patient started undergoing an intravenous acyclovir therapy with a mild recovery of neurological manifestations. Varicella-zoster virus should be included as a cause of acute meningoencephalomyelitis in patients with AIDS. Early diagnosis followed by specific therapy should modify the rapid and fulminant course for this kind of patients.

  4. Deletions of the hypervariable region (HVR) in open reading frame 1 of hepatitis E virus do not abolish virus infectivity: evidence for attenuation of HVR deletion mutants in vivo.

    Science.gov (United States)

    Pudupakam, R S; Huang, Y W; Opriessnig, T; Halbur, P G; Pierson, F W; Meng, X J

    2009-01-01

    Hepatitis E virus (HEV) is an important human pathogen, although little is known about its biology and replication. Comparative sequence analysis revealed a hypervariable region (HVR) with extensive sequence variations in open reading frame 1 of HEV. To elucidate the role of the HVR in HEV replication, we first constructed two HVR deletion mutants, hHVRd1 and hHVRd2, with in-frame deletion of amino acids (aa) 711 to 777 and 747 to 761 in the HVR of a genotype 1 human HEV replicon. Evidence of HEV replication was detected in Huh7 cells transfected with RNA transcripts from mutant hHVRd2, as evidenced by expression of enhanced green fluorescent protein. To confirm the in vitro results, we constructed three avian HEV mutants with various HVR deletions: mutants aHVRd1, with deletion of aa 557 to 585 (Delta557-585); aHVRd2 (Delta612-641); and aHVRd3 (Delta557-641). Chickens intrahepatically inoculated with capped RNA transcripts from mutants aHVRd1 and aHVRd2 developed active viral infection, as evidenced by seroconversion, viremia, and fecal virus shedding, although mutant aHVRd3, with complete HVR deletion, was apparently attenuated in chickens. To further verify the results, we constructed four additional HVR deletion mutants using the genotype 3 swine HEV as the backbone. Mutants sHVRd2 (Delta722-781), sHVRd3 (Delta735-765), and sHVRd4 (Delta712-765) were shown to tolerate deletions and were infectious in pigs intrahepatically inoculated with capped RNA transcripts from the mutants, whereas mutant sHVRd1 (Delta712-790), with a nearly complete HVR deletion, exhibited an attenuation phenotype in infected pigs. The data from these studies indicate that deletions in HVR do not abolish HEV infectivity in vitro or in vivo, although evidence for attenuation was observed for HEV mutants with a larger or nearly complete HVR deletion.

  5. Differences in gay men's AIDS risk knowledge and behavior patterns in high and low AIDS prevalence cities.

    OpenAIRE

    St Lawrence, J S; Hood, H V; Brasfield, T; Kelly, J A

    1989-01-01

    Several studies have found reductions in acquired immunodeficiency syndrome (AIDS) risk practices among gay men in high AIDS-prevalence cities since the start of the AIDS crisis. Much less is known about risk behavior patterns among gay men in smaller cities, where AIDS cases are less common and the prevalence of human immunodeficiency virus infection is relatively lower. In the study, men entering gay bars in three cities, one large and two small, completed anonymous surveys of sexual practi...

  6. A novel live-attenuated vaccine candidate for mayaro Fever.

    Directory of Open Access Journals (Sweden)

    William J Weise

    2014-08-01

    Full Text Available Mayaro virus (MAYV is an emerging, mosquito-borne alphavirus that causes a dengue-like illness in many regions of South America, and which has the potential to urbanize. Because no specific treatment or vaccine is available for MAYV infection, we capitalized on an IRES-based approach to develop a live-attenuated MAYV vaccine candidate. Testing in infant, immunocompetent as well as interferon receptor-deficient mice demonstrated a high degree of attenuation, strong induction of neutralizing antibodies, and efficacy against lethal challenge. This vaccine strain was also unable to infect mosquito cells, a major safety feature for a live vaccine derived from a mosquito-borne virus. Further preclinical development of this vaccine candidate is warranted to protect against this important emerging disease.

  7. Immunogenicity and protective efficacy of a live attenuated H5N1 vaccine in nonhuman primates.

    Directory of Open Access Journals (Sweden)

    Shufang Fan

    2009-05-01

    Full Text Available The continued spread of highly pathogenic H5N1 influenza viruses among poultry and wild birds, together with the emergence of drug-resistant variants and the possibility of human-to-human transmission, has spurred attempts to develop an effective vaccine. Inactivated subvirion or whole-virion H5N1 vaccines have shown promising immunogenicity in clinical trials, but their ability to elicit protective immunity in unprimed human populations remains unknown. A cold-adapted, live attenuated vaccine with the hemagglutinin (HA and neuraminidase (NA genes of an H5N1 virus A/VN/1203/2004 (clade 1 was protective against the pulmonary replication of homologous and heterologous wild-type H5N1 viruses in mice and ferrets. In this study, we used reverse genetics to produce a cold-adapted, live attenuated H5N1 vaccine (AH/AAca that contains HA and NA genes from a recent H5N1 isolate, A/Anhui/2/05 virus (AH/05 (clade 2.3, and the backbone of the cold-adapted influenza H2N2 A/AnnArbor/6/60 virus (AAca. AH/AAca was attenuated in chickens, mice, and monkeys, and it induced robust neutralizing antibody responses as well as HA-specific CD4+ T cell immune responses in rhesus macaques immunized twice intranasally. Importantly, the vaccinated macaques were fully protected from challenge with either the homologous AH/05 virus or a heterologous H5N1 virus, A/bar-headed goose/Qinghai/3/05 (BHG/05; clade 2.2. These results demonstrate for the first time that a cold-adapted H5N1 vaccine can elicit protective immunity against highly pathogenic H5N1 virus infection in a nonhuman primate model and provide a compelling argument for further testing of double immunization with live attenuated H5N1 vaccines in human trials.

  8. Detection of intracellular canine distemper virus antigen in mink inoculated with an attenuated or a virulent strain of canine distemper virus.

    Science.gov (United States)

    Blixenkrone-Møller, M

    1989-09-01

    Using an indirect immunofluorescence technique, the distribution of viral antigen in various tissues and blood mononuclear leukocytes was studied in wild mink, either vaccinated with an attenuated vaccine strain of canine distemper virus (CDV) or experimentally inoculated with the virulent Snyder-Hill strain of CDV. Viral antigen was detected in cells of the lymphoid system 6 to 12 days after vaccination. From 2 to 3 days after inoculation with the virulent strain, CDV antigen was demonstrated in cells of the lymphoid system and, during the incubation period, the antigen had spread to the epithelia and brain at days 6 and 12, respectively. In clinical cases of acute fatal canine distemper, the viral antigen was detected in a wide variety of tissues, including the cells of the lymphoid system, epithelial cells of skin, mucous membranes, lung, kidney, and cells of the CNS. The diagnostic importance of CDV antigen detection is discussed on the basis of these findings.

  9. De novo generation of helper virus-satellite chimera RNAs results in disease attenuation and satellite sequence acquisition in a host-dependent manner.

    Science.gov (United States)

    Pyle, J D; Scholthof, Karen-Beth G

    2018-01-15

    Panicum mosaic virus (PMV) is a helper RNA virus for satellite RNAs (satRNAs) and a satellite virus (SPMV). Here, we describe modifications that occur at the 3'-end of a satRNA of PMV, satS. Co-infections of PMV+satS result in attenuation of the disease symptoms induced by PMV alone in Brachypodium distachyon and proso millet. The 375 nt satS acquires ~100-200 nts from the 3'-end of PMV during infection and is associated with decreased abundance of the PMV RNA and capsid protein in millet. PMV-satS chimera RNAs were isolated from native infections of St. Augustinegrass and switchgrass. Phylogenetic analyses revealed that the chimeric RNAs clustered according to the host species from which they were isolated. Additionally, the chimera satRNAs acquired non-viral "linker" sequences in a host-specific manner. These results highlight the dynamic regulation of viral pathogenicity by satellites, and the selective host-dependent, sequence-based pressures for driving satRNA generation and genome compositions. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Comparative virology and AIDS (review).

    Science.gov (United States)

    Kodama, M; Kodama, T

    1996-03-01

    The scientific debate between pros and cons of the HIV criminal theory of AIDS still remains unsettled. The purpose of this review is to promote resolution of the problem by extracting a common principle of the host-virus relation using data resources for each of 4 viruses as follows: a) polyoma virus, b) Marek's disease virus, c) Ebola virus, d) Korean hemorrhagic fever virus. Conclusions drawn from this study are given as follows: i) Environment emerged as the cardinal factor to modify the process of virus infection in all of the 4 viruses studied. Above all, an accelerating effect of environmental stress on the progression of virus infection was noted in vivo in the majority of viral diseases. ii) Evidence is available to indicate that a healthy cell (or a healthy individual) may harbor virus genes of multiple species without manifesting any pathologic sign. iii) Evidence also suggests that the biological property as well as morphological structure of a virus may vary in reponse to a change of the bioenvironment. On the basis of the above information, we propose to renounce 2 assumptions of classical infection model: a) the hereditarily determined virulence of a microorganism (including virus) be the sole determinant of infection to the effect that its invasion into the host should automatically complete the programmed course of infection; b) virus, a quasi-living creature, should reserve its behavioral independence irrespective of a change of the bioenvironment. The new infection model was constructed on the basis of the selfish gene concept that had been invented by Richard Dawkins to explain the altruistic behavior of an individual. That is, the fate of an exogenous or endogenous virus is under the dual control of the host genome (selfish gene) and the outer environment. The progression of virus infection is conditioned by a crosstalk between them. The selfish gene may use virus (a lifeless substance) as a magic bullet to induce a designated host response. In

  11. Newcastle disease virus (NDV) recombinants expressing infectious laryngotracheitis virus (ILTV) glycoproteins gB and gD protect chickens against ILTV and NDV challenges.

    Science.gov (United States)

    Zhao, Wei; Spatz, Stephen; Zhang, Zhenyu; Wen, Guoyuan; Garcia, Maricarmen; Zsak, Laszlo; Yu, Qingzhong

    2014-08-01

    Infectious laryngotracheitis (ILT) is a highly contagious acute respiratory disease of chickens caused by infectious laryngotracheitis virus (ILTV). The disease is controlled mainly through biosecurity and vaccination with live attenuated strains of ILTV and vectored vaccines based on turkey herpesvirus (HVT) and fowlpox virus (FPV). The current live attenuated vaccines (chicken embryo origin [CEO] and tissue culture origin [TCO]), although effective, can regain virulence, whereas HVT- and FPV-vectored ILTV vaccines are less efficacious than live attenuated vaccines. Therefore, there is a pressing need to develop safer and more efficacious ILTV vaccines. In the present study, we generated Newcastle disease virus (NDV) recombinants, based on the LaSota vaccine strain, expressing glycoproteins B (gB) and D (gD) of ILTV using reverse genetics technology. These recombinant viruses, rLS/ILTV-gB and rLS/ILTV-gD, were slightly attenuated in vivo yet retained growth dynamics, stability, and virus titers in vitro that were similar to those of the parental LaSota virus. Expression of ILTV gB and gD proteins in the recombinant virus-infected cells was detected by immunofluorescence assay. Vaccination of specific-pathogen-free chickens with these recombinant viruses conferred significant protection against virulent ILTV and velogenic NDV challenges. Immunization of commercial broilers with rLS/ILTV-gB provided a level of protection against clinical disease similar to that provided by the live attenuated commercial vaccines, with no decrease in body weight gains. The results of the study suggested that the rLS/ILTV-gB and -gD viruses are safe, stable, and effective bivalent vaccines that can be mass administered via aerosol or drinking water to large chicken populations. This paper describes the development and evaluation of novel bivalent vaccines against chicken infectious laryngotracheitis (ILT) and Newcastle disease (ND), two of the most economically important infectious

  12. Nairobi sheep disease virus/Ganjam virus.

    Science.gov (United States)

    M D, Baron; B, Holzer

    2015-08-01

    Nairobi sheep disease virus (NSDV) is a tick-borne virus which causes a severe disease in sheep and goats, and has been responsible for several outbreaks of disease in East Africa. The virus is also found in the Indian subcontinent, where it is known as Ganjam virus. The virus only spreads through the feeding of competent infected ticks, and is therefore limited in its geographic distribution by the distribution of those ticks, Rhipicephalus appendiculata in Africa and Haemaphysalis intermedia in India. Animals bred in endemic areas do not normally develop disease, and the impact is therefore primarily on animals being moved for trade or breeding purposes. The disease caused by NSDV has similarities to several other ruminant diseases, and laboratory diagnosis is necessary for confirmation. There are published methods for diagnosis based on polymerase chain reaction, for virus growth in cell culture and for other simple diagnostic tests, though none has been commercialised. There is no established vaccine against NSDV, although cell-culture attenuated strains have been developed which show promise and could be put into field trials if it were deemed necessary. The virus is closely related to Crimean-Congo haemorrhagic fever virus, and studies on NSDV may therefore be useful in understanding this important human pathogen.

  13. Persistence of attenuated HIV-1 rev alleles in an epidemiologically linked cohort of long-term survivors infected with nef-deleted virus

    Directory of Open Access Journals (Sweden)

    Wesselingh Steven L

    2007-07-01

    Full Text Available Abstract Background The Sydney blood bank cohort (SBBC of long-term survivors consists of multiple individuals infected with nef-deleted, attenuated strains of human immunodeficiency virus type 1 (HIV-1. Although the cohort members have experienced differing clinical courses and now comprise slow progressors (SP as well as long-term nonprogressors (LTNP, longitudinal analysis of nef/long-terminal repeat (LTR sequences demonstrated convergent nef/LTR sequence evolution in SBBC SP and LTNP. Thus, the in vivo pathogenicity of attenuated HIV-1 strains harboured by SBBC members is dictated by factors other than nef/LTR. Therefore, to determine whether defects in other viral genes contribute to attenuation of these HIV-1 strains, we characterized dominant HIV-1 rev alleles that persisted in 4 SBBC subjects; C18, C64, C98 and D36. Results The ability of Rev derived from D36 and C64 to bind the Rev responsive element (RRE in RNA binding assays was reduced by approximately 90% compared to Rev derived from HIV-1NL4-3, C18 or C98. D36 Rev also had a 50–60% reduction in ability to express Rev-dependent reporter constructs in mammalian cells. In contrast, C64 Rev had only marginally decreased Rev function despite attenuated RRE binding. In D36 and C64, attenuated RRE binding was associated with rare amino acid changes at 3 highly conserved residues; Gln to Pro at position 74 immediately N-terminal to the Rev activation domain, and Val to Leu and Ser to Pro at positions 104 and 106 at the Rev C-terminus, respectively. In D36, reduced Rev function was mapped to an unusual 13 amino acid extension at the Rev C-terminus. Conclusion These findings provide new genetic and mechanistic insights important for Rev function, and suggest that Rev function, not Rev/RRE binding may be rate limiting for HIV-1 replication. In addition, attenuated rev alleles may contribute to viral attenuation and long-term survival of HIV-1 infection in a subset of SBBC members.

  14. Stress, needs, and quality of life of people living with human immunodeficiency virus/AIDS in Taiwan

    Directory of Open Access Journals (Sweden)

    Ming-Chu Feng

    2015-09-01

    Full Text Available Human immunodeficiency virus (HIV/AIDS is a manageable infectious disease by the effectiveness of highly active antiretroviral therapy. AIDS-related stigma and conflict may create distress and deteriorate quality of life (QoL of people living with HIV/AIDS (PLWHA. This cross-sectional, descriptive, correlational study using structural questionnaires aimed to explore the stress, needs, QoL, and associated factors of PLWHA in Taiwan. A total of 200 PLWHA participating in this study needed most on treatment of HIV and prevention of AIDS, and health maintenance. They had worse QoL in physical, psychological, and social domains (all p < 0.001 than the general population. Stress was the most significant predictor (β = −0.25 to −0.54, p < 0.01 for all four domains of QoL. Needs was not significantly associated with QoL. The QoL of PLWHA can be explained by demographics, self-perception on health, needs, and stress for 25.3–40.7% of variances. No association existed between CD4+ counts and QoL in Taiwanese PLWHA. It is important to recognize the perception of PLWHA on their health status, which is significantly associated with their QoL, besides monitoring their physical indicators of health (CD4+ counts. To recognize the stress and needs that PLWHA experience and to develop intervention programs targeting strategies on HIV disclosure, prevention and health maintenance are crucial for PLWHA's QoL.

  15. Temperature-sensitive mutants of influenza A virus. XIV. Production and evaluation of influenza A/Georgia/74-ts-1[E] recombinant viruses in human adults.

    Science.gov (United States)

    Richman, D D; Murphy, B R; Belshe, R B; Rusten, H M; Chanock, R M; Blacklow, N R; Parrino, T A; Rose, F B; Levine, M M; Caplan, E

    1977-08-01

    The two temperature-sensitive (ts) lesions present in influenza A/Hong Kong/68-ts-1[E] (H3N2 68) virus were transferred via genetic reassortment to influenza A/Georgia/74 (H3N2 74) wild-type virus. A recombinant clone possessing both ts lesions and the shutoff temperature of 38 C of the Hong Kong/68 ts donor and the two surface antigens of the Georgia/74 wild-type virus was administered to 32 seronegative adult volunteers. Thirty-one volunteers were infected, of whom only five experienced mild afebrile upper respiratory tract illness. The wild-type recipient virus was a cloned population that induced illness in five of six infected volunteers. Therfore, the attenuation exhibited by the Georgia/74-ts-1[E] virus could reasonably be assumed to be due to the acquisition of the two ts-1[E] lesions by the Georgia/74 wild-type virus. The serum and nasal wash antibody responses of the ts-1[E] vaccinees were equivalent to those of the volunteers who received wild-type virus. The two ts lesions present in the Hong Kong/68-ts-1[E] virus have now been transferred three times to a wild-type virus bearing a new hemagglutinin, and in each instance the new ts recombination exhibited a similar, satisfactory level of attenuation and antigenicity for adults. It seems likely that the transfer of the ts-1[E] lesions to any new influenza virus will regularly result in attenuation of a recombinat virus possessing the new surface antigens.

  16. Soluble Urokinase Plasminogen Activator Receptor Is a Predictor of Incident Non-AIDS Comorbidity and All-Cause Mortality in Human Immunodeficiency Virus Type 1 Infection

    DEFF Research Database (Denmark)

    Kirkegaard-Klitbo, Ditte M.; Langkilde, Anne; Mejer, Niels

    2017-01-01

    Persistent inflammation and immune activation have been associated with non-AIDS comorbidity and mortality in human immunodeficiency virus (HIV) infection. We aimed to investigate the potential association between soluble urokinase plasminogen activator receptor (suPAR) and incident non......-AIDS comorbidity and all-cause mortality in a well-treated HIV-infected population. suPAR was measured by enzyme-linked immunosorbent assay, and events of comorbidity and mortality were ascertained by registry linkage. The study showed an independent association between a high suPAR level at baseline and increased...... hazard rates for both non-AIDS comorbidities (cardiovascular disease, chronic kidney disease, chronic lung disease, liver disease, and cancer) and all-cause mortality....

  17. HIV/AIDS in Women

    Science.gov (United States)

    HIV stands for human immunodeficiency virus. It harms your immune system by destroying the white blood cells ... It is the final stage of infection with HIV. Not everyone with HIV develops AIDS. HIV often ...

  18. Vesicular Stomatitis Virus Pseudotyped with Ebola Virus Glycoprotein Serves as a Highly Protective, Non-infectious Vaccine Against Ebola Virus Challenge

    Science.gov (United States)

    2016-07-01

    Single-Injection Trivalent Filovirus 428 Vaccine: Proof of Concept Study in Outbred Guinea Pigs . J Infect Dis. 429 29. Murin, C. D., M. L. Fusco, Z...Jahrling, and J. F. Smith. 2000. Recombinant RNA replicons derived from attenuated 442 Venezuelan equine encephalitis virus protect guinea pigs and...platform, 65 including ease of production and characterization, absence of virus replication concerns and the 66 robust immune stimulatory activity

  19. Stigma, HIV and AIDS: An Exploration and Elaboration of the Illness Trajectory Surrounding HIV Infection and AIDS.

    Science.gov (United States)

    Alonzo, Angelo A.; Reynolds, Nancy R.

    In this paper, human immunodeficiency virus (HIV) and Acquired Immune Deficiency Syndrome (AIDS) are analyzed in terms of stigma and illness trajectory. The primary purpose is to conceptualize how individuals with HIV/AIDS experience stigma and to demonstrate how these experiences are affected by the social and biophysical dimensions of the…

  20. Live Attenuated Influenza Vaccine Enhances Colonization of Streptococcus pneumoniae and Staphylococcus aureus in Mice

    Science.gov (United States)

    Mina, Michael J.; McCullers, Jonathan A.; Klugman, Keith P.

    2014-01-01

    ABSTRACT Community interactions at mucosal surfaces between viruses, like influenza virus, and respiratory bacterial pathogens are important contributors toward pathogenesis of bacterial disease. What has not been considered is the natural extension of these interactions to live attenuated immunizations, and in particular, live attenuated influenza vaccines (LAIVs). Using a mouse-adapted LAIV against influenza A (H3N2) virus carrying the same mutations as the human FluMist vaccine, we find that LAIV vaccination reverses normal bacterial clearance from the nasopharynx and significantly increases bacterial carriage densities of the clinically important bacterial pathogens Streptococcus pneumoniae (serotypes 19F and 7F) and Staphylococcus aureus (strains Newman and Wright) within the upper respiratory tract of mice. Vaccination with LAIV also resulted in 2- to 5-fold increases in mean durations of bacterial carriage. Furthermore, we show that the increases in carriage density and duration were nearly identical in all aspects to changes in bacterial colonizing dynamics following infection with wild-type (WT) influenza virus. Importantly, LAIV, unlike WT influenza viruses, had no effect on severe bacterial disease or mortality within the lower respiratory tract. Our findings are, to the best of our knowledge, the first to demonstrate that vaccination with a live attenuated viral vaccine can directly modulate colonizing dynamics of important and unrelated human bacterial pathogens, and does so in a manner highly analogous to that seen following wild-type virus infection. PMID:24549845

  1. Interferon alpha inhibits replication of a live-attenuated porcine reproductive and respiratory syndrome virus vaccine preventing development of an adaptive immune response in swine.

    Science.gov (United States)

    Brockmeier, Susan L; Loving, Crystal L; Eberle, Kirsten C; Hau, Samantha J; Buckley, Alexandra; Van Geelen, Albert; Montiel, Nestor A; Nicholson, Tracy; Lager, Kelly M

    2017-12-01

    Type I interferons, such as interferon alpha (IFN-α), contribute to innate antiviral immunity by promoting production of antiviral mediators and are also involved in promoting an adaptive immune response. Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the most devastating and costly viruses to the swine industry world-wide and has been shown to induce a meager IFN-α response. Previously we administered porcine IFN-α using a replication-defective adenovirus vector (Ad5-IFN-α) at the time of challenge with virulent PRRSV and demonstrated an increase in the number of virus-specific IFNγ secreting cells, indicating that the presence of IFN-α at the time of infection can alter the adaptive immune responses to PRRSV. In the current experiment, we explored the use of IFN-α as an adjuvant administered with live-attenuated PRRSV vaccine as a method to enhance immune response to the vaccine. Unlike the previous studies with fully virulent virus, one injection of the Ad5-IFN-α abolished replication of the vaccine virus and as a result there was no detectible adaptive immune response. Although IFN-α did not have the desired adjuvant effect, the results further highlight the use of IFN-α as a treatment for PRRSV infection. Published by Elsevier B.V.

  2. Vaccination of rhesus macaques with a vif-deleted simian immunodeficiency virus proviral DNA vaccine

    International Nuclear Information System (INIS)

    Sparger, Ellen E.; Dubie, Robert A.; Shacklett, Barbara L.; Cole, Kelly S.; Chang, W.L.; Luciw, Paul A.

    2008-01-01

    Studies in non-human primates, with simian immunodeficiency virus (SIV) and simian/human immunodeficiency virus (SHIV) have demonstrated that live-attenuated viral vaccines are highly effective; however these vaccine viruses maintain a low level of pathogenicity. Lentivirus attenuation associated with deletion of the viral vif gene carries a significantly reduced risk for pathogenicity, while retaining the potential for virus replication of low magnitude in the host. This report describes a vif-deleted simian immunodeficiency virus (SIV)mac239 provirus that was tested as an attenuated proviral DNA vaccine by inoculation of female rhesus macaques. SIV-specific interferon-γ enzyme-linked immunospot responses of low magnitude were observed after immunization with plasmid containing the vif-deleted SIV provirus. However, vaccinated animals displayed strong sustained virus-specific T cell proliferative responses and increasing antiviral antibody titers. These immune responses suggested either persistent vaccine plasmid expression or low level replication of vif-deleted SIV in the host. Immunized and unvaccinated macaques received a single high dose vaginal challenge with pathogenic SIVmac251. A transient suppression of challenge virus load and a greater median survival time was observed for vaccinated animals. However, virus loads for vaccinated and unvaccinated macaques were comparable by twenty weeks after challenge and overall survival curves for the two groups were not significantly different. Thus, a vif-deleted SIVmac239 proviral DNA vaccine is immunogenic and capable of inducing a transient suppression of pathogenic challenge virus, despite severe attenuation of the vaccine virus

  3. Pathogenicity and transmission of triple reassortant H3N2 swine influenza A viruses is attenuated following Turkey embryo propagation.

    Science.gov (United States)

    Raghunath, Shobana; Pudupakam, Raghavendra Sumanth; Deventhiran, Jagadeeswaran; Tevatia, Rahul; Leroith, Tanya

    2017-03-01

    Genetic lineages of swine influenza A viruses (SIVs) have recently been established in Turkeys in the United States. To identify molecular determinants that are involved in virulence and transmission of SIVs to Turkeys, we sequentially passaged two triple reassortant H3N2 SIV isolates from Minnesota in ten day old specific-pathogen free (SPF) Turkey embryos and tested them in seven-day old Turkey poults. We found that SIV replication in Turkey embryos led to minimal mutations in and around the receptor binding and antigenic sites of the HA molecule, while other gene segments were unchanged. The predominant changes associated with Turkey embryo passage were A223V, V226A and T248I mutations in the receptor-binding and glycosylation sites of the HA molecule. Furthermore, Turkey embryo propagation altered receptor specificity in SIV strain 07-1145. Embryo passaged 07-1145 virus showed a decrease in α2, 6 sialic acid receptor binding compared to the wild type virus. Intranasal infection of wild type SIVs in one-week-old Turkey poults resulted in persistent diarrhea and all the infected birds seroconverted at ten days post infection. The 07-1145 wild type virus also transmitted to age matched in-contact birds introduced one-day post infection. Turkeys infected with embryo passaged viruses displayed no clinical signs and were not transmitted to in-contact poults. Our results suggest that Turkey embryo propagation attenuates recent TR SIVs for infectivity and transmission in one week old Turkeys. Our findings will have important implications in identifying molecular determinants that control the transmission and virulence of TR SIVs in Turkeys and other species. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Risky sexual behaviour and human immunodeficiency virus (HIV) and acquired immune deficiency syndrome (AIDS) among healthcare workers.

    Science.gov (United States)

    Khamisa, Natasha; Mokgobi, Maboe

    2018-01-01

    South Africa is known to have one of the highest prevalence rates of human immunodeficiency virus (HIV) and acquired immune deficiency syndrome (AIDS) globally, with one in seven healthcare workers being HIV-positive. An HIV-positive healthcare workforce is less equipped to respond to the increasing spread of the epidemic. Assessment of the factors contributing to high HIV prevalence rates among healthcare workers is important in planning the development of human resources. This review sought to identify and understand predominant risky sexual behaviours among healthcare workers in HIV and AIDS-affected countries. This study reviewed articles focusing on sexual behaviour among healthcare workers. Major health science databases (e.g. ProQuest, Cochrane, PubMed and CINAHL) were searched for combinations of keywords including 'healthcare workers', 'risky sexual behaviour' and 'HIV and AIDS'. Articles from a range of countries met inclusion and exclusion criteria. Findings of the study revealed three main contributing factors: unprotected sex, multiple sex partners and sexual violence. Sexual violence emerged as the dominant risk factor in the majority of the studies. Most research was conducted in developed countries where the HIV infection rate is much lower than it is in developing countries. More research needs to be conducted in developing countries and appropriate strategies should be implemented to reduce sexual violence among healthcare workers. Appropriate procedures on reporting sexual violence coupled with education on HIV and AIDS as well as influencing attitudes and belief systems could assist in reducing the spread of HIV and AIDS within the healthcare workforce while minimising the effect on patient care.

  5. Unique Safety Issues Associated with Virus Vectored Vaccines: Potential for and Theoretical Consequences of Recombination with Wild Type Virus Strains

    Science.gov (United States)

    Condit, Richard C.; Williamson, Anna-Lise; Sheets, Rebecca; Seligman, Stephen J.; Monath, Thomas P.; Excler, Jean-Louis; Gurwith, Marc; Bok, Karin; Robertson, James S.; Kim, Denny; Hendry, Michael; Singh, Vidisha; Mac, Lisa M.; Chen, Robert T.

    2016-01-01

    In 2003 and 2013, the World Health Organization convened informal consultations on characterization and quality aspects of vaccines based on live virus vectors. In the resulting reports, one of several issues raised for future study was the potential for recombination of virus-vectored vaccines with wild type pathogenic virus strains. This paper presents an assessment of this issue formulated by the Brighton Collaboration. To provide an appropriate context for understanding the potential for recombination of virus-vectored vaccines, we review briefly the current status of virus vectored vaccines, mechanisms of recombination between viruses, experience with recombination involving live attenuated vaccines in the field, and concerns raised previously in the literature regarding recombination of virus-vectored vaccines with wild type virus strains. We then present a discussion of the major variables that could influence recombination between a virus-vectored vaccine and circulating wild type virus and the consequences of such recombination, including intrinsic recombination properties of the parent virus used as a vector; sequence relatedness of vector and wild virus; virus host range, pathogenesis and transmission; replication competency of vector in target host; mechanism of vector attenuation; additional factors potentially affecting virulence; and circulation of multiple recombinant vectors in the same target population. Finally, we present some guiding principles for vector design and testing intended to anticipate and mitigate the potential for and consequences of recombination of virus-vectored vaccines with wild type pathogenic virus strains. PMID:27346303

  6. African Swine Fever Virus Biology and Vaccine Approaches.

    Science.gov (United States)

    Revilla, Yolanda; Pérez-Núñez, Daniel; Richt, Juergen A

    2018-01-01

    African swine fever (ASF) is an acute and often fatal disease affecting domestic pigs and wild boar, with severe economic consequences for affected countries. ASF is endemic in sub-Saharan Africa and the island of Sardinia, Italy. Since 2007, the virus emerged in the republic of Georgia, and since then spread throughout the Caucasus region and Russia. Outbreaks have also been reported in Belarus, Ukraine, Lithuania, Latvia, Estonia, Romania, Moldova, Czech Republic, and Poland, threatening neighboring West European countries. The causative agent, the African swine fever virus (ASFV), is a large, enveloped, double-stranded DNA virus that enters the cell by macropinocytosis and a clathrin-dependent mechanism. African Swine Fever Virus is able to interfere with various cellular signaling pathways resulting in immunomodulation, thus making the development of an efficacious vaccine very challenging. Inactivated preparations of African Swine Fever Virus do not confer protection, and the role of antibodies in protection remains unclear. The use of live-attenuated vaccines, although rendering suitable levels of protection, presents difficulties due to safety and side effects in the vaccinated animals. Several African Swine Fever Virus proteins have been reported to induce neutralizing antibodies in immunized pigs, and vaccination strategies based on DNA vaccines and recombinant proteins have also been explored, however, without being very successful. The complexity of the virus particle and the ability of the virus to modulate host immune responses are most likely the reason for this failure. Furthermore, no permanent cell lines able to sustain productive virus infection by both virulent and naturally attenuated African Swine Fever Virus strains exist so far, thus impairing basic research and the commercial production of attenuated vaccine candidates. © 2018 Elsevier Inc. All rights reserved.

  7. Rational design of human metapneumovirus live attenuated vaccine candidates by inhibiting viral mRNA cap methyltransferase.

    Science.gov (United States)

    Zhang, Yu; Wei, Yongwei; Zhang, Xiaodong; Cai, Hui; Niewiesk, Stefan; Li, Jianrong

    2014-10-01

    The paramyxoviruses human respiratory syncytial virus (hRSV), human metapneumovirus (hMPV), and human parainfluenza virus type 3 (hPIV3) are responsible for the majority of pediatric respiratory diseases and inflict significant economic loss, health care costs, and emotional burdens. Despite major efforts, there are no vaccines available for these viruses. The conserved region VI (CR VI) of the large (L) polymerase proteins of paramyxoviruses catalyzes methyltransferase (MTase) activities that typically methylate viral mRNAs at positions guanine N-7 (G-N-7) and ribose 2'-O. In this study, we generated a panel of recombinant hMPVs carrying mutations in the S-adenosylmethionine (SAM) binding site in CR VI of L protein. These recombinant viruses were specifically defective in ribose 2'-O methylation but not G-N-7 methylation and were genetically stable and highly attenuated in cell culture and viral replication in the upper and lower respiratory tracts of cotton rats. Importantly, vaccination of cotton rats with these recombinant hMPVs (rhMPVs) with defective MTases triggered a high level of neutralizing antibody, and the rats were completely protected from challenge with wild-type rhMPV. Collectively, our results indicate that (i) amino acid residues in the SAM binding site in the hMPV L protein are essential for 2'-O methylation and (ii) inhibition of mRNA cap MTase can serve as a novel target to rationally design live attenuated vaccines for hMPV and perhaps other paramyxoviruses, such as hRSV and hPIV3. Human paramyxoviruses, including hRSV, hMPV, and hPIV3, cause the majority of acute upper and lower respiratory tract infections in humans, particularly in infants, children, the elderly, and immunocompromised individuals. Currently, there is no licensed vaccine available. A formalin-inactivated vaccine is not suitable for these viruses because it causes enhanced lung damage upon reinfection with the same virus. A live attenuated vaccine is the most promising

  8. Non-specific Effect of Vaccines: Immediate Protection against Respiratory Syncytial Virus Infection by a Live Attenuated Influenza Vaccine

    Directory of Open Access Journals (Sweden)

    Young J. Lee

    2018-01-01

    Full Text Available The non-specific effects (NSEs of vaccines have been discussed for their potential long-term beneficial effects beyond direct protection against a specific pathogen. Cold-adapted, live attenuated influenza vaccine (CAIV induces local innate immune responses that provide a broad range of antiviral immunity. Herein, we examined whether X-31ca, a donor virus for CAIVs, provides non-specific cross-protection against respiratory syncytial virus (RSV. The degree of RSV replication was significantly reduced when X-31ca was administered before RSV infection without any RSV-specific antibody responses. The vaccination induced an immediate release of cytokines and infiltration of leukocytes into the respiratory tract, moderating the immune perturbation caused by RSV infection. The potency of protection against RSV challenge was significantly reduced in TLR3-/- TLR7-/- mice, confirming that the TLR3/7 signaling pathways are necessary for the observed immediate and short-term protection. The results suggest that CAIVs provide short-term, non-specific protection against genetically unrelated respiratory pathogens. The additional benefits of CAIVs in mitigating acute respiratory infections for which vaccines are not yet available need to be assessed in future studies.

  9. A Reverse Genetics Approach for the Design of Methyltransferase-Defective Live Attenuated Avian Metapneumovirus Vaccines.

    Science.gov (United States)

    Zhang, Yu; Sun, Jing; Wei, Yongwei; Li, Jianrong

    2016-01-01

    Avian metapneumovirus (aMPV), also known as avian pneumovirus or turkey rhinotracheitis virus, is the causative agent of turkey rhinotracheitis and is associated with swollen head syndrome in chickens. aMPV belongs to the family Paramyxoviridae which includes many important human pathogens such as human respiratory syncytial virus (RSV), human metapneumovirus (hMPV), and human parainfluenza virus type 3 (PIV3). The family also includes highly lethal emerging pathogens such as Nipah virus and Hendra virus, as well as agriculturally important viruses such as Newcastle disease virus (NDV). For many of these viruses, there is no effective vaccine. Here, we describe a reverse genetics approach to develop live attenuated aMPV vaccines by inhibiting the viral mRNA cap methyltransferase. The viral mRNA cap methyltransferase is an excellent target for the attenuation of paramyxoviruses because it plays essential roles in mRNA stability, efficient viral protein translation and innate immunity. We have described in detail the materials and methods used to generate recombinant aMPVs that lack viral mRNA cap methyltransferase activity. We have also provided methods to evaluate the genetic stability, pathogenesis, and immunogenicity of live aMPV vaccine candidates in turkeys.

  10. [Stress, Needs, and Quality of Life of People Living With Human Immunodeficiency Virus/AIDS in North East China].

    Science.gov (United States)

    Tsai, Meng-Chu; Lu, Po-Liang; Wu, Shiau-Jiun; Feng, Ming-Chu

    2017-04-01

    HIV/AIDS has become a chronic disease since anti-retroviral therapy has reduced the related rates of morbidity and mortality and maintained the immunity of people living with the human immunodeficiency virus / AIDS (PLWHA). PLWHA have psychological needs and many hope to improve their quality of life (QoL) over the long course of their treatment. Despite the large number of AIDS cases, there are limited reports addressing the issue of QoL among PLWHA in China. The present study aims to explore the stress, needs, QoL, and related factors among PLWHA in China. This cross-sectional, descriptive study used a structural questionnaire to assess the stress, needs, and QoL of 100 PLWHA in Shenyang, China. The most stressful issues faced by the participants were admitting HIV/AIDS status publicly and explaining their illness to others. Their needs were mainly related to receiving adequate information about HIV-related medical services, examination, and treatment and learning how to prevent disease progression. Among the four domains of QoL, the score in the physical domain was the lowest. The stress, needs, and QoL of the participants were significantly inter-correlated. However, only stress was found to predict QoL (β = -.25 to -.60, p stress, meet the needs, and improve the QoL of PLWHA, healthcare providers should work to lower the risk of divulgence, provide adequate healthcare information, and work to reduce the stigma and discrimination that is associated with having HIV/AIDS.

  11. The production of antibody by invading B cells is required for the clearance of rabies virus from the central nervous system.

    Directory of Open Access Journals (Sweden)

    D Craig Hooper

    2009-10-01

    Full Text Available The pathogenesis of rabies is associated with the inability to deliver immune effectors across the blood-brain barrier and to clear virulent rabies virus from CNS tissues. However, the mechanisms that facilitate immune effector entry into CNS tissues are induced by infection with attenuated rabies virus.Infection of normal mice with attenuated rabies virus but not immunization with killed virus can promote the clearance of pathogenic rabies virus from the CNS. T cell activity in B cell-deficient mice can control the replication of attenuated virus in the CNS, but viral mRNA persists. Low levels of passively administered rabies virus-neutralizing antibody reach infected cells in the cerebellum of B cell-deficient mice but are not sufficient to mediate virus clearance. Production of rabies virus-specific antibody by B cells invading CNS tissues is required for this process, and a substantial proportion of the B cells that accumulate in the CNS of mice infected with attenuated rabies virus produce virus-specific antibodies.The mechanisms required for immune effectors to enter rabies virus-infected tissues are induced by infection with attenuated rabies virus but not by infection with pathogenic rabies viruses or immunization with killed virus. T cell activities can inhibit rabies virus replication, but the production of rabies virus-specific antibodies by infiltrating B cells, as opposed to the leakage of circulating antibody across the BBB, is critical to elimination of the virus. These findings suggest that a pathogenic rabies virus infection may be treatable after the virus has reached the CNS tissues, providing that the appropriate immune effectors can be targeted to the infected tissues.

  12. Competitive virus assay method for titration of noncytopathogenic bovine viral diarrhea viruses (END⁺ and END⁻ viruses).

    Science.gov (United States)

    Muhsen, Mahmod; Ohi, Kota; Aoki, Hiroshi; Ikeda, Hidetoshi; Fukusho, Akio

    2013-03-01

    A new, reliable and secure virus assay method, named the competitive virus assay (CVA) method, has been established for the titration of bovine viral diarrhea viruses (BVDVs) that either show the exaltation of Newcastle disease virus (END) phenomenon or heterologous interference phenomenon (but not the END phenomenon). This method is based on the principle of (1) homologous interference between BVDVs, by using BVDV RK13/E(-) or BVDV RK13/E(+) strains as competitor virus, and (2) END phenomenon and heterologous interference, by using attenuated Newcastle disease virus (NDV) TCND strain as challenge virus. In titration of BVDV END(+) and BVDV END(-) viruses, no significant difference in estimated virus titer was observed between CVA and conventional methods. CVA method demonstrated comparable levels of sensitivity and accuracy as conventional END and interference methods, which require the use of a velogenic Miyadera strain of NDV and vesicular stomatitis virus (VSV), both of which are agents of high-risk diseases. As such, the CVA method is a safer alternative, with increased bio-safety and bio-containment, through avoidance of virulent strains that are commonly employed with conventional methods. Copyright © 2012 Elsevier B.V. All rights reserved.

  13. Herpes Simplex Vaccines: Prospects of Live-attenuated HSV Vaccines to Combat Genital and Ocular infections

    Science.gov (United States)

    Stanfield, Brent; Kousoulas, Konstantin Gus

    2015-01-01

    Herpes simplex virus type-1 (HSV-1) and its closely related type-2 (HSV-2) viruses cause important clinical manifestations in humans including acute ocular disease and genital infections. These viruses establish latency in the trigeminal ganglionic and dorsal root neurons, respectively. Both viruses are widespread among humans and can frequently reactivate from latency causing disease. Currently, there are no vaccines available against herpes simplex viral infections. However, a number of promising vaccine approaches are being explored in pre-clinical investigations with few progressing to early phase clinical trials. Consensus research findings suggest that robust humoral and cellular immune responses may partially control the frequency of reactivation episodes and reduce clinical symptoms. Live-attenuated viral vaccines have long been considered as a viable option for generating robust and protective immune responses against viral pathogens. Varicella zoster virus (VZV) belongs to the same alphaherpesvirus subfamily with herpes simplex viruses. A live-attenuated VZV vaccine has been extensively used in a prophylactic and therapeutic approach to combat primary and recurrent VZV infection indicating that a similar vaccine approach may be feasible for HSVs. In this review, we summarize pre-clinical approaches to HSV vaccine development and current efforts to test certain vaccine approaches in human clinical trials. Also, we discuss the potential advantages of using a safe, live-attenuated HSV-1 vaccine strain to protect against both HSV-1 and HSV-2 infections. PMID:27114893

  14. Progress toward an enhanced vaccine: Eight marked attenuated viruses to porcine reproductive and respiratory disease virus.

    Science.gov (United States)

    Spear, Allyn; Wang, Feng-Xue; Kappes, Matthew A; Das, Phani B; Faaberg, Kay S

    2018-03-01

    Recombinant viruses of strain Ingelvac® PRRS porcine reproductive and respiratory syndrome virus (PRRSV) modified live virus vaccine were produced with two individual small in-frame deletions in nonstructural protein 2 (nsp2; Δ23 and Δ87) and also the same deletions supplanted with foreign tags (Δ23-V5, Δ23-FLAG, Δ23-S, Δ87-V5, Δ87-FLAG, Δ87-S). The viruses, but one (Δ87-FLAG), were stable for 10 passages and showed minimal effects on in vitro growth. Northern hybridization showed that the Δ23-tagged probe detected intracellular viral genome RNA as well as shorter RNAs that may represent heteroclite species, while the Δ87-tagged probe detected predominantly only genome length RNAs. When the tagged viruses were used to probe nsp2 protein in infected cells, perinuclear localization similar to native nsp2 was seen. Dual infection of Δ23-S and Δ87-S viruses allowed some discrimination of individual tagged nsp2 protein, facilitating future research. The mutants could potentially also be used to differentiate infected from vaccinated animals. Published by Elsevier Inc.

  15. Lab-Attenuated Rabies Virus Causes Abortive Infection and Induces Cytokine Expression in Astrocytes by Activating Mitochondrial Antiviral-Signaling Protein Signaling Pathway

    Directory of Open Access Journals (Sweden)

    Bin Tian

    2018-01-01

    Full Text Available Rabies is an ancient disease but remains endemic in most parts of the world and causes approximately 59,000 deaths annually. The mechanism through which the causative agent, rabies virus (RABV, evades the host immune response and infects the host central nervous system (CNS has not been completely elucidated thus far. Our previous studies have shown that lab-attenuated, but not wild-type (wt, RABV activates the innate immune response in the mouse and dog models. In this present study, we demonstrate that lab-attenuated RABV causes abortive infection in astrocytes, the most abundant glial cells in the CNS. Furthermore, we found that lab-attenuated RABV produces more double-stranded RNA (dsRNA than wt RABV, which is recognized by retinoic acid-inducible gene I (RIG-I or melanoma differentiation-associated protein 5 (MDA5. Activation of mitochondrial antiviral-signaling protein (MAVS, the common adaptor molecule for RIG-I and MDA5, results in the production of type I interferon (IFN and the expression of hundreds of IFN-stimulated genes, which suppress RABV replication and spread in astrocytes. Notably, lab-attenuated RABV replicates in a manner identical to that of wt RABV in MAVS−/− astrocytes. It was also found that lab-attenuated, but not wt, RABV induces the expression of inflammatory cytokines via the MAVS- p38/NF-κB signaling pathway. These inflammatory cytokines increase the blood–brain barrier permeability and thus enable immune cells and antibodies infiltrate the CNS parenchyma, resulting in RABV control and elimination. In contrast, wt RABV restricts dsRNA production and thus evades innate recognition by RIG-I/MDA5 in astrocytes, which could be one of the mechanisms by which wt RABV evades the host immune response in resident CNS cells. Our findings suggest that astrocytes play a critical role in limiting the replication of lab-attenuated RABV in the CNS.

  16. Epstein-Barr virus-associated adult respiratory distress syndrome in a patient with AIDS: a case report and review

    DEFF Research Database (Denmark)

    Stopyra, G A; Multhaupt, H A; Alexa, L

    1999-01-01

    BACKGROUND: Epstein-Barr virus (EBV) infection has been associated with fatal pneumonitis in immunocompetent patients. We present a case of fatal adult respiratory distress syndrome caused by EBV infection in a patient with acquired immunodeficiency syndrome (AIDS), to our knowledge the first....... RESULTS: Strikingly numerous lymphocytes were positive for EBV early RNA in the case patient's spleen, lymph nodes, and hepatic portal areas. In addition to positive lymphocytes in the lung, EBV-infected pneumocytes were also present. Electron microscopy also demonstrated viral material in lymphocytes...

  17. The Science of AIDS. Readings from Scientific American Magazine.

    Science.gov (United States)

    Scientific American, Inc., New York, NY.

    This collection of scientific articles on the subject of acquired immune deficiency syndrome (AIDS) covers many facets of the physical and social aspects of the disease. Technical articles deal with the molecular and cellular biology of AIDS and the Human Immunodeficiency Virus (HIV). The national and international epidemiology of AIDS and HIV are…

  18. Bone Marrow Gene Therapy for HIV/AIDS

    Directory of Open Access Journals (Sweden)

    Elena Herrera-Carrillo

    2015-07-01

    Full Text Available Bone marrow gene therapy remains an attractive option for treating chronic immunological diseases, including acquired immunodeficiency syndrome (AIDS caused by human immunodeficiency virus (HIV. This technology combines the differentiation and expansion capacity of hematopoietic stem cells (HSCs with long-term expression of therapeutic transgenes using integrating vectors. In this review we summarize the potential of bone marrow gene therapy for the treatment of HIV/AIDS. A broad range of antiviral strategies are discussed, with a particular focus on RNA-based therapies. The idea is to develop a durable gene therapy that lasts the life span of the infected individual, thus contrasting with daily drug regimens to suppress the virus. Different approaches have been proposed to target either the virus or cellular genes encoding co-factors that support virus replication. Some of these therapies have been tested in clinical trials, providing proof of principle that gene therapy is a safe option for treating HIV/AIDS. In this review several topics are discussed, ranging from the selection of the antiviral molecule and the viral target to the optimal vector system for gene delivery and the setup of appropriate preclinical test systems. The molecular mechanisms used to formulate a cure for HIV infection are described, including the latest antiviral strategies and their therapeutic applications. Finally, a potent combination of anti-HIV genes based on our own research program is described.

  19. Primary effusion lymphomas in AIDS: CT findings in two cases

    Energy Technology Data Exchange (ETDEWEB)

    Ferrozzi, F.; Tognini, G.; Mulonzia, N.W.; Pavone, P. [Ist. di Scienze Radiologiche, Univ. di Parma (Italy); Bova, D.

    2001-04-01

    Primary effusion lymphomas represent an unusual subset of AIDS-related non-Hodgkin's lymphomas. They are associated with herpes virus 8 and Epstein-Barr virus and characterized by predominant involvement of the serous body cavities (pleura, pericardium, peritoneum) as lymphomatous effusion without any identifiable tumour mass. We report herein CT findings in two patients with primary effusion lymphoma emphasizing the possible neoplastic nature of a pleural effusion in a patient with AIDS. (orig.) (orig.)

  20. Primary effusion lymphomas in AIDS: CT findings in two cases

    International Nuclear Information System (INIS)

    Ferrozzi, F.; Tognini, G.; Mulonzia, N.W.; Pavone, P.; Bova, D.

    2001-01-01

    Primary effusion lymphomas represent an unusual subset of AIDS-related non-Hodgkin's lymphomas. They are associated with herpes virus 8 and Epstein-Barr virus and characterized by predominant involvement of the serous body cavities (pleura, pericardium, peritoneum) as lymphomatous effusion without any identifiable tumour mass. We report herein CT findings in two patients with primary effusion lymphoma emphasizing the possible neoplastic nature of a pleural effusion in a patient with AIDS. (orig.) (orig.)

  1. Characterization of Equine Infectious Anemia Virus Long Terminal Repeat Quasispecies In Vitro and In Vivo.

    Science.gov (United States)

    Wang, Xue-Feng; Liu, Qiang; Wang, Yu-Hong; Wang, Shuai; Chen, Jie; Lin, Yue-Zhi; Ma, Jian; Zhou, Jian-Hua; Wang, Xiaojun

    2018-04-15

    The equine infectious anemia virus (EIAV) attenuated vaccine was developed by long-term passaging of a field-isolated virulent strain in cross-species hosts, followed by successive cultivation in cells in vitro To explore the molecular mechanism underlying the evolution of the EIAV attenuated vaccine, a systematic study focusing on long-terminal-repeat (LTR) variation in numerous virus strains ranging from virulent EIAV to attenuated EIAV was performed over time both in vitro and in vivo Two hypervariable regions were identified within the U3 region in the enhancer region (EHR) and the negative regulatory element (NRE) and within the R region in the transcription start site (TSS) and the Tat-activating region (TAR). Among these sites, variation in the U3 region resulted in the formation of additional transcription factor binding sites; this variation of the in vitro -adapted strains was consistent with the loss of pathogenicity. Notably, the same LTR variation pattern was observed both in vitro and in vivo Generally, the LTR variation in both the attenuated virus and the virulent strain fluctuated over time in vivo Interestingly, the attenuated-virus-specific LTR variation was also detected in horses infected with the virulent strain, supporting the hypothesis that the evolution of an attenuated virus might have involved branching from EIAV quasispecies. This hypothesis was verified by phylogenetic analysis. The present systematic study examining the molecular evolution of attenuated EIAV from EIAV quasispecies may provide an informative model reflecting the evolution of similar lentiviruses. IMPORTANCE The attenuated EIAV vaccine was the first lentiviral vaccine used to successfully control for equine infectious anemia in China. This vaccine provides an important reference for studying the relationship between EIAV gene variation and changes in biological characteristics. Importantly, the vaccine provides a model for the investigation of lentiviral quasispecies

  2. At the Intersection of HIV/AIDS and Cancer: A Qualitative Needs Assessment of Community-Based HIV/AIDS Service Organizations

    Science.gov (United States)

    Burkhalter, Jack E.; Cahill, Sean; Shuk, Elyse; Guidry, John; Corner, Geoffrey; Berk, Alexandra; Candelario, Norman; Kornegay, Mark; Lubetkin, Erica I.

    2013-01-01

    Due to advances in treatment, persons living with human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) are living longer, but with aging, immune deficits, and lifestyle factors, they are at increased risk for cancer. This challenges community-based AIDS service organizations (ASOs) to address the growing cancer needs of…

  3. Psychiatric interventions for AIDS-spectrum disorders.

    Science.gov (United States)

    Perry, S W; Markowitz, J

    1986-10-01

    Although the medical and psychosocial problems posed by acquired immune deficiency syndrome (AIDS) are unique, interventions to treat AIDS-related psychiatric disorders are currently available. The depression, delirium, and denial that occur in medically hospitalized patients with AIDS respond to standard psychotherapeutic and psychopharmacological approaches. Outpatients with AIDS or AIDS-related complex benefit from clarification, abreaction, and support if the therapist accepts the regression associated with the sick role, focuses initially on somatic rather than on psychological concerns, and overcomes unwarranted fears of contagion. Patients with AIDS-related dementia are helped considerably by early diagnosis and planning, and patients with antibodies to the AIDS virus require a psycho-educational approach that includes stress inoculation and problem-solving techniques. The authors describe the above interventions as well as common countertransference responses that impede their implementation.

  4. MicroRNA reduction of neuronal West Nile virus replication attenuates and affords a protective immune response in mice.

    Science.gov (United States)

    Brostoff, Terza; Pesavento, Patricia A; Barker, Christopher M; Kenney, Joan L; Dietrich, Elizabeth A; Duggal, Nisha K; Bosco-Lauth, Angela M; Brault, Aaron C

    2016-10-17

    West Nile virus (WNV) is an important agent of human encephalitis that has quickly become endemic across much of the United States since its identification in North America in 1999. While the majority (∼75%) of infections are subclinical, neurologic disease can occur in a subset of cases, with outcomes including permanent neurologic damage and death. Currently, there are no WNV vaccines approved for use in humans. This study introduces a novel vaccine platform for WNV to reduce viral replication in the central nervous system while maintaining peripheral replication to elicit strong neutralizing antibody titers. Vaccine candidates were engineered to incorporate microRNA (miRNA) target sequences for a cognate miRNA expressed only in neurons, allowing the host miRNAs to target viral transcription through endogenous RNA silencing. To maintain stability, these targets were incorporated in multiple locations within the 3'-untranslated region, flanking sequences essential for viral replication without affecting the viral open reading frame. All candidates replicated comparably to wild type WNV in vitro within cells that did not express the cognate miRNA. Insertional control viruses were also capable of neuroinvasion and neurovirulence in vivo in CD-1 mice. Vaccine viruses were safe at all doses tested and did not demonstrate mutations associated with a reversion to virulence when serially passaged in mice. All vaccine constructs were protective from lethal challenge in mice, producing 93-100% protection at the highest dose tested. Overall, this is a safe and effective attenuation strategy with broad potential application for vaccine development. Published by Elsevier Ltd.

  5. Deletion of a 197-Amino-Acid Region in the N-Terminal Domain of Spike Protein Attenuates Porcine Epidemic Diarrhea Virus in Piglets.

    Science.gov (United States)

    Hou, Yixuan; Lin, Chun-Ming; Yokoyama, Masaru; Yount, Boyd L; Marthaler, Douglas; Douglas, Arianna L; Ghimire, Shristi; Qin, Yibin; Baric, Ralph S; Saif, Linda J; Wang, Qiuhong

    2017-07-15

    We previously isolated a porcine epidemic diarrhea virus (PEDV) strain, PC177, by blind serial passaging of the intestinal contents of a diarrheic piglet in Vero cell culture. Compared with the highly virulent U.S. PEDV strain PC21A, the tissue culture-adapted PC177 (TC-PC177) contains a 197-amino-acid (aa) deletion in the N-terminal domain of the spike (S) protein. We orally inoculated neonatal, conventional suckling piglets with TC-PC177 or PC21A to compare their pathogenicities. Within 7 days postinoculation, TC-PC177 caused mild diarrhea and lower fecal viral RNA shedding, with no mortality, whereas PC21A caused severe clinical signs and 55% mortality. To investigate whether infection with TC-PC177 can induce cross-protection against challenge with a highly virulent PEDV strain, all the surviving piglets were challenged with PC21A at 3 weeks postinoculation. Compared with 100% protection in piglets initially inoculated with PC21A, 88% and 100% TC-PC177- and mock-inoculated piglets had diarrhea following challenge, respectively, indicating incomplete cross-protection. To investigate whether this 197-aa deletion was the determinant for the attenuation of TC-PC177, we generated a mutant (icPC22A-S1Δ197) bearing the 197-aa deletion from an infectious cDNA clone of the highly virulent PEDV PC22A strain (infectious clone PC22A, icPC22A). In neonatal gnotobiotic pigs, the icPC22A-S1Δ197 virus caused mild to moderate diarrhea, lower titers of viral shedding, and no mortality, whereas the icPC22A virus caused severe diarrhea and 100% mortality. Our data indicate that deletion of this 197-aa fragment in the spike protein can attenuate a highly virulent PEDV, but the virus may lose important epitopes for inducing robust protective immunity. IMPORTANCE The emerging, highly virulent PEDV strains have caused substantial economic losses worldwide. However, the virulence determinants are not established. In this study, we found that a 197-aa deletion in the N-terminal region

  6. Stages of AIDS-Related Lymphoma

    Science.gov (United States)

    ... and treatment options. AIDS-related lymphoma is a disease in which malignant (cancer) cells form in the ... cord. The sample may also be checked for Epstein-Barr virus . This procedure is also called an LP ...

  7. Vaccination against Canine Distemper Virus Infection in Infant Ferrets with and without Maternal Antibody Protection, Using Recombinant Attenuated Poxvirus Vaccines

    Science.gov (United States)

    Welter, Janet; Taylor, Jill; Tartaglia, James; Paoletti, Enzo; Stephensen, Charles B.

    2000-01-01

    Canine distemper virus (CDV) infection of ferrets is clinically and immunologically similar to measles, making this a useful model for the human disease. The model was used to determine if parenteral or mucosal immunization of infant ferrets at 3 and 6 weeks of age with attenuated vaccinia virus (NYVAC) or canarypox virus (ALVAC) vaccine strains expressing the CDV hemagglutinin (H) and fusion (F) protein genes (NYVAC-HF and ALVAC-HF) would induce serum neutralizing antibody and protect against challenge infection at 12 weeks of age. Ferrets without maternal antibody that were vaccinated parenterally with NYVAC-HF (n = 5) or ALVAC-HF (n = 4) developed significant neutralizing titers (log10 inverse mean titer ± standard deviation of 2.30 ± 0.12 and 2.20 ± 0.34, respectively) by the day of challenge, and all survived with no clinical or virologic evidence of infection. Ferrets without maternal antibody that were vaccinated intranasally (i.n.) developed lower neutralizing titers, with NYVAC-HF producing higher titers at challenge (1.11 ± 0.57 versus 0.40 ± 0.37, P = 0.02) and a better survival rate (6/7 versus 0/5, P = 0.008) than ALVAC-HF. Ferrets with maternal antibody that were vaccinated parenterally with NYVAC-HF (n = 7) and ALVAC-HF (n = 7) developed significantly higher antibody titers (1.64 ± 0.54 and 1.28 ± 0.40, respectively) than did ferrets immunized with an attenuated CDV vaccine (0.46 ± 0.59; n = 7) or the recombinant vectors expressing rabies glycoprotein (RG) (0.19 ± 0.32; n = 8, P = 7 × 10−6). The NYVAC vaccine also protected against weight loss, and both the NYVAC and attenuated CDV vaccines protected against the development of some clinical signs of infection, although survival in each of the three vaccine groups was low (one of seven) and not significantly different from the RG controls (none of eight). Combined i.n.-parenteral immunization of ferrets with maternal antibody using NYVAC-HF (n = 9) produced higher titers (1.63 ± 0

  8. Vaccination against canine distemper virus infection in infant ferrets with and without maternal antibody protection, using recombinant attenuated poxvirus vaccines.

    Science.gov (United States)

    Welter, J; Taylor, J; Tartaglia, J; Paoletti, E; Stephensen, C B

    2000-07-01

    Canine distemper virus (CDV) infection of ferrets is clinically and immunologically similar to measles, making this a useful model for the human disease. The model was used to determine if parenteral or mucosal immunization of infant ferrets at 3 and 6 weeks of age with attenuated vaccinia virus (NYVAC) or canarypox virus (ALVAC) vaccine strains expressing the CDV hemagglutinin (H) and fusion (F) protein genes (NYVAC-HF and ALVAC-HF) would induce serum neutralizing antibody and protect against challenge infection at 12 weeks of age. Ferrets without maternal antibody that were vaccinated parenterally with NYVAC-HF (n = 5) or ALVAC-HF (n = 4) developed significant neutralizing titers (log(10) inverse mean titer +/- standard deviation of 2.30 +/- 0.12 and 2.20 +/- 0.34, respectively) by the day of challenge, and all survived with no clinical or virologic evidence of infection. Ferrets without maternal antibody that were vaccinated intranasally (i.n.) developed lower neutralizing titers, with NYVAC-HF producing higher titers at challenge (1.11 +/- 0.57 versus 0.40 +/- 0.37, P = 0.02) and a better survival rate (6/7 versus 0/5, P = 0.008) than ALVAC-HF. Ferrets with maternal antibody that were vaccinated parenterally with NYVAC-HF (n = 7) and ALVAC-HF (n = 7) developed significantly higher antibody titers (1.64 +/- 0. 54 and 1.28 +/- 0.40, respectively) than did ferrets immunized with an attenuated CDV vaccine (0.46 +/- 0.59; n = 7) or the recombinant vectors expressing rabies glycoprotein (RG) (0.19 +/- 0.32; n = 8, P = 7 x 10(-6)). The NYVAC vaccine also protected against weight loss, and both the NYVAC and attenuated CDV vaccines protected against the development of some clinical signs of infection, although survival in each of the three vaccine groups was low (one of seven) and not significantly different from the RG controls (none of eight). Combined i.n.-parenteral immunization of ferrets with maternal antibody using NYVAC-HF (n = 9) produced higher titers (1

  9. Horizontal transmission of the Leningrad-3 live attenuated mumps vaccine virus.

    Science.gov (United States)

    Atrasheuskaya, A V; Neverov, A A; Rubin, S; Ignatyev, G M

    2006-03-06

    Here we describe symptomatic transmission of the Leningrad-3 mumps vaccine virus from healthy vaccinees to previously vaccinated contacts. Throat swab and serum samples were taken from six symptomatic mumps cases and from 13 family contacts. Assessment of serum IgG and IgM anti-mumps virus antibodies and IgG avidity testing was performed using commercial test kits. Sera neutralizing antibodies were measured by plaque reduction neutralization assay using the L-3 vaccine mumps virus as the target. All six of the symptomatic mumps cases and three contact subjects tested positive for mumps by RT-PCR. The genomic sequences tested (F, SH and HN genes) of all nine of these samples were identical to the L-3 mumps vaccine strain. All 13 contacts were asymptomatic; however clear serological evidence of mumps infection was found in some of them. The likely epidemiological source of the transmitted L-3 mumps virus was children who were recently vaccinated at the schools attended by the six symptomatic mumps patients described here. The L-3 mumps vaccine virus can be shed and transmitted horizontally, even to subjects previously vaccinated with the same virus.

  10. Attenuated Recombinant Influenza A Virus Expressing HPV16 E6 and E7 as a Novel Therapeutic Vaccine Approach.

    Directory of Open Access Journals (Sweden)

    Christoph Jindra

    Full Text Available Persistent infection with high-risk human papillomavirus (HPV types, most often HPV16 and HPV18, causes all cervical and most anal cancers, and a subset of vulvar, vaginal, penile and oropharyngeal carcinomas. Two prophylactic virus-like particle (VLPs-based vaccines, are available that protect against vaccine type-associated persistent infection and associated disease, yet have no therapeutic effect on existing lesions or infections. We have generated recombinant live-attenuated influenza A viruses expressing the HPV16 oncogenes E6 and E7 as experimental immunotherapeutic vaccine candidates. The influenza A virus life cycle lacks DNA intermediates as important safety feature. Different serotypes were generated to ensure efficient prime and boost immunizations. The immune response to vaccination in C57BL/6 mice was characterized by peptide ELISA and IFN-γ ELISpot, demonstrating induction of cell-mediated immunity to HPV16 E6 and E7 oncoproteins. Prophylactic and therapeutic vaccine efficacy was analyzed in the murine HPV16-positive TC-1 tumor challenge model. Subcutaneous (s.c. prime and boost vaccinations of mice with recombinant influenza A serotypes H1N1 and H3N2, followed by challenge with TC-1 cells resulted in complete protection or significantly reduced tumor growth as compared to control animals. In a therapeutic setting, s.c. vaccination of mice with established TC-1 tumors decelerated tumor growth and significantly prolonged survival. Importantly, intralesional vaccine administration induced complete tumor regression in 25% of animals, and significantly reduced tumor growth in 50% of mice. These results suggest recombinant E6E7 influenza viruses as a promising new approach for the development of a therapeutic vaccine against HPV-induced disease.

  11. Attenuation of Pathogenic Immune Responses during Infection with Human and Simian Immunodeficiency Virus (HIV/SIV) by the Tetracycline Derivative Minocycline

    Science.gov (United States)

    Drewes, Julia L.; Szeto, Gregory L.; Engle, Elizabeth L.; Liao, Zhaohao; Shearer, Gene M.; Zink, M. Christine; Graham, David R.

    2014-01-01

    HIV immune pathogenesis is postulated to involve two major mechanisms: 1) chronic innate immune responses that drive T cell activation and apoptosis and 2) induction of immune regulators that suppress T cell function and proliferation. Both arms are elevated chronically in lymphoid tissues of non-natural hosts, which ultimately develop AIDS. However, these mechanisms are not elevated chronically in natural hosts of SIV infection that avert immune pathogenesis despite similarly high viral loads. In this study we investigated whether minocycline could modulate these pathogenic antiviral responses in non-natural hosts of HIV and SIV. We found that minocycline attenuated in vitro induction of type I interferon (IFN) and the IFN-stimulated genes indoleamine 2,3-dioxygenase (IDO1) and TNF-related apoptosis inducing ligand (TRAIL) in human plasmacytoid dendritic cells and PBMCs exposed to aldrithiol-2 inactivated HIV or infectious influenza virus. Activation-induced TRAIL and expression of cytotoxic T-lymphocyte antigen 4 (CTLA-4) in isolated CD4+ T cells were also reduced by minocycline. Translation of these in vitro findings to in vivo effects, however, were mixed as minocycline significantly reduced markers of activation and activation-induced cell death (CD25, Fas, caspase-3) but did not affect expression of IFNβ or the IFN-stimulated genes IDO1, FasL, or Mx in the spleens of chronically SIV-infected pigtailed macaques. TRAIL expression, reflecting the mixed effects of minocycline on activation and type I IFN stimuli, was reduced by half, but this change was not significant. These results show that minocycline administered after infection may protect against aspects of activation-induced cell death during HIV/SIV immune disease, but that in vitro effects of minocycline on type I IFN responses are not recapitulated in a rapid progressor model in vivo. PMID:24732038

  12. Inactivated Recombinant Rabies Viruses Displaying Canine Distemper Virus Glycoproteins Induce Protective Immunity against Both Pathogens.

    Science.gov (United States)

    da Fontoura Budaszewski, Renata; Hudacek, Andrew; Sawatsky, Bevan; Krämer, Beate; Yin, Xiangping; Schnell, Matthias J; von Messling, Veronika

    2017-04-15

    The development of multivalent vaccines is an attractive methodology for the simultaneous prevention of several infectious diseases in vulnerable populations. Both canine distemper virus (CDV) and rabies virus (RABV) cause lethal disease in wild and domestic carnivores. While RABV vaccines are inactivated, the live-attenuated CDV vaccines retain residual virulence for highly susceptible wildlife species. In this study, we developed recombinant bivalent vaccine candidates based on recombinant vaccine strain rabies virus particles, which concurrently display the protective CDV and RABV glycoprotein antigens. The recombinant viruses replicated to near-wild-type titers, and the heterologous glycoproteins were efficiently expressed and incorporated in the viral particles. Immunization of ferrets with beta-propiolactone-inactivated recombinant virus particles elicited protective RABV antibody titers, and animals immunized with a combination of CDV attachment protein- and fusion protein-expressing recombinant viruses were protected from lethal CDV challenge. However, animals that were immunized with only a RABV expressing the attachment protein of CDV vaccine strain Onderstepoort succumbed to infection with a more recent wild-type strain, indicating that immune responses to the more conserved fusion protein contribute to protection against heterologous CDV strains. IMPORTANCE Rabies virus and canine distemper virus (CDV) cause high mortality rates and death in many carnivores. While rabies vaccines are inactivated and thus have an excellent safety profile and high stability, live-attenuated CDV vaccines can retain residual virulence in highly susceptible species. Here we generated recombinant inactivated rabies viruses that carry one of the CDV glycoproteins on their surface. Ferrets immunized twice with a mix of recombinant rabies viruses carrying the CDV fusion and attachment glycoproteins were protected from lethal CDV challenge, whereas all animals that received

  13. Virus-host interaction in feline immunodeficiency virus (FIV) infection.

    Science.gov (United States)

    Taniwaki, Sueli Akemi; Figueiredo, Andreza Soriano; Araujo, João Pessoa

    2013-12-01

    Feline immunodeficiency virus (FIV) infection has been the focus of several studies because this virus exhibits genetic and pathogenic characteristics that are similar to those of the human immunodeficiency virus (HIV). FIV causes acquired immunodeficiency syndrome (AIDS) in cats, nevertheless, a large fraction of infected cats remain asymptomatic throughout life despite of persistent chronic infection. This slow disease progression may be due to the presence of factors that are involved in the natural resistance to infection and the immune response that is mounted by the animals, as well as due to the adaptation of the virus to the host. Therefore, the study of virus-host interaction is essential to the understanding of the different patterns of disease course and the virus persistence in the host, and to help with the development of effective vaccines and perhaps the cure of FIV and HIV infections. Copyright © 2013 Elsevier Ltd. All rights reserved.

  14. Single-cycle immunodeficiency viruses provide strategies for uncoupling in vivo expression levels from viral replicative capacity and for mimicking live-attenuated SIV vaccines

    International Nuclear Information System (INIS)

    Kuate, Seraphin; Stahl-Hennig, Christiane; Haaft, Peter ten; Heeney, Jonathan; Ueberla, Klaus

    2003-01-01

    To reduce the risks associated with live-attenuated immunodeficiency virus vaccines, single-cycle immunodeficiency viruses (SCIVs) were developed by primer complementation and production of the vaccine in the absence of vif in a vif-independent cell line. After a single intravenous injection of SCIVs into rhesus monkeys, peak viral RNA levels of 10 3 to 10 4 copies/ml plasma were observed, indicating efficient expression of SCIV in the vaccinee. After booster immunizations with SCIVs, SIV-specific humoral and cellular immune responses were observed. Although the vaccine doses used in this pilot study could not protect vaccinees from subsequent intravenous challenge with pathogenic SIVmac239, our results demonstrate that the novel SCIV approach allows us to uncouple in vivo expression levels from the viral replicative capacity facilitating the analysis of the relationship between viral expression levels or viral genes and immune responses induced by SIV

  15. 21 CFR 866.3520 - Rubeola (measles) virus serological reagents.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Rubeola (measles) virus serological reagents. 866... Rubeola (measles) virus serological reagents. (a) Identification. Rubeola (measles) virus serological... to rubeola virus in serum. The identification aids in the diagnosis of measles and provides...

  16. Contamination of infectious RD-114 virus in vaccines produced using non-feline cell lines.

    Science.gov (United States)

    Yoshikawa, Rokusuke; Sato, Eiji; Miyazawa, Takayuki

    2011-01-01

    All domestic cats have a replication-competent endogenous retrovirus, termed RD-114 virus, in their genome and several feline cell lines produce RD-114 viruses. Recently, we found that a portion of live attenuated feline and canine vaccines produced using feline cell lines was contaminated with infectious RD-114 viruses. In this study, we expanded our survey and examined canine vaccines produced using 'non-feline' cell lines. Consequently, we found two vaccines containing RD-114 viral RNA by reverse transcriptase (RT)-polymerase chain reaction (PCR) and real-time RT-PCR. We also confirmed the presence of infectious RD-114 virus in the vaccines by the LacZ marker rescue assay and PCR to detect proviral DNA in TE671 cells (human rhabdomyosarcoma cells) inoculated with the vaccines. It is impossible to investigate the definitive cause of contamination with RD-114 virus; however, we suspect that a seed canine parvovirus type 2 was contaminated with RD-114 virus, because many canine parvoviruses have been isolated and attenuated using feline cell lines. To exclude RD-114 virus from live attenuated vaccines, we must pay attention to the contamination of seed viruses with RD-114 virus in addition to avoiding feline cell lines producing RD-114 virus when manufacturing vaccines. Copyright © 2010 The International Association for Biologicals. Published by Elsevier Ltd. All rights reserved.

  17. AIDS and adolescents: why should we be concerned?

    Science.gov (United States)

    1987-11-01

    AIDS most often strikes people aged 20-40 years old. However, due to the long period of incubation from initial infection with HIV to the development of AIDS, many young adults with AIDS may have been infected with the virus while they were teenagers. Many adolescents could be unsuspecting carriers of the virus. It is normal for developing adolescents to experiment with their bodies and those of their peers. Inherent to this experimentation and growth is risk taking with sex and drugs. Sexual intercourse without condom use and IV drug use with non-sterile injecting equipment are risk factors for contracting and transmitting HIV. Without creating undue fear, teenagers must be taught how AIDS is spread, how it is not spread, and how they can protect themselves from HIV. They need to understand that certain behaviors are risky, not belonging to a certain population subgroup. This article describes efforts underway in Finland, Mexico, Chile, the US, and Thailand to teach adolescents about AIDS. At the start of Finland's AIDS education campaign in early January 1987, the use of a condom was demonstrated on national television news. The country's National Board of Health also distributed a booklet on AIDS and a sample condom to all 16-21 year olds in Finland. Teens themselves can also be effective AIDS educators. Efforts to teach adolescents about HIV/AIDS and promote behavior change should be the product of comprehensive community involvement.

  18. Immunogenicity of seven new recombinant yellow fever viruses 17D expressing fragments of SIVmac239 Gag, Nef, and Vif in Indian rhesus macaques.

    Directory of Open Access Journals (Sweden)

    Mauricio A Martins

    Full Text Available An effective vaccine remains the best solution to stop the spread of human immunodeficiency virus (HIV. Cellular immune responses have been repeatedly associated with control of viral replication and thus may be an important element of the immune response that must be evoked by an efficacious vaccine. Recombinant viral vectors can induce potent T-cell responses. Although several viral vectors have been developed to deliver HIV genes, only a few have been advanced for clinical trials. The live-attenuated yellow fever vaccine virus 17D (YF17D has many properties that make it an attractive vector for AIDS vaccine regimens. YF17D is well tolerated in humans and vaccination induces robust T-cell responses that persist for years. Additionally, methods to manipulate the YF17D genome have been established, enabling the generation of recombinant (rYF17D vectors carrying genes from unrelated pathogens. Here, we report the generation of seven new rYF17D viruses expressing fragments of simian immunodeficiency virus (SIVmac239 Gag, Nef, and Vif. Studies in Indian rhesus macaques demonstrated that these live-attenuated vectors replicated in vivo, but only elicited low levels of SIV-specific cellular responses. Boosting with recombinant Adenovirus type-5 (rAd5 vectors resulted in robust expansion of SIV-specific CD8(+ T-cell responses, particularly those targeting Vif. Priming with rYF17D also increased the frequency of CD4(+ cellular responses in rYF17D/rAd5-immunized macaques compared to animals that received rAd5 only. The effect of the rYF17D prime on the breadth of SIV-specific T-cell responses was limited and we also found evidence that some rYF17D vectors were more effective than others at priming SIV-specific T-cell responses. Together, our data suggest that YF17D - a clinically relevant vaccine vector - can be used to prime AIDS virus-specific T-cell responses in heterologous prime boost regimens. However, it will be important to optimize rYF17D

  19. Inactivated Recombinant Rabies Viruses Displaying Canine Distemper Virus Glycoproteins Induce Protective Immunity against Both Pathogens

    OpenAIRE

    da Fontoura Budaszewski, Renata; Hudacek, Andrew; Sawatsky, Bevan; Krämer, Beate; Yin, Xiangping; Schnell, Matthias J.; von Messling, Veronika

    2017-01-01

    The development of multivalent vaccines is an attractive methodology for the simultaneous prevention of several infectious diseases in vulnerable populations. Both canine distemper virus (CDV) and rabies virus (RABV) cause lethal disease in wild and domestic carnivores. While RABV vaccines are inactivated, the live-attenuated CDV vaccines retain residual virulence for highly susceptible wildlife species. In this study, we developed recombinant bivalent vaccine candidates based on recombinant ...

  20. Insights into the Impact of CD8+ Immune Modulation on Human Immunodeficiency Virus Evolutionary Dynamics in Distinct Anatomical Compartments by Using Simian Immunodeficiency Virus-Infected Macaque Models of AIDS Progression.

    Science.gov (United States)

    Rife Magalis, Brittany; Nolan, David J; Autissier, Patrick; Burdo, Tricia H; Williams, Kenneth C; Salemi, Marco

    2017-12-01

    A thorough understanding of the role of human immunodeficiency virus (HIV) intrahost evolution in AIDS pathogenesis has been limited by the need for longitudinally sampled viral sequences from the vast target space within the host, which are often difficult to obtain from human subjects. CD8 + lymphocyte-depleted macaques infected with simian immunodeficiency virus (SIV) provide an increasingly utilized model of pathogenesis due to clinical manifestations similar to those for HIV-1 infection and AIDS progression, as well as a characteristic rapid disease onset. Comparison of this model with SIV-infected non-CD8 + lymphocyte-depleted macaques also provides a unique opportunity to investigate the role of CD8 + cells in viral evolution and population dynamics throughout the duration of infection. Using several different phylogenetic methods, we analyzed viral gp120 sequences obtained from extensive longitudinal sampling of multiple tissues and enriched leukocyte populations from SIVmac251-infected macaques with or without CD8 + lymphocyte depletion. SIV evolutionary and selection patterns in non-CD8 + lymphocyte-depleted animals were characterized by sequential population turnover and continual viral adaptation, a scenario readily comparable to intrahost evolutionary patterns during human HIV infection in the absence of antiretroviral therapy. Alternatively, animals that were depleted of CD8 + lymphocytes exhibited greater variation in population dynamics among tissues and cell populations over the course of infection. Our findings highlight the major role for CD8 + lymphocytes in prolonging disease progression through continual control of SIV subpopulations from various anatomical compartments and the potential for greater independent viral evolutionary behavior among these compartments in response to immune modulation. IMPORTANCE Although developments in combined antiretroviral therapy (cART) strategies have successfully prolonged the time to AIDS onset in HIV-1

  1. Risk of AIDS related complex and AIDS in homosexual men with persistent HIV antigenaemia.

    OpenAIRE

    de Wolf, F; Goudsmit, J; Paul, D A; Lange, J M; Hooijkaas, C; Schellekens, P; Coutinho, R A; van der Noordaa, J

    1987-01-01

    One hundred and ninety eight men seropositive for human immunodeficiency virus (HIV) antibody and 58 HIV antibody seroconverters were studied for an average of 19.3 (SEM 0.5) months to assess the relation between HIV antigenaemia and the risk of developing the acquired immune deficiency syndrome (AIDS) and AIDS related complex. Forty (20.2%) of the 198 HIV antibody seropositive men were antigen positive at entry and remained so during follow up. Eight (13.8%) of the 58 HIV antibody seroconver...

  2. CT of AIDS-related musculoskeletal infections

    International Nuclear Information System (INIS)

    Magid, D.; Fishman, E.K.

    1990-01-01

    This paper characterizes musculoskeletal inflammatory diseases in human immunodeficiency virus-positive patients and with acquired immunodeficiency syndrome (AIDS). CT, radiographic, and clinical data were reviewed in 10 patients, and patterns and features were compared with those in musculoskeletal infections occurring in non-AIDS patients. Infection was confirmed by means of biopsy or aspiration in eight cases and strongly suggested in the other two by blood cultures, cell counts, and other data

  3. Radiotherapy for HIV/Aids Related Cancers: A South African Perspective. Chapter 22

    International Nuclear Information System (INIS)

    Sharma, V.; Kotzen, J.

    2017-01-01

    Cancer is a significant cause of morbidity and mortality in people infected with the human immunodeficiency virus (HIV). In fact, 30–40% of people with this condition will develop a malignancy during their lifetime. The majority of cancers affecting HIV positive people are those established as AIDS defining: Kaposi’s sarcoma (KS), non-Hodgkin’s lymphoma (NHL) and invasive cervical cancer. However, other types of cancer also appear to be more common among those infected with HIV. While not classified as AIDS defining, these malignancies are affecting the HIV/AIDS community greatly and have been referred to as ‘AIDS-associated malignancies’ or ‘opportunistic’ cancers. Two analyses have revealed a two to three fold increase in the overall risk of developing these cancers. The introduction of highly active antiretroviral therapy (HAART) has resulted in decreased mortality and morbidity, and the majority of people in developed countries infected with HIV are living with only mild to moderate immunosuppression because of wide access to antiretroviral therapy. HIV positive persons have a markedly elevated risk for two malignancies: KS and NHL, which are themselves considered sufficient to signify progression to AIDS. KS and NHL are caused by a loss of immune control of latent infection with oncogenic viruses (human herpes virus 8 (HHV-8) for KS, Epstein–Barr virus for certain NHL subtypes). Other cancers caused by viruses (e.g. cervical and anal canal cancers caused by human papillomavirus (HPV), liver cancer caused by hepatitis B and C) also occur with increased frequency in this population, although for them, the importance of immune suppression is less clear.

  4. Computational fitness landscape for all gene-order permutations of an RNA virus.

    Directory of Open Access Journals (Sweden)

    Kwang-il Lim

    2009-02-01

    Full Text Available How does the growth of a virus depend on the linear arrangement of genes in its genome? Answering this question may enhance our basic understanding of virus evolution and advance applications of viruses as live attenuated vaccines, gene-therapy vectors, or anti-tumor therapeutics. We used a mathematical model for vesicular stomatitis virus (VSV, a prototype RNA virus that encodes five genes (N-P-M-G-L, to simulate the intracellular growth of all 120 possible gene-order variants. Simulated yields of virus infection varied by 6,000-fold and were found to be most sensitive to gene-order permutations that increased levels of the L gene transcript or reduced levels of the N gene transcript, the lowest and highest expressed genes of the wild-type virus, respectively. Effects of gene order on virus growth also depended upon the host-cell environment, reflecting different resources for protein synthesis and different cell susceptibilities to infection. Moreover, by computationally deleting intergenic attenuations, which define a key mechanism of transcriptional regulation in VSV, the variation in growth associated with the 120 gene-order variants was drastically narrowed from 6,000- to 20-fold, and many variants produced higher progeny yields than wild-type. These results suggest that regulation by intergenic attenuation preceded or co-evolved with the fixation of the wild type gene order in the evolution of VSV. In summary, our models have begun to reveal how gene functions, gene regulation, and genomic organization of viruses interact with their host environments to define processes of viral growth and evolution.

  5. Treatment Option Overview (AIDS Related-Lymphoma)

    Science.gov (United States)

    ... and treatment options. AIDS-related lymphoma is a disease in which malignant (cancer) cells form in the ... cord. The sample may also be checked for Epstein-Barr virus . This procedure is also called an LP ...

  6. General Information about AIDS-Related Lymphoma

    Science.gov (United States)

    ... and treatment options. AIDS-related lymphoma is a disease in which malignant (cancer) cells form in the ... cord. The sample may also be checked for Epstein-Barr virus . This procedure is also called an LP ...

  7. Dual miRNA targeting restricts host range and attenuates neurovirulence of flaviviruses.

    Directory of Open Access Journals (Sweden)

    Konstantin A Tsetsarkin

    2015-04-01

    Full Text Available Mosquito-borne flaviviruses are among the most significant arboviral pathogens worldwide. Vaccinations and mosquito population control programs remain the most reliable means for flavivirus disease prevention, and live attenuated viruses remain one of the most attractive flavivirus vaccine platforms. Some live attenuated viruses are capable of infecting principle mosquito vectors, as demonstrated in the laboratory, which in combination with their intrinsic genetic instability could potentially lead to a vaccine virus reversion back to wild-type in nature, followed by introduction and dissemination of potentially dangerous viral strains into new geographic locations. To mitigate this risk we developed a microRNA-targeting approach that selectively restricts replication of flavivirus in the mosquito host. Introduction of sequences complementary to a mosquito-specific mir-184 and mir-275 miRNAs individually or in combination into the 3'NCR and/or ORF region resulted in selective restriction of dengue type 4 virus (DEN4 replication in mosquito cell lines and adult Aedes mosquitos. Moreover a combined targeting of DEN4 genome with mosquito-specific and vertebrate CNS-specific mir-124 miRNA can silence viral replication in two evolutionally distant biological systems: mosquitoes and mouse brains. Thus, this approach can reinforce the safety of newly developed or existing vaccines for use in humans and could provide an additional level of biosafety for laboratories using viruses with altered pathogenic or transmissibility characteristics.

  8. Risky sexual behaviour and human immunodeficiency virus (HIV and acquired immune deficiency syndrome (AIDS among healthcare workers

    Directory of Open Access Journals (Sweden)

    Natasha Khamisa

    2018-01-01

    Full Text Available Background: South Africa is known to have one of the highest prevalence rates of human immunodeficiency virus (HIV and acquired immune deficiency syndrome (AIDS globally, with one in seven healthcare workers being HIV-positive. An HIV-positive healthcare workforce is less equipped to respond to the increasing spread of the epidemic. Objectives: Assessment of the factors contributing to high HIV prevalence rates among healthcare workers is important in planning the development of human resources. This review sought to identify and understand predominant risky sexual behaviours among healthcare workers in HIV and AIDS-affected countries. Methods: This study reviewed articles focusing on sexual behaviour among healthcare workers. Major health science databases (e.g. ProQuest, Cochrane, PubMed and CINAHL were searched for combinations of keywords including ‘healthcare workers’, ‘risky sexual behaviour’ and ‘HIV and AIDS’. Articles from a range of countries met inclusion and exclusion criteria. Results: Findings of the study revealed three main contributing factors: unprotected sex, multiple sex partners and sexual violence. Sexual violence emerged as the dominant risk factor in the majority of the studies. Most research was conducted in developed countries where the HIV infection rate is much lower than it is in developing countries. Conclusion: More research needs to be conducted in developing countries and appropriate strategies should be implemented to reduce sexual violence among healthcare workers. Appropriate procedures on reporting sexual violence coupled with education on HIV and AIDS as well as influencing attitudes and belief systems could assist in reducing the spread of HIV and AIDS within the healthcare workforce while minimising the effect on patient care.

  9. Epidemiology of AIDS in Africa--part 2.

    Science.gov (United States)

    Cigielski, J P

    1988-03-01

    A recently completed study involving over 10,000 people from 6 Central African countries found seroprevalence rates generally under 1% for the acquired immunodeficiency syndrome (AIDS); however, rates were significantly higher for urban residents, prostitutes and their sexual contacts, and patients attending sexually transmitted disease clinics. The 4 major modes of transmission of AIDS in Africa are sexual contact, perinatal transmission, transfusion of infected blood or blood products, and the reuse of equipment such as needles and syringes. In 1985, a 2nd AIDS virus, human immunodeficiency virus (HIV)-2, was discovered in West Africa--a finding with important implications for epidemiologic surveillance, screening programs, and clinical diagnostic testing. Although 45 of the 50 African countries have developed concrete public health policies and strategies for the prevention and control of AIDS, most nations of sub-Saharan Africa lack the economic and social resources to implement these programs effectively. Thus, international cooperation and a commitment on the part of the US and Western Europe to provide assistance will be essential. Needs must be addressed on 2 fronts: treatment of those already infected or suffering from the disease and containment of the AIDS epidemic. Public health efforts should focus initially on high risk behaviors through health education. At the same time, it should be recognized that AIDS is not the largest health issue facing Africans, and there is a complex interaction between AIDS and other health problems such as malnutrition, genital ulcers, diarrhea, and tuberculosis. An approach to AIDS requires an expansion of public health initiatives in areas such as clean water supplies, maternal-child health programs, nutrition and immunization programs, and sexually transmitted disease clinics.

  10. Major histocompatibility complex-linked immune response of young chickens vaccinated with an attenuated live infectious bursal disease virus vaccine followed by an infection

    DEFF Research Database (Denmark)

    Juul-Madsen, Helle; Nielsen, O.L.; Krogh-Maibom, T.

    2002-01-01

    The influence of the MHC on infectious bursal disease virus (IBDV) vaccine response in chickens was investigated in three different chicken lines containing four different MHC haplotypes. Two MHC haplotypes were present in all three lines with one haplotype (1319) shared between the lines. Line I...... further contains the BW1 haplotype isolated from a Red jungle Fowl. Line 131 further contains the B131 haplotype isolated from a meat-type chicken, Finally, Line 21 further contains the international B21 haplotype. The chickens were vaccinated with live attenuated commercial IBDV vaccine at 3 wk of age...

  11. Linfomas asociados con la infección por el virus de la inmunodeficiencia humana: subtipos histológicos y asociación con los virus de Epstein Barr y Herpes-8 AIDS related lymphomas: Histopathological subtypes and association with Epstein Barr virus and Human Herpes virus type-8

    Directory of Open Access Journals (Sweden)

    Marcelo Corti

    2010-04-01

    Full Text Available Los linfomas no Hodgkin (LNH constituyen la segunda neoplasia definitoria de Sida más frecuente. En el presente trabajo se evaluaron 48 casos de linfomas asociados con la enfermedad debida al virus de la inmunodeficiencia humana (HIV diagnosticados en la División Histopatología del Instituto de Investigaciones Hematológicas de la Academia Nacional de Medicina. Se incluyeron en la investigación 5 mujeres y 43 hombres con una mediana de edad al momento del diagnóstico de la neoplasia de 37 años. La evaluación morfológica se realizó en cortes coloreados con hematoxilina-eosina, estudio inmunohistoquímico para la detección del virus de Epstein Barr (VEB en 48/48 casos, y mediante sonda oligonucleotídica biotinilada para la detección del ADN del Herpes virus humano tipo-8 (HHV-8 en 14/14 linfomas plasmoblásticos (LP. Todos fueron linfomas de fenotipo B, con un curso clínico agresivo y enfermedad neoplásica avanzada al momento del diagnóstico. Se pudo demostrar la fuerte asociación del VEB con los linfomas asociados al sida, con frecuencias que variaron según el subtipo histológico: 16/21 (76% para los linfomas difusos de grandes células; 1/3 casos (33% de linfomas de Burkitt y 3/4 (75% en los linfomas primarios del sistema nervioso central. Globalmente, el genoma del VEB se detectó en 20/28 (71% de las muestras de biopsias de LNH de esta serie. La detección del HHV-8 resultó negativa en los 14 LP. Los linfomas de Hodgkin fueron más frecuentes en varones,18/20 (90%, con un curso clínico agresivo y franco predominio de los subtipos histológicos de peor pronóstico (90% de casos. En estas neoplasias también se comprobó una frecuente asociación patogénica con el VEB (90% de casos.Non-Hodgkin lymphomas (NHL of the B-cell type are the second most common neoplasm among patients with human immunodeficiency virus (HIV infection and AIDS. Here, we evaluated 48 cases of AIDS-related lymphomas (ARL diagnosed at the

  12. Reverse genetics of measles virus and resulting multivalent recombinant vaccines: applications of recombinant measles viruses.

    Science.gov (United States)

    Billeter, M A; Naim, H Y; Udem, S A

    2009-01-01

    An overview is given on the development of technologies to allow reverse genetics of RNA viruses, i.e., the rescue of viruses from cDNA, with emphasis on nonsegmented negative-strand RNA viruses (Mononegavirales), as exemplified for measles virus (MV). Primarily, these technologies allowed site-directed mutagenesis, enabling important insights into a variety of aspects of the biology of these viruses. Concomitantly, foreign coding sequences were inserted to (a) allow localization of virus replication in vivo through marker gene expression, (b) develop candidate multivalent vaccines against measles and other pathogens, and (c) create candidate oncolytic viruses. The vector use of these viruses was experimentally encouraged by the pronounced genetic stability of the recombinants unexpected for RNA viruses, and by the high load of insertable genetic material, in excess of 6 kb. The known assets, such as the small genome size of the vector in comparison to DNA viruses proposed as vectors, the extensive clinical experience of attenuated MV as vaccine with a proven record of high safety and efficacy, and the low production cost per vaccination dose are thus favorably complemented.

  13. Operator aids for prediction of source term attenuation

    International Nuclear Information System (INIS)

    Powers, D.A.

    2004-01-01

    Simplified expressions for the attenuation of radionuclide releases by sprays and by water pools are devised. These expressions are obtained by correlation of the 10th, 50th and 90th percentiles of uncertainty distributions for the water pool decontamination factor and the spray decontamination coefficient. These uncertainty distributions were obtained by Monte Carlo uncertainty analyses using detailed, mechanistic models of the pools and sprays. Uncertainties considered in the analyses include uncertainties in the phenomena and uncertainties in the initial and boundary conditions dictated by the progression of severe accidents. Final results are graphically displayed in terms of the decontamination factor achieved at selected levels of conservatism versus pool depth and water subcooling or, in the case of sprays, versus time. (author)

  14. Establishment of a high production system for AIDS retroviruses with a human T-leukemic cell line Molt-4

    International Nuclear Information System (INIS)

    Koyanagi, Yoshio; Harada, Shinji; Yamamoto, Naoki

    1986-01-01

    A cell culture system was developed for the continuous and efficient production of acquired immune deficiency syndrome (AIDS) retrovirus. After infection of a human T-cell line Molt-4 with HTLV-III and LAV the cells grow permanently and produce large amounts of virus continuously. The yields of production of virus were assessed either with reverse transcriptase activity or a newly established biological quantitation assay of active virus. The amounts of virus with this cell system were much higher than those of the H9 cell system. This procedure enabled us first to compare the two viral isolates HTLV-III and LAV directly in the same cell lines. Establishment of the culture system, allowing efficient production of AIDS retroviruses, provides a useful tool for the isolation of the virus from patients with AIDS and for more basic research, such as the mechanisms of immune destruction caused by the virus leading to the occurence of various malignancies (author)

  15. Is a picture worth a thousand words? The interaction of visual display and attribute representation in attenuating framing bias}

    OpenAIRE

    Eyal Gamliel; Hamutal Kreiner

    2013-01-01

    The attribute framing bias is a well-established phenomenon, in which an object or an event is evaluated more favorably when presented in a positive frame such as ``the half full glass'' than when presented in the complementary negative framing. Given that previous research showed that visual aids can attenuate this bias, the current research explores the factors underlying the attenuating effect of visual aids. In a series of three experiments, we examined how attribute framing bias is affec...

  16. [Origin and evolution of human immunodeficiency viruses].

    Science.gov (United States)

    Marian, Constantin V

    2009-01-01

    After the diagnosis of the AIDS symptoms, in 1981, and after the discovery of the virus that causes AIDS, in 1983, the virologists have formulated different theories about its origin. Some of them involved natural causes, e.g., HIV origin from SIV strains. Other theories go further to the possibility of a deadly man-made virus escaped from laboratories or voluntary spread by some conspirative organisations. At this moment, the scientists limits themselves to search proofs to sustain the zoonotic origin of HIV from SIV and its accomodation to human body conditions.

  17. The cytoprotective enzyme heme oxygenase-1 suppresses Ebola virus replication.

    Science.gov (United States)

    Hill-Batorski, Lindsay; Halfmann, Peter; Neumann, Gabriele; Kawaoka, Yoshihiro

    2013-12-01

    Ebola virus (EBOV) is the causative agent of a severe hemorrhagic fever in humans with reported case fatality rates as high as 90%. There are currently no licensed vaccines or antiviral therapeutics to combat EBOV infections. Heme oxygenase-1 (HO-1), an enzyme that catalyzes the rate-limiting step in heme degradation, has antioxidative properties and protects cells from various stresses. Activated HO-1 was recently shown to have antiviral activity, potently inhibiting the replication of viruses such as hepatitis C virus and human immunodeficiency virus. However, the effect of HO-1 activation on EBOV replication remains unknown. To determine whether the upregulation of HO-1 attenuates EBOV replication, we treated cells with cobalt protoporphyrin (CoPP), a selective HO-1 inducer, and assessed its effects on EBOV replication. We found that CoPP treatment, pre- and postinfection, significantly suppressed EBOV replication in a manner dependent upon HO-1 upregulation and activity. In addition, stable overexpression of HO-1 significantly attenuated EBOV growth. Although the exact mechanism behind the antiviral properties of HO-1 remains to be elucidated, our data show that HO-1 upregulation does not attenuate EBOV entry or budding but specifically targets EBOV transcription/replication. Therefore, modulation of the cellular enzyme HO-1 may represent a novel therapeutic strategy against EBOV infection.

  18. Dermatology and HIV/AIDS in Africa

    Directory of Open Access Journals (Sweden)

    Jenny Hu

    2011-01-01

    Full Text Available Human immunodeficiency virus and the acquired immunodeficiency syndrome (HIV/AIDS have greatly complicated dermatologic disease and the required care in most regions of Africa. Opportunistic infections, ectoparasites, Kaposi sarcoma, and skin manifestations of systemic infections are exceedingly common in patients with HIV/AIDS. Dermatologists have contributed significantly to our knowledge base about HIV/AIDS and have played an important educational role regarding the clinical manifestations historically. Because of the increased burden of skin disease in Africa due to the HIV/AIDS epidemic we must redouble our efforts to provide dermatology education to care providers in Africa. We review the burden of skin disease in Africa, how it relates to HIV/AIDS and global infectious disease, current educational strategies in Africa to address this need, and suggest potential solutions to move these efforts forward.

  19. Human immunodeficiency virus-associated disruption of mucosal barriers and its role in HIV transmission and pathogenesis of HIV/AIDS disease

    Science.gov (United States)

    Tugizov, Sharof

    2016-01-01

    Abstract Oral, intestinal and genital mucosal epithelia have a barrier function to prevent paracellular penetration by viral, bacterial and other pathogens, including human immunodeficiency virus (HIV). HIV can overcome these barriers by disrupting the tight and adherens junctions of mucosal epithelia. HIV-associated disruption of epithelial junctions may also facilitate paracellular penetration and dissemination of other viral pathogens. This review focuses on possible molecular mechanisms of HIV-associated disruption of mucosal epithelial junctions and its role in HIV transmission and pathogenesis of HIV and acquired immune deficiency syndrome (AIDS). PMID:27583187

  20. Attenuated Salmonella enterica Serovar Typhi and Shigella flexneri 2a Strains Mucosally Deliver DNA Vaccines Encoding Measles Virus Hemagglutinin, Inducing Specific Immune Responses and Protection in Cotton Rats

    OpenAIRE

    Pasetti, Marcela F.; Barry, Eileen M.; Losonsky, Genevieve; Singh, Mahender; Medina-Moreno, Sandra M.; Polo, John M.; Ulmer, Jeffrey; Robinson, Harriet; Sztein, Marcelo B.; Levine, Myron M.

    2003-01-01

    Measles remains a leading cause of child mortality in developing countries. Residual maternal measles antibodies and immunologic immaturity dampen immunogenicity of the current vaccine in young infants. Because cotton rat respiratory tract is susceptible to measles virus (MV) replication after intranasal (i.n.) challenge, this model can be used to assess the efficacy of MV vaccines. Pursuing a new measles vaccine strategy that might be effective in young infants, we used attenuated Salmonella...

  1. An attenuated herpes simplex virus type 1 (HSV1 encoding the HIV-1 Tat protein protects mice from a deadly mucosal HSV1 challenge.

    Directory of Open Access Journals (Sweden)

    Mariaconcetta Sicurella

    Full Text Available Herpes simplex virus types 1 and 2 (HSV1 and HSV2 are common infectious agents in both industrialized and developing countries. They cause recurrent asymptomatic and/or symptomatic infections, and life-threatening diseases and death in newborns and immunocompromised patients. Current treatment for HSV relies on antiviral medications, which can halt the symptomatic diseases but cannot prevent the shedding that occurs in asymptomatic patients or, consequently, the spread of the viruses. Therefore, prevention rather than treatment of HSV infections has long been an area of intense research, but thus far effective anti-HSV vaccines still remain elusive. One of the key hurdles to overcome in anti-HSV vaccine development is the identification and effective use of strategies that promote the emergence of Th1-type immune responses against a wide range of epitopes involved in the control of viral replication. Since the HIV1 Tat protein has several immunomodulatory activities and increases CTL recognition of dominant and subdominant epitopes of heterologous antigens, we generated and assayed a recombinant attenuated replication-competent HSV1 vector containing the tat gene (HSV1-Tat. In this proof-of-concept study we show that immunization with this vector conferred protection in 100% of mice challenged intravaginally with a lethal dose of wild-type HSV1. We demonstrate that the presence of Tat within the recombinant virus increased and broadened Th1-like and CTL responses against HSV-derived T-cell epitopes and elicited in most immunized mice detectable IgG responses. In sharp contrast, a similarly attenuated HSV1 recombinant vector without Tat (HSV1-LacZ, induced low and different T cell responses, no measurable antibody responses and did not protect mice against the wild-type HSV1 challenge. These findings strongly suggest that recombinant HSV1 vectors expressing Tat merit further investigation for their potential to prevent and/or contain HSV1

  2. An attenuated herpes simplex virus type 1 (HSV1) encoding the HIV-1 Tat protein protects mice from a deadly mucosal HSV1 challenge.

    Science.gov (United States)

    Sicurella, Mariaconcetta; Nicoli, Francesco; Gallerani, Eleonora; Volpi, Ilaria; Berto, Elena; Finessi, Valentina; Destro, Federica; Manservigi, Roberto; Cafaro, Aurelio; Ensoli, Barbara; Caputo, Antonella; Gavioli, Riccardo; Marconi, Peggy C

    2014-01-01

    Herpes simplex virus types 1 and 2 (HSV1 and HSV2) are common infectious agents in both industrialized and developing countries. They cause recurrent asymptomatic and/or symptomatic infections, and life-threatening diseases and death in newborns and immunocompromised patients. Current treatment for HSV relies on antiviral medications, which can halt the symptomatic diseases but cannot prevent the shedding that occurs in asymptomatic patients or, consequently, the spread of the viruses. Therefore, prevention rather than treatment of HSV infections has long been an area of intense research, but thus far effective anti-HSV vaccines still remain elusive. One of the key hurdles to overcome in anti-HSV vaccine development is the identification and effective use of strategies that promote the emergence of Th1-type immune responses against a wide range of epitopes involved in the control of viral replication. Since the HIV1 Tat protein has several immunomodulatory activities and increases CTL recognition of dominant and subdominant epitopes of heterologous antigens, we generated and assayed a recombinant attenuated replication-competent HSV1 vector containing the tat gene (HSV1-Tat). In this proof-of-concept study we show that immunization with this vector conferred protection in 100% of mice challenged intravaginally with a lethal dose of wild-type HSV1. We demonstrate that the presence of Tat within the recombinant virus increased and broadened Th1-like and CTL responses against HSV-derived T-cell epitopes and elicited in most immunized mice detectable IgG responses. In sharp contrast, a similarly attenuated HSV1 recombinant vector without Tat (HSV1-LacZ), induced low and different T cell responses, no measurable antibody responses and did not protect mice against the wild-type HSV1 challenge. These findings strongly suggest that recombinant HSV1 vectors expressing Tat merit further investigation for their potential to prevent and/or contain HSV1 infection and

  3. AIDS in the developing countries.

    Science.gov (United States)

    Tinker, J

    1988-01-01

    Without a medical miracle, it seems inevitable that the Acquired Immune Deficiency Syndrome (AIDS) pandemic will become not only the most serious public health problem of this generation but a dominating issue in 3rd world development. As a present-day killer, AIDS in developing countries is insignificant compared to malaria, tuberculosis, or infant diarrhea, but this number is misleading in 3 ways. First, it fails to reflect the per capita rate of AIDS cases. On this basis, Bermuda, French Guyana, and the Bahamas have much higher rates than the US. Second, there is extensive underreporting of AIDS cases in most developing nations. Finally, the number of AIDS cases indicates where the epidemic was 5-7 years ago, when these people became infected. Any such projections of the growth of 3rd world AIDS epidemics are at this time based on epidemiologic data from the industrialized rations of the north and on the assumption that the virus acts similarly in the south as it does in the US and Europe. Yet, 3rd world conditions differ. Sexually transmitted diseases usually are more prevalent, and people have a different burden of other diseases and of other stresses to the immune system. In Africa, AIDS already is heavily affecting the mainstream population in some nations. Some regions will approach net population declines over the next decade. How far their populations eventually could decline because of AIDS is unclear and will depend crucially on countermeasures taken or not taken over the next 1-2 years. In purely economic terms, AIDS will affect the direct costs of health care, expenses which are unrealistic for most 3rd world countries. Further, the vast majority of deaths from AIDS in developing countries will occur among those in the sexually active age groups -- the wage earners and food producers. Deaths in this age group also will reduce the labor available for farming and industry. AIDS epidemics also may have significant effects on foreign investment in the 3rd

  4. Is a picture worth a thousand words? The interaction of visual display and attribute representation in attenuating framing bias}

    Directory of Open Access Journals (Sweden)

    Eyal Gamliel

    2013-07-01

    Full Text Available The attribute framing bias is a well-established phenomenon, in which an object or an event is evaluated more favorably when presented in a positive frame such as ``the half full glass'' than when presented in the complementary negative framing. Given that previous research showed that visual aids can attenuate this bias, the current research explores the factors underlying the attenuating effect of visual aids. In a series of three experiments, we examined how attribute framing bias is affected by two factors: (a The display mode---verbal versus visual; and (b the representation of the critical attribute---whether one outcome, either the positive or the negative, is represented or both outcomes are represented. In Experiment 1 a marginal attenuation of attribute framing bias was obtained when verbal description of either positive or negative information was accompanied by corresponding visual representation. In Experiment 2 similar marginal attenuation was obtained when both positive and negative outcomes were verbally represented. In Experiment 3, where the verbal description represented both positive and negative outcomes, significant attenuation was obtained when it was accompanied by a visual display that represented a single outcome, and complete attenuation, totally eliminating the framing bias, was obtained when it was accompanied by a visual display that represented both outcomes. Thus, our findings showed that interaction between the display mode and the representation of the critical attribute attenuated the framing bias. Theoretical and practical implications of the interaction between verbal description, visual aids and representation of the critical attribute are discussed, and future research is suggested.

  5. Prior DNA vaccination does not interfere with the live-attenuated measles vaccine.

    Science.gov (United States)

    Premenko-Lanier, Mary; Rota, Paul; Rhodes, Gary; Bellini, William; McChesney, Michael

    2004-01-26

    The currently used live-attenuated measles vaccine is very effective although maternal antibody prevents its administration prior to 6 months of age. We are investigating the ability of a DNA vaccine encoding the measles viral hemagglutinin, fusion and nucleoprotein to protect newborn infants from measles. Here, we show that a measles DNA vaccine protects juvenile macaques from pathogenic measles virus challenge and that macaques primed and boosted with this DNA vaccine have anemnestic antibody and cell-mediated responses after vaccination with a live-attenuated canine distemper-measles vaccine. Therefore, this DNA vaccine administered to newborn infants may not hinder the subsequent use of live-attenuated measles vaccine.

  6. Ebola virus disease in a humanitarian aid worker - New York City, October 2014.

    Science.gov (United States)

    Yacisin, Kari; Balter, Sharon; Fine, Annie; Weiss, Don; Ackelsberg, Joel; Prezant, David; Wilson, Ross; Starr, David; Rakeman, Jennifer; Raphael, Marisa; Quinn, Celia; Toprani, Amita; Clark, Nancy; Link, Nathan; Daskalakis, Demetre; Maybank, Aletha; Layton, Marcelle; Varma, Jay K

    2015-04-03

    In late October 2014, Ebola virus disease (Ebola) was diagnosed in a humanitarian aid worker who recently returned from West Africa to New York City (NYC). The NYC Department of Health and Mental Hygiene (DOHMH) actively monitored three close contacts of the patient and 114 health care personnel. No secondary cases of Ebola were detected. In collaboration with local and state partners, DOHMH had developed protocols to respond to such an event beginning in July 2014. These protocols included safely transporting a person at the first report of symptoms to a local hospital prepared to treat a patient with Ebola, laboratory testing for Ebola, and monitoring of contacts. In response to this single case of Ebola, initial health care worker active monitoring protocols needed modification to improve clarity about what types of exposure should be monitored. The response costs were high in both human resources and money: DOHMH alone spent $4.3 million. However, preparedness activities that include planning and practice in effectively monitoring the health of workers involved in Ebola patient care can help prevent transmission of Ebola.

  7. Live Attenuated Recombinant Vaccine Protects Nonhuman Primates Against Ebola and Marburg Viruses

    National Research Council Canada - National Science Library

    Jones, Steven M; Feldmann, Heinz; Stroher, Ute; Geisbert, Joan B; Fernando, Lisa; Grolla, Allen; Klenk, Hans-Dieter; Sullivan, Nancy J; Volchkov, Viktor E; Fritz, Elizabeth A; Daddario, Kathleen M; Hensley, Lisa E; Jahrling, Peter B; Geisbert, Thomas W

    2005-01-01

    Vaccines and therapies are urgently needed to address public health needs stemming from emerging pathogens and biological threat agents such as the filoviruses Ebola virus (EBOV) and Marburg virus (MARV...

  8. Experimental inoculation of late term pregnant sows with a field isolate of porcine reproductive and respiratory syndrome vaccine-derived virus

    DEFF Research Database (Denmark)

    Nielsen, Jens; Bøtner, Anette; Bille-Hansen, Vivi

    2002-01-01

    The use of a live attenuated porcine reproductive and respiratory syndrome virus (PRRSV) vaccine in piglets has been associated with reproductive disorders in non-vaccinated sows. Vaccine-derived virus (VDV) has been isolated from foctuses, stillborn pigs, and dead: piglets, indicating that the l......The use of a live attenuated porcine reproductive and respiratory syndrome virus (PRRSV) vaccine in piglets has been associated with reproductive disorders in non-vaccinated sows. Vaccine-derived virus (VDV) has been isolated from foctuses, stillborn pigs, and dead: piglets, indicating...... than 99.6% identity to the attenuated vaccine virus, originated from the lungs of a stillborn pig from a swine herd with a sudden high level of stillborn pigs and increased piglet mortality in the nursing period. Intranasal inoculation of sows with the virus isolate resulted in congenital infection......, foetal death, and preweaning pig mortality. As such, the present study showed that vaccine-derived PRRSV can cause disease in swine consistent with PRRS....

  9. A recombinant canine distemper virus expressing a modified rabies virus glycoprotein induces immune responses in mice.

    Science.gov (United States)

    Li, Zhili; Wang, Jigui; Yuan, Daoli; Wang, Shuang; Sun, Jiazeng; Yi, Bao; Hou, Qiang; Mao, Yaping; Liu, Weiquan

    2015-06-01

    Canine distemper virus (CDV) and rabies virus (RV) are two important pathogens of the dog. CDV, a member of the morbillivirus genus, has shown promise as an expression vector. The glycoprotein from RV is a main contributor to protective immunity and capable of eliciting the production of virus-neutralizing antibodies. In this study, we recovered an attenuated strain of canine distemper virus and constructed a recombinant virus, rCDV-RV-G, expressing a modified (R333Q) rabies virus glycoprotein (RV-G) of RV Flury strain LEP. RV-G expression by the recombinant viruses was confirmed. Furthermore, G was proved to be incorporated into the surface of CDV particles. While replication of the recombinant virus was slightly reduced compared with the parental CDV, it stably expressed the RV-G over ten serial passages. Inoculation of mice induced specific neutralizing antibodies against both RV-G and CDV. Therefore, the rCDV-RV-G has the potential as a vaccine that may be used to control rabies virus infection in dogs and other animals.

  10. AIDS: It's Not What You Know, It's What You Do.

    Science.gov (United States)

    Hochhauser, Mark

    This document reviews five psychological domains of prevention of the behavioral disease of Acquired Immune Deficiency Syndrome (AIDS). First the limits of AIDS education are discussed, noting that increasing amounts of education will not necessarily reduce the spread of the virus, since information and education do not control behavior. Research…

  11. Disruption of M-T5, a novel myxoma virus gene member of poxvirus host range superfamily, results in dramatic attenuation of myxomatosis in infected European rabbits.

    Science.gov (United States)

    Mossman, K; Lee, S F; Barry, M; Boshkov, L; McFadden, G

    1996-07-01

    Myxoma virus is a pathogenic poxvirus that induces a lethal myxomatosis disease profile in European rabbits, which is characterized by fulminating lesions at the primary site of inoculation, rapid dissemination to secondary internal organs and peripheral external sites, and supervening gram-negative bacterial infection. Here we describe the role of a novel myxoma virus protein encoded by the M-T5 open reading frame during pathogenesis. The myxoma virus M-T5 protein possesses no significant sequence homology to nonviral proteins but is a member of a larger poxviral superfamily designated host range proteins. An M-T5- mutant virus was constructed by disruption of both copies of the M-T5 gene followed by insertion of the selectable marker p7.5Ecogpt. Although the M-T5- deletion mutant replicated with wild-type kinetics in rabbit fibroblasts, infection of a rabbit CD4+ T-cell line (RL5) with the myxoma virus M-T5- mutant virus resulted in the rapid and complete cessation of both host and viral protein synthesis, accompanied by the manifestation of all the classical features of programmed cell death. Infection of primary rabbit peripheral mononuclear cells with the myxoma virus M-T5-mutant virus resulted in the apoptotic death of nonadherent lymphocytes but not adherent monocytes. Within the European rabbit, disruption of the M-T5 open reading frame caused a dramatic attenuation of the rapidly lethal myxomatosis infection, and none of the infected rabbits displayed any of the characteristic features of myxomatosis. The two most significant histological observations in rabbits infected with the M-T5-mutant virus were (i) the lack of progression of the infection past the primary site of inoculation, coupled with the establishment of a rapid and effective inflammatory reaction, and (ii) the inability of the virus to initiate a cellular reaction within secondary immune organs. We conclude that M-T5 functions as a critical virulence factor by allowing productive infection of

  12. Bone Marrow-Derived Mesenchymal Stem Cells Attenuate Immune-Mediated Liver Injury and Compromise Virus Control During Acute Hepatitis B Virus Infection in Mice.

    Science.gov (United States)

    Qu, Mengmeng; Yuan, Xu; Liu, Dan; Ma, Yuhong; Zhu, Jun; Cui, Jun; Yu, Mengxue; Li, Changyong; Guo, Deyin

    2017-06-01

    Mesenchymal stem cells (MSCs) have been used as therapeutic tools not only for their ability to differentiate toward different cells, but also for their unique immunomodulatory properties. However, it is still unknown how MSCs may affect immunity during hepatitis B virus (HBV) infection. This study was designed to explore the effect of bone marrow-derived MSCs (BM-MSCs) on hepatic natural killer (NK) cells in a mouse model of acute HBV infection. Mice were injected with 1 × 10 6 BM-MSCs, which stained with chloromethyl derivatives of fluorescein diacetate fluorescent probe, 24 h before hydrodynamic injection of viral DNA (pHBV1.3) through the tail vein. In vivo imaging system revealed that BM-MSCs were accumulated in the injured liver, and they attenuated immune-mediated liver injury during HBV infection, as shown by lower alanine aminotransferase levels, reduced proinflammatory cytokine production, and decreased inflammatory cell infiltration in the liver. Importantly, administration of BM-MSCs restrained the increased expression of natural-killer group 2, member D (NKG2D), an important receptor required for NK cell activation in the liver from HBV-infected mice. BM-MSCs also reduced NKG2D expression on NK cells and suppressed the cytotoxicity of NK cells in vitro. Furthermore, BM-MSC-derived transforming growth factor-β1 suppressed NKG2D expression on NK cells. As a consequence, BM-MSC treatment enhanced HBV gene expression and replication in vivo. These results demonstrate that adoptive transfer of BM-MSCs influences innate immunity and limits immune-mediated liver injury during acute HBV infection by suppressing NK cell activity. Meanwhile, the effect of BM-MSCs on prolonging virus clearance needs to be considered in the future.

  13. Rational design of a live attenuated dengue vaccine: 2'-o-methyltransferase mutants are highly attenuated and immunogenic in mice and macaques.

    Directory of Open Access Journals (Sweden)

    Roland Züst

    Full Text Available Dengue virus is transmitted by Aedes mosquitoes and infects at least 100 million people every year. Progressive urbanization in Asia and South-Central America and the geographic expansion of Aedes mosquito habitats have accelerated the global spread of dengue, resulting in a continuously increasing number of cases. A cost-effective, safe vaccine conferring protection with ideally a single injection could stop dengue transmission. Current vaccine candidates require several booster injections or do not provide protection against all four serotypes. Here we demonstrate that dengue virus mutants lacking 2'-O-methyltransferase activity are highly sensitive to type I IFN inhibition. The mutant viruses are attenuated in mice and rhesus monkeys and elicit a strong adaptive immune response. Monkeys immunized with a single dose of 2'-O-methyltransferase mutant virus showed 100% sero-conversion even when a dose as low as 1,000 plaque forming units was administrated. Animals were fully protected against a homologous challenge. Furthermore, mosquitoes feeding on blood containing the mutant virus were not infected, whereas those feeding on blood containing wild-type virus were infected and thus able to transmit it. These results show the potential of 2'-O-methyltransferase mutant virus as a safe, rationally designed dengue vaccine that restrains itself due to the increased susceptibility to the host's innate immune response.

  14. Live attenuated hepatitis A vaccines developed in China

    Science.gov (United States)

    Xu, Zhi-Yi; Wang, Xuan-Yi

    2014-01-01

    Two live, attenuated hepatitis A vaccines, H2 and LA-1 virus strains, were developed through serial passages of the viruses in cell cultures at 32 °C and 35 °C respectively. Both vaccines were safe and immunogenic, providing protection against clinical hepatitis A in 95% of the vaccinees, with a single dose by subcutaneous injection. The vaccine recipients were not protected from asymptomatic, subclinical hepatitis A virus (HAV) infection, which induced a similar antibody response as for unvaccinated subjects. A second dose caused anamnestic response and can be used for boosting. Oral immunization of human with H2 vaccine or of marmoset with LA-1 vaccine failed, and no evidence was found for person-to-person transmission of H2 strain or for marmoset-to-marmoset transmission of LA-1 strain by close contact. H2 strain was genetically stable when passaged in marmosets, humans or cell cultures at 37 °C; 3 consecutive passages of the virus in marmosets did not cause virulence mutation. The live vaccines offer the benefits of low cost, single dose injection, long- term protection, and increased duration of immunity through subclinical infection. Improved sanitation and administration of 150 million doses of the live vaccines to children had led to a 90% reduction in the annual national incidence rate of hepatitis A in China during the 16-year period, from 1991 to 2006. Hepatitis A (HA) immunization with both live and inactivated HA vaccines was implemented in the national routine childhood immunization program in 2008 and around 92% of the 16 million annual births received the affordable live, attenuated vaccines at 18 months of age. Near elimination of the disease was achieved in a county of China for 14 years following introduction of the H2 live vaccine into the Expanded Immunization Program (EPI) in 1992. PMID:24280971

  15. Detection of rainbow trout antibodies against viral haemorrhagic septicaemia virus (VHSV) by neutralisation test is highly dependent on the virus isolate used

    DEFF Research Database (Denmark)

    Fregeneda-Grandes, J.M.; Olesen, Niels Jørgen

    2007-01-01

    with VHS but with no clinical signs of infection. When the sera were examined by 50%PNT using the VHSV reference isolate DK-F1 or the heat attenuated DK-F25 mutant strain, no neutralizing antibodies were found. In contrast, when one of the virus isolates from the farm (homologous virus) was used in the 50...

  16. The origins of AIDS

    National Research Council Canada - National Science Library

    Pepin, Jacques

    2011-01-01

    ... urbanisation, prostitution and large-scale colonial medical campaigns intended to eradicate tropical diseases combined to disastrous effect to fuel the spread of the virus from its origins in Léopoldville to the rest of Africa, the Caribbean and ultimately worldwide. This is an essential new perspective on HIV/ AIDS and on the lessons that must be learned if we are to avoi...

  17. The health literacy needs of women living with HIV/AIDS

    Directory of Open Access Journals (Sweden)

    Judy Thompson

    2015-10-01

    Full Text Available Women in Sub-Saharan Africa are disproportionately affected by the virus and constitute 60% of the total HIV/AIDS infections in this region. Current recommendations endorse the involvement of people living with HIV in the development of programmes for people living with the virus. The purpose of the study was to explore and describe the health literacy needs of women living with HIV. The research design was qualitative, explorative, descriptive and contextual. After women living with HIV/AIDS were sampled purposively, semi-structured interviews were conducted with eight women and qualitative content analysis done. The findings revealed that the women expressed a need to increase their knowledge about HIV/AIDS. The knowledge they needed ranged from basic pathophysiology about HIV/AIDS, to the impact of HIV/AIDS on their health, to an awareness of the modes of HIV transmission and methods of protecting others from being infected. Other important health literacy needs related to self-care and correct antiretroviral use. A need for psychosocial skills was also identified in order for women to build and maintain their relationships. Recommendations were made for nursing practice, education and further research, based on these findings.

  18. Prevalence of human immunodeficiency virus (HIV) infection among ...

    African Journals Online (AJOL)

    AJB SERVER

    2007-02-05

    Feb 5, 2007 ... ... virus (HIV) was disco- vered in 1983 (two years after the diseases AIDS was ... de this lipid bilayer is a matrix (MA) protein (p17). Below the matrix is ... conformational changes in the viral envelope to permit virus-cell fusion.

  19. Opportunistic infections and malignancies in 231 Danish AIDS patients

    DEFF Research Database (Denmark)

    Pedersen, C; Gerstoft, J; Tauris, P

    1990-01-01

    diseases caused by cytomegalovirus and atypical mycobacteria tended to occur later in the course of AIDS. Compared with all other AIDS patients, homosexual men were more likely to develop Kaposi's sarcoma, cytomegalovirus chorioretinitis and mucocutaneous herpes simplex virus infection. The proportion......We analysed cumulative disease frequencies in the first 231 adult Danish AIDS patients with life tables. There was a certain hierarchical pattern in the occurrence of complicating diseases. Herpes zoster, Kaposi's sarcoma and Pneumocystis carinii pneumonia were early manifestations, whereas...

  20. Use of tissue-specific microRNA to control pathology of wild-type adenovirus without attenuation of its ability to kill cancer cells.

    Science.gov (United States)

    Cawood, Ryan; Chen, Hannah H; Carroll, Fionnadh; Bazan-Peregrino, Miriam; van Rooijen, Nico; Seymour, Leonard W

    2009-05-01

    Replicating viruses have broad applications in biomedicine, notably in cancer virotherapy and in the design of attenuated vaccines; however, uncontrolled virus replication in vulnerable tissues can give pathology and often restricts the use of potent strains. Increased knowledge of tissue-selective microRNA expression now affords the possibility of engineering replicating viruses that are attenuated at the RNA level in sites of potential pathology, but retain wild-type replication activity at sites not expressing the relevant microRNA. To assess the usefulness of this approach for the DNA virus adenovirus, we have engineered a hepatocyte-safe wild-type adenovirus 5 (Ad5), which normally mediates significant toxicity and is potentially lethal in mice. To do this, we have included binding sites for hepatocyte-selective microRNA mir-122 within the 3' UTR of the E1A transcription cassette. Imaging versions of these viruses, produced by fusing E1A with luciferase, showed that inclusion of mir-122 binding sites caused up to 80-fold decreased hepatic expression of E1A following intravenous delivery to mice. Animals administered a ten-times lethal dose of wild-type Ad5 (5x10(10) viral particles/mouse) showed substantial hepatic genome replication and extensive liver pathology, while inclusion of 4 microRNA binding sites decreased replication 50-fold and virtually abrogated liver toxicity. This modified wild-type virus retained full activity within cancer cells and provided a potent, liver-safe oncolytic virus. In addition to providing many potent new viruses for cancer virotherapy, microRNA control of virus replication should provide a new strategy for designing safe attenuated vaccines applied across a broad range of viral diseases.

  1. Type III Interferon-Mediated Signaling Is Critical for Controlling Live Attenuated Yellow Fever Virus Infection In Vivo

    Directory of Open Access Journals (Sweden)

    Florian Douam

    2017-08-01

    Full Text Available Yellow fever virus (YFV is an arthropod-borne flavivirus, infecting ~200,000 people worldwide annually and causing about 30,000 deaths. The live attenuated vaccine strain, YFV-17D, has significantly contributed in controlling the global burden of yellow fever worldwide. However, the viral and host contributions to YFV-17D attenuation remain elusive. Type I interferon (IFN-α/β signaling and type II interferon (IFN-γ signaling have been shown to be mutually supportive in controlling YFV-17D infection despite distinct mechanisms of action in viral infection. However, it remains unclear how type III IFN (IFN-λ integrates into this antiviral system. Here, we report that while wild-type (WT and IFN-λ receptor knockout (λR−/− mice were largely resistant to YFV-17D, deficiency in type I IFN signaling resulted in robust infection. Although IFN-α/β receptor knockout (α/βR−/− mice survived the infection, mice with combined deficiencies in both type I signaling and type III IFN signaling were hypersusceptible to YFV-17D and succumbed to the infection. Mortality was associated with viral neuroinvasion and increased permeability of the blood-brain barrier (BBB. α/βR−/− λR−/− mice also exhibited distinct changes in the frequencies of multiple immune cell lineages, impaired T-cell activation, and severe perturbation of the proinflammatory cytokine balance. Taken together, our data highlight that type III IFN has critical immunomodulatory and neuroprotective functions that prevent viral neuroinvasion during active YFV-17D replication. Type III IFN thus likely represents a safeguard mechanism crucial for controlling YFV-17D infection and contributing to shaping vaccine immunogenicity.

  2. New Animal Model Could Boost Research on AIDS Drugs and Vaccines | FNLCR

    Science.gov (United States)

    In a research milestone reported in the June 20 issue of the journal Science, scientists have developed a minimally modified version of HIV-1, the virus that causes AIDS in infected humans, that is capable of causing progressive infection and AIDS i

  3. Selection and Characterization of Drug-Resistant Variants of Human Immunodeficiency Virus (AIDS).

    Science.gov (United States)

    1995-10-01

    on Antiviral Reserach, Santa Fe, New Mexico , 1995. Page 18 APPENDIX Page 19 p - FACTFILE Mutations in HIV-1 Reverse Transcriptase and Protease...including herpes simplex viruses, varicella -zoster Resistance of clinical HIV-1 isolates to foscarnet has not virus, cytomegalovirus (CMV), hepatitis B...This effect of the Tyr-208 substitution was not ob- reported previously for herpes simplex viruses, varicella -zoster served in MT-2 cells, however. virus

  4. Public Knowledge about HIV / AIDS: A survey of Dental School ...

    African Journals Online (AJOL)

    Results: The study revealed that 90% of the respondents knew what AIDS was and how to protect themselves against the virus but only 58% rated their knowledge as being a lot. The highly educated had lower scores in ... More males (98%) than females (84%) wanted to know more about AIDS. Conclusion: Knowledge of ...

  5. Education about HIV/AIDS--Theoretical Underpinnings for a Practical Response

    Science.gov (United States)

    Miedema, Esther A. J.; Maxwell, Claire; Aggleton, Peter

    2011-01-01

    Human immunodeficiency virus (HIV)- and acquired immunodeficiency syndrome (AIDS)-related education is seen by many as central to increasing young people's awareness of, as well as decreasing their vulnerability to, HIV. There is less agreement, however, on the central goals of HIV- and AIDS-related education and the form it might best take. This…

  6. Differences in gay men's AIDS risk knowledge and behavior patterns in high and low AIDS prevalence cities.

    Science.gov (United States)

    St Lawrence, J S; Hood, H V; Brasfield, T; Kelly, J A

    1989-01-01

    Several studies have found reductions in acquired immunodeficiency syndrome (AIDS) risk practices among gay men in high AIDS-prevalence cities since the start of the AIDS crisis. Much less is known about risk behavior patterns among gay men in smaller cities, where AIDS cases are less common and the prevalence of human immunodeficiency virus infection is relatively lower. In the study, men entering gay bars in three cities, one large and two small, completed anonymous surveys of sexual practices and AIDS risk knowledge. Men in high AIDS-prevalence areas were found to have had a greater number of sexual partners, were more knowledgeable about AIDS, were much more likely to engage in low-risk practices (such as mutual masturbation or body rubbing), and had unprotected anal intercourse less frequently than gay men in smaller cities. The most common sexual activity among gay men in the larger city was mutual masturbation, a low-risk practice. The most common sexual activity among gay men in the smaller cities was unprotected anal intercourse. Increased efforts are needed to educate gay men and to promote risk behavior changes among those living in smaller cities and in communities outside the prominent AIDS epicenters.

  7. Older Americans and AIDS: Transmission Risks and Primary Prevention Research Needs.

    Science.gov (United States)

    Catania, Joseph A.; And Others

    1989-01-01

    Growing number of Acquired Immune Deficiency Syndrome (AIDS) cases among older Americans is of increasing concern. In context of primary prevention, reviews findings that bear on modes of human immunodeficiency virus (HIV) transmission (blood transfusions, sexual) among older individuals and knowledge of magnitude of the AIDS problem represented…

  8. Family Structure and Functions Identified by Persons Living with HIV/AIDS.

    Science.gov (United States)

    Wong-Wylie, Gina; Doherty-Poirier, Maryanne; Kieren, Dianne

    1999-01-01

    A study looked at the structural and functional aspects of family from the perspective of six people living with acquired immune deficiency syndrome (AIDS) or human immunodeficiency virus (HIV). Results showing how HIV/AIDS affects all members of the sufferer's family have implications for family practitioners. (Author/JOW)

  9. Burden of non-AIDS-defining and non-virus-related cancers among HIV-infected patients in the combined antiretroviral therapy era.

    Science.gov (United States)

    Albini, Laura; Calabresi, Alessandra; Gotti, Daria; Ferraresi, Alice; Festa, Andrea; Donato, Francesco; Magoni, Michele; Castelli, Francesco; Quiros-Roldan, Eugenia

    2013-08-01

    The risk of cancer is substantially increased in HIV-infected patients. However, little is known about non-AIDS-defining cancers (NADCs) without an infectious etiology. A total of 5,090 HIV-infected patients registered in the Local Health Authority (LHA) of Brescia and receiving primary care at our clinic were included in a retrospective (1999-2009) analysis. The cancer diagnoses were obtained through a record-linkage procedure between our database and the LHA general database and population-based Cancer Registry of LHA. We compared risks of these malignancies with those of the general population living in the same health area by using age-standardized incidence ratios (SIRs). Poisson regression analysis was used to assess factors associated with non-virus-related NADCs. We recorded an increase in the SIR of non-virus-related NADCs over time, with 138 cancers diagnosed in 131 patients. The mean incidence rate was 42.6/10,000 person years and the median age at the diagnosis was 49 (range, 28-78) years old. Stratifying for gender, only HIV-infected males had an increased risk of non-virus-related NADCs [SIR=1.86; 95% confidence interval (CI), 1.55-2.26]. Risk was higher for lung (SIR=3.59; 95% CI, 2.36-5.45) and testis cancer (SIR=3.11; 95% CI, 1.48-6.52). However,, cancers of the prostate and breast in HIV-positive men and women were null (SIR=1.10; 95% CI, 0.53-2.32 and SIR=0.91; 95% CI, 0.47-1.74, respectively). The only predictors of non-virus-related NADCs included older age [incidence rate ratio (IRR)=1.10; 95% CI, 1.08-1.12 per each additional year, prisk of non-virus-related NADCs compared to the general population. However, the use of cART appeared to be beneficial in protecting against the development of these malignancies.

  10. Mechanisms of Cytotoxicity of the Aids Virus

    Science.gov (United States)

    1992-10-10

    Baskin , G.B., Cho, E.-S., Murphey-Corb, Skillman, D., Kalter, D.C., Orenstein, J.M., Hoover, M., Blumberg, B.M. & Epstein, L.G. (1988), Com- D.L...423-6. ciency virus type 1 negative factor (nef) is a transcriptional 20. Clouse KA, Robbins PB, Fernie B, et al. Viral antigen stimu- silencer. Proc

  11. Viral protein synthesis in cowpea mosaic virus infected protoplasts

    International Nuclear Information System (INIS)

    Rottier, P.

    1980-01-01

    Some aspects of cowpea mosaic virus (CPMV) multiplication in cowpea mesophyll protoplasts were studied. The detection and characterization of proteins whose synthesis is induced or is stimulated upon virus infection was performed with the aid of radioactive labelling. (Auth.)

  12. TGF-β Suppression of HBV RNA through AID-Dependent Recruitment of an RNA Exosome Complex

    Science.gov (United States)

    Kitamura, Kouichi; Wang, Zhe; Chowdhury, Sajeda; Monjurul, Ahasan Md; Wakae, Kousho; Koura, Miki; Shimadu, Miyuki; Kinoshita, Kazuo; Muramatsu, Masamichi

    2015-01-01

    Transforming growth factor (TGF)-β inhibits hepatitis B virus (HBV) replication although the intracellular effectors involved are not determined. Here, we report that reduction of HBV transcripts by TGF-β is dependent on AID expression, which significantly decreases both HBV transcripts and viral DNA, resulting in inhibition of viral replication. Immunoprecipitation reveals that AID physically associates with viral P protein that binds to specific virus RNA sequence called epsilon. AID also binds to an RNA degradation complex (RNA exosome proteins), indicating that AID, RNA exosome, and P protein form an RNP complex. Suppression of HBV transcripts by TGF-β was abrogated by depletion of either AID or RNA exosome components, suggesting that AID and the RNA exosome involve in TGF-β mediated suppression of HBV RNA. Moreover, AID-mediated HBV reduction does not occur when P protein is disrupted or when viral transcription is inhibited. These results suggest that induced expression of AID by TGF-β causes recruitment of the RNA exosome to viral RNP complex and the RNA exosome degrades HBV RNA in a transcription-coupled manner. PMID:25836330

  13. Varicella zoster virus vaccines: potential complications and possible improvements.

    Science.gov (United States)

    Silver, Benjamin; Zhu, Hua

    2014-10-01

    Varicella zoster virus (VZV) is the causative agent of varicella (chicken pox) and herpes zoster (shingles). After primary infection, the virus remains latent in sensory ganglia, and reactivates upon weakening of the cellular immune system due to various conditions, erupting from sensory neurons and infecting the corresponding skin tissue. The current varicella vaccine (v-Oka) is highly attenuated in the skin, yet retains its neurovirulence and may reactivate and damage sensory neurons. The reactivation is sometimes associated with postherpetic neuralgia (PHN), a severe pain along the affected sensory nerves that can linger for years, even after the herpetic rash resolves. In addition to the older population that develops a secondary infection resulting in herpes zoster, childhood breakthrough herpes zoster affects a small population of vaccinated children. There is a great need for a neuro-attenuated vaccine that would prevent not only the varicella manifestation, but, more importantly, any establishment of latency, and therefore herpes zoster. The development of a genetically-defined live-attenuated VZV vaccine that prevents neuronal and latent infection, in addition to primary varicella, is imperative for eventual eradication of VZV, and, if fully understood, has vast implications for many related herpesviruses and other viruses with similar pathogenic mechanisms.

  14. The health literacy needs of women living with HIV/AIDS | Thompson ...

    African Journals Online (AJOL)

    Women in Sub-Saharan Africa are disproportionately affected by the virus and constitute 60% of the total HIV/AIDS infections in this region. Current recommendations endorse the involvement of people living with HIV in the development of programmes for people living with the virus. The purpose of the study was to explore ...

  15. Production and immunogenicity of chimeric virus-like particles containing the spike glycoprotein of infectious bronchitis virus.

    Science.gov (United States)

    Lv, Lishan; Li, Xiaoming; Liu, Genmei; Li, Ran; Liu, Qiliang; Shen, Huifang; Wang, Wei; Xue, Chunyi; Cao, Yongchang

    2014-01-01

    Infectious bronchitis virus (IBV) poses a severe threat to the poultry industry and causes heavy economic losses worldwide. Vaccination is the most effective method of preventing infection and controlling the spread of IBV, but currently available inactivated and attenuated virus vaccines have some disadvantages. We developed a chimeric virus-like particle (VLP)-based candidate vaccine for IBV protection. The chimeric VLP was composed of matrix 1 protein from avian influenza H5N1 virus and a fusion protein neuraminidase (NA)/spike 1 (S1) that was generated by fusing IBV S1 protein to the cytoplasmic and transmembrane domains of NA protein of avian influenza H5N1 virus. The chimeric VLPs elicited significantly higher S1-specific antibody responses in intramuscularly immunized mice and chickens than inactivated IBV viruses. Furthermore, the chimeric VLPs induced significantly higher neutralization antibody levels than inactivated H120 virus in SPF chickens. Finally, the chimeric VLPs induced significantly higher IL-4 production in mice. These results demonstrate that chimeric VLPs have the potential for use in vaccines against IBV infection.

  16. On the attenuation of the ambient seismic field

    International Nuclear Information System (INIS)

    Weemstra, C.

    2013-01-01

    Although myriad applications exploiting the ambient seismic field have been reported to date, comparatively little attention has been paid to its potential to resolve subsurface attenuation. The ambient seismic field, however, may ultimately prove itself an invaluable asset in constraining subsurface attenuation structure. Especially areas with dense seismometer coverage hold great potential. Moreover, since this coverage continues to grow, significant developments may await in the future. Subsurface structure in terms of attenuation is of great importance for many reasons. For example, knowledge of the attenuation structure may aid in predicting ground motions caused by future large earthquakes. From a scientific perspective, a great deal of new information may be extracted, potentially fostering research in related fields (e.g., geodynamics, hydrology). Both from an environmental and economic point of view, inversion of the ambient seismic wavefield for attenuation structure may in the future provide a means to image hydrocarbon reservoirs. In sufficiently diffuse wavefields, simple cross-correlation of long noise time series recorded by two receivers results in the response at one of the receivers as if there was a source at the position of the other. I present a case study that shows that thus retrieved surface waves can be used to recover attenuation beneath an array of ocean-bottom seismometers. Given the small aperture of the seismic survey, this is unprecedented. Unambiguous interpretation of recovered attenuation values is of major importance. Lack of understanding of the effect that preprocessing has on the amplitude of the noise cross-correlation prevents such unambiguous interpretation. I carefully examine the effect spectral whitening has on the noise cross-correlation. Emphasis is given to the dependence of the amplitudes on the length of the time windows employed in the cross-correlation procedure. Short time-window lengths may require an additional

  17. Distribution of attenuated goose parvoviruses in Muscovy ducklings.

    Science.gov (United States)

    Takehara, K; Saitoh, M; Kiyono, M; Nakamura, M

    1998-03-01

    With a polymerase chain reaction (PCR) method, goose parvovirus (GPV) DNA was detected in Muscovy ducklings inoculated with attenuated GPV strains, IH and IHC. Strain IH that had been passed 20 times in Muscovy duck embryos could be detected in ducklings at 2- to 28-days after oral inoculation by PCR, however, a cell culture adapted strain IHC that had been passed 15 times in Muscovy duck embryos and then successively 50 times in Muscovy duck embryo fibroblasts could not be detected by 6 days postinoculation by the oral route, but via intramuscular inoculation the virus was detected from 6 dpi. With both strains Muscovy ducklings produced neutralizing antibodies against GPV, but GPV could be recovered from heart muscles even in birds that had high titer of neutralizing antibody. This means that GPV remains in birds for a long period under the presence of high titer of neutralizing antibody in the serum. Recovery of the virus was consistent with PCR results with one exception in which the bird had a neutralizing antibody titer of more than 100,000. After inoculation of these strains, no clinical signs were detected in ducklings. These results suggest that strains IH and IHC can be candidates for live attenuated vaccine for GPV infection.

  18. Development of Recombinant Newcastle Disease Viruses Expressing the Glycoprotein (G) of Avian Metapneumovirus as Bivalent Vaccines

    Science.gov (United States)

    Using reverse genetics technology, Newcastle disease virus (NDV) LaSota strain-based recombinant viruses were engineered to express the glycoprotein (G) of avian metapneumovirus (aMPV), subtype A, B or C, as bivalent vaccines. These recombinant viruses were slightly attenuated in vivo, yet maintaine...

  19. Fatal vaccine-induced canine distemper virus infection in black-footed ferrets

    Science.gov (United States)

    Carpenter, J.W.; Appel, M.J.G.; Erickson, R.C.; Novilla, M.N.

    1976-01-01

    Four black-footed ferrets that were live-trapped in South Dakota and transported to the Patuxent Wildlife Research Center died within 21 days after vaccination with modified live canine distemper virus. Immunofluorescence, European ferret inoculation, virus isolation attempts, and serum-neutralization tests indicated insufficient attenuation of the vaccine for this species.

  20. Neurologic manifestations of human immunodeficiency virus infection in children

    NARCIS (Netherlands)

    Epstein, L. G.; Sharer, L. R.; Oleske, J. M.; Connor, E. M.; Goudsmit, J.; Bagdon, L.; Robert-Guroff, M.; Koenigsberger, M. R.

    1986-01-01

    This report describes the neurologic manifestations of 36 children with human immunodeficiency virus (HIV) infection. In this cohort, in 16 of 21 children with acquired immunodeficiency syndrome (AIDS), three of 12 children with AIDS-related complex, and one of three asymptomatic seropositive

  1. Characterization of sheep pox virus vaccine for cattle against lumpy skin disease virus

    Science.gov (United States)

    Tuppurainen, Eeva S.M.; Pearson, Caroline R.; Bachanek-Bankowska, Katarzyna; Knowles, Nick J.; Amareen, Shadi; Frost, Lorraine; Henstock, Mark R.; Lamien, Charles E.; Diallo, Adama; Mertens, Peter P.C.

    2014-01-01

    Lumpy skin disease is of significant economic impact for the cattle industry in Africa. The disease is currently spreading aggressively in the Near East, posing a threat of incursion to Europe and Asia. Due to cross-protection within the Capripoxvirus genus, sheep pox virus (SPPV) vaccines have been widely used for cattle against lumpy skin disease virus (LSDV). In the Middle East and the Horn of Africa these vaccines have been associated with incomplete protection and adverse reactions in cattle post-vaccination. The present study confirms that the real identity of the commonly used Kenyan sheep and goat pox vaccine virus (KSGP) O-240 is not SPPV but is actually LSDV. The low level attenuation of this virus is likely to be not sufficient for safe use in cattle, causing clinical disease in vaccinated animals. In addition, Isiolo and Kedong goat pox strains, capable of infecting sheep, goats and cattle are identified for potential use as broad-spectrum vaccine candidates against all capripox diseases. PMID:24973760

  2. The Heterologous Expression of the p22 RNA Silencing Suppressor of the Crinivirus Tomato Chlorosis Virus from Tobacco Rattle Virus and Potato Virus X Enhances Disease Severity but Does Not Complement Suppressor-Defective Mutant Viruses.

    Science.gov (United States)

    Landeo-Ríos, Yazmín; Navas-Castillo, Jesús; Moriones, Enrique; Cañizares, M. Carmen

    2017-11-24

    To counteract host antiviral RNA silencing, plant viruses express suppressor proteins that function as pathogenicity enhancers. The genome of the Tomato chlorosis virus (ToCV) (genus Crinivirus , family Closteroviridae ) encodes an RNA silencing suppressor, the protein p22, that has been described as having one of the longest lasting local suppressor activities when assayed in Nicotiana benthamiana . Since suppression of RNA silencing and the ability to enhance disease severity are closely associated, we analyzed the effect of expressing p22 in heterologous viral contexts. Thus, we studied the effect of the expression of ToCV p22 from viral vectors Tobacco rattle virus (TRV) and Potato virus X (PVX), and from attenuated suppressor mutants in N. benthamiana plants. Our results show that although an exacerbation of disease symptoms leading to plant death was observed in the heterologous expression of ToCV p22 from both viruses, only in the case of TRV did increased viral accumulation occur. The heterologous expression of ToCV p22 could not complement suppressor-defective mutant viruses.

  3. Enteric and indicator virus removal by surface flow wetlands.

    Science.gov (United States)

    Rachmadi, Andri T; Kitajima, Masaaki; Pepper, Ian L; Gerba, Charles P

    2016-01-15

    We investigated the occurrence and attenuation of several human enteric viruses (i.e., norovirus, adenovirus, Aichi virus 1, polyomaviruses, and enterovirus) as well as a plant virus, pepper mild mottle virus (PMMoV), at two surface flow wetlands in Arizona. The retention time in one of the wetlands was seven days, whereas in the other wetland it could not be defined. Water samples were collected at the inlet and outlet from the wetlands over nine months, and concentration of viral genomes was determined by quantitative polymerase chain reaction (qPCR). Of the human enteric viruses tested, adenovirus and Aichi virus 1 were found in the greatest prevalence in treated wastewater (i.e., inlet of the wetlands). Reduction efficiencies of enteric viruses by the wetlands ranged from 1 to 3 log10. Polyomaviruses were generally removed to below detection limit, indicating at least 2 to 4 log10 removal. PMMoV was detected in a greater concentration in the inlet of both wetlands for all the viruses tested (10(4) to 10(7) genome copies/L), but exhibited little or no removal (1 log10 or less). To determine the factors associated with virus genome attenuation (as determined by qPCR), the persistence of PMMoV and poliovirus type 1 (an enterovirus) was studied in autoclaved and natural wetland water, and deionized water incubated under three different temperatures for 21 days. A combination of elevated water temperature and biological activities reduced poliovirus by 1 to 4 log10, while PMMoV was not significantly reduced during this time period. Overall, PMMoV showed much greater persistence than human viruses in the wetland treatment. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. Nuclear medicine in the management of the AIDS patient

    International Nuclear Information System (INIS)

    Kramer, E.L.; Sanger, J.J.

    1990-01-01

    For the medical diagnostic imaging specialist in general, and for the nuclear medicine physician specifically, the AIDS epidemic has generated an enormous demand to develop a means of making early diagnoses of the complications of AIDS. For the most part this has meant the early detection, and when possible, the characterization of the opportunistic infections and neoplasms that are a major source of morbidity and mortality for the AIDS patient. Detection of opportunistic infections has been helpful in reclassifying HIV-seropositive patients as having AIDS. This paper reports on nuclear medicine used to evaluate the efficacy and the complications of treatment in human immunodeficiency virus infection. Most recently, functional brain imaging has been used for the diagnosis and follow-up of the AIDS dementia complex

  5. Opportunistic infections and malignancies in 231 Danish AIDS patients

    DEFF Research Database (Denmark)

    Pedersen, C; Gerstoft, J; Tauris, P

    1990-01-01

    We analysed cumulative disease frequencies in the first 231 adult Danish AIDS patients with life tables. There was a certain hierarchical pattern in the occurrence of complicating diseases. Herpes zoster, Kaposi's sarcoma and Pneumocystis carinii pneumonia were early manifestations, whereas...... diseases caused by cytomegalovirus and atypical mycobacteria tended to occur later in the course of AIDS. Compared with all other AIDS patients, homosexual men were more likely to develop Kaposi's sarcoma, cytomegalovirus chorioretinitis and mucocutaneous herpes simplex virus infection. The proportion...... of patients who developed particular diseases changed with calendar time. Most striking was a three to fourfold decrease in diseases caused by cytomegalovirus. In conclusion, the study showed that disease frequencies in patients with AIDS may vary with the patients risk behaviour and duration of AIDS...

  6. Use of Tissue-Specific MicroRNA to Control Pathology of Wild-Type Adenovirus without Attenuation of Its Ability to Kill Cancer Cells

    NARCIS (Netherlands)

    Cawood, R.; Chen, H.H.; Carroll, F.; Bazan-Peregrino, M.; Rooijen, van N.; Seymour, L.W.

    2009-01-01

    Replicating viruses have broad applications in biomedicine, notably in cancer virotherapy and in the design of attenuated vaccines; however, uncontrolled virus replication in vulnerable tissues can give pathology and often restricts the use of potent strains. Increased knowledge of tissue-selective

  7. Immunogenicity of NYVAC Prime-Protein Boost Human Immunodeficiency Virus Type 1 Envelope Vaccination and Simian-Human Immunodeficiency Virus Challenge of Nonhuman Primates.

    Science.gov (United States)

    Saunders, Kevin O; Santra, Sampa; Parks, Robert; Yates, Nicole L; Sutherland, Laura L; Scearce, Richard M; Balachandran, Harikrishnan; Bradley, Todd; Goodman, Derrick; Eaton, Amanda; Stanfield-Oakley, Sherry A; Tartaglia, James; Phogat, Sanjay; Pantaleo, Giuseppe; Esteban, Mariano; Gomez, Carmen E; Perdiguero, Beatriz; Jacobs, Bertram; Kibler, Karen; Korber, Bette; Montefiori, David C; Ferrari, Guido; Vandergrift, Nathan; Liao, Hua-Xin; Tomaras, Georgia D; Haynes, Barton F

    2018-04-15

    A preventive human immunodeficiency virus type 1 (HIV-1) vaccine is an essential part of the strategy to eradicate AIDS. A critical question is whether antibodies that do not neutralize primary isolate (tier 2) HIV-1 strains can protect from infection. In this study, we investigated the ability of an attenuated poxvirus vector (NYVAC) prime-envelope gp120 boost to elicit potentially protective antibody responses in a rhesus macaque model of mucosal simian-human immunodeficiency virus (SHIV) infection. NYVAC vector delivery of a group M consensus envelope, trivalent mosaic envelopes, or a natural clade B isolate B.1059 envelope elicited antibodies that mediated neutralization of tier 1 viruses, cellular cytotoxicity, and phagocytosis. None of the macaques made neutralizing antibodies against the tier 2 SHIV SF162P3 used for mucosal challenge. Significant protection from infection was not observed for the three groups of vaccinated macaques compared to unvaccinated macaques, although binding antibody to HIV-1 Env correlated with decreased viremia after challenge. Thus, NYVAC Env prime-gp120 boost vaccination elicited polyfunctional, nonneutralizing antibody responses with minimal protective activity against tier 2 SHIV mucosal challenge. IMPORTANCE The antibody responses that confer protection against HIV-1 infection remain unknown. Polyfunctional antibody responses correlated with time to infection in previous macaque studies. Determining the ability of vaccines to induce these types of responses is critical for understanding how to improve upon the one efficacious human HIV-1 vaccine trial completed thus far. We characterized the antibody responses induced by a NYVAC-protein vaccine and determined the protective capacity of polyfunctional antibody responses in an R5, tier 2 mucosal SHIV infection model. Copyright © 2018 American Society for Microbiology.

  8. An unusual alphasatellite associated with monopartite begomoviruses attenuates symptoms and reduces betasatellite accumulation

    KAUST Repository

    Idris, Ali

    2010-11-17

    The Oman strain of Tomato yellow leaf curl virus (TYLCV-OM) and its associated betasatellite, an isolate of Tomato leaf curl betasatellite (ToLCB), were previously reported from Oman. Here we report the isolation of a second, previously undescribed, begomovirus [Tomato leaf curl Oman virus (ToLCOMV)] and an alphasatellite from that same plant sample. This alphasatellite is closely related (90% shared nucleotide identity) to an unusual DNA-2-type Ageratum yellow vein Singapore alphasatellite (AYVSGA), thus far identified only in Singapore. ToLCOMV was found to have a recombinant genome comprising sequences derived from two extant parents, TYLCV-OM, which is indigenous to Oman, and Papaya leaf curl virus from the Indian subcontinent. All possible combinations of ToLCOMV, TYLCV-OM, ToLCB and AYVSGA were used to agro-inoculate tomato and Nicotiana benthamiana. Infection with ToLCOMV yielded mild leaf-curl symptoms in both hosts; however, plants inoculated with TYLCV-OM developed more severe symptoms. Plants infected with ToLCB in the presence of either helper begomovirus resulted in more severe symptoms. Surprisingly, symptoms in N. benthamiana infected with the alphasatellite together with either of the helper viruses and the betasatellite were attenuated and betasatellite DNA accumulation was substantially reduced. However, in the latter plants no concomitant reduction in the accumulation of helper virus DNA was observed. This is the first example of an attenuation of begomovirus-betasatellite symptoms by this unusual class of alphasatellites. This observation suggests that some DNA-2 alphasatellites encode a pathogenicity determinant that may modulate begomovirus-betasatellite infection by reducing betasatellite DNA accumulation. © 2011 SGM.

  9. An unusual alphasatellite associated with monopartite begomoviruses attenuates symptoms and reduces betasatellite accumulation

    KAUST Repository

    Idris, Ali; Shahid, Muhammad Shafiq; Briddon, Rob William; Khan, Akhtarjamal; Zhu, Jian-Kang; Brown, Judith K.

    2010-01-01

    The Oman strain of Tomato yellow leaf curl virus (TYLCV-OM) and its associated betasatellite, an isolate of Tomato leaf curl betasatellite (ToLCB), were previously reported from Oman. Here we report the isolation of a second, previously undescribed, begomovirus [Tomato leaf curl Oman virus (ToLCOMV)] and an alphasatellite from that same plant sample. This alphasatellite is closely related (90% shared nucleotide identity) to an unusual DNA-2-type Ageratum yellow vein Singapore alphasatellite (AYVSGA), thus far identified only in Singapore. ToLCOMV was found to have a recombinant genome comprising sequences derived from two extant parents, TYLCV-OM, which is indigenous to Oman, and Papaya leaf curl virus from the Indian subcontinent. All possible combinations of ToLCOMV, TYLCV-OM, ToLCB and AYVSGA were used to agro-inoculate tomato and Nicotiana benthamiana. Infection with ToLCOMV yielded mild leaf-curl symptoms in both hosts; however, plants inoculated with TYLCV-OM developed more severe symptoms. Plants infected with ToLCB in the presence of either helper begomovirus resulted in more severe symptoms. Surprisingly, symptoms in N. benthamiana infected with the alphasatellite together with either of the helper viruses and the betasatellite were attenuated and betasatellite DNA accumulation was substantially reduced. However, in the latter plants no concomitant reduction in the accumulation of helper virus DNA was observed. This is the first example of an attenuation of begomovirus-betasatellite symptoms by this unusual class of alphasatellites. This observation suggests that some DNA-2 alphasatellites encode a pathogenicity determinant that may modulate begomovirus-betasatellite infection by reducing betasatellite DNA accumulation. © 2011 SGM.

  10. A new approach for weed control in a cucurbit field employing an attenuated potyvirus-vector for herbicide resistance.

    Science.gov (United States)

    Shiboleth, Y M; Arazi, T; Wang, Y; Gal-On, A

    2001-12-14

    Expression of bar, a phosphinothricin acetyltransferase, in plant tissues, leads to resistance of these plants to glufosinate ammonium based herbicides. We have created a bar expressing, attenuated zucchini yellow mosaic potyvirus-vector, AGII-Bar, to enable herbicide use in cucurbit fields. The parental vector, ZYMV-AGII, has been rendered environmentally safe by both disease-symptom attenuation and aphid-assisted virus transmission abolishment. The recombinant AGII-Bar virus-encoding cDNA, when inoculated on diverse cucurbits was highly infectious, accumulated to similar levels as AGII, and elicited attenuated AGII-like symptoms. Potted cucurbits inoculated with AGII-Bar became herbicide resistant about a week post-inoculation. Herbicide resistance was sustained in squash over a period of at least 26 days and for at least 60 days in cucumber grown in a net-house under commercial conditions. To test the applicability of AGII-Bar use in a weed-infested field, a controlled experiment including more than 450 plants inoculated with this construct, was performed. Different dosages of glufosinate ammonium were sprayed, 2 weeks after planting, on the foliage of melons, cucumbers, squash, and watermelons. AGII-Bar provided protection to all inoculated plants, of every variety tested, at each dosage applied, including the highest doses that totally eradicated weeds. This study demonstrates that AGII-Bar can be utilized to facilitate weed control in cucurbits and exemplifies the practical potential of attenuated virus-vector use in agriculture.

  11. Recombination of Globally Circulating Varicella-Zoster Virus

    Science.gov (United States)

    Depledge, Daniel P.; Kundu, Samit; Atkinson, Claire; Brown, Julianne; Haque, Tanzina; Hussaini, Yusuf; MacMahon, Eithne; Molyneaux, Pamela; Papaevangelou, Vassiliki; Sengupta, Nitu; Koay, Evelyn S. C.; Tang, Julian W.; Underhill, Gillian S.; Grahn, Anna; Studahl, Marie; Breuer, Judith; Bergström, Tomas

    2015-01-01

    ABSTRACT Varicella-zoster virus (VZV) is a human herpesvirus, which during primary infection typically causes varicella (chicken pox) and establishes lifelong latency in sensory and autonomic ganglia. Later in life, the virus may reactivate to cause herpes zoster (HZ; also known as shingles). To prevent these diseases, a live-attenuated heterogeneous vaccine preparation, vOka, is used routinely in many countries worldwide. Recent studies of another alphaherpesvirus, infectious laryngotracheitis virus, demonstrate that live-attenuated vaccine strains can recombine in vivo, creating virulent progeny. These findings raised concerns about using attenuated herpesvirus vaccines under conditions that favor recombination. To investigate whether VZV may undergo recombination, which is a prerequisite for VZV vaccination to create such conditions, we here analyzed 115 complete VZV genomes. Our results demonstrate that recombination occurs frequently for VZV. It thus seems that VZV is fully capable of recombination if given the opportunity, which may have important implications for continued VZV vaccination. Although no interclade vaccine-wild-type recombinant strains were found, intraclade recombinants were frequently detected in clade 2, which harbors the vaccine strains, suggesting that the vaccine strains have already been involved in recombination events, either in vivo or in vitro during passages in cell culture. Finally, previous partial and complete genomic studies have described strains that do not cluster phylogenetically to any of the five established clades. The additional VZV strains sequenced here, in combination with those previously published, have enabled us to formally define a novel sixth VZV clade. IMPORTANCE Although genetic recombination has been demonstrated to frequently occur for other human alphaherpesviruses, herpes simplex viruses 1 and 2, only a few ancient and isolated recent recombination events have hitherto been demonstrated for VZV. In the

  12. Aids-relaterede non-Hodgkin-lymfomer. Klinisk billede og prognose

    DEFF Research Database (Denmark)

    Penkowa, M; Hansen, P B

    1998-01-01

    to be a clear association between Epstein-Barr virus (EBV) and immunoblastic lymphomas (a subtype of large cell lymphomas) in AIDS patients. Patients with AIDS often have widespread disease at presentation and frequent involvement of extranodal sites (CNS, liver, bone marrow, the digestive tract and skin...... below 130 x 10(9)/l, widespread symptoms of disease, presence of EBV in the lymphoma and immunoblastic histology. Udgivelsesdato: 1998-Apr-27...

  13. Protection of chickens against H5N1 highly pathogenic avian influenza virus infection by live vaccination with infectious laryngotracheitis virus recombinants expressing H5 hemagglutinin and N1 neuraminidase.

    Science.gov (United States)

    Pavlova, Sophia P; Veits, Jutta; Keil, Günther M; Mettenleiter, Thomas C; Fuchs, Walter

    2009-01-29

    Attenuated vaccine strains of the alphaherpesvirus causing infectious laryngotracheitis of chickens (ILTV, gallid herpesvirus 1) can be used for mass application. Previously, we showed that live virus vaccination with recombinant ILTV expressing hemagglutinin of highly pathogenic avian influenza viruses (HPAIV) protected chickens against ILT and fowl plague caused by HPAIV carrying the corresponding hemagglutinin subtypes [Lüschow D, Werner O, Mettenleiter TC, Fuchs W. Protection of chickens from lethal avian influenza A virus infection by live-virus vaccination with infectious laryngotracheitis virus recombinants expressing the hemagglutinin (H5) gene. Vaccine 2001;19(30):4249-59; Veits J, Lüschow D, Kindermann K, Werner O, Teifke JP, Mettenleiter TC, et al. Deletion of the non-essential UL0 gene of infectious laryngotracheitis (ILT) virus leads to attenuation in chickens, and UL0 mutants expressing influenza virus haemagglutinin (H7) protect against ILT and fowl plague. J Gen Virol 2003;84(12):3343-52]. However, protection against H5N1 HPAIV was not satisfactory. Therefore, a newly designed dUTPase-negative ILTV vector was used for rapid insertion of the H5-hemagglutinin, or N1-neuraminidase genes of a recent H5N1 HPAIV isolate. Compared to our previous constructs, protein expression was considerably enhanced by insertion of synthetic introns downstream of the human cytomegalovirus immediate-early promoter within the 5'-nontranslated region of the transgenes. Deletion of the viral dUTPase gene did not affect in vitro replication of the ILTV recombinants, but led to sufficient attenuation in vivo. After a single ocular immunization, all chickens developed H5- or N1-specific serum antibodies. Nevertheless, animals immunized with N1-ILTV died after subsequent H5N1 HPAIV challenge, although survival times were prolonged compared to non-vaccinated controls. In contrast, all chickens vaccinated with either H5-ILTV alone, or H5- and N1-ILTV simultaneously, survived

  14. HAART in HIV/AIDS Treatments: Future Trends.

    Science.gov (United States)

    Lu, Da-Yong; Wu, Hong-Ying; Yarla, Nagendra Sastry; Xu, Bin; Ding, Jian; Lu, Ting-Ren

    2018-01-01

    AIDS (acquired immune deficient syndrome) is a deadly human viral infectious disease caused by HIV (human immune-deficient virus) infection. Almost every AIDS patient losses his/her life before mid 1990s. AIDS was once the 1st disease killer in US (1993). After one decade hard work, antiviral drug cocktails-high active anti-retroviral therapy (HAART) have been invented for almost all HIV infection treatments. Due to the invention of HAART, 80-90% HIV/AIDS patients still effectively response to HAART for deadly AIDS episode controls and life saving. Yet, this type of HIV therapeutics is incurable. HIV/AIDS patients need to take HAART medications regularly and even life-long. To counteract this therapeutic drawback, more revolutionary efforts (different angles of therapeutic modes/attempts) are urgently needed. In this article, the major progresses and drawbacks of HIV/AIDS chemotherapy (HAART) to HIV/AIDS patients have been discussed. Future trends (updating pathogenesis study, next generations of drug developments, new drug target discovery, different scientific disciplinary and so on) are highlighted. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  15. Use of Condoms among Human Immunodeficiency Virus Positive ...

    African Journals Online (AJOL)

    goals and its spread promotes poverty.[2] It has increased ... Virus Positive Women Attending Antenatal Clinic in. Nnewi, South ... This may lead to infection of uninfected partners with its multiplier .... Gender inequalities, power relations and HIV/AIDS: exploring the ... workers in a high HIV prevalent state of India. AIDS Care.

  16. Opportunistic infection of HIV/AIDS patients in West Papua

    Science.gov (United States)

    Witaningrum, A. M.; Khairunisa, S. Q.; Yunifiar, M. Q.; Bramanthi, R.; Rachman, B. E.; Nasronudin

    2018-03-01

    Human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) had a major impact on health problemin Indonesia. HIV type 1 (HIV-1) epidemic is currently infected with HIV viruses developing rapidly in Indonesia.Papua provinces have the highest prevalence rate of human immunodeficiency virus type 1 (HIV-1) infection in Indonesia; however, data on opportunistic infection of HIV-1 are limited. The study using medical records as a research sample was conducted among HIV patients from January 2013 - December 2014 in Sele be Solu hospital among 49 patients. Opportunistic infections commonly occur in HIV-infected patients. The aim of the study was to know theprevalence of opportunistic infection among HIV positive patients in West Papua. Forty-nine HIV-1 patients were collected in Sele be Solu Hospital, West Papua.Opportunistic infection was identified such as tuberculosis, tuberculosis Pulmo, tuberculosis and candidiasis, candidiasis and diarrhea. The clinical sign appeared in HIV infected patients such as itchy, cough and loss weight. The prevalence of opportunistic infection indicated the necessity of monitoring the opportunistic infection of HIV/AIDS patients in Indonesia.

  17. Knowledge and attitude of Indian clinical dental students towards the dental treatment of patients with human immunodeficiency virus (HIV)/acquired immune-deficiency syndrome (AIDS).

    Science.gov (United States)

    Oberoi, Sukhvinder Singh; Marya, Charu Mohan; Sharma, Nilima; Mohanty, Vikrant; Marwah, Mohita; Oberoi, Avneet

    2014-12-01

    Oral health care of patients with human immunodeficiency virus (HIV)/acquired immune-deficiency syndrome (AIDS) is a growing area of concern. Information on HIV- and AIDS-related knowledge among dental students provides a crucial foundation for efforts aimed at developing an appropriate dental curriculum on HIV and AIDS. The purpose of this study was to assess the knowledge and attitude of Indian clinical dental students towards the treatment of patients with HIV/AIDS and perceived sources of information regarding HIV-related issues. Data were collected from clinical dental students (third year, fourth year and internship) from three dental institutions in Delhi National Capital Region (NCR). The questions assessed the knowledge and attitude towards treatment of patients with HIV and the perceived source of information related to HIV. The willingness to treat HIV-positive patients among dental students was 67.0%, and 74.20% were confident of treating a patient with HIV/AIDS. The potential problems in rendering treatment to these patients were effect on the attitude of other patients (49.90%) and staff fears (52.50%). The correct knowledge regarding the infection-control practice (barrier technique) was found among only 15.50% of respondents. The respondents had sufficient knowledge regarding the oral manifestations of HIV/AIDS. There was no correlation between the knowledge and attitude score, demonstrating a gap between knowledge and attitude among dental students regarding treatment of HIV-infected patients. Appropriate knowledge has to be delivered through the dental education curriculum, which can instil confidence in students about their ability to manage HIV-positive patients. © 2014 FDI World Dental Federation.

  18. Sequence evidence for RNA recombination in field isolates of avian coronavirus infectious bronchitis virus

    NARCIS (Netherlands)

    Kusters, J G; Jager, E J; Niesters, H G; van der Zeijst, B A

    1990-01-01

    Under laboratory conditions coronaviruses were shown to have a high frequency of recombination. In The Netherlands, vaccination against infectious bronchitis virus (IBV) is performed with vaccines that contain several life-attenuated virus strains. These highly effective vaccines may create ideal

  19. Lymphocyte transformation response to pokeweed mitogen as a predictive marker for development of AIDS and AIDS related symptoms in homosexual men with HIV antibodies

    DEFF Research Database (Denmark)

    Hofmann, B; Lindhardt, B O; Gerstoft, J

    1987-01-01

    To identify factors that may predict the development of the acquired immune deficiency syndrome (AIDS) or AIDS related symptoms various immunological measurements were studied in a group of homosexual men attending screening clinics for AIDS in Copenhagen. Fifty seven men whose ratio of T helper...... lymphocytes to T suppressor lymphocytes (CD4:CD8 ratio) was less than 1.0 before the study began were included. Forty two were positive for antibody to the human immunodeficiency virus (HIV), of whom 38 were reinvestigated after a median observation period of 10 months. Among the seropositive men...

  20. Vaccines in Development against West Nile Virus

    Directory of Open Access Journals (Sweden)

    Frederic Tangy

    2013-09-01

    Full Text Available West Nile encephalitis emerged in 1999 in the United States, then rapidly spread through the North American continent causing severe disease in human and horses. Since then, outbreaks appeared in Europe, and in 2012, the United States experienced a new severe outbreak reporting a total of 5,387 cases of West Nile virus (WNV disease in humans, including 243 deaths. So far, no human vaccine is available to control new WNV outbreaks and to avoid worldwide spreading. In this review, we discuss the state-of-the-art of West Nile vaccine development and the potential of a novel safe and effective approach based on recombinant live attenuated measles virus (MV vaccine. MV vaccine is a live attenuated negative-stranded RNA virus proven as one of the safest, most stable and effective human vaccines. We previously described a vector derived from the Schwarz MV vaccine strain that stably expresses antigens from emerging arboviruses, such as dengue, West Nile or chikungunya viruses, and is strongly immunogenic in animal models, even in the presence of MV pre-existing immunity. A single administration of a recombinant MV vaccine expressing the secreted form of WNV envelope glycoprotein elicited protective immunity in mice and non-human primates as early as two weeks after immunization, indicating its potential as a human vaccine.

  1. Functional Evolution of Influenza Virus NS1 Protein in Currently Circulating Human 2009 Pandemic H1N1 Viruses.

    Science.gov (United States)

    Clark, Amelia M; Nogales, Aitor; Martinez-Sobrido, Luis; Topham, David J; DeDiego, Marta L

    2017-09-01

    In 2009, a novel H1N1 influenza virus emerged in humans, causing a global pandemic. It was previously shown that the NS1 protein from this human 2009 pandemic H1N1 (pH1N1) virus was an effective interferon (IFN) antagonist but could not inhibit general host gene expression, unlike other NS1 proteins from seasonal human H1N1 and H3N2 viruses. Here we show that the NS1 protein from currently circulating pH1N1 viruses has evolved to encode 6 amino acid changes (E55K, L90I, I123V, E125D, K131E, and N205S) with respect to the original protein. Notably, these 6 residue changes restore the ability of pH1N1 NS1 to inhibit general host gene expression, mainly by their ability to restore binding to the cellular factor CPSF30. This is the first report describing the ability of the pH1N1 NS1 protein to naturally acquire mutations that restore this function. Importantly, a recombinant pH1N1 virus containing these 6 amino acid changes in the NS1 protein (pH1N1/NSs-6mut) inhibited host IFN and proinflammatory responses to a greater extent than that with the parental virus (pH1N1/NS1-wt), yet virus titers were not significantly increased in cell cultures or in mouse lungs, and the disease was partially attenuated. The pH1N1/NSs-6mut virus grew similarly to pH1N1/NSs-wt in mouse lungs, but infection with pH1N1/NSs-6mut induced lower levels of proinflammatory cytokines, likely due to a general inhibition of gene expression mediated by the mutated NS1 protein. This lower level of inflammation induced by the pH1N1/NSs-6mut virus likely accounts for the attenuated disease phenotype and may represent a host-virus adaptation affecting influenza virus pathogenesis. IMPORTANCE Seasonal influenza A viruses (IAVs) are among the most common causes of respiratory infections in humans. In addition, occasional pandemics are caused when IAVs circulating in other species emerge in the human population. In 2009, a swine-origin H1N1 IAV (pH1N1) was transmitted to humans, infecting people then and up

  2. Female Secondary School Adolescents' Sexual Behavior and School Based HIV/AIDS Education Program

    Science.gov (United States)

    Inyang, Mfrekemfon P.

    2013-01-01

    Most adolescents engage in indiscriminate sexual experimentations. This practice exposes them to the risk of contracting sexually transmitted infections including HIV/AIDS. Human immunodeficiency virus (HIV) and acquired immune deficiency syndromes (AIDS) are among the deadly diseases that exist globally. Twice as many girls, compared to boys…

  3. Avian influenza virus transmission to mammals.

    Science.gov (United States)

    Herfst, S; Imai, M; Kawaoka, Y; Fouchier, R A M

    2014-01-01

    Influenza A viruses cause yearly epidemics and occasional pandemics. In addition, zoonotic influenza A viruses sporadically infect humans and may cause severe respiratory disease and fatalities. Fortunately, most of these viruses do not have the ability to be efficiently spread among humans via aerosols or respiratory droplets (airborne transmission) and to subsequently cause a pandemic. However, adaptation of these zoonotic viruses to humans by mutation or reassortment with human influenza A viruses may result in airborne transmissible viruses with pandemic potential. Although our knowledge of factors that affect mammalian adaptation and transmissibility of influenza viruses is still limited, we are beginning to understand some of the biological traits that drive airborne transmission of influenza viruses among mammals. Increased understanding of the determinants and mechanisms of airborne transmission may aid in assessing the risks posed by avian influenza viruses to human health, and preparedness for such risks. This chapter summarizes recent discoveries on the genetic and phenotypic traits required for avian influenza viruses to become airborne transmissible between mammals.

  4. Presentation and outcome amongst older Singaporeans living with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS): does age alone drive excess mortality?

    Science.gov (United States)

    Huggan, Paul J; Foo, Rui Min; Olszyna, Dariusz; Chew, Nicholas S; Smitasen, Nares; Mukhopadhyay, Amartya; Archuleta, Sophia

    2012-12-01

    There is little detailed information on human immunodeficiency virus (HIV) amongst older adults in Singapore. A retrospective study of 121 consecutive referrals of patients presenting for HIV care was conducted. Demographic, clinical and laboratory variables were collected. A prognostic model derived from the North American Veterans' Affairs Cohort Study (VACS) was used to estimate prognosis. The median age at presentation was 43 (range, 18 to 76). Thirty-eight patients (31%) were aged 50 or older and 106 patients (88%) were male. Older patients were more likely to be of Chinese ethnicity (P = 0.035), married (P = 0.0001), unemployed or retired (P = 0.0001), and to have acquired their infection heterosexually (P = 0.0002). The majority of patients in both groups were symptomatic at presentation. Eighty-one (67%) had CD4 counts less than 200 at baseline with no observable differences in HIV ribonucleic acid (RNA) or clinical stage based on age. Non-Acquired Immunodeficiency Syndrome (AIDS) morbidity was observed more frequently amongst older patients. The estimated prognosis of patients differed significantly based on age. Using the VACS Index and comparing younger patients with those aged 50 and above, mean 5 year mortality estimates were 25% and 50% respectively (P HIV/AIDS cases and present with more non-AIDS morbidity. This confers a poor prognosis despite comparable findings with younger patients in terms of clinical stage, AIDS-defining illness, CD4 count and HIV viral load.

  5. Development of a challenge-protective vaccine concept by modification of the viral RNA-dependent RNA polymerase of canine distemper virus.

    Science.gov (United States)

    Silin, D; Lyubomska, O; Ludlow, M; Duprex, W P; Rima, B K

    2007-12-01

    We demonstrate that insertion of the open reading frame of enhanced green fluorescent protein (EGFP) into the coding sequence for the second hinge region of the viral L (large) protein (RNA-dependent RNA polymerase) attenuates a wild-type canine distemper virus. Moreover, we show that single intranasal immunization with this recombinant virus provides significant protection against challenge with the virulent parental virus. Protection against wild-type challenge was gained either after recovery of cellular immunity postimmunization or after development of neutralizing antibodies. Insertion of EGFP seems to result in overattenuation of the virus, while our previous experiments demonstrated that the insertion of an epitope tag into a similar position did not affect L protein function. Thus, a desirable level of attenuation could be reached by manipulating the length of the insert (in the second hinge region of the L protein), providing additional tools for optimization of controlled attenuation. This strategy for controlled attenuation may be useful for a "quick response" in vaccine development against well-known and "new" viral infections and could be combined efficiently with other strategies of vaccine development and delivery systems.

  6. Nuclear medicine in the management of the aids patient

    International Nuclear Information System (INIS)

    Kramer, E.L.; Sanger, J.J.

    1995-01-01

    For the medical diagnostic imaging specialist in general, and for the nuclear medicine physician specifically, the AIDS epidemic has generated an enormous demand to develop a means of making early diagnoses of the complications of AIDS. For the most part this has meant the early detection, and when possible, the characterization of the opportunistic infections and neoplasms that are a major source of morbidity and mortality for the AIDS patient. Detection of opportunistic infections has been helpful in reclassifying HIV-seropositive patients as having AIDS. This paper reports on nuclear medicine used to evaluate the efficacy and the complications of treatment in human immunodeficiency virus infection. Most recently, functional brain imaging has been used for the diagnosis and follow-up of the AIDS dementia complex. (author). 77 refs., 8 figs

  7. The analysis of HIV/AIDS drug-resistant on networks

    Science.gov (United States)

    Liu, Maoxing

    2014-01-01

    In this paper, we present an Human Immunodeficiency Virus (HIV)/Acquired Immune Deficiency Syndrome (AIDS) drug-resistant model using an ordinary differential equation (ODE) model on scale-free networks. We derive the threshold for the epidemic to be zero in infinite scale-free network. We also prove the stability of disease-free equilibrium (DFE) and persistence of HIV/AIDS infection. The effects of two immunization schemes, including proportional scheme and targeted vaccination, are studied and compared. We find that targeted strategy compare favorably to a proportional condom using has prominent effect to control HIV/AIDS spread on scale-free networks.

  8. Bovine herpes virus infections in cattle.

    Science.gov (United States)

    Nandi, S; Kumar, Manoj; Manohar, M; Chauhan, R S

    2009-06-01

    Bovine herpes virus 1 (BHV-1) is primarily associated with clinical syndromes such as rhinotracheitis, pustular vulvovaginitis and balanoposthitis, abortion, infertility, conjunctivitis and encephalitis in bovine species. The main sources of infection are the nasal exudates and the respiratory droplets, genital secretions, semen, fetal fluids and tissues. The BHV-1 virus can become latent following a primary infection with a field isolate or vaccination with an attenuated strain. The viral genomic DNA has been demonstrated in the sensory ganglia of the trigeminal nerve in infectious bovine rhinotracheitis (IBR) and in sacral spinal ganglia in pustular vulvovaginitis and balanoposthitis cases. BHV-1 infections can be diagnosed by detection of virus or virus components and antibody by serological tests or by detection of genomic DNA by polymerase chain reaction (PCR), nucleic acid hybridization and sequencing. Inactivated vaccines and modified live virus vaccines are used for prevention of BHV-1 infections in cattle; subunit vaccines and marker vaccines are under investigation.

  9. 21 CFR 866.3332 - Reagents for detection of specific novel influenza A viruses.

    Science.gov (United States)

    2010-04-01

    ... HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological... novel influenza A viruses in patients with clinical risk of infection with these viruses, and also aids...

  10. [Behavior of Orf virus in permissive and nonpermissive systems].

    Science.gov (United States)

    Büttner, M; Czerny, C P; Schumm, M

    1995-04-01

    Dogs were immunized i.m. with attenuated poxvirus vaccines (vaccinia virus, Orf-virus) and a bovine herpesvirus-1 (BHV-1) vaccine. After intradermal (i.d.) application of the vaccine viruses a specific delayed type hypersensitivity (DTH) reaction of the skin occurred only with vaccinia virus. The i.d. application of Orf-virus caused a short-term, non-specific inflammatory reaction of the skin, even in dogs not immunized with Orf-virus. Out of 30 sera from Orf-virus immunized beagles (n = 4) only eight were found reactive to Orf-virus in a competition ELISA. Three sera from dogs not Orf-virus immunized but skin-tested with the virus contained low antibody titers. Using indirect immunofluorescence (IIF) in flow cytometry, the existence of Orf-virus antigens was examined on the surface and in the cytoplasm of permissive (BFK and Vero)- and questionable permissive MDCK cells. The canine kidney MDCK cell line was found to be non-permissive for Orf-virus replication; the occurrence of an Orf-(ecthyma contagiosum) like disease in dogs is unlikely.

  11. Failure of orally administered attenuated goose parvovirus strain B to induce a humoral immune response in adult geese.

    Science.gov (United States)

    Kisary, J; Kelemen, M

    1981-01-01

    Two-month-old geese responded with the production of virus neutralising antibodies against virulent goose parvovirus strain B administered either per os or intramuscularly. They were shedding the virus within a short period after exposure. Humoral immune response in geese of the same age was induced by the attenuated goose parvovirus strain B only by intramuscular injection but not with per os administration.

  12. Correlation between live attenuated measles viral load and growth inhibition percentage in non-small cell lung cancer cell line

    Directory of Open Access Journals (Sweden)

    Rasha Fadhel Obaid

    2018-03-01

    Conclusion Live attenuated measles virus strain induced cytotoxic effect against human lung cancer cell line (A549 by induction of apoptosis as an important mechanism of anti-tumor activity, in addition, it indicates a correlation between the quantity of MV genomesand percentage of growth inhibition. This relation  has proved that measles virus had anticancer effect.

  13. [History and the development of the studies on HIV and AIDS].

    Science.gov (United States)

    Rogala, Maciej

    2011-01-01

    The article describes the progress of medical knowledge which has been observed since the finding and discovery of the first case of the immune deficiency syndrome in the world in 1981. During this period the methods of diagnosis and treatment of HIV/AIDS has changed significantly. The progress in this area of examinations which is presently achieved allows unambiguous diagnosis of the virus and the disease. The recognition of the pathogenesis of the HIV and AIDS enabled the beginning of the studies on the medicines having antiretroviral properties. The utilization of the potential of the currently used medicines inhibits the progress of the disease and, in consequence, the elongation of the patients' life span. However, despite excessive clinical experiments in numerous research centres world-wide, until now there has not been found an effective medicine which could totally eradicate this virus from the body nor the vaccine which could prevent the further spread of this virus in the world.

  14. Safety and infectivity of two doses of live-attenuated recombinant cold-passaged human parainfluenza type 3 virus vaccine rHPIV3cp45 in HPIV3-seronegative young children.

    Science.gov (United States)

    Englund, Janet A; Karron, Ruth A; Cunningham, Coleen K; Larussa, Philip; Melvin, Ann; Yogev, Ram; Handelsman, Ed; Siberry, George K; Thumar, Bhavanji; Schappell, Elizabeth; Bull, Catherine V; Chu, Helen Y; Schaap-Nutt, Anne; Buchholz, Ursula; Collins, Peter L; Schmidt, Alexander C

    2013-11-19

    Human parainfluenza virus type 3 (HPIV3) is a common cause of upper and lower respiratory tract illness in infants and young children. Live-attenuated cold-adapted HPIV3 vaccines have been evaluated in infants but a suitable interval for administration of a second dose of vaccine has not been defined. HPIV3-seronegative children between the ages of 6 and 36 months were randomized 2:1 in a blinded study to receive two doses of 10⁵ TCID₅₀ (50% tissue culture infectious dose) of live-attenuated, recombinant cold-passaged human PIV3 vaccine (rHPIV3cp45) or placebo 6 months apart. Serum antibody levels were assessed prior to and approximately 4-6 weeks after each dose. Vaccine virus infectivity, defined as detection of vaccine-HPIV3 in nasal wash and/or a≥4-fold rise in serum antibody titer, and reactogenicity were assessed on days 3, 7, and 14 following immunization. Forty HPIV3-seronegative children (median age 13 months; range 6-35 months) were enrolled; 27 (68%) received vaccine and 13 (32%) received placebo. Infectivity was detected in 25 (96%) of 26 evaluable vaccinees following doses 1 and 9 of 26 subject (35%) following dose 2. Among those who shed virus, the median duration of viral shedding was 12 days (range 6-15 days) after dose 1 and 6 days (range 3-8 days) after dose 2, with a mean peak log₁₀ viral titer of 3.4 PFU/mL (SD: 1.0) after dose 1 compared to 1.5 PFU/mL (SD: 0.92) after dose 2. Overall, reactogenicity was mild, with no difference in rates of fever and upper respiratory infection symptoms between vaccine and placebo groups. rHPIV3cp45 was immunogenic and well-tolerated in seronegative young children. A second dose administered 6 months after the initial dose was restricted in those previously infected with vaccine virus; however, the second dose boosted antibody responses and induced antibody responses in two previously uninfected children. Copyright © 2013 Elsevier Ltd. All rights reserved.

  15. Biological characteristics of genetic variants of Urabe AM9 mumps vaccine virus.

    Science.gov (United States)

    Wright, K E; Dimock, K; Brown, E G

    2000-03-01

    The Urabe AM9 mumps vaccine is composed of a mixture of variants distinguishable by a difference at nucleotide (nt) 1081 of the hemagglutinin-neuraminidase (HN) gene (Brown, E.G., Dimock, K., Wright, K.E., 1996. The Urabe AM9 mumps vaccine is a mixture of viruses differing at amino acid (aa) 335 of the hemagglutinin-neuraminidase gene with one form associated with disease. J. Infect. Dis. 174, 619-622.). Further genetic and biological variation was detected in plaque purified viruses from the Urabe AM9 vaccine by examining the HN gene sequence, plaque morphology, cytopathic effects and growth in Vero cells, and temperature sensitivity (ts). Infection of Vero cells with plaque purified viruses with a G at nt 1081 of the HN gene produced large, clear plaques, caused significant CPE early after infection but yielded lower titres of virus than other purified viruses. None of these viruses were ts. In contrast, half of the plaque purified viruses with an A at nt 1081 were sensitive to a temperature of 39.5 degrees C. These viruses produced small plaques, caused significant CPE and grew to low titres. Two ts viruses possessed a unique aa substitution at aa 468 of HN. The remaining A(1081) viruses were not ts, produced large plaques but little CPE, and grew to titres 10-fold higher than the G(1081) viruses. Isolates of Urabe AM9 associated with post-vaccination illness were similar to these non-ts A(1081) viruses, but could be further sub-divided into two groups on the basis of a difference at aa 464 of HN. The post-vaccination isolates may represent insufficiently attenuated components of the vaccine, while the G(1081) and ts subset of A(1081) viruses may be more fully attenuated.

  16. Radiological features of pulmonary complications in patients with AIDS

    International Nuclear Information System (INIS)

    Ruebesam, D.; Fuchs, H.F.

    1988-01-01

    Our experience with over 200 AIDS-patients emphasizes the good knowledge in radiological features of pulmonary complications in patients with AIDS for early diagnosis. We show the radiological appearance of the most frequent opportunistic infection of the lung, pneumocystis carinii pneumonia, and the different appearance of the other most frequently seen pulmonary complications as Kaposisarkoma, cytomegaly-virus-pneumonia, non-typical-mycobacteria-infection and tuberculosis. A synopsis over the most important symptoms is made for easier differential diagnosis. (orig.) [de

  17. Approaches and Perspectives for Development of African Swine Fever Virus Vaccines

    Directory of Open Access Journals (Sweden)

    Marisa Arias

    2017-10-01

    Full Text Available African swine fever (ASF is a complex disease of swine, caused by a large DNA virus belonging to the family Asfarviridae. The disease shows variable clinical signs, with high case fatality rates, up to 100%, in the acute forms. ASF is currently present in Africa and Europe where it circulates in different scenarios causing a high socio-economic impact. In most affected regions, control has not been effective in part due to lack of a vaccine. The availability of an effective and safe ASFV vaccines would support and enforce control–eradication strategies. Therefore, work leading to the rational development of protective ASF vaccines is a high priority. Several factors have hindered vaccine development, including the complexity of the ASF virus particle and the large number of proteins encoded by its genome. Many of these virus proteins inhibit the host’s immune system thus facilitating virus replication and persistence. We review previous work aimed at understanding ASFV–host interactions, including mechanisms of protective immunity, and approaches for vaccine development. These include live attenuated vaccines, and “subunit” vaccines, based on DNA, proteins, or virus vectors. In the shorter to medium term, live attenuated vaccines are the most promising and best positioned candidates. Gaps and future research directions are evaluated.

  18. Persistent HIV antigenaemia and decline of HIV core antibodies associated with transition to AIDS

    NARCIS (Netherlands)

    Lange, J. M.; Paul, D. A.; Huisman, H. G.; de Wolf, F.; van den Berg, H.; Coutinho, R. A.; Danner, S. A.; van der Noordaa, J.; Goudsmit, J.

    1986-01-01

    Sequential serum samples from 13 homosexual men who seroconverted for antibodies to human immunodeficiency virus (HIV) were tested for HIV antigen. In one of these men, who developed the acquired immune deficiency syndrome (AIDS), HIV antigenaemia preceded the onset of AIDS by more than a year and

  19. Characterization of sheep pox virus vaccine for cattle against lumpy skin disease virus.

    Science.gov (United States)

    Tuppurainen, Eeva S M; Pearson, Caroline R; Bachanek-Bankowska, Katarzyna; Knowles, Nick J; Amareen, Shadi; Frost, Lorraine; Henstock, Mark R; Lamien, Charles E; Diallo, Adama; Mertens, Peter P C

    2014-09-01

    Lumpy skin disease is of significant economic impact for the cattle industry in Africa. The disease is currently spreading aggressively in the Near East, posing a threat of incursion to Europe and Asia. Due to cross-protection within the Capripoxvirus genus, sheep pox virus (SPPV) vaccines have been widely used for cattle against lumpy skin disease virus (LSDV). In the Middle East and the Horn of Africa these vaccines have been associated with incomplete protection and adverse reactions in cattle post-vaccination. The present study confirms that the real identity of the commonly used Kenyan sheep and goat pox vaccine virus (KSGP) O-240 is not SPPV but is actually LSDV. The low level attenuation of this virus is likely to be not sufficient for safe use in cattle, causing clinical disease in vaccinated animals. In addition, Isiolo and Kedong goat pox strains, capable of infecting sheep, goats and cattle are identified for potential use as broad-spectrum vaccine candidates against all capripox diseases. Crown Copyright © 2014. Published by Elsevier B.V. All rights reserved.

  20. Development of a human live attenuated West Nile infectious DNA vaccine: Identification of a minimal mutation set conferring the attenuation level acceptable for a human vaccine

    Energy Technology Data Exchange (ETDEWEB)

    Yamshchikov, Vladimir, E-mail: yaximik@gmail.com; Manuvakhova, Marina; Rodriguez, Efrain; Hébert, Charles

    2017-01-15

    ABSTRACT: For the development of a human West Nile (WN) infectious DNA (iDNA) vaccine, we created highly attenuated chimeric virus W1806 with the serological identity of highly virulent WN-NY99. Earlier, we attempted to utilize mutations found in the E protein of the SA14-14-2 vaccine to bring safety of W1806 to the level acceptable for human use (). Here, we analyzed effects of the SA14-14-2 changes on growth properties and neurovirulence of W1806. A set including the E138K, K279M, K439R and G447D changes was identified as the perspective subset for satisfying the target safety profile without compromising immunogenicity of the vaccine candidate. The genetic stability of the attenuated phenotype was found to be unsatisfactory being dependent on a subset of attenuating changes incorporated in W1806. Elucidation of underlying mechanisms influencing selection of pathways for restoration of the envelope protein functionality will facilitate resolution of the emerged genetic stability issue. - Highlights: •Effect of mutations in E on properties of WN1806 is determined. •A subset of attenuating mutations suitable for a human vaccine is defined. •Mechanism of attenuation is proposed and illustrated. •Underlying mechanisms of neurovirulence reversion are suggested.

  1. MR imaging of white matter lesions in AIDS

    International Nuclear Information System (INIS)

    Olsen, W.L.; Longo, F.; Norman, D.

    1987-01-01

    Autopsy reports have shown white-matter abnormalities from infection of the brain by the human immunodeficiency virus (HIV), the agent that causes acquired immunodeficiency syndrome (AIDS). The authors observed abnormal signal on T2-weighted images in the white matter of approximately one third of all AIDS patients. Of 50 patients with white-matter lesions, approximately two thirds had no clinical or biopsy evidence of cytomegalovirus, toxoplasmosis, PML, or lymphoma. Several patients were shown at autopsy to have isolated evidence of HIV encephalitis. The authors conclude that white-matter lesions are common in AIDS and are frequently caused by infection with HIV. Some MR findings may be helpful in characterizing these lesions, but the various etiologies are often indistinguishable

  2. Radiographic evaluation of AIDS patients

    International Nuclear Information System (INIS)

    Le Blang, S.D.; Witheman, M.L.; Donovan Post, M.J.; Casillas, J.V.

    1995-01-01

    Morphological imaging, based on the use of various techniques including ultrasound, X-ray computed tomography (CT), and magnetic resonance imaging (MRI), plays an important role in the characterization, diagnosis and follow-up of patients with Human Immunodeficiency Virus (HIV) infection and Acquired Immunodeficiency Syndrome (AIDS). While the presence of thoracic infections, the most frequently observed illnesses in AIDS patients, can best be performed by using conventional chest films and CT, the assessment of cerebral involvement in AIDS patients - characterized by the presence of focal masses, demyelination, meningitis, and infarction - is best achieved using MRI. The work-up of patients with gastrointestinal symptoms should include the use of ultrasound for the evaluation of visceral involvement and lymphadenopathy, completed by CT to further characterize pathologic conditions in either the bowel or visceral organs. Ultrasound is the screening exam of choice in AIDS patients with suspected renal disease, but other methods may be necessary for the assessment of the complications due to pharmacological treatment. Musculoskeletal complications may require the combined use of all the above methods, since they may be caused by infections, tumors and rheumatologic illness. The use of the radiographic methods for the detection of the numerous forms of infections and malignancies in AIDS patients is described in detail for the various body districts

  3. Factors Associated with HIV/AIDS in Sudan

    Directory of Open Access Journals (Sweden)

    Badreldin Abdelrhman Mohamed

    2013-01-01

    Full Text Available Objectives. To assess participants’ knowledge about HIV/AIDS and to identify the factors associated with HIV/AIDS in Sudan. Methods. Observational cross-sectional study carried out at Omdurman National Voluntary Counseling and Testing Centre, Sudan covered 870 participants. Sociodemographic data as well as information related to sexual behavior were collected. Results. Most of the respondents were knowledgeable about the true transmission modes for AIDS virus. Very few respondents knew someone infected with AIDS (4.5%, died of AIDS (8.1%, accepted to live with someone infected with AIDS (4.7% or to work with someone infected with AIDS (2.1%. Regarding sexual behavior, 96.5% had reported their first sexual experience between 20 and 30 years, with 85.7% reporting one or two partners, and only 1.8% reported using condom. Multivariate logistic regression showed that circumcision, religion, marital status, age at first sex, number of sexual partners, education level, and misconception of knowledge are the main risk factors associated with HIV/AIDS. Conclusion. Our results showed that a number of diversity risk factors were associated with HIV/AIDS. It is unlikely that a holistic approach will be found to immediately change sexual-risk-relating behavior. Interventions including sustained educational programs, promotion of condom, and encouragement of voluntary testing and active involvement of the country’s political and religious leaders will be needed to alleviate this problem.

  4. Global prevention, funding, accountability debated in fight against HIV / AIDS.

    Science.gov (United States)

    1999-10-18

    World leaders, physicians, economists, governmental health organizations, and pharmaceutical manufacturers attended the Third International Conference on Healthcare Resource Allocation for HIV/AIDS and Other Life-threatening Illnesses in Vienna, Austria. The conference participants discussed the economic, ethical, and human rights issues underlying health care resource allocation. Some highlights of the meeting included: the prevention strategies in fighting AIDS virus; the use of high medical ethical standards; the affordability and accessibility of essential therapies; the economic aspects affecting the medical assistance mechanisms; the need to improve the pharmaceutical industry; the need to improve HIV/AIDS care access in developing countries; promoting the development of HIV/AIDS vaccines; and developing rapid diagnosis of HIV.

  5. Pulmonary diseases in children with AIDS

    Energy Technology Data Exchange (ETDEWEB)

    Stoever, B.; Cammann, U.

    1988-03-01

    The opportunistic infections evident in children with AIDS are similar to those reported in adults. However malignant lymphoma or sarcoma are seen in only 4%. Pneumocystis carinii pneumonia is frequently seen. CMV infections, streptococcus pneumonia and lung infections causes by gram negative bacterial infections occur as well. In cases with lymhoid interstitial pneumonia evidence of Epstein-Barr virus infection is common in children.

  6. Conocimiento de Transmision de SIDA y Percepcion Hacia los Ninos con SIDA en el Salon de Clases de los Maestros de Educacion Especial (Knowledge of AIDS Transmission and Special Education Teachers' Attitudes towards Children with AIDS in the Classroom).

    Science.gov (United States)

    Lopez de Williams, Milka

    This Spanish-language master's thesis presents a study which measured special education teachers' knowledge of AIDS (Acquired Immune Deficiency Syndrome) virus transmission and their attitudes toward children with AIDS in schools. Attitudes were then related to social variables such as sex, teacher's age, and knowing someone with AIDS. A survey of…

  7. A heterologous prime-boosting strategy with replicating Vaccinia virus vectors and plant-produced HIV-1 Gag/dgp41 virus-like particles

    Energy Technology Data Exchange (ETDEWEB)

    Meador, Lydia R. [Ira A. Fulton School of Engineering, Arizona State University, Tempe, AZ (United States); Center for Infectious Diseases and Vaccinology, The Biodesign Institute, Arizona State University, Tempe, AZ (United States); Kessans, Sarah A. [Center for Infectious Diseases and Vaccinology, The Biodesign Institute, Arizona State University, Tempe, AZ (United States); School of Life Sciences, Arizona State University, Tempe, AZ (United States); Kilbourne, Jacquelyn; Kibler, Karen V. [Center for Infectious Diseases and Vaccinology, The Biodesign Institute, Arizona State University, Tempe, AZ (United States); Pantaleo, Giuseppe [Division of Immunology and Allergy, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne (Switzerland); Swiss Vaccine Research Institute, Lausanne (Switzerland); Roderiguez, Mariano Esteban [Department of Molecular and Cellular Biology, Centro Nacional de Biotecnologia – CSIC, Madrid (Spain); Blattman, Joseph N. [Center for Infectious Diseases and Vaccinology, The Biodesign Institute, Arizona State University, Tempe, AZ (United States); School of Life Sciences, Arizona State University, Tempe, AZ (United States); Jacobs, Bertram L., E-mail: bjacobs@asu.edu [Center for Infectious Diseases and Vaccinology, The Biodesign Institute, Arizona State University, Tempe, AZ (United States); School of Life Sciences, Arizona State University, Tempe, AZ (United States); Mor, Tsafrir S., E-mail: tsafrir.mor@asu.edu [Center for Infectious Diseases and Vaccinology, The Biodesign Institute, Arizona State University, Tempe, AZ (United States); School of Life Sciences, Arizona State University, Tempe, AZ (United States)

    2017-07-15

    Showing modest efficacy, the RV144 HIV-1 vaccine clinical trial utilized a non-replicating canarypox viral vector and a soluble gp120 protein boost. Here we built upon the RV144 strategy by developing a novel combination of a replicating, but highly-attenuated Vaccinia virus vector, NYVAC-KC, and plant-produced HIV-1 virus-like particles (VLPs). Both components contained the full-length Gag and a membrane anchored truncated gp41 presenting the membrane proximal external region with its conserved broadly neutralizing epitopes in the pre-fusion conformation. We tested different prime/boost combinations of these components in mice and showed that the group primed with NYVAC-KC and boosted with both the viral vectors and plant-produced VLPs have the most robust Gag-specific CD8 T cell responses, at 12.7% of CD8 T cells expressing IFN-γ in response to stimulation with five Gag epitopes. The same immunization group elicited the best systemic and mucosal antibody responses to Gag and dgp41 with a bias towards IgG1. - Highlights: • We devised a prime/boost anti HIV-1 vaccination strategy modeled after RV144. • We used plant-derived virus-like particles (VLPs) consisting of Gag and dgp41. • We used attenuated, replicating vaccinia virus vectors expressing the same antigens. • The immunogens elicited strong cellular and humoral immune responses.

  8. The High Degree of Sequence Plasticity of the Arenavirus Noncoding Intergenic Region (IGR) Enables the Use of a Nonviral Universal Synthetic IGR To Attenuate Arenaviruses.

    Science.gov (United States)

    Iwasaki, Masaharu; Cubitt, Beatrice; Sullivan, Brian M; de la Torre, Juan C

    2016-01-06

    Hemorrhagic fever arenaviruses (HFAs) pose important public health problems in regions where they are endemic. Concerns about human-pathogenic arenaviruses are exacerbated because of the lack of FDA-licensed arenavirus vaccines and because current antiarenaviral therapy is limited to an off-label use of ribavirin that is only partially effective. We have recently shown that the noncoding intergenic region (IGR) present in each arenavirus genome segment, the S and L segments (S-IGR and L-IGR, respectively), plays important roles in the control of virus protein expression and that this knowledge could be harnessed for the development of live-attenuated vaccine strains to combat HFAs. In this study, we further investigated the sequence plasticity of the arenavirus IGR. We demonstrate that recombinants of the prototypic arenavirus lymphocytic choriomeningitis virus (rLCMVs), whose S-IGRs were replaced by the S-IGR of Lassa virus (LASV) or an entirely nonviral S-IGR-like sequence (Ssyn), are viable, indicating that the function of S-IGR tolerates a high degree of sequence plasticity. In addition, rLCMVs whose L-IGRs were replaced by Ssyn or S-IGRs of the very distantly related reptarenavirus Golden Gate virus (GGV) were viable and severely attenuated in vivo but able to elicit protective immunity against a lethal challenge with wild-type LCMV. Our findings indicate that replacement of L-IGR by a nonviral Ssyn could serve as a universal molecular determinant of arenavirus attenuation. Hemorrhagic fever arenaviruses (HFAs) cause high rates of morbidity and mortality and pose important public health problems in regions where they are endemic. Implementation of live-attenuated vaccines (LAVs) will represent a major step to combat HFAs. Here we document that the arenavirus noncoding intergenic region (IGR) has a high degree of plasticity compatible with virus viability. This observation led us to generate recombinant LCMVs containing nonviral synthetic IGRs. These r

  9. Revisiting the AIDS Epidemic in Pakistan: Where We Stand and What We Must Aim For.

    Science.gov (United States)

    Dar, Hamza Arshad; Mubashir, Areeba; Adil, Manal; Farzeen, Aiman; Naseer, Hasaan; Ayub, Gohar; Mansoor, Sajid; Javed, Aneela

    2017-10-01

    Human immunodeficiency virus type 1 (HIV-1) is the major cause of acquired immunodeficiency syndrome (AIDS) in humans, where the immune system totally succumbs to the virus. A large proportion of the AIDS infected belong to developing countries and AIDS prevalence is intensified by severe poverty, malnutrition, and famine; fatal illnesses with a scorn shortage of medical amenities complemented with the lack of education and development. Current Pakistani health system setting is in a dire need of improvement. Low literacy rates, high birth rates, and associated maternal mortality plus a lack of clean drinking water and appropriate sanitation system have a serious impact on general living conditions contributing to a relatively short lifespan. HIV is, therefore, becoming a growing health concern in Pakistan with a rapid rise in the reported cases. AIDS is most prevalent among injection drug users (IDUs), male/female sex workers, and unchecked deported migrant workforce. To combat this virus, the Pakistan Government has been working hard over the past few years with local bodies and international organizations in an effort to combat this menace. This review aims to discuss the risk factors for the rise of this epidemic in the country and the recommendations, efforts to be done to address this alarming issue.

  10. Demonstration of 1-year duration of immunity for attenuated Bordetella bronchiseptica vaccines in dogs.

    Science.gov (United States)

    Lehar, Craig; Jayappa, Huchappa; Erskine, Jason; Brown, Alicia; Sweeney, Diane; Wassmoen, Terri

    2008-01-01

    Three groups of healthy dogs with low antibody titers to Bordetella bronchiseptica (Bb), canine parainfluenza virus (CPI), and canine adenovirus type 2 (CAV-2) were used in this study. One group was vaccinated with a single dose of monovalent attenuated Bb vaccine and one group with a trivalent vaccine containing attenuated Bb, CPI, and CAV-2; dogs were vaccinated intranasally with a single dose of the respective vaccines. The third group served as unvaccinated controls. All vaccinated dogs subsequently developed serum antibody titers to Bb that persisted for at least 1 year. Following Bb challenge 1 year after vaccination, all vaccinated dogs, regardless of group, showed significantly fewer clinical signs and shed significantly fewer challenge organisms than unvaccinated controls. These results demonstrate that intranasal administration of a single dose of monovalent attenuated Bb vaccine or trivalent vaccine containing attenuated Bb, CPI, and CAV-2 provides 1 year of protection against Bb.

  11. Correlation between Lymphocyte CD4 Count, Treatment Duration, Opportunistic Infection and Cognitive Function in Human Immunodeficiency Virus-Acquired Immunodeficiency Syndrome (HIV-AIDS) Patients.

    Science.gov (United States)

    Fitri, Fasihah Irfani; Rambe, Aldy Safruddin; Fitri, Aida

    2018-04-15

    Human immunodeficiency virus (HIV) infection is an epidemic worldwide, despite the marked benefits of antiretroviral therapy (ARV) in reducing severe HIV-associated dementia. A milder form of neurocognitive disorders are still prevalent and remain a challenge. This study aimed to determine the correlation between plasma cluster of differentiation 4 (CD4) lymphocyte, duration of ARV treatment, opportunistic infections, and cognitive function in HIV-AIDS patients. A cross-sectional study involving 85 HIV-AIDS patients was conducted at Adam Malik General Hospital Medan, Indonesia. All subjects were subjected to physical, neurologic examination and Montreal Cognitive Assessment-Indonesian Version (MoCA-INA) to assess cognitive function and measurement of lymphocyte CD4 counts. Out of the 85 subjects evaluated, the proportion concerning sexes include 52 males (61.2 %) and 33 females (38.8%). The mean age was 38.53 ± 9.77 years old. There was a significant correlation between CD4 lymphocyte counts and MoCA-INA score (r = 0.271, p = 0.012), but there was no significant correlation between duration of ARV treatment and MoCA-INA score. There was also no difference in MoCA-INA score based on the presence of opportunistic infection. Lymphocyte CD4 count was independently correlated with cognitive function in HIV-AIDS patients.

  12. Attenuated Salmonella choleraesuis-mediated RNAi targeted to conserved regions against foot-and-mouth disease virus in guinea pigs and swine

    Science.gov (United States)

    Cong, Wei; Jin, Hong; Jiang, Chengda; Yan, Weiyao; Liu, Mingqiu; Chen, Jiulian; Zuo, Xiaoping; Zheng, Zhaoxin

    2010-01-01

    In this study, specific sequences within three genes (3D, VP4 and 2B) of the foot-and-mouth disease virus (FMDV) genome were determined to be effective RNAi targets. These sequences are highly conserved among different serotype viruses based on sequence analysis. Small interfering RNA (siRNA)-expressing plasmids (p3D-NT19, p3D-NT56, pVP4-NT19, pVP4-NT65 and p2B-NT25) were constructed to express siRNA targeting 3D, VP4 and 2B, respectively. The antiviral potential of these siRNA for various FMDV isolates was investigated in baby hamster kidney (BHK-21) cells and suckling mice. The results show that these siRNA inhibited virus yield 10- to 300-fold for different FMDV isolates of serotype O and serotype Asia I at 48 h post infection in BHK-21 cells compared to control cells. In suckling mice, p3D-NT56 and p2B-NT25 delayed the death of mice. Twenty percent to 40% of the animals that received a single siRNA dose survived 5 days post infection with serotype O or serotype Asia I. We used an attenuated Salmonella choleraesuis (C500) vaccine strain, to carry the plasmid that expresses siRNA directed against the polymerase gene 3D (p3D-NT56) of FMDV. We used guinea pigs to evaluate the inhibitory effects of recombinant S. cho (p3D-NT56/S. cho) on FMDV infection. The results show that 80% of guinea pigs inoculated with 109 CFU of p3D-NT56/S. cho and challenged 36 h later with 50 ID50 of homologous FMDV were protected. We also measured the antiviral activity of p3D-NT56/S. cho in swine. The results indicate that 100% of the animals treated with 5 × 109 CFU of p3D-NT56/S. cho were protected in 9 days. PMID:20167192

  13. New Animal Model Could Boost Research on AIDS Drugs and Vaccines | Poster

    Science.gov (United States)

    By Frank Blanchard, Staff Writer, and Jeff Lifson, Guest Writer In a research milestone reported in the June 20 issue of the journal Science, scientists have developed a minimally modified version of HIV-1, the virus that causes AIDS in infected humans, that is capable of causing progressive infection and AIDS in monkeys. The advance should help create more authentic animal

  14. Specific Mutations in the PB2 Protein of Influenza A Virus Compensate for the Lack of Efficient Interferon Antagonism of the NS1 Protein of Bat Influenza A-Like Viruses.

    Science.gov (United States)

    Aydillo, Teresa; Ayllon, Juan; Pavlisin, Amzie; Martinez-Romero, Carles; Tripathi, Shashank; Mena, Ignacio; Moreira-Soto, Andrés; Vicente-Santos, Amanda; Corrales-Aguilar, Eugenia; Schwemmle, Martin; García-Sastre, Adolfo

    2018-04-01

    Recently, two new influenza A-like viruses have been discovered in bats, A/little yellow-shouldered bat/Guatemala/060/2010 (HL17NL10) and A/flat-faced bat/Peru/033/2010 (HL18NL11). The hemagglutinin (HA)-like (HL) and neuraminidase (NA)-like (NL) proteins of these viruses lack hemagglutination and neuraminidase activities, despite their sequence and structural homologies with the HA and NA proteins of conventional influenza A viruses. We have now investigated whether the NS1 proteins of the HL17NL10 and HL18NL11 viruses can functionally replace the NS1 protein of a conventional influenza A virus. For this purpose, we generated recombinant influenza A/Puerto Rico/8/1934 (PR8) H1N1 viruses containing the NS1 protein of the PR8 wild-type, HL17NL10, and HL18NL11 viruses. These viruses (r/NS1PR8, r/NS1HL17, and r/NS1HL18, respectively) were tested for replication in bat and nonbat mammalian cells and in mice. Our results demonstrate that the r/NS1HL17 and r/NS1HL18 viruses are attenuated in vitro and in vivo However, the bat NS1 recombinant viruses showed a phenotype similar to that of the r/NS1PR8 virus in STAT1 -/- human A549 cells and mice, both in vitro and in vivo systems being unable to respond to interferon (IFN). Interestingly, multiple mouse passages of the r/NS1HL17 and r/NS1HL18 viruses resulted in selection of mutant viruses containing single amino acid mutations in the viral PB2 protein. In contrast to the parental viruses, virulence and IFN antagonism were restored in the selected PB2 mutants. Our results indicate that the NS1 protein of bat influenza A-like viruses is less efficient than the NS1 protein of its conventional influenza A virus NS1 counterpart in antagonizing the IFN response and that this deficiency can be overcome by the influenza virus PB2 protein. IMPORTANCE Significant gaps in our understanding of the basic features of the recently discovered bat influenza A-like viruses HL17NL10 and HL18NL11 remain. The basic biology of these unique

  15. Identification of sequence changes in live attenuated goose parvovirus vaccine strains developed in Asia and Europe.

    Science.gov (United States)

    Shien, J-H; Wang, Y-S; Chen, C-H; Shieh, H K; Hu, C-C; Chang, P-C

    2008-10-01

    Live attenuated vaccines have been used for control of the disease caused by goose parvovirus (GPV), but the mechanism involved in attenuation of GPV remains elusive. This report presents the complete nucleotide sequences of two live attenuated strains of GPV (82-0321V and VG32/1) that were independently developed in Taiwan and Europe, together with the parental strain of 82-0321V and a field strain isolated in Taiwan in 2006. Sequence comparisons showed that 82-0321V and VG32/1 had multiple deletions and substitutions in the inverted terminal repeats region when compared with their parental strain or the field virus, but these changes did not affect the formation of the hairpin structure essential for viral replication. Moreover, 82-0321V and VG32/1 had five amino acid changes in the non-structural protein, but these changes were located at positions distant from known functional motifs in the non-structural protein. In contrast, 82-0321V had nine changes and VG32/1 had 11 changes in their capsid proteins (VP1), and the majority of these changes occurred at positions close to the putative receptor binding sites of VP1, as predicted using the structure of adeno-associated virus 2 as the model system. Taken together, the results suggest that changes in sequence near the receptor binding sites of VP1 might be responsible for attenuation of GPV. This is the first report of complete nucleotide sequences of GPV other than the virulent B strain, and suggests a possible mechanism for attenuation of GPV.

  16. Alternative Medicines for HIV/AIDS in Resource-Poor Settings ...

    African Journals Online (AJOL)

    Purpose: To document the utilization of traditional medicines in managing human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) opportunistic infections in sub-Saharan Africa. Methods: This study is based on a review of literature published in scientific journals, books, reports from national, ...

  17. Generation and characterization of P gene-deficient rabies virus

    International Nuclear Information System (INIS)

    Shoji, Youko; Inoue, Satoshi; Nakamichi, Kazuo; Kurane, Ichiro; Sakai, Takeo; Morimoto, Kinjiro

    2004-01-01

    Rabies virus (RV) deficient in the P gene was generated by reverse genetics from cDNA of HEP-Flury strain lacking the entire P gene. The defective virus was propagated and amplified by rescue of virus, using a cell line that complemented the functions of the deficient gene. The P gene-deficient (def-P) virus replicated its genome and produced progeny viruses in the cell lines that constitutively expressed the P protein, although it grew at a slightly retarded rate compared to the parental strain. In contrast, no progeny virus was produced in the infected host when the def-P virus-infected cells that did not express the P protein. However, we found that the def-P virus had the ability to perform primary transcription (by the virion-associated polymerase) in the infected host without de novo P protein synthesis. The def-P virus was apathogenic in adult and suckling mice, even when inoculated intracranially. Inoculation of def-P virus in mice induced high levels of virus-neutralizing antibody (VNA) and conferred protective immunity against a lethal rabies infection. These results demonstrate the potential utility of gene-deficient virus as a novel live attenuated rabies vaccine

  18. Vaccine and Wild-Type Strains of Yellow Fever Virus Engage Distinct Entry Mechanisms and Differentially Stimulate Antiviral Immune Responses.

    Science.gov (United States)

    Fernandez-Garcia, Maria Dolores; Meertens, Laurent; Chazal, Maxime; Hafirassou, Mohamed Lamine; Dejarnac, Ophélie; Zamborlini, Alessia; Despres, Philippe; Sauvonnet, Nathalie; Arenzana-Seisdedos, Fernando; Jouvenet, Nolwenn; Amara, Ali

    2016-02-09

    The live attenuated yellow fever virus (YFV) vaccine 17D stands as a "gold standard" for a successful vaccine. 17D was developed empirically by passaging the wild-type Asibi strain in mouse and chicken embryo tissues. Despite its immense success, the molecular determinants for virulence attenuation and immunogenicity of the 17D vaccine are poorly understood. 17D evolved several mutations in its genome, most of which lie within the envelope (E) protein. Given the major role played by the YFV E protein during virus entry, it has been hypothesized that the residues that diverge between the Asibi and 17D E proteins may be key determinants of attenuation. In this study, we define the process of YFV entry into target cells and investigate its implication in the activation of the antiviral cytokine response. We found that Asibi infects host cells exclusively via the classical clathrin-mediated endocytosis, while 17D exploits a clathrin-independent pathway for infectious entry. We demonstrate that the mutations in the 17D E protein acquired during the attenuation process are sufficient to explain the differential entry of Asibi versus 17D. Interestingly, we show that 17D binds to and infects host cells more efficiently than Asibi, which culminates in increased delivery of viral RNA into the cytosol and robust activation of the cytokine-mediated antiviral response. Overall, our study reveals that 17D vaccine and Asibi enter target cells through distinct mechanisms and highlights a link between 17D attenuation, virus entry, and immune activation. The yellow fever virus (YFV) vaccine 17D is one of the safest and most effective live virus vaccines ever developed. The molecular determinants for virulence attenuation and immunogenicity of 17D are poorly understood. 17D was generated by serially passaging the virulent Asibi strain in vertebrate tissues. Here we examined the entry mechanisms engaged by YFV Asibi and the 17D vaccine. We found the two viruses use different entry

  19. A mathematical model of the spread of the AIDS virus

    Energy Technology Data Exchange (ETDEWEB)

    Hyman, J.M.; Stanley, E.A.

    1987-01-01

    A mathematical computer model of the spread of the AIDS epidemic in the US is being developed at Los Alamos National Laboratory. This model predicts the spreading of the HIV infection, and subsequent development of clinical AIDS in various population groups. These groups are chosen according to age, frequency and type of sexual contact, population density, and region of the country. Type of sexual contact includes not only the heterosexual, homosexual differentiation but also repeated contacts with such primary partners as spouses. In conjunction with the computer model, we are developing a database containing relevant information on the natural history of the viral infection, the prevalence of the infection and of clinical AIDS in the population, the distribution of people into sexual behavior groups as a function of age and information on interregional contacts. The effects of variable infectiousness and sexual activity during the long period from infection to disease are found to have a major impact on the predictions of the model. 24 refs., 5 figs.

  20. Emerging viruses in the Felidae: shifting paradigms.

    Science.gov (United States)

    O'Brien, Stephen J; Troyer, Jennifer L; Brown, Meredith A; Johnson, Warren E; Antunes, Agostinho; Roelke, Melody E; Pecon-Slattery, Jill

    2012-02-01

    The domestic cat is afflicted with multiple viruses that serve as powerful models for human disease including cancers, SARS and HIV/AIDS. Cat viruses that cause these diseases have been studied for decades revealing detailed insight concerning transmission, virulence, origins and pathogenesis. Here we review recent genetic advances that have questioned traditional wisdom regarding the origins of virulent Feline infectious peritonitis (FIP) diseases, the pathogenic potential of Feline Immunodeficiency Virus (FIV) in wild non-domestic Felidae species, and the restriction of Feline Leukemia Virus (FeLV) mediated immune impairment to domestic cats rather than other Felidae species. The most recent interpretations indicate important new evolutionary conclusions implicating these deadly infectious agents in domestic and non-domestic felids.

  1. Presence of infectious RD-114 virus in a proportion of canine parvovirus isolates.

    Science.gov (United States)

    Yoshikawa, Rokusuke; Sato, Eiji; Miyazawa, Takayuki

    2012-03-01

    We recently found that certain canine live attenuated vaccines produced using `non-feline' cell lines were contaminated with an infectious feline endogenous retrovirus, termed RD-114 virus. We suspected that RD-114 virus may have contaminated the seed stock of canine parvovirus (CPV) during the production of the contaminated vaccines. In this study, we collected stock viruses of CPVs propagated in a feline cell line, and checked the presence of infectious RD-114 virus. Consequently, we found that RD-114 viral RNA was present in all stock viruses, and 7 out of 18 stock viruses were contaminated with infectious RD-114 virus. We also found that RD-114 virus was stable physically and is capable of retaining its infectivity for a long period at -80°C.

  2. Magnetic resonance imaging findings of the brain in adult HIV and AIDS patients; Magnetresonanztomografische Befunde des Gehirns bei adulten Patienten mit HIV und AIDS

    Energy Technology Data Exchange (ETDEWEB)

    Kloska, S.P.; Schlegel, P.M.; Fischbach, R.; Heindel, W. [Inst. fuer Klinische Radiologie, Universitaetsklinikum Muenster (Germany); Husstedt, I.W.; Anneken, K.; Evers, S. [Klinik und Poliklinik fuer Neurologie, Universitaetsklinikum Muenster (Germany)

    2008-01-15

    The spectrum of pathology affecting the central nervous system (CNS) in patients suffering from acquired immunodeficiency syndrome (AIDS) includes not only the human immunodeficiency virus (HIV) infection itself but also opportunistic infections and tumors secondary to AIDS. Despite progress in antiretroviral therapy and the subsequent decrease in the incidence of associated diseases, opportunistic infections and tumors secondary to the HIV infection continue to be the limiting factor in terms of survival with AIDS. Therefore, the therapeutic aim is permanent antiretroviral therapy as well as early diagnosis and treatment of opportunistic infections. Magnetic resonance imaging is often the diagnostic method of choice in suspected CNS pathology of HIV patients. In the following, the typical clinical and radiological features of several AIDS-related pathologies are presented and discussed. (orig.)

  3. Extended Preclinical Safety, Efficacy and Stability Testing of a Live-attenuated Chikungunya Vaccine Candidate.

    Directory of Open Access Journals (Sweden)

    Kenneth S Plante

    Full Text Available We recently described a new, live-attenuated vaccine candidate for chikungunya (CHIK fever, CHIKV/IRES. This vaccine was shown to be well attenuated, immunogenic and efficacious in protecting against CHIK virus (CHIKV challenge of mice and nonhuman primates. To further evaluate its preclinical safety, we compared CHIKV/IRES distribution and viral loads in interferon-α/β receptor-incompetent A129 mice to another CHIK vaccine candidate, 181/clone25, which proved highly immunogenic but mildly reactive in human Phase I/II clinical trials. Compared to wild-type CHIK virus, (wt-CHIKV, both vaccines generated lower viral loads in a wide variety of tissues and organs, including the brain and leg muscle, but CHIKV/IRES exhibited marked restrictions in dissemination and viral loads compared to 181/clone25, and was never found outside the blood, spleen and muscle. Unlike wt-CHIKV, which caused disrupted splenic architecture and hepatic lesions, histopathological lesions were not observed in animals infected with either vaccine strain. To examine the stability of attenuation, both vaccines were passaged 5 times intracranially in infant A129 mice, then assessed for changes in virulence by comparing parental and passaged viruses for footpad swelling, weight stability and survival after subcutaneous infection. Whereas strain 181/clone25 p5 underwent a significant increase in virulence as measured by weight loss (from 30% and mortality (from 0 to 100%, CHIKV/IRES underwent no detectible change in any measure of virulence (no significant weight loss and no mortality. These data indicate greater nonclinical safety of the CHIKV/IRES vaccine candidate compared to 181/clone25, further supporting its eligibility for human testing.

  4. The imaging appearances of intracranial CNS infections in adult HIV and AIDS patients

    Energy Technology Data Exchange (ETDEWEB)

    Offiah, C.E. [Department of Neuroradiology, Hope Hospital, Stott Lane, Salford, Manchester (United Kingdom)]. E-mail: chockycj@yahoo.co.uk; Turnbull, I.W. [Department of Neuroradiology, Hope Hospital, Stott Lane, Salford, Manchester (United Kingdom)

    2006-05-15

    The spectrum of pathology affecting the central nervous system (CNS) in patients suffering from acquired immunodeficiency syndrome (AIDS) is broad and comprises predominantly opportunistic infections and neoplasms. It is estimated that approximately one-third of all patients with AIDS develop neurological complications. The organisms responsible for AIDS are human retroviruses: primarily the human immunodeficiency virus type 1 (HIV). In this review we shall focus on the neurological complications of HIV and AIDS which are applicable to the more frequently occurring intracranial infective organisms. Attention will be paid specifically to those CNS manifestations occurring in the adult HIV and AIDS population as infection in the paediatric HIV and AIDS group, although bearing some similarities, demonstrates some important differences.

  5. The imaging appearances of intracranial CNS infections in adult HIV and AIDS patients

    International Nuclear Information System (INIS)

    Offiah, C.E.; Turnbull, I.W.

    2006-01-01

    The spectrum of pathology affecting the central nervous system (CNS) in patients suffering from acquired immunodeficiency syndrome (AIDS) is broad and comprises predominantly opportunistic infections and neoplasms. It is estimated that approximately one-third of all patients with AIDS develop neurological complications. The organisms responsible for AIDS are human retroviruses: primarily the human immunodeficiency virus type 1 (HIV). In this review we shall focus on the neurological complications of HIV and AIDS which are applicable to the more frequently occurring intracranial infective organisms. Attention will be paid specifically to those CNS manifestations occurring in the adult HIV and AIDS population as infection in the paediatric HIV and AIDS group, although bearing some similarities, demonstrates some important differences

  6. [AIDS-related primary CNS non-Hodgkin's lymphoma in a patient with previous Epstein-Barr virus panuveitis. A clinico-pathological report].

    Science.gov (United States)

    Ruiz-Bilbao, S; Hernández, À; Gómez-Sánchez, S; Romeu, J; Llobera L, L; Carrato, C; Anglada, R; Sabala, A; Matas, L

    2015-05-01

    Patient with AIDS and Epstein-Barr virus (EBV) uveitis. The PCR of the aqueous and vitreous humor was positive for EBV, and DNA quantification was 56.602×10(6) copies/ml in the vitreous humor, 173,400 copies/ml in the peripheral blood, and negative in the cerebrospinal fluid (CSF). The patient developed a non-Hodgkin's lymphoma (NHL), diagnosed in the autopsy. The EBV is a rare cause of uveitis and it may be necessary to perform a quantitative PCR to reach the diagnosis. High amounts of EBV DNA are associated with a greater incidence of NHL. Copyright © 2014 Sociedad Española de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.

  7. Vectors expressing chimeric Japanese encephalitis dengue 2 viruses.

    Science.gov (United States)

    Wei, Y; Wang, S; Wang, X

    2014-01-01

    Vectors based on self-replicating RNAs (replicons) of flaviviruses are becoming powerful tool for expression of heterologous genes in mammalian cells and development of novel antiviral and anticancer vaccines. We constructed two vectors expressing chimeric viruses consisting of attenuated SA14-14-2 strain of Japanese encephalitis virus (JEV) in which the PrM/M-E genes were replaced fully or partially with those of dengue 2 virus (DENV-2). These vectors, named pJED2 and pJED2-1770 were transfected to BHK-21 cells and produced chimeric viruses JED2V and JED2-1770V, respectively. The chimeric viruses could be passaged in C6/36 but not BHK-21 cells. The chimeric viruses produced in C6/36 cells CPE 4-5 days after infection and RT-PCR, sequencing, immunofluorescence assay (IFA) and Western blot analysis confirmed the chimeric nature of produced viruses. The immunogenicity of chimeric viruses in mice was proved by detecting DENV-2 E protein-specific serum IgG antibodies with neutralization titer of 10. Successful preparation of infectious clones of chimeric JEV-DENV-2 viruses showed that JEV-based expression vectors are fully functional.

  8. Implementation of an Integrated Approach to the National HIV/AIDS Strategy for Improving Human Immunodeficiency Virus Care for Youths.

    Science.gov (United States)

    Fortenberry, J Dennis; Koenig, Linda J; Kapogiannis, Bill G; Jeffries, Carrie L; Ellen, Jonathan M; Wilson, Craig M

    2017-07-01

    Youths aged 13 to 24 years old living with human immunodeficiency virus (HIV) are less likely than adults to receive the health and prevention benefits of HIV treatments, with only a small proportion having achieved sustained viral suppression. These age-related disparities in HIV continuum of care are owing in part to the unique developmental issues of adolescents and young adults as well as the complexity and fragmentation of HIV care and related services. This article summarizes a national, multiagency, and multilevel approach to HIV care for newly diagnosed youths designed to bridge some of these fragmentations by addressing National HIV/AIDS Strategy goals for people living with HIV. Three federal agencies developed memoranda of understanding to sequentially implement 3 protocols addressing key National HIV/AIDS Strategy goals. The goals were addressed in the Adolescent Trials Network, with protocols implemented in 12 to 15 sites across the United States. Outcome data were collected from recently diagnosed youth referred to the program. Cross-agency collaboration, youth-friendly linkage to care services, community mobilization to address structural barriers to care, cooperation among services, proportion of all men who have sex with men who tested, and rates of linkage to prevention services. The program addressed National HIV/AIDS Strategy goals 2 through 4 including steps within each goal. A total of 3986 HIV-positive youths were referred for care, with more than 75% linked to care within 6 weeks of referral, with almost 90% of those youths engaged in subsequent HIV care. Community mobilization efforts implemented and completed structural change objectives to address local barriers to care. Age and racial/ethnic group disparities were addressed through targeted training for culturally competent, youth-friendly care, and intensive motivational interviewing training. A national program to address the National HIV/AIDS Strategy specifically for youths can

  9. How to develop a company AIDS policy.

    Science.gov (United States)

    Bompey, S H

    1986-07-01

    It is for most businesses only a matter of time before they will have experience with Acquired Immune Deficiency Syndrome (AIDS), and the experience could be very costly for companies which fail to implement an effective AIDS policy. Potential AIDS problems include: antidiscrimination suits based on firing or failing to hire an individual who had AIDS or carries the AIDS virus antibodies; defamation suits from employees who are wrongly identified; disability claims that do not fit the pattern for other diseases; civil rights penalties in some situations when AIDS victims are prevented from working; and run-ins with the Occupational Safety and Health Administration or the National Labor Relations Board if healthy workers refuse to work alongside AIDS victims. A company needs to think through its AIDS policy, but that does not mean establishing a "special" AIDS policy which may create paranoia among employees. The best approach is to develop a health policy that includes all catastrophic illnesses, not just AIDS. There have been few court decisions involving AIDS because AIDS is a recent illness, victims often do not live long enough to pursue the matter, and it often pays to settle AIDS cases out of court. Employers need to know that judges, administrative agencies, and arbitrators take the position that AIDS is a disability. As such, AIDS is treated under the anti-handicap discrimination laws on the books of most states. Additionally, the Federal Rehabilitation Act of 1973 prohibits discrimination against the disabled by companies that contract with the federal government or receive federal financial assistance. It usually is illegal to discriminate against the disabled workers, and in some states against workers who are perceived to have a disability. The best defense against the fear of working alongside and AIDs sufferer is education.

  10. Psychological Disorders among Human Immunodeficiency Virus ...

    African Journals Online (AJOL)

    AJRH Managing Editor

    Abstract. Persons living with HIV/AIDS (PLWHA) have been reported to be more at risk of ... effort is in place to control the spread of the virus, ... social situations) Depression (Loss of vital energy, ..... Experiences of stigma in older adults living.

  11. Identification of an attenuated barley stripe mosaic virus for the virus-induced gene silencing of pathogenesis-related wheat genes

    OpenAIRE

    Buhrow, Leann M.; Clark, Shawn M.; Loewen, Michele C.

    2016-01-01

    Background Virus-induced gene silencing (VIGS) has become an emerging technology for the rapid, efficient functional genomic screening of monocot and dicot species. The barley stripe mosaic virus (BSMV) has been described as an effective VIGS vehicle for the evaluation of genes involved in wheat and barley phytopathogenesis; however, these studies have been obscured by BSMV-induced phenotypes and defense responses. The utility of BSMV VIGS may be improved using a BSMV genetic background which...

  12. Pulmonary diseases in children with AIDS

    International Nuclear Information System (INIS)

    Stoever, B.; Cammann, U.

    1988-01-01

    The opportunistic infections evident in children with AIDS are similar to those reported in adults. However malignant lymphoma or sarcoma are seen in only 4%. Pneumocystis carinii pneumonia is frequently seen. CMV infections, streptococcus pneumonia and lung infections causes by gram negative bacterial infections occur as well. In cases with lymhoid interstitial pneumonia evidence of Epstein-Barr virus infection is common in children. (orig./MG) [de

  13. Level of HIV/AIDS Information Consciousness among Secondary ...

    African Journals Online (AJOL)

    FIRST LADY

    1996-10-01

    Oct 1, 1996 ... Indexed African Journals Online: www.ajol.info. An International ... Two decades ago, acquired Immuno Deficiency Syndrome (AIDS) was ... The virus can live in a person's body for several years without causing any obvious ... spend long hours of the day away from home, and with peers who belong to.

  14. Prostitution, AIDS, and preventive health behavior.

    Science.gov (United States)

    Campbell, C A

    1991-01-01

    Although considerable attention has been placed on the role of prostitutes in the AIDS epidemic, little attention has been directed to features of prostitutes' work lives which are relevant to the control of AIDS. This article reviews several aspects of prostitution in the United States which have implications for control of the epidemic. The article first reviews the epidemiology of human immunodeficiency virus (HIV) infection among prostitutes. The legalized system of prostitution in Nevada serves as a basis for comparison to illegal prostitution. This article examines the effectiveness of mandatory testing of prostitutes for monitoring and controlling the epidemic. And finally, a peer education approach as a means to control HIV infection among prostitutes is explored.

  15. Generation and Selection of Orf Virus (ORFV) Recombinants.

    Science.gov (United States)

    Rziha, Hanns-Joachim; Rohde, Jörg; Amann, Ralf

    2016-01-01

    Orf virus (ORFV) is an epitheliotropic poxvirus, which belongs to the genus Parapoxvirus. Among them the highly attenuated, apathogenic strain D1701-V is regarded as a promising candidate for novel virus vector vaccines. Our recent work demonstrated that those ORFV-based recombinants were able to induce protective, long-lasting immunity in various hosts that are non-permissive for ORFV. In this chapter we describe procedures for the generation, selection, propagation, and titration of ORFV recombinants as well as transgene detection by PCR or immunohistochemical staining.

  16. AIDS: there's hope.

    Science.gov (United States)

    1993-06-01

    In 1993, 10 years after realizing that AIDS posed a threat to the future of mankind, social mobilization will improve the odds against AIDS. The objective is to create awareness about the virus, and to affect positive behavioral change through advocacy, communication, and grass-roots actions. The first goal is to change the societal attitude about the status of youth and women in order to understand that gender inequality fuels the pandemic. They are the most vulnerable groups, therefore their economic and social power must be improved. The Convention on the Rights of the Child and the Convention on the Elimination of All Forms of Discrimination against Women constitute a platform for broader action by governmental, nongovernmental, and religious institutions. In addition, these organizations need strong allies in society: 1) the media, which can communicate the importance of youth, women, and attitudes in the epidemic; 2) religious leaders, who can be powerful sources of advocacy for change in attitudes as well as support and care for AIDS-affected individuals and families; 3) policy makers, who can be crucial in changing existing policies and altering the allocation of government resources to youth and women; 4) human rights organizations, which play an important role in promoting the concept of health as a human right and for enhancing the understanding of AIDS in the context of discrimination and poverty; 5) the private sector, including commerce and industry, which can promote changes in attitude within the work force and AIDS prevention initiatives; and 6) parent-teacher groups and models for youth, who can educate them about socially acceptable and unacceptable behavior and can empower them to make responsible behavior choices.

  17. Movement, Knowledge, Emotion : gay activism and HIV/AIDS in Australia

    OpenAIRE

    x

    2011-01-01

    This book is about community activism around HIV/AIDS in Australia. It looks at the role that the gay community played in the social, medical and political response to the virus. Drawing conclusions about the cultural impact of social movements, the author argues that AIDS activism contributed to improving social attitudes towards gay men and lesbians in Australia, while also challenging some entrenched cultural patterns of the Australian medical system, allowing greater scope for non-medical...

  18. 78 FR 43219 - Prospective Grant of Exclusive License: Live Attenuated Dengue Tetravalent Vaccine Containing a...

    Science.gov (United States)

    2013-07-19

    ...) E-120-2001/0, Whitehead et al., ``Development of Mutations Useful for Attenuating Dengue Viruses and..., and (3) E-139-2006/0, Whitehead et al., ``Development of Dengue Vaccine Components'', Australian... August 15, 2007, Chinese Patent Application Number 200780031489.4, filed August 15, 2007, European Patent...

  19. ANALYSI S ON SECONDARY I NFECTI ON- TRI GGERI NG MICROORGANISMS IN HIV/AIDS PATIENTS AS A MODEL FOR POLICY CONTROL

    Directory of Open Access Journals (Sweden)

    Retno Pudji Rahayu

    2015-01-01

    Full Text Available HIV infection is associated with immune-compromised and rising in opportunistic infection (secondary infection. Therefore, the number of mortality caused by HIV/AIDS is increasing. The use of ARV and development of HIV/AIDS management are expected to suppress the progress of HIV infection into AIDS and, therefore, the mortality can be diminished, while in fact most of the patients eventually suffer from AIDS due to secondary infection that commonly causes death. There should be a management by analysing microorganisms that trigger secondary infection. The method of this study was observational descriptive with cross sectional design. HIV infected blood samples were using ELISA Antibody (IgG and IgM and Polymerase Chain Reaction (PCR on laboratory test. The result showed correlation between HIV/AIDS severity and the amount and types of secondary infection. The most common secondary infections were toxoplasm (96.77%, hepatitis C (22.58%, tuberculosis (19.35%, and hepatitis B (3.22%. Other less frequent secondary infections, which were quite difficult to diagnose and not commonly found in Indonesia, were West Nile Virus (25.81%, Japanese Encephalitis Virus (3.22%, and Enterovirus (3.22%. Due to MDGs (Millenium Development Goals target and the results above, researchers are highly demanded to contribute in decreasing mortality related to AIDS through early detection of secondary infection,including type of infection which have not been commonly found in Indonesia, such as West Nile Virus and Nipah Virus. The discovery of secondary infection in this study was not enough to suppress the occurrence of infection in HIV/AIDS patients. Antimicrobes and good nutrition are required. Moreover, there should be either a primary or secondary prophylaxis to prevent secondary infection that raises the number of mortality and morbidity of HIV/AIDS patients. The result of this study was to meet the target of MDGs by establishing new policies in handling HIV/AIDS

  20. Control of feline leukaemia virus.

    NARCIS (Netherlands)

    K. Weijer (Kees); F.G.C.M. Uytdehaag (Fons); A.D.M.E. Osterhaus (Albert)

    1989-01-01

    textabstractFeline leukaemia virus (FeLV) usually occurs in its natural species, the domestic cat. FeLV is also important to human individuals as a comparative model, as it may cause a variety of diseases, some malignant and some benign, such as immunosuppression, which bears a resemblance to AIDS

  1. In vitro infection of salmonid epidermal tissues by infectious hematopoietic necrosis virus and viral hemorrhagic septicemia virus

    Science.gov (United States)

    Yamamoto, T.; Batts, W.N.; Winton, J.R.

    1992-01-01

    The ability of two rhabdoviruses, infectious hematopoietic necrosis virus (IHNV) and viral hemorrhagic septicemia virus (VHSV), to infect fish skin was investigated by in vitro infection of excised tissues. Virus replication was determined by plaque assay of homogenized tissue extracts, and the virus antigen was detected by immunohistology of tissue sections. Gill, fin, and ventral abdominal skin tissues of rainbow trout Oncorhynchus mykiss that had been infected in vitro with a virulent strain of IHNV (193–110) produced substantial increases in virus titer within 24 h. Titers continued to increase up until day 3 of incubation; by this time, virus had increased 1,000-fold or more. This increase in IHNV titer occurred in epidermal tissues of fingerlings and of older fish. In another experiment, IHNV replicated in excised rainbow trout tissues whether the fish had been subject to prior infection with a virulent strain of IHNV (Western Regional Aquaculture Consortium isolate) or whether the fish had been infected previously with an attenuated strain of the virus (Nan Scott Lake, with 100 passes in culture). A virulent strain of VHSV (23/75) replicated effectively in excised gill tissues and epidermal tissues of rainbow trout and chinook salmon O. tshawytscha; however, the avirulent North American strain of VHSV (Makah) replicated poorly or not at all.

  2. Emerging nanotechnology approaches for HIV/AIDS treatment and prevention

    Science.gov (United States)

    Mamo, Tewodros; Moseman, E Ashley; Kolishetti, Nagesh; Salvador-Morales, Carolina; Shi, Jinjun; Kuritzkes, Daniel R; Langer, Robert; von Andrian, Ulrich

    2010-01-01

    Currently, there is no cure and no preventive vaccine for HIV/AIDS. Combination antiretroviral therapy has dramatically improved treatment, but it has to be taken for a lifetime, has major side effects and is ineffective in patients in whom the virus develops resistance. Nanotechnology is an emerging multidisciplinary field that is revolutionizing medicine in the 21st century. It has a vast potential to radically advance the treatment and prevention of HIV/AIDS. In this review, we discuss the challenges with the current treatment of the disease and shed light on the remarkable potential of nanotechnology to provide more effective treatment and prevention for HIV/AIDS by advancing antiretroviral therapy, gene therapy, immunotherapy, vaccinology and microbicides. PMID:20148638

  3. Attenuated Salmonella enterica serovar Typhi and Shigella flexneri 2a strains mucosally deliver DNA vaccines encoding measles virus hemagglutinin, inducing specific immune responses and protection in cotton rats.

    Science.gov (United States)

    Pasetti, Marcela F; Barry, Eileen M; Losonsky, Genevieve; Singh, Mahender; Medina-Moreno, Sandra M; Polo, John M; Ulmer, Jeffrey; Robinson, Harriet; Sztein, Marcelo B; Levine, Myron M

    2003-05-01

    Measles remains a leading cause of child mortality in developing countries. Residual maternal measles antibodies and immunologic immaturity dampen immunogenicity of the current vaccine in young infants. Because cotton rat respiratory tract is susceptible to measles virus (MV) replication after intranasal (i.n.) challenge, this model can be used to assess the efficacy of MV vaccines. Pursuing a new measles vaccine strategy that might be effective in young infants, we used attenuated Salmonella enterica serovar Typhi CVD 908-htrA and Shigella flexneri 2a CVD 1208 vaccines to deliver mucosally to cotton rats eukaryotic expression plasmid pGA3-mH and Sindbis virus-based DNA replicon pMSIN-H encoding MV hemagglutinin (H). The initial i.n. dose-response with bacterial vectors alone identified a well-tolerated dosage (1 x 10(9) to 7 x 10(9) CFU) and a volume (20 micro l) that elicited strong antivector immune responses. Animals immunized i.n. on days 0, 28, and 76 with bacterial vectors carrying DNA plasmids encoding MV H or immunized parenterally with these naked DNA vaccine plasmids developed MV plaque reduction neutralizing antibodies and proliferative responses against MV antigens. In a subsequent experiment of identical design, cotton rats were challenged with wild-type MV 1 month after the third dose of vaccine or placebo. MV titers were significantly reduced in lung tissue of animals immunized with MV DNA vaccines delivered either via bacterial live vectors or parenterally. Since attenuated serovar Typhi and S. flexneri can deliver measles DNA vaccines mucosally in cotton rats, inducing measles immune responses (including neutralizing antibodies) and protection, boosting strategies can now be evaluated in animals primed with MV DNA vaccines.

  4. Mortality Due to Porcine Reproductive and Respiratory Syndrome Virus in Immunocompromised G?ttingen Minipigs (Sus scrofa domestica)

    OpenAIRE

    Pils, Marina C; Dreckmann, Karla; Jansson, Katharina; Glage, Silke; Held, Nadine; Sommer, Wiebke; L?nger, Florian; Avsar, Murat; Warnecke, Gregor; Bleich, Andr?

    2016-01-01

    Porcine reproductive and respiratory syndrome virus (PRRSV) infection was diagnosed in 6 G?ttingen minipigs (Sus scrofa domestica) with severe interstitial pneumonia. The virus was defined as a North American (NA) subtype virus, which is common in the commercial pig population and might be derived from a widely used attenuated live-virus vaccine in Europe. The ORF5 sequence of the isolated PRRSV was 98% identical to the vaccine virus. The affected pigs were part of a lung transplantation mode...

  5. APPLICATION OF COMPUTER AIDED TOMOGRAPHY (CAT) TO THE STUDY OF MARINE BENTIC COMMUNITIES

    Science.gov (United States)

    Sediment cores were imaged using a Computer-Aided Tomography (CT) scanner at Massachusetts General Hospital, Boston, Massachusetts, United States. Procedures were developed, using the attenuation of X-rays, to differentiate between sediment and the water contained in macrobenthic...

  6. Stepping toward a Macaque Model of HIV-1 Induced AIDS

    Directory of Open Access Journals (Sweden)

    Jason T. Kimata

    2014-09-01

    Full Text Available HIV-1 exhibits a narrow host range, hindering the development of a robust animal model of pathogenesis. Past studies have demonstrated that the restricted host range of HIV-1 may be largely due to the inability of the virus to antagonize and evade effector molecules of the interferon response in other species. They have also guided the engineering of HIV-1 clones that can replicate in CD4 T-cells of Asian macaque species. However, while replication of these viruses in macaque hosts is persistent, it has been limited and without progression to AIDS. In a new study, Hatziioannou et al., demonstrate for the first time that adapted macaque-tropic HIV-1 can persistently replicate at high levels in pigtailed macaques (Macaca nemestrina, but only if CD8 T-cells are depleted at the time of inoculation. The infection causes rapid disease and recapitulates several aspects of AIDS in humans. Additionally, the virus undergoes genetic changes to further escape innate immunity in association with disease progression. Here, the importance of these findings is discussed, as they relate to pathogenesis and model development.

  7. Comparison of the live attenuated yellow fever vaccine 17D-204 strain to its virulent parental strain Asibi by deep sequencing.

    Science.gov (United States)

    Beck, Andrew; Tesh, Robert B; Wood, Thomas G; Widen, Steven G; Ryman, Kate D; Barrett, Alan D T

    2014-02-01

    The first comparison of a live RNA viral vaccine strain to its wild-type parental strain by deep sequencing is presented using as a model the yellow fever virus (YFV) live vaccine strain 17D-204 and its wild-type parental strain, Asibi. The YFV 17D-204 vaccine genome was compared to that of the parental strain Asibi by massively parallel methods. Variability was compared on multiple scales of the viral genomes. A modeled exploration of small-frequency variants was performed to reconstruct plausible regions of mutational plasticity. Overt quasispecies diversity is a feature of the parental strain, whereas the live vaccine strain lacks diversity according to multiple independent measurements. A lack of attenuating mutations in the Asibi population relative to that of 17D-204 was observed, demonstrating that the vaccine strain was derived by discrete mutation of Asibi and not by selection of genomes in the wild-type population. Relative quasispecies structure is a plausible correlate of attenuation for live viral vaccines. Analyses such as these of attenuated viruses improve our understanding of the molecular basis of vaccine attenuation and provide critical information on the stability of live vaccines and the risk of reversion to virulence.

  8. Protection of chickens against infectious bronchitis by a recombinant fowlpox virus co-expressing IBV-S1 and chicken IFNgamma.

    Science.gov (United States)

    Wang, Yun-Feng; Sun, Yong-Ke; Tian, Zhan-Cheng; Shi, Xing-Ming; Tong, Guang-Zhi; Liu, Sheng-Wang; Zhi, Hai-Dong; Kong, Xian-Gang; Wang, Mei

    2009-11-23

    A fowlpox virus expressing the chicken infectious bronchitis virus (IBV) S1 gene of the LX4 strain (rFPV-IBVS1) and a fowlpox virus co-expressing the S1 gene and the chicken type II interferon gene (rFPV-IBVS1-ChIFNgamma) were constructed. These viruses were assessed for their immunological efficacy on specific-pathogen-free (SPF) chickens challenged with a virulent IBV. Although the antibody levels in the rFPV-IBVS1-ChIFNgamma-vaccinated group were lower than those in the attenuated live IB vaccine H120 group and the rFPV-IBVS1 group, the rFPV-IBVS1-ChIFNgamma provided the strongest protection against an IBV LX4 virus challenge (15 out of 16 chickens immunized with rFPV-IBVS1-ChIFNgamma were protected), followed by the attenuated live IB vaccine (13/16 protected) and the rFPV-IBVS1 (12/16 protected). Compared to those of the rFPV-IBVS1 and the attenuated live IB vaccine groups, chickens in the rFPV-IBVS1-ChIFNgamma group eliminated virus more quickly and decreased the presence of viral antigen more significantly in renal tissue. Examination of affected tissues revealed abnormalities in the liver, spleen, kidney, lung and trachea of chickens vaccinated with the attenuated live IB vaccine and the rFPV-IBVS1 vaccine. In rFPV-IBVS1-ChIFNgamma-vaccinated chickens, pathological changes were also observed in those organs, but were milder and lasted shorter. The lesions in the mock control group were the most severe and lasted for at least 20 days. This study demonstrated that chicken type II interferon increased the immunoprotective efficacy of rFPV-IBVS1-ChIFNgamma and normal weight gain in vaccinated chickens although it inhibited serum antibody production.

  9. Emerging Viruses in the Felidae: Shifting Paradigms

    Directory of Open Access Journals (Sweden)

    Meredith A. Brown

    2012-02-01

    Full Text Available The domestic cat is afflicted with multiple viruses that serve as powerful models for human disease including cancers, SARS and HIV/AIDS. Cat viruses that cause these diseases have been studied for decades revealing detailed insight concerning transmission, virulence, origins and pathogenesis. Here we review recent genetic advances that have questioned traditional wisdom regarding the origins of virulent Feline infectious peritonitis (FIP diseases, the pathogenic potential of Feline Immunodeficiency Virus (FIV in wild non-domestic Felidae species, and the restriction of Feline Leukemia Virus (FeLV mediated immune impairment to domestic cats rather than other Felidae species. The most recent interpretations indicate important new evolutionary conclusions implicating these deadly infectious agents in domestic and non-domestic felids.

  10. The Role of Faith-Based Organizations in the Education, Support, and Services for Persons Living with Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome.

    Science.gov (United States)

    Stephens, Teresa M

    2018-03-01

    Faith-based organizations are in a unique position to provide resilience-enhancing efforts for persons living with human immunodeficiency virus/AIDS. Many persons living with human immunodeficiency virus/AIDS report having a strong faith or religious affiliation, with a large percentage attending church services on a regular basis. Faith-based organizations can use these factors to reach out to these individuals and effectively promote health, well-being, education, and support. Faith-based organizations can contribute to the reduction of stigma and isolation for persons living with human immunodeficiency virus/AIDS. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Critical amino acids within the human immunodeficiency virus type 1 envelope glycoprotein V4 N- and C-terminals contribute to virus entry.

    Directory of Open Access Journals (Sweden)

    Yan Li

    Full Text Available The importance of the fourth variable (V4 region of the human immunodeficiency virus 1 (HIV-1 envelope glycoprotein (Env in virus infection has not been well clarified, though the polymorphism of this region has been found to be associated with disease progression to acquired immunodeficiency syndrome (AIDS. In the present work, we focused on the correlation between HIV-1 gp120 V4 region polymorphism and the function of the region on virus entry, and the possible mechanisms for how the V4 region contributes to virus infectivity. Therefore, we analyzed the differences in V4 sequences along with coreceptor usage preference from CCR5 to CXCR4 and examined the importance of the amino acids within the V4 region for CCR5- and CXCR4-tropic virus entry. In addition, we determined the influence of the V4 amino acids on Env expression and gp160 processing intracellularly, as well as the amount of Env on the pseudovirus surface. The results indicated that V4 tended to have a shorter length, fewer potential N-linked glycosylation sites (PNGS, greater evolutionary distance, and a lower negative net charge when HIV-1 isolates switched from a coreceptor usage preference for CCR5 to CXCR4. The N- and C-terminals of the HIV-1 V4 region are highly conserved and critical to maintain virus entry ability, but only the mutation at position 417 in the context of ADA (a R5-tropic HIV-1 strain resulted in the ability to utilize CXCR4. In addition, 390L, 391F, 414I, and 416L are critical to maintain gp160 processing and maturation. It is likely that the hydrophobic properties and the electrostatic surface potential of gp120, rather than the conformational structure, greatly contribute to this V4 functionality. The findings provide information to aid in the understanding of the functions of V4 in HIV-1 entry and offer a potential target to aid in the development of entry inhibitors.

  12. A Rapid and Improved Method to Generate Recombinant Dengue Virus Vaccine Candidates.

    Science.gov (United States)

    Govindarajan, Dhanasekaran; Guan, Liming; Meschino, Steven; Fridman, Arthur; Bagchi, Ansu; Pak, Irene; ter Meulen, Jan; Casimiro, Danilo R; Bett, Andrew J

    2016-01-01

    Dengue is one of the most important mosquito-borne infections accounting for severe morbidity and mortality worldwide. Recently, the tetravalent chimeric live attenuated Dengue vaccine Dengvaxia® was approved for use in several dengue endemic countries. In general, live attenuated vaccines (LAV) are very efficacious and offer long-lasting immunity against virus-induced disease. Rationally designed LAVs can be generated through reverse genetics technology, a method of generating infectious recombinant viruses from full length cDNA contained in bacterial plasmids. In vitro transcribed (IVT) viral RNA from these infectious clones is transfected into susceptible cells to generate recombinant virus. However, the generation of full-length dengue virus cDNA clones can be difficult due to the genetic instability of viral sequences in bacterial plasmids. To circumvent the need for a single plasmid containing a full length cDNA, in vitro ligation of two or three cDNA fragments contained in separate plasmids can be used to generate a full-length dengue viral cDNA template. However, in vitro ligation of multiple fragments often yields low quality template for IVT reactions, resulting in inconsistent low yield RNA. These technical difficulties make recombinant virus recovery less efficient. In this study, we describe a simple, rapid and efficient method of using LONG-PCR to recover recombinant chimeric Yellow fever dengue (CYD) viruses as potential dengue vaccine candidates. Using this method, we were able to efficiently generate several viable recombinant viruses without introducing any artificial mutations into the viral genomes. We believe that the techniques reported here will enable rapid and efficient recovery of recombinant flaviviruses for evaluation as vaccine candidates and, be applicable to the recovery of other RNA viruses.

  13. Feline immunodeficiency virus in South America.

    Science.gov (United States)

    Teixeira, Bruno M; Hagiwara, Mitika K; Cruz, Juliano C M; Hosie, Margaret J

    2012-03-01

    The rapid emergence of AIDS in humans during the period between 1980 and 2000 has led to extensive efforts to understand more fully similar etiologic agents of chronic and progressive acquired immunodeficiency disease in several mammalian species. Lentiviruses that have gene sequence homology with human immunodeficiency virus (HIV) have been found in different species (including sheep, goats, horses, cattle, cats, and several Old World monkey species). Lentiviruses, comprising a genus of the Retroviridae family, cause persistent infection that can lead to varying degrees of morbidity and mortality depending on the virus and the host species involved. Feline immunodeficiency virus (FIV) causes an immune system disease in domestic cats (Felis catus) involving depletion of the CD4+ population of T lymphocytes, increased susceptibility to opportunistic infections, and sometimes death. Viruses related to domestic cat FIV occur also in a variety of nondomestic felids. This is a brief overview of the current state of knowledge of this large and ancient group of viruses (FIVs) in South America.

  14. Enhanced tumor control of human Glioblastoma Multiforme xenografts with the concomitant use of radiotherapy and an attenuated herpes simplex-1 virus (ASTRO research fellowship)

    International Nuclear Information System (INIS)

    Song, Paul Y.; Sibley, Gregory S.; Advani, Sunil; Hallahan, Dennis; Hyland, John; Kufe, Donald W.; Chou, Joany; Roizman, Bernard; Weichselbaum, Ralph R.

    1996-01-01

    Purpose: Glioblastoma Multiforme remains one of the most incurable of human tumors. The current treatment outcomes are dismal. There are several recent reports which suggest that some human glioblastoma xenografts implanted in the brains of athymic mice may be potentially cured with the use of an attenuated herpes simplex-1 virus alone. We have chosen a replication competent, non-neurovirulent HSV-1 mutant, designated R3616 to determine whether there is an interactive cell killing and enhanced tumor control with radiotherapy in the treatment of a human glioblastoma xenograft. Materials and Methods: In vivo, 1 mm 3 pieces of U-87 human glioblastoma cell line xenografts were implanted into the right hind limb of athymic mice and grown to > 200 mm 3 . A total of 112 mice were then equally distributed within four treatment arms (see chart below) based upon tumor volume. Xenografts selected to receive virus as part of the therapy were inoculated with three injections of 2 x 10 7 plaque forming units (PFU) of R3616 virus given on day 1, 2, and 3 for a total dose of 6 x 10 7 PFU. R3616 is a non-neurovirulent HSV-1 mutant created by the deletion of the γ 34.5 gene. Local field irradiation was delivered on day 2 (20 Gy) and day 3 (25 Gy). The mice were then followed for 60 days during which time the xenografts were measured twice weekly. A clinically non-palpable tumor (< 10% original volume) was scored as a cure. In addition percent-fractional tumor volume (FTV) and mean tumor volume (MTV) were calculated for each group. Results: Conclusion: While our tumor control with R3616 alone is similar to that reported in the literature, we have seen significantly enhanced tumor control and cell killing with the addition of RT suggesting a synergistic interaction between an oncolytic virus and radiation in the treatment of human glioblastoma multiforme xenografts

  15. The value of haematological screening for AIDS in an at risk population

    OpenAIRE

    1986-01-01

    The haematological variables measured by automated full blood count in matched homosexual and heterosexual men attending a clinic for sexually transmitted diseases (STD) were compared with those of normal controls and patients infected with the human T lymphotropic virus type III (HTLV-III). Homosexual and heterosexual men were statistically identical for all variables, but both differed noticeably from patients with clinical diagnoses of the acquired immune deficiency syndrome (AIDS) or AIDS...

  16. The Medical Research Council (UK)/Uganda Virus Research Institute Uganda Research Unit on AIDS--'25 years of research through partnerships'.

    Science.gov (United States)

    Kaleebu, P; Kamali, A; Seeley, J; Elliott, A M; Katongole-Mbidde, E

    2015-02-01

    For the past 25 years, the Medical Research Council/Uganda Virus Research Institute Uganda Research Unit on AIDS has conducted research on HIV-1, coinfections and, more recently, on non-communicable diseases. Working with various partners, the research findings of the Unit have contributed to the understanding and control of the HIV epidemic both in Uganda and globally, and informed the future development of biomedical HIV interventions, health policy and practice. In this report, as we celebrate our silver jubilee, we describe some of these achievements and the Unit's multidisciplinary approach to research. We also discuss the future direction of the Unit; an exemplar of a partnership that has been largely funded from the north but led in the south. © 2014 The Authors. Tropical Medicine & International Health Published by John Wiley & Sons Ltd.

  17. Viroporin Activity of the Foot-and-Mouth Disease Virus Non-Structural 2B Protein.

    Directory of Open Access Journals (Sweden)

    Da Ao

    Full Text Available Viroporins are a family of low-molecular-weight hydrophobic transmembrane proteins that are encoded by various animal viruses. Viroporins form transmembrane pores in host cells via oligomerization, thereby destroying cellular homeostasis and inducing cytopathy for virus replication and virion release. Among the Picornaviridae family of viruses, the 2B protein encoded by enteroviruses is well understood, whereas the viroporin activity of the 2B protein encoded by the foot-and-mouth disease virus (FMDV has not yet been described. An analysis of the FMDV 2B protein domains by computer-aided programs conducted in this study revealed that this protein may contain two transmembrane regions. Further biochemical, biophysical and functional studies revealed that the protein possesses a number of features typical of a viroporin when it is overexpressed in bacterial and mammalian cells as well as in FMDV-infected cells. The protein was found to be mainly localized in the endoplasmic reticulum (ER, with both the N- and C-terminal domains stretched into the cytosol. It exhibited cytotoxicity in Escherichia coli, which attenuated 2B protein expression. The release of virions from cells infected with FMDV was inhibited by amantadine, a viroporin inhibitor. The 2B protein monomers interacted with each other to form both intracellular and extracellular oligomers. The Ca(2+ concentration in the cells increased, and the integrity of the cytoplasmic membrane was disrupted in cells that expressed the 2B protein. Moreover, the 2B protein induced intense autophagy in host cells. All of the results of this study demonstrate that the FMDV 2B protein has properties that are also found in other viroporins and may be involved in the infection mechanism of FMDV.

  18. HIV/AIDS vaccines for Africa: scientific opportunities, challenges and strategies

    Science.gov (United States)

    Chin'ombe, Nyasha; Ruhanya, Vurayai

    2015-01-01

    More than decades have already elapsed since human immunodeficiency virus (HIV) was identified as the causative agent of acquired immunodeficiency syndrome (AIDS). The HIV has since spread to all parts of the world with devastating effects. In sub-saharan Africa, the HIV/AIDS epidemic has reached unprecedented proportions. Safe, effective and affordable HIV/AIDS vaccines for Africans are therefore urgently needed to contain this public health problem. Although, there are challenges, there are also scientific opportunities and strategies that can be exploited in the development of HIV/AIDS vaccines for Africa. The recent RV144 Phase III trial in Thailand has demonstrated that it is possible to develop a vaccine that can potentially elicit modest protective immunity against HIV infection. The main objective of this review is to outline the key scientific opportunities, challenges and strategies in HIV/AIDS vaccine development in Africa. PMID:26185576

  19. Gendered differences in AIDS and AIDS-related cause of death among youth with secondary education in South Africa, 2009-2011.

    Science.gov (United States)

    De Wet, Nicole

    2016-12-01

    The prevalence of human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) is higher among females than males in Sub-Saharan Africa. Education is associated with better health outcomes. For this and other reasons, African countries have made a concerted effort to increase youth education rates. However, in South Africa males have lower secondary education rates than females, yet females have a higher prevalence of HIV/AIDS. This study examines if a gender disparity exists in AIDS mortality rates among youth with secondary education in South Africa. This study uses descriptive statistics and life table techniques. A sample of 4386 deaths of youth with secondary education is used. Of this total sample, 987 deaths were among males and 340 were among females with secondary education. This study shows that AIDS mortality is higher among females than males in South Africa. Males and females with secondary education have lower AIDS mortality than all males and females in the population, yet the rates are higher for females. Using cause-deleted life tables, the probability of youth dying from HIV/AIDS practically disappears for both males and females. Odds ratio calculations show that secondary education does not have a protective effect from AIDS mortality among male and female youth. Given the gendered difference in AIDS mortality among youth with secondary education, efforts to increase secondary education among males and further research into other factors exacerbating AIDS mortality among females with secondary education is needed in the country.

  20. Spinal cord toxoplasmosis in human immunodeficiency virus infection/acquired immunodeficiency syndrome.

    Science.gov (United States)

    García-García, Concepción; Castillo-Álvarez, Federico; Azcona-Gutiérrez, José M; Herraiz, María J; Ibarra, Valvanera; Oteo, José A

    2015-05-01

    Neurological complications in patients with human immunodeficiency virus infection/acquired immunodeficiency syndrome (HIV/AIDS) are still common, even in the era of highly active antiretroviral therapy. Opportunistic infections, immune reconstitution, the virus itself, antiretroviral drugs and neurocognitive disorders have to be considered when establishing the differential diagnosis. Toxoplasmic encephalitis remains the major cause of space-occupying lesions in the brain of patients with HIV/AIDS; however, spinal cord involvement has been reported infrequently. Here, we review spinal cord toxoplasmosis in HIV infection and illustrate the condition with a recent case from our hospital. We suggest that most patients with HIV/AIDS and myelitis with enhanced spine lesions, multiple brain lesions and positive serology for Toxoplasma gondii should receive immediate empirical treatment for toxoplasmosis, and a biopsy should be performed in those cases without clinical improvement or with deterioration.

  1. Nucleocytoplasmic transport of nucleocapsid proteins of enveloped RNA viruses

    Directory of Open Access Journals (Sweden)

    Wahyu eWulan

    2015-06-01

    Full Text Available Most viruses with non-segmented single stranded RNA genomes complete their life cycle in the cytoplasm of infected cells. However, despite undergoing replication in the cytoplasm, the structural proteins of some of these RNA viruses localize to the nucleus at specific times in the virus life cycle, primarily early in infection. Limited evidence suggests that this enhances successful viral replication by interfering with or inhibiting the host antiviral response. Nucleocapsid proteins of RNA viruses have a well-established, essential cytoplasmic role in virus replication and assembly. Intriguingly, nucleocapsid proteins of some RNA viruses also localize to the nucleus/nucleolus of infected cells. Their nuclear function is less well understood although significant advances have been made in recent years. This review will focus on the nucleocapsid protein of cytoplasmic enveloped RNA viruses, including their localization to the nucleus/nucleolus and function therein. A greater understanding of the nuclear localization of nucleocapsid proteins has the potential to enhance therapeutic strategies as it can be a target for the development of live-attenuated vaccines or antiviral drugs.

  2. Recombinant cold-adapted attenuated influenza A vaccines for use in children: molecular genetic analysis of the cold-adapted donor and recombinants.

    OpenAIRE

    Ghendon, Y Z; Polezhaev, F I; Lisovskaya, K V; Medvedeva, T E; Alexandrova, G I; Klimov, A I

    1984-01-01

    A previously described cold-adapted attenuated virus, A/Leningrad/134/17/57 (H2N2), was further modified by 30 additional passages in chicken embryos at 25 degrees C. This virus had a distinct temperature-sensitive (ts) phenotype, grew well in chicken embryos at 25 degrees C, and failed to recombine with reference ts mutants of fowl plague virus containing ts lesions in five genes coding for non-glycosylated proteins (genes 1, 2, 5, 7, and 8). Recombination of A/Leningrad/134/47/57 with wild-...

  3. Proof-of-principle that a decoy virus protects oncolytic measles virus against neutralizing antibodies

    OpenAIRE

    Xu C; Goß AV; Dorneburg C; Debatin KM; Wei J; Beltinger C

    2018-01-01

    Chun Xu,1,2,* Annika Verena Goß,1,* Carmen Dorneburg,1 Klaus-Michael Debatin,1 Jiwu Wei,2 Christian Beltinger1 1Department of Pediatrics and Adolescent Medicine, Section of Experimental Pediatric Oncology, University Medical Center Ulm, Ulm, Germany; 2Jiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University, China *These authors contributed equally to this work Background: Attenuated oncolytic measles virus (OMV) is a promising antitumor agent in early-phase cl...

  4. Designing herpes viruses as oncolytics

    Science.gov (United States)

    Peters, Cole; Rabkin, Samuel D

    2015-01-01

    Oncolytic herpes simplex virus (oHSV) was one of the first genetically-engineered oncolytic viruses. Because HSV is a natural human pathogen that can cause serious disease, it is incumbent that it can be genetically-engineered or significantly attenuated for safety. Here, we present a detailed explanation of the functions of HSV-1 genes frequently mutated to endow oncolytic activity. These genes are nonessential for growth in tissue culture cells but are important for growth in postmitotic cells, interfering with intrinsic antiviral and innate immune responses or causing pathology, functions dispensable for replication in cancer cells. Understanding the function of these genes leads to informed creation of new oHSVs with better therapeutic efficacy. Virus infection and replication can also be directed to cancer cells through tumor-selective receptor binding and transcriptional- or post-transcriptional miRNA-targeting, respectively. In addition to the direct effects of oHSV on infected cancer cells and tumors, oHSV can be “armed” with transgenes that are: reporters, to track virus replication and spread; cytotoxic, to kill uninfected tumor cells; immune modulatory, to stimulate antitumor immunity; or tumor microenvironment altering, to enhance virus spread or to inhibit tumor growth. In addition to HSV-1, other alphaherpesviruses are also discussed for their oncolytic activity. PMID:26462293

  5. Ocular Adnexal and Anterior Segment Manifestations of HIV/AIDS ...

    African Journals Online (AJOL)

    Background: Benue State has the highest rate of sero-prevalence to human immuno virus (HIV) infections among the ten hyper-endemic states in Nigeria. This study evaluates the pattern of ocular adnexal and anterior segment manifestations in HIV/AIDS patients attending the HIV clinic at the NAF Hospital in Makurdi, ...

  6. A constitution for AIDS.

    Science.gov (United States)

    Koshy, L M

    1996-01-15

    The Indian Health Organization projected the number of deaths per day due to AIDS by the year 2000 at 10,000. An interdisciplinary international conference was held in New Delhi to draft an international law governing the issues related to AIDS. Human freedom and public health policies are the most affected by this disease. In the absence of an international AIDS law, judicial verdicts set precedents and could have serious ramifications. A participant from the John Marshall Law School, Chicago, suggested that instead of making new laws, the existing ones from the colonial past should be repealed. This includes Section 377 of the Indian Penal Code, which provides criminal sanctions against those who indulge in unnatural relations with man, woman, or animal. Penalizing homosexuality will only perpetuate clandestine relations and spread the virus into their families. Another participant seconded this motion stating that even a sex worker must be protected from abuse and indignity. The National AIDS Control Organization responded to the criticism that the government had not utilized all the World Bank funds allocated for anti-AIDS projects. The trends of the epidemic were the most important indicators not just the numbers. In Manipur and Mizoram, infection was almost entirely due to injecting drug use. The Saheli project undertaken in the red-light areas of Bombay encompassed brothel owners and prostitutes, which could be replicated in other areas. Because existing government policies were focusing on prevention, there was no protection of an HIV-infected individual's privacy, one participant from Madras stated. The confidentiality issue was also echoed by a US participant. The New Delhi Declaration and Action Plan on HIV/AIDS was also discussed. It forbids discrimination in employment, education, housing, health care, social security, travel, and marital and reproductive rights. Providing sterile needles and ensuring the safety of the blood supply were other concerns

  7. Virus-neutralizing antibody response of mice to consecutive infection with human and avian influenza A viruses.

    Science.gov (United States)

    Janulíková, J; Stropkovská, A; Bobišová, Z; Košík, I; Mucha, V; Kostolanský, F; Varečková, E

    2015-06-01

    In this work we simulated in a mouse model a naturally occurring situation of humans, who overcame an infection with epidemic strains of influenza A, and were subsequently exposed to avian influenza A viruses (IAV). The antibody response to avian IAV in mice previously infected with human IAV was analyzed. We used two avian IAV (A/Duck/Czechoslovakia/1956 (H4N6) and the attenuated virus rA/Viet Nam/1203-2004 (H5N1)) as well as two human IAV isolates (virus A/Mississippi/1/1985 (H3N2) of medium virulence and A/Puerto Rico/8/1934 (H1N1) of high virulence). Two repeated doses of IAV of H4 or of H5 virus elicited virus-specific neutralizing antibodies in mice. Exposure of animals previously infected with human IAV (of H3 or H1 subtype) to IAV of H4 subtype led to the production of antibodies neutralizing H4 virus in a level comparable with the level of antibodies against the human IAV used for primary infection. In contrast, no measurable levels of virus-neutralizing (VN) antibodies specific to H5 virus were detected in mice infected with H5 virus following a previous infection with human IAV. In both cases the secondary infection with avian IAV led to a significant increase of the titer of VN antibodies specific to the corresponding human virus used for primary infection. Moreover, cross-reactive HA2-specific antibodies were also induced by sequential infection. By virtue of these results we suggest that the differences in the ability of avian IAV to induce specific antibodies inhibiting virus replication after previous infection of mice with human viruses can have an impact on the interspecies transmission and spread of avian IAV in the human population.

  8. AIDS--viden, adfaerd og holdning på Aarhus Universitet i 1990. En spørgeskemaundersøgelse

    DEFF Research Database (Denmark)

    Andersen, M R; Nielsen, I; Nørrelund, Helene

    1993-01-01

    %) were returned. The study group had an excellent knowledge about AIDS and the transmission of HIV-virus. However, when defining "risk behaviour" in relation to transmission of HIV-virus among heterosexuals as "> or = 2 sexual partners within the past year without using condoms" 27% of the male and 20...

  9. Recombinant infectious bronchitis virus (IBV) H120 vaccine strain expressing the hemagglutinin-neuraminidase (HN) protein of Newcastle disease virus (NDV) protects chickens against IBV and NDV challenge.

    Science.gov (United States)

    Yang, Xin; Zhou, Yingshun; Li, Jianan; Fu, Li; Ji, Gaosheng; Zeng, Fanya; Zhou, Long; Gao, Wenqian; Wang, Hongning

    2016-05-01

    Infectious bronchitis (IB) and Newcastle disease (ND) are common viral diseases of chickens, which are caused by infectious bronchitis virus (IBV) and Newcastle disease virus (NDV), respectively. Vaccination with live attenuated strains of IBV-H120 and NDV-LaSota are important for the control of IB and ND. However, conventional live attenuated vaccines are expensive and result in the inability to differentiate between infected and vaccinated chickens. Therefore, there is an urgent need to develop new efficacious vaccines. In this study, using a previously established reverse genetics system, we generated a recombinant IBV virus based on the IBV H120 vaccine strain expressing the haemagglutinin-neuraminidase (HN) protein of NDV. The recombinant virus, R-H120-HN/5a, exhibited growth dynamics, pathogenicity and viral titers that were similar to those of the parental IBV H120, but it had acquired hemagglutination activity from NDV. Vaccination of SPF chickens with the R-H120-HN/5a virus induced a humoral response at a level comparable to that of the LaSota/H120 commercial bivalent vaccine and provided significant protection against challenge with virulent IBV and NDV. In summary, the results of this study indicate that the IBV H120 strain could serve as an effective tool for designing vaccines against IB and other infectious diseases, and the generation of IBV R-H120-HN/5a provides a solid foundation for the development of an effective bivalent vaccine against IBV and NDV.

  10. Using participatory action research to develop an HIV and Aids ...

    African Journals Online (AJOL)

    Using participatory action research to develop an HIV and Aids school plan. ... South African Journal of Education ... In this article we report on the manner in which participatory action research (PAR) was utilised by teachers in developing a Human Immunodeficiency Virus (HIV) and Acquired Immunodeficiency Syndrome ...

  11. Facilitating Support Groups for Professionals Working with People with AIDS.

    Science.gov (United States)

    Grossman, Arnold H.; Silverstein, Charles

    1993-01-01

    Describes support groups for health care professionals who work with people with human immunodeficiency virus (HIV) or Acquired Immune Deficiency Syndrome (AIDS) and who are experiencing burnout from excessive demands on their energy, strength, and resources. Discusses group administration, effective intervention techniques, and issues of health…

  12. Antigenic variants of yellow fever virus with an altered neurovirulence phenotype in mice.

    Science.gov (United States)

    Ryman, K D; Xie, H; Ledger, T N; Campbell, G A; Barrett, A D

    1997-04-14

    The live-attenuated yellow fever (YF) vaccine virus, strain 17D-204, has long been known to consist of a heterologous population of virions. Gould et al. (J. Gen. Virol. 70, 1889-1894 (1989)) previously demonstrated that variant viruses exhibiting a YF wild-type-specific envelope (E) protein epitope are present at low frequency in the vaccine pool and were able to isolate representative virus variants with and without this epitope, designated 17D(+wt) and 17D(-wt), respectively. These variants were employed here in an investigation of YF virus pathogenesis in the mouse model. Both the 17D-204 parent and the 17D(+wt) variant viruses were lethal for adult outbred mice by the intracerebral route of inoculation. However, the 17D(-wt) variant was significantly attenuated (18% mortality rate) and replicated to much lower titer in the brains of infected mice. A single amino acid substitution in the envelope (E) protein at E-240 (Ala-->Val) was identified as responsible for the restricted replication of the 17D(-wt) variant in vivo. The 17D(+wt) variant has an additional second-site mutation, believed to encode a reversion to the neurovirulence phenotype of the 17D-204 parent virus. The amino acid substitution in the E protein at E-173 (Thr-->Ile) of the 17D(+wt) variant which results in the appearance of the wild-type-specific epitope or nucleotide changes in the 5' and 3' noncoding regions of the virus are proposed as a candidates.

  13. AIDS. 1st annual George H. Gallup Memorial Survey.

    Science.gov (United States)

    1988-06-01

    Acquired immunodeficiency syndrome (AIDS) was selected as the subject for the 1st annual George H Gallup Memorial Survey. This survey, conducted in August 1987-April 1988 in 35 countries, measured the level of awareness of AIDS, the extent of concern about AIDS, knowledge, changes in behavior resulting form the AIDS epidemic, and attitudes toward people with AIDS. Overall, the poll's findings attest to the effectiveness of the health education efforts of governmental and nongovernmental organizations. Awareness that AIDS poses an urgent international health problem was almost universal in the 35 samples. In about half of these countries, AIDS was identified as the most important national health problem; in the remaining countries, AIDS was ranked 2nd to cancer. The proportion of respondents expressing a fear of personally contracting the AIDS virus ranged from lows of under 10% in most of Europe to a high of 45% among South African blacks. A majority of respondents in the US, Colombia, the Philippines, Brazil, Nigeria, Ecuador, El Salvador, and Chile believed that AIDS will soon spread beyond current risk groups to the general population. Despite widespread awareness of the grave threat posed by AIDS, insufficient numbers of respondents reported that they had made specific behavioral changes intended to protect themselves form HIV infection. Overall, about half of those interviewed indicated they are now more cautious in their choice of sexual partners; similarly, about half are using condoms more or for the 1st time.

  14. The emergence of HIV/AIDS in the Americas and beyond

    DEFF Research Database (Denmark)

    Gilbert, M Thomas P; Rambaut, Andrew; Wlasiuk, Gabriela

    2007-01-01

    HIV-1 group M subtype B was the first HIV discovered and is the predominant variant of AIDS virus in most countries outside of sub-Saharan Africa. However, the circumstances of its origin and emergence remain unresolved. Here we propose a geographic sequence and time line for the origin of subtype...... B and the emergence of pandemic HIV/AIDS out of Africa. Using HIV-1 gene sequences recovered from archival samples from some of the earliest known Haitian AIDS patients, we find that subtype B likely moved from Africa to Haiti in or around 1966 (1962-1970) and then spread there for some years before...... HIV/AIDS epidemic outside sub-Saharan Africa and the most genetically diverse subtype B epidemic, which might present challenges for HIV-1 vaccine design and testing. The emergence of the pandemic variant of subtype B was an important turning point in the history of AIDS, but its spread was likely...

  15. Human immunodeficiency virus/human parvovirus B19 co-infection in blood donors and AIDS patients in Sichuan, China

    Science.gov (United States)

    He, Miao; Zhu, Jiang; Yin, Huimin; Ke, Ling; Gao, Lei; Pan, Zhihong; Yang, Xiuhua; Li, Wuping

    2012-01-01

    Background Human parvovirus B19 (B19) is a common pathogen which causes a variety of diseases. Persistent B19 infection is related to the degree of host immunodeficiency in patients with human immunodeficiency virus (HIV) infection. However, the existence, loading, virus evolution and distribution of B19 in Chinese HIV-positive patients have not been determined. Materials and methods. We investigated 573 HIV-positive blood donors and AIDS patients in Sichuan, China in the last two decades. Bl9-specific serology and quantitative polymerase chain reaction were used to determine the prevalence of B19/HIV co-infection. Viral genome fragments were subjected to phylogeny and haplotype analysis. Results B19 genomic DNA was found in 26 of 573 (4.5%) HIV-positive individuals, a higher prevalence than in blood donors. DNA levels ranged from 5.3×102–1.1×105 copies/mL. The seroprevalence of IgG was significantly lower in HIV-positive samples than in HIV-negative blood donors, indicating deficient production of B19-specific IgG in the former. The B19 isolates were genotype-1 subtype B19-1A which formed a monophyletic group; seven distinct haplotypes were discovered with 60% of the B19/HIV co-infected variants sharing one central haplotype. Discussion. This study on the prevalence, phylogeny and distribution of human parvovirus B19 in Sichuan, China, demonstrates the persistence of B19 in the circulation of both immunocompetent and immunocompromised subjects, with implications for blood safety. PMID:22790259

  16. A Rapid and Improved Method to Generate Recombinant Dengue Virus Vaccine Candidates.

    Directory of Open Access Journals (Sweden)

    Dhanasekaran Govindarajan

    Full Text Available Dengue is one of the most important mosquito-borne infections accounting for severe morbidity and mortality worldwide. Recently, the tetravalent chimeric live attenuated Dengue vaccine Dengvaxia® was approved for use in several dengue endemic countries. In general, live attenuated vaccines (LAV are very efficacious and offer long-lasting immunity against virus-induced disease. Rationally designed LAVs can be generated through reverse genetics technology, a method of generating infectious recombinant viruses from full length cDNA contained in bacterial plasmids. In vitro transcribed (IVT viral RNA from these infectious clones is transfected into susceptible cells to generate recombinant virus. However, the generation of full-length dengue virus cDNA clones can be difficult due to the genetic instability of viral sequences in bacterial plasmids. To circumvent the need for a single plasmid containing a full length cDNA, in vitro ligation of two or three cDNA fragments contained in separate plasmids can be used to generate a full-length dengue viral cDNA template. However, in vitro ligation of multiple fragments often yields low quality template for IVT reactions, resulting in inconsistent low yield RNA. These technical difficulties make recombinant virus recovery less efficient. In this study, we describe a simple, rapid and efficient method of using LONG-PCR to recover recombinant chimeric Yellow fever dengue (CYD viruses as potential dengue vaccine candidates. Using this method, we were able to efficiently generate several viable recombinant viruses without introducing any artificial mutations into the viral genomes. We believe that the techniques reported here will enable rapid and efficient recovery of recombinant flaviviruses for evaluation as vaccine candidates and, be applicable to the recovery of other RNA viruses.

  17. Horizontal transmissible protection against myxomatosis and rabbit hemorrhagic disease by using a recombinant myxoma virus.

    Science.gov (United States)

    Bárcena, J; Morales, M; Vázquez, B; Boga, J A; Parra, F; Lucientes, J; Pagès-Manté, A; Sánchez-Vizcaíno, J M; Blasco, R; Torres, J M

    2000-02-01

    We have developed a new strategy for immunization of wild rabbit populations against myxomatosis and rabbit hemorrhagic disease (RHD) that uses recombinant viruses based on a naturally attenuated field strain of myxoma virus (MV). The recombinant viruses expressed the RHDV major capsid protein (VP60) including a linear epitope tag from the transmissible gastroenteritis virus (TGEV) nucleoprotein. Following inoculation, the recombinant viruses induced specific antibody responses against MV, RHDV, and the TGEV tag. Immunization of wild rabbits by the subcutaneous and oral routes conferred protection against virulent RHDV and MV challenges. The recombinant viruses showed a limited horizontal transmission capacity, either by direct contact or in a flea-mediated process, promoting immunization of contact uninoculated animals.

  18. Subjective knowledge of AIDS and use of HIV testing.

    Science.gov (United States)

    Phillips, K A

    1993-10-01

    Increasing knowledge is an important goal of human immunodeficiency virus (HIV) prevention strategies, although increased knowledge may not be associated with increased preventive behaviors. This study examines the association of (1) objective and subjective acquired immunodeficiency syndrome (AIDS) knowledge, and (2) both objective and subjective AIDS knowledge with HIV testing use. Data are from the 1988 National Health Interview Survey. Objective and subjective knowledge were only moderately correlated. In regression analyses, higher subjective knowledge was significantly associated with higher testing use, but objective knowledge was not. The results are relevant to other preventive behaviors for which knowledge is an important factor.

  19. A situational analysis of HIV and AIDS in Pakistan

    Directory of Open Access Journals (Sweden)

    Sarwar Muhammad

    2011-04-01

    Full Text Available Abstract HIV (Human immunodeficiency virus transmission has been reduced by protected sex and screening of blood products and other body fluids in the developed countries. It has been reported that Pakistan is at high risk of HIV/AIDS infection but presently the prevalence rate is considerably low. The number of reported cases of HIV/AIDS in Pakistan has been continuously increasing since 1987. By 2010 the total number of registered cases has reached to 6000 and this figure is on the rise with the passage of time. Some serious strategies must be implemented to control this deadly disease.

  20. Mutation of the N-Terminal Region of Chikungunya Virus Capsid Protein: Implications for Vaccine Design.

    Science.gov (United States)

    Taylor, Adam; Liu, Xiang; Zaid, Ali; Goh, Lucas Y H; Hobson-Peters, Jody; Hall, Roy A; Merits, Andres; Mahalingam, Suresh

    2017-02-21

    Mosquito-transmitted chikungunya virus (CHIKV) is an arthritogenic alphavirus of the Togaviridae family responsible for frequent outbreaks of arthritic disease in humans. Capsid protein, a structural protein encoded by the CHIKV RNA genome, is able to translocate to the host cell nucleolus. In encephalitic alphaviruses, nuclear translocation induces host cell transcriptional shutoff; however, the role of capsid protein nucleolar localization in arthritogenic alphaviruses remains unclear. Using recombinant enhanced green fluorescent protein (EGFP)-tagged expression constructs and CHIKV infectious clones, we describe a nucleolar localization sequence (NoLS) in the N-terminal region of capsid protein, previously uncharacterized in CHIKV. Mutation of the NoLS by site-directed mutagenesis reduced efficiency of nuclear import of CHIKV capsid protein. In the virus, mutation of the capsid protein NoLS (CHIKV-NoLS) attenuated replication in mammalian and mosquito cells, producing a small-plaque phenotype. Attenuation of CHIKV-NoLS is likely due to disruption of the viral replication cycle downstream of viral RNA synthesis. In mice, CHIKV-NoLS infection caused no disease signs compared to wild-type CHIKV (CHIKV-WT)-infected mice; lack of disease signs correlated with significantly reduced viremia and decreased expression of proinflammatory factors. Mice immunized with CHIKV-NoLS, challenged with CHIKV-WT at 30 days postimmunization, develop no disease signs and no detectable viremia. Serum from CHIKV-NoLS-immunized mice is able to efficiently neutralize CHIKV infection in vitro Additionally, CHIKV-NoLS-immunized mice challenged with the related alphavirus Ross River virus showed reduced early and peak viremia postchallenge, indicating a cross-protective effect. The high degree of CHIKV-NoLS attenuation may improve CHIKV antiviral and rational vaccine design. IMPORTANCE CHIKV is a mosquito-borne pathogen capable of causing explosive epidemics of incapacitating joint pain

  1. Protection of macaques with diverse MHC genotypes against a heterologous SIV by vaccination with a deglycosylated live-attenuated SIV.

    Directory of Open Access Journals (Sweden)

    Chie Sugimoto

    Full Text Available HIV vaccine development has been hampered by issues such as undefined correlates of protection and extensive diversity of HIV. We addressed these issues using a previously established SIV-macaque model in which SIV mutants with deletions of multiple gp120 N-glycans function as potent live attenuated vaccines to induce near-sterile immunity against the parental pathogenic SIVmac239. In this study, we investigated the protective efficacy of these mutants against a highly pathogenic heterologous SIVsmE543-3 delivered intravenously to rhesus macaques with diverse MHC genotypes. All 11 vaccinated macaques contained the acute-phase infection with blood viral loads below the level of detection between 4 and 10 weeks postchallenge (pc, following a transient but marginal peak of viral replication at 2 weeks in only half of the challenged animals. In the chronic phase, seven vaccinees contained viral replication for over 80 weeks pc, while four did not. Neutralizing antibodies against challenge virus were not detected. Although overall levels of SIV specific T cell responses did not correlate with containment of acute and chronic viral replication, a critical role of cellular responses in the containment of viral replication was suggested. Emergence of viruses with altered fitness due to recombination between the vaccine and challenge viruses and increased gp120 glycosylation was linked to the failure to control SIV. These results demonstrate the induction of effective protective immune responses in a significant number of animals against heterologous virus by infection with deglycosylated attenuated SIV mutants in macaques with highly diverse MHC background. These findings suggest that broad HIV cross clade protection is possible, even in hosts with diverse genetic backgrounds. In summary, results of this study indicate that deglycosylated live-attenuated vaccines may provide a platform for the elucidation of correlates of protection needed for a

  2. HIV/AIDS and older adults in Cameroon: Emerging issues and ...

    African Journals Online (AJOL)

    The burden of human immunodeficiency virus (HIV) infection and acquired immune deficiency syndrome (AIDS) on the elderly population in three divisions within the Northwest Region of Cameroon was examined. Data for this paper were extracted from a larger study which had been conducted concerning the burden of ...

  3. Malaysia urges ASEAN to tackle AIDS crisis.

    Science.gov (United States)

    2000-08-07

    Urgent action is needed to fight the alarming spread of HIV/AIDS that infected 1.3 million people in Southeast Asia last year alone, Malaysia's foreign minister said July 24, 2000. Syed Hamid said the Association of Southeast Asian Nations (ASEAN) should tackle at regional and national level an epidemic that was taking its most drastic toll among the region's youth. "HIV/AIDS not only represents a major public health and social problem but is a serious challenge to development as well," Syed Hamid told the opening ceremony of ASEAN's 33rd annual foreign ministers' meeting. The crisis requires commitment at the "highest political level," he said, warning that HIV/AIDS could become a transnational problem within the 10-member group. Foreign ministers have recommended their leaders discuss the crisis later this year at an informal summit in Singapore and hold a summit on HIV/AIDS in conjunction with the 7th ASEAN Summit in Brunei next year. "I think people recognized the importance and the adverse impacts on our social development," Syed Hamid told reporters later. "I think it is a real issue that we cannot run away from." Among ASEAN members, Thailand, Cambodia, and Myanmar have some of the highest infection rates in Asia of HIV, the virus that causes AIDS. full text

  4. Characterization of Rift Valley fever virus MP-12 strain encoding NSs of Punta Toro virus or sandfly fever Sicilian virus.

    Science.gov (United States)

    Lihoradova, Olga A; Indran, Sabarish V; Kalveram, Birte; Lokugamage, Nandadeva; Head, Jennifer A; Gong, Bin; Tigabu, Bersabeh; Juelich, Terry L; Freiberg, Alexander N; Ikegami, Tetsuro

    2013-01-01

    Rift Valley fever virus (RVFV; genus Phlebovirus, family Bunyaviridae) is a mosquito-borne zoonotic pathogen which can cause hemorrhagic fever, neurological disorders or blindness in humans, and a high rate of abortion in ruminants. MP-12 strain, a live-attenuated candidate vaccine, is attenuated in the M- and L-segments, but the S-segment retains the virulent phenotype. MP-12 was manufactured as an Investigational New Drug vaccine by using MRC-5 cells and encodes a functional NSs gene, the major virulence factor of RVFV which 1) induces a shutoff of the host transcription, 2) inhibits interferon (IFN)-β promoter activation, and 3) promotes the degradation of dsRNA-dependent protein kinase (PKR). MP-12 lacks a marker for differentiation of infected from vaccinated animals (DIVA). Although MP-12 lacking NSs works for DIVA, it does not replicate efficiently in type-I IFN-competent MRC-5 cells, while the use of type-I IFN-incompetent cells may negatively affect its genetic stability. To generate modified MP-12 vaccine candidates encoding a DIVA marker, while still replicating efficiently in MRC-5 cells, we generated recombinant MP-12 encoding Punta Toro virus Adames strain NSs (rMP12-PTNSs) or Sandfly fever Sicilian virus NSs (rMP12-SFSNSs) in place of MP-12 NSs. We have demonstrated that those recombinant MP-12 viruses inhibit IFN-β mRNA synthesis, yet do not promote the degradation of PKR. The rMP12-PTNSs, but not rMP12-SFSNSs, replicated more efficiently than recombinant MP-12 lacking NSs in MRC-5 cells. Mice vaccinated with rMP12-PTNSs or rMP12-SFSNSs induced neutralizing antibodies at a level equivalent to those vaccinated with MP-12, and were efficiently protected from wild-type RVFV challenge. The rMP12-PTNSs and rMP12-SFSNSs did not induce antibodies cross-reactive to anti-RVFV NSs antibody and are therefore applicable to DIVA. Thus, rMP12-PTNSs is highly efficacious, replicates efficiently in MRC-5 cells, and encodes a DIVA marker, all of which are

  5. HIV/AIDS Pandemia — a Problem Requiring Rethinking On the 30th Anniversary of the Discovery of Human Immunodeficiency Virus

    Directory of Open Access Journals (Sweden)

    M.V. Supotnitsky

    2014-09-01

    Full Text Available Hazard of HIV/AIDS pandemia is greatly underestimated due to lack of understanding of its role in the processes that are not related to medicine. The principal difference between HIV/AIDS pandemia and the pandemic processes, against which the advances were made in the ХХ century, lies in the fact that it is caused by a virus of the retrovirus family. Retroviruses are ancient tools of evolution. They cause epidemia (epizooty, which are the main mechanism of discontinuous evolution of species. This mechanism is implemented by endogenization of retroviruses in the genome of the surviving species and amplification of their genome through the formation of new copies of retroelements; complexity of the genome by the formation of new exons from introns and/or increased number of genes that are alternatively spliced. Evolutionary past of the immune system of multicellular organisms suggests securing her in the process of natural selection as the reservoir with respect to retroviruses. Thanks to the cells of the immune system there is the multiplication and accumulation of exogenous retroviruses to a certain critical mass, which allows some of them to endogenize in the germline of some specimens of infected species and further transmitted vertically, changing its evolutionary trajectory. HIV/AIDS pandemia among the species homo sapiens — a common manifestation of this process in the evolution of primate taxon. Infectious and epidemic processes caused by HIV, are multicomponent non-cyclic processes that have no mechanisms for termination. To fight with them, experience gained in the XX century during smallpox eradication or in when controlling outbreaks of influenza, plague and other cyclical infections is inapplicable. Given in the article data indicate the need to develop self-control strategy to fight against non-cyclic multicomponent epidemic processes.

  6. My secret: the social meaning of HIV/AIDS stigma.

    Science.gov (United States)

    Judgeo, N; Moalusi, K P

    2014-01-01

    This study uses Goffman's [1963. Stigma: Notes on the Management of Spoiled Identity, New Jersey, Prentice-Hall] theory of stigma as an intellectual scaffold to help understand the social meaning of HIV/AIDS stigma from People Living with HIV/AIDS. The study adopts a qualitative approach because of its appropriateness for unravelling subjective phenomena such as the experiences of HIV/AIDS stigma. In-depth interviews were conducted with 10 HIV-positive employees of a retailing company located in the Western Cape province of South Africa who volunteered to participate in the study. The participants with the discreditable stigma internalised society's prejudice towards those living with the virus. As a result, the participants relied on self-isolation and social withdrawal to cope with enacted stigma. Managing information about one's status and deciding whether, who, when, etc., to tell are crucial questions. The participants feared being devalued by family, friends, co-workers and the community. In concurrence with Goffman [1963], the HIV/AIDS stigma is seen as about relationships.

  7. Gender and HIV/AIDS: Exploring Men and Vulnerability Towards Effective HIV/AIDS Policy Interventions and Sub-Saharan Africa

    Directory of Open Access Journals (Sweden)

    Ogochukwu Nzewi

    2012-06-01

    Full Text Available This article examines the dynamics between HIV/Aids gender policy strategies and the socio-political demands on HIV/Aids interventions in sub-Saharan Africa. Gender in HIV/Aids intervention seems inescapable. Nowhere else is this more marked than in the social dimensions of HIV/Aids prevention in sub-Saharan Africa. This has resulted in prevention strategies, which are encumbered by the reality of poverty, gender, access, power and the various debates on behavioural change. The social constructions of gender roles and power relations play a significant role in the region’s HIV /Aids dynamic. To this end, the mainstreaming of gender issues into national political, social and economic agenda and policies has been championed by international development and economic institutions. In developing HIV/Aids intervention policies, gender has also been mainstreamed, especially where epidemiological data show the disparity in infection rates between men and women, where women are seen as more susceptible to infection. The gendered approach to HIV/Aids appears to typecast women as the vulnerable and suffering face of HIV/Aids, while men, as ‘the other’, are generally regarded as the perpetuators and spreaders of the virus. While there is no doubt that women’s vulnerability in this milieu has been proven within known research evidence to exist, the neglect of institutional (social, cultural and economic and historical vulnerabilities of African men’s realities are sometimes overlooked. Recently, greater focus has shifted to curbing infection rates in men based on new scientific evidence that shows that risk of transmission in circumcised men is reduced. The article argues that such movement towards showing areas of men’s vulnerability as a focus in HIV/Aids policy interventions may have the potential to shift the observed burden that current HIV/Aids policy thrusts inadvertently place on African women. The article will put forward an argument for

  8. Feline Immunodeficiency Virus in South America

    Directory of Open Access Journals (Sweden)

    Bruno M. Teixeira

    2012-03-01

    Full Text Available The rapid emergence of AIDS in humans during the period between 1980 and 2000 has led to extensive efforts to understand more fully similar etiologic agents of chronic and progressive acquired immunodeficiency disease in several mammalian species. Lentiviruses that have gene sequence homology with human immunodeficiency virus (HIV have been found in different species (including sheep, goats, horses, cattle, cats, and several Old World monkey species. Lentiviruses, comprising a genus of the Retroviridae family, cause persistent infection that can lead to varying degrees of morbidity and mortality depending on the virus and the host species involved. Feline immunodeficiency virus (FIV causes an immune system disease in domestic cats (Felis catus involving depletion of the CD4+ population of T lymphocytes, increased susceptibility to opportunistic infections, and sometimes death. Viruses related to domestic cat FIV occur also in a variety of nondomestic felids. This is a brief overview of the current state of knowledge of this large and ancient group of viruses (FIVs in South America.

  9. The effect of HIV/AIDS on sexuality among HIV positive females ...

    African Journals Online (AJOL)

    Introduction: The impact and stigma associated with Human Immunodeficiency Virus/Acquired Immune Deficiency Syndrome (HIV/AIDS) has led to different sexual behaviours in affected individuals the resultant lack of proper sexual information and various accompanying misconception has led to a high transmission of HIV ...

  10. 77 FR 30293 - Recommendations for the Identification of Hepatitis C Virus (HCV) Chronic Infection

    Science.gov (United States)

    2012-05-22

    ...: Division of Viral Hepatitis, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, Centers... Morgan, Division of Viral Hepatitis, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB...-2012-0005] Recommendations for the Identification of Hepatitis C Virus (HCV) Chronic Infection AGENCY...

  11. Risk analysis. HIV / AIDS country profile: Senegal.

    Science.gov (United States)

    1996-12-01

    Since the first acquired immunodeficiency syndrome (AIDS) case was confirmed in 1986, Senegal has conducted an aggressive prevention campaign. Senegal's National AIDS Committee has noted the contributions of poverty and migration to the spread of AIDS. By June 1994, 1297 AIDS cases had been reported and an estimated 500,000 people (1.4% of the population) were infected with human immunodeficiency virus (HIV)-1 and 2. The highest rate of HIV infection (14%) exists among commercial sex workers. At present, HIV/AIDS cases are concentrated in Dakar, Kaolack, the Matam region, and Ziguinchor; however, the growing importance of inter-regional trading is expected to spread HIV to the smaller towns and rural areas. Also salient is the recent devaluation by 50% of the CFA franc, which has reduced the public sector workforce and led many poor urban residents into commercial sex work. CFA devaluation has made Senegal attractive to tourists and business visitors--another factor responsible for growth of the legalized commercial sex industry. Although sex workers are instructed in condom use and tested annually for HIV, only 850 of the 2000 registered sex workers have reported for check-ups, and the majority of prostitutes are unregistered. Senegal's AIDS Plan for 1994-98 focuses on care of AIDS patients, pressures placed on family structures by HIV, and AIDS-related erosions in the status of women. Each health service region has its own local plan for AIDS/HIV and sexually transmitted diseases, supervised by a regional committee. Public education has involved outreach to religious leaders, promotion of affordable condoms, and distribution of over 75,000 leaflets to key target populations. About US $16 million of the $25,688,875-budget HIV/AIDS program for 1994-98 was pledged by external donors.

  12. The yellow fever 17D vaccine virus as a vector for the expression of foreign proteins: development of new live flavivirus vaccines

    Directory of Open Access Journals (Sweden)

    Myrna C Bonaldo

    2000-01-01

    Full Text Available The Flaviviridae is a family of about 70 mostly arthropod-borne viruses many of which are major public health problems with members being present in most continents. Among the most important are yellow fever (YF, dengue with its four serotypes and Japanese encephalitis virus. A live attenuated virus is used as a cost effective, safe and efficacious vaccine against YF but no other live flavivirus vaccines have been licensed. The rise of recombinant DNA technology and its application to study flavivirus genome structure and expression has opened new possibilities for flavivirus vaccine development. One new approach is the use of cDNAs encopassing the whole viral genome to generate infectious RNA after in vitro transcription. This methodology allows the genetic mapping of specific viral functions and the design of viral mutants with considerable potential as new live attenuated viruses. The use of infectious cDNA as a carrier for heterologous antigens is gaining importance as chimeric viruses are shown to be viable, immunogenic and less virulent as compared to the parental viruses. The use of DNA to overcome mutation rates intrinsic of RNA virus populations in conjunction with vaccine production in cell culture should improve the reliability and lower the cost for production of live attenuated vaccines. The YF virus despite a long period ignored by researchers probably due to the effectiveness of the vaccine has made a come back, both in nature as human populations grow and reach endemic areas as well as in the laboratory being a suitable model to understand the biology of flaviviruses in general and providing new alternatives for vaccine development through the use of the 17D vaccine strain.

  13. Association of TLR7 variants with AIDS-like disease and AIDS vaccine efficacy in rhesus macaques.

    Directory of Open Access Journals (Sweden)

    Roman A Siddiqui

    Full Text Available In HIV infection, TLR7-triggered IFN-α production exerts a direct antiviral effect through the inhibition of viral replication, but may also be involved in immune pathogenesis leading to AIDS. TLR7 could also be an important mediator of vaccine efficacy. In this study, we analyzed polymorphisms in the X-linked TLR7 gene in the rhesus macaque model of AIDS. Upon resequencing of the TLR7 gene in 36 rhesus macaques of Indian origin, 12 polymorphic sites were detected. Next, we identified three tightly linked single nucleotide polymorphisms (SNP as being associated with survival time. Genotyping of 119 untreated, simian immunodeficiency virus (SIV-infected male rhesus macaques, including an 'MHC adjusted' subset, revealed that the three TLR7 SNPs are also significantly associated with set-point viral load. Surprisingly, this effect was not observed in 72 immunized SIV-infected male monkeys. We hypothesize (i that SNP c.13G>A in the leader peptide is causative for the observed genotype-phenotype association and that (ii the underlying mechanism is related to RNA secondary structure formation. Therefore, we investigated a fourth SNP (c.-17C>T, located 17 bp upstream of the ATG translation initiation codon, that is also potentially capable of influencing RNA structure. In c.13A carriers, neither set-point viral load nor survival time were related to the c.-17C>T genotype. In c.13G carriers, by contrast, the c.-17C allele was significantly associated with prolonged survival. Again, no such association was detected among immunized SIV-infected macaques. Our results highlight the dual role of TLR7 in immunodeficiency virus infection and vaccination and imply that it may be important to control human AIDS vaccine trials, not only for MHC genotype, but also for TLR7 genotype.

  14. Spread of human T-cell leukemia virus (HTLV-I) in the Dutch homosexual community

    NARCIS (Netherlands)

    Goudsmit, J.; de Wolf, F.; van de Wiel, B.; Smit, L.; Bakker, M.; Albrecht-van Lent, N.; Coutinho, R. A.

    1987-01-01

    Sequential sera of 697 homosexual men, participating in a prospective study (1984-1986) of the risk to acquire human immunodeficiency virus (HIV) or AIDS, were tested for antibodies to human T-cell leukaemia virus (HTLV-I) by particle agglutination and immunoblotting. No intravenous drug users were

  15. An integrated approach of network-based systems biology, molecular docking, and molecular dynamics approach to unravel the role of existing antiviral molecules against AIDS-associated cancer.

    Science.gov (United States)

    Omer, Ankur; Singh, Poonam

    2017-05-01

    A serious challenge in cancer treatment is to reposition the activity of various already known drug candidates against cancer. There is a need to rewrite and systematically analyze the detailed mechanistic aspect of cellular networks to gain insight into the novel role played by various molecules. Most Human Immunodeficiency Virus infection-associated cancers are caused by oncogenic viruses like Human Papilloma Viruses and Epstein-Bar Virus. As the onset of AIDS-associated cancers marks the severity of AIDS, there might be possible interconnections between the targets and mechanism of both the diseases. We have explored the possibility of certain antiviral compounds to act against major AIDS-associated cancers: Kaposi's Sarcoma, Non-Hodgkin Lymphoma, and Cervical Cancer with the help of systems pharmacology approach that includes screening for targets and molecules through the construction of a series of drug-target and drug-target-diseases network. Two molecules (Calanolide A and Chaetochromin B) and the target "HRAS" were finally screened with the help of molecular docking and molecular dynamics simulation. The results provide novel antiviral molecules against HRAS target to treat AIDS defining cancers and an insight for understanding the pharmacological, therapeutic aspects of similar unexplored molecules against various cancers.

  16. Reverse genetics with animal viruses. NSV reverse genetics

    International Nuclear Information System (INIS)

    Mebatsion, T.

    2005-01-01

    New strategies to genetically manipulate the genomes of several important animal pathogens have been established in recent years. This article focuses on the reverse genetics techniques, which enables genetic manipulation of the genomes of non-segmented negative-sense RNA viruses. Recovery of a negative-sense RNA virus entirely from cDNA was first achieved for rabies virus in 1994. Since then, reverse genetic systems have been established for several pathogens of medical and veterinary importance. Based on the reverse genetics technique, it is now possible to design safe and more effective live attenuated vaccines against important viral agents. In addition, genetically tagged recombinant viruses can be designed to facilitate serological differentiation of vaccinated animals from infected animals. The approach of delivering protective immunogens of different pathogens using a single vector was made possible with the introduction of the reverse genetics system, and these novel broad-spectrum vaccine vectors have potential applications in improving animal health in developing countries. (author)

  17. Health Care and the Social Construction of AIDS: Impact of Disease Definitions on Psychosocial Adaptation and Economic Circumstances.

    Science.gov (United States)

    Crystal, Stephen; Jackson, Marguerite

    As with other illnesses, Acquired Immune Deficiency Syndrome (AIDS) is a socially constructed phenomenon, not simply a biological entity. Biologically, Human Immunodeficiency Virus (HIV) infection causes immunosuppression, which in turn causes a spectrum of disease states. The official definition of AIDS by the Centers for Disease Control requires…

  18. Should HIV and AIDS workplace programmes still be advocated in the automotive industry?

    OpenAIRE

    Liana Steenkamp; Jill von der Marwitz; Friederike Baasner-Weihs; Jacques Pietersen

    2015-01-01

    Orientation: In light of the human immunodeficiency virus (HIV) pandemic, and in order to improve competitiveness in the South African private sector, many structures have implemented subsidised workplace programmes. Research purpose: The aim of this study was to collect baseline data regarding the knowledge, attitudes, practices and belief (KAPB) of employees in the automotive industry in relation to HIV and AIDS, in order to assess the need for HIV and AIDS workplace programmes. Mot...

  19. Whole transcriptome sequencing enables discovery and analysis of viruses in archived primary central nervous system lymphomas.

    Directory of Open Access Journals (Sweden)

    Christopher DeBoever

    Full Text Available Primary central nervous system lymphomas (PCNSL have a dramatically increased prevalence among persons living with AIDS and are known to be associated with human Epstein Barr virus (EBV infection. Previous work suggests that in some cases, co-infection with other viruses may be important for PCNSL pathogenesis. Viral transcription in tumor samples can be measured using next generation transcriptome sequencing. We demonstrate the ability of transcriptome sequencing to identify viruses, characterize viral expression, and identify viral variants by sequencing four archived AIDS-related PCNSL tissue samples and analyzing raw sequencing reads. EBV was detected in all four PCNSL samples and cytomegalovirus (CMV, JC polyomavirus (JCV, and HIV were also discovered, consistent with clinical diagnoses. CMV was found to express three long non-coding RNAs recently reported as expressed during active infection. Single nucleotide variants were observed in each of the viruses observed and three indels were found in CMV. No viruses were found in several control tumor types including 32 diffuse large B-cell lymphoma samples. This study demonstrates the ability of next generation transcriptome sequencing to accurately identify viruses, including DNA viruses, in solid human cancer tissue samples.

  20. Designing herpes viruses as oncolytics

    Directory of Open Access Journals (Sweden)

    Cole Peters

    Full Text Available Oncolytic herpes simplex virus (oHSV was one of the first genetically-engineered oncolytic viruses. Because HSV is a natural human pathogen that can cause serious disease, it is incumbent that it can be genetically-engineered or significantly attenuated for safety. Here, we present a detailed explanation of the functions of HSV-1 genes frequently mutated to endow oncolytic activity. These genes are nonessential for growth in tissue culture cells but are important for growth in postmitotic cells, interfering with intrinsic antiviral and innate immune responses or causing pathology, functions dispensable for replication in cancer cells. Understanding the function of these genes leads to informed creation of new oHSVs with better therapeutic efficacy. Virus infection and replication can also be directed to cancer cells through tumor-selective receptor binding and transcriptional- or post-transcriptional miRNA-targeting, respectively. In addition to the direct effects of oHSV on infected cancer cells and tumors, oHSV can be “armed” with transgenes that are: reporters, to track virus replication and spread; cytotoxic, to kill uninfected tumor cells; immune modulatory, to stimulate antitumor immunity; or tumor microenvironment altering, to enhance virus spread or to inhibit tumor growth. In addition to HSV-1, other alphaherpesviruses are also discussed for their oncolytic activity.

  1. Consultation on AIDS and the workplace.

    Science.gov (United States)

    1988-12-01

    The 1988 Consultation on Acquired Immunodeficiency Syndrome (AIDS) and the Workplace, organized by the World Health Organization (WHO), addressed 3 issues: 1) risk factors associated with human immunodeficiency virus (HIV) infection in the workplace, 2) the response of businesses and workers to the AIDS epidemic, and 3) use of the workplace for AIDS education. There is no evidence to suggest that HIV can be transmitted by casual, person-to-person contact in the workplace. The central policy issue for businesses concerns protection of the human rights of workers with HIV infection. Most workers with HIV/AIDS want to continue working as long as they are able to, and they should be enabled to contribute their creativity and productivity in a supportive occupational setting. Consistent policies and procedures should be developed at national and enterprise levels before HIV-related questions arise in the workplace. Such policies should be communicated to all concerned, continually reviewed in the light of scientific and epidemiologic evidence, monitored for their successful implementation, and evaluated for their effectiveness. Pre-employment HIV/AIDS screening, whether for assessment of fitness to work or for insurance purposes, should not be required and raises serious concerns about discrimination. Moreover, there should be no obligation on the worker's part to inform his or her employer if HIV infection develops. Information and educational activities at the workplace are essential to create the climate of collective responsibility and mutual understanding required to protect individuals with HIV or AIDS from stigmatization and discrimination by co-workers, employers or clients, and unions.

  2. A Promising IFN-Deficient System to Manufacture IFN-Sensitive Influenza Vaccine Virus.

    Science.gov (United States)

    Chen, Can; Fan, Wenhui; Li, Jing; Zheng, Weinan; Zhang, Shuang; Yang, Limin; Liu, Di; Liu, Wenjun; Sun, Lei

    2018-01-01

    Interferon (IFN)-sensitive and replication-incompetent influenza viruses are likely to be the alternatives to inactivated and attenuated virus vaccines. Some IFN-sensitive influenza vaccine candidates with modified non-structural protein 1 (NS1) are highly attenuated in IFN-competent hosts but induce robust antiviral immune responses. However, little research has been done on the manufacturability of these IFN-sensitive vaccine viruses. Here, RIG-I-knockout 293T cells were used to package the IFN-sensitive influenza A/WSN/33 (H1N1) virus expressing the mutant NS1 R38A/K41A. We found that the packaging efficiency of the NS1 R38A/K41A virus in RIG-I-knockout 293T cells was much higher than that in 293T cells. Moreover, the NS1 R38A/K41A virus almost lost its IFN antagonist activity and could no longer replicate in A549, MDCK, and Vero cells after 3-6 passages. This indicated that the replication of NS1 R38A/K41A virus is limited in conventional cells. Therefore, we further established a stable Vero cell line expressing the wild-type (WT) NS1 of the WSN virus, based on the Tet-On 3G system. The NS1 R38A/K41A virus was able to steadily propagate in this IFN-deficient cell line for at least 20 passages. In a mouse model, the NS1 R38A/K41A virus showed more than a 4-log reduction in lung virus titers compared to the WT virus at 3 and 5 days post infection. Furthermore, we observed that the NS1 R38A/K41A virus triggered high-level of IFN-α/β production in lung tissues and was eliminated from the host in a relatively short period of time. Additionally, this virus induced high-titer neutralizing antibodies against the WT WSN, A/Puerto Rico/8/1934 (PR8), or A/California/04/2009 (CA04) viruses and provided 100% protection against the WT WSN virus. Thus, we found that the replication of the NS1 R38A/K41A virus was limited in IFN-competent cells and mice. We also presented a promising IFN-deficient system, involving a RIG-I-knockout 293T cell line to package the IFN

  3. HIV INFECTION AND AIDS: EPIDEMIOLOGY AND PREVENTION

    Directory of Open Access Journals (Sweden)

    Mustafa Alparslan BABAYIÐIT

    Full Text Available Human Immune-deficiency Virus (HIV was first discovered in 1981 in the United States of America and the day of December 1, was announced as ?World AIDS Day? by WHO (World Health Organization. In Turkey, the first announcement of the people living with HIV was made in 1985. HIV/AIDS has killed more than 20 millions people and more than 16,000 people become newly infected each day since the first cases were diagnosed in 1981. It is estimated that 39.4 million people would have been infected with HIV at the end of 2004, with 4.9 million new cases that year. Sub-Saharan Africa is the worst-hit region, with 70 percent of all people living with HIV. In Africa alone, 10,000 people become infected each day. This year?s main theme is ?Women, Girls, HIV and AIDS,? which reflects a focus on how the effects of HIV/AIDS have significantly increased among women. Women now make up half of all people living with HIV worldwide with the number of 17,6 million. [TAF Prev Med Bull 2004; 3(11.000: 280-290

  4. Attenuation of vaccinia virus by the expression of human Flt3 ligand

    Czech Academy of Sciences Publication Activity Database

    Žurková, K.; Hainz, P.; Kryštofová, J.; Kutinová, L.; Šanda, Miloslav; Němečková, Š.

    2010-01-01

    Roč. 7, č. 1 (2010), 109/1-109/15 ISSN 1743-422X Institutional research plan: CEZ:AV0Z40550506 Keywords : vaccinia virus * antibodies * virulence Subject RIV: CE - Biochemistry Impact factor: 2.546, year: 2010

  5. Non-AIDS-defining cancers in New Orleans.

    Science.gov (United States)

    Ruiz, Marco; Johnson, Daniel; Reske, Tom; Cefalu, Charles; Estrada, John

    2013-01-01

    Non-AIDS-defining cancers in HIV-infected patients in the highly active antiretroviral therapy era have increased. To our knowledge a comprehensive review of non-AIDS-related malignancies in New Orleans has not yet been conducted. Databases from main institutions in New Orleans were queried retrospectively for the years 2001 to 2011. The International Classification of Diseases, Ninth Revision codes were used to search for HIV infection and cancer comorbidity. A total of 16 patients were diagnosed with lung cancer (mean age 50 years) with 81% of the patients presenting with advanced stages. In all, 20 (mean age 47 years) were diagnosed with anal cancer, and 35% presented in late stages. In all, 14 patients (mean age 42 years) were diagnosed with Hodgkin Lymphoma, and 64% were diagnosed at late stage. A total of 5 women (mean age 44 years) were diagnosed with breast cancer with 40% of them presenting at late stage. Malignancies were diagnosed at late stages in the majority of the cases, presented with worse outcomes, and had higher recurrence rates. The role of HIV and other viruses (Epstein Barr virus, human papillomavirus) and the potential mechanisms or pathways of oncogene activation also need to be clarified.

  6. Influenza A infection attenuates relaxation responses of mouse tracheal smooth muscle evoked by acrolein.

    Science.gov (United States)

    Cheah, Esther Y; Mann, Tracy S; Burcham, Philip C; Henry, Peter J

    2015-02-15

    The airway epithelium is an important source of relaxant mediators, and damage to the epithelium caused by respiratory tract viruses may contribute to airway hyperreactivity. The aim of this study was to determine whether influenza A-induced epithelial damage would modulate relaxation responses evoked by acrolein, a toxic and prevalent component of smoke. Male BALB/c mice were inoculated intranasally with influenza A/PR-8/34 (VIRUS-infected) or allantoic fluid (SHAM-infected). On day 4 post-inoculation, isometric tension recording studies were conducted on carbachol pre-contracted tracheal segments isolated from VIRUS and SHAM mice. Relaxant responses to acrolein (30 μM) were markedly smaller in VIRUS segments compared to SHAM segments (2 ± 1% relaxation vs. 28 ± 5%, n=14, pacrolein and SP were reduced in VIRUS segments (>35% reduction, n=6, pacrolein were profoundly diminished in tracheal segments isolated from influenza A-infected mice. The mechanism through which influenza A infection attenuates this response appears to involve reduced production of PGE2 in response to SP due to epithelial cell loss, and may provide insight into the airway hyperreactivity observed with influenza A infection. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. Aids prevention in sub-Saharan Africa: as easy as ABC? | Bertrand ...

    African Journals Online (AJOL)

    Background: The failure to stem HIV in sub-Saharan Africa and the unique epidemiological modes of infection within this region have demonstrated that unique strategies for combatting the virus are required. This review article discusses why international AIDS campaigns in sub- Saharan Africa have largely been ...

  8. Ultraviolet-C irradiation for inactivation of viruses in foetal bovine serum.

    Science.gov (United States)

    Vaidya, Vivek; Dhere, Rajeev; Agnihotri, Snehal; Muley, Ravindra; Patil, Sanjay; Pawar, Amit

    2018-07-05

    Foetal Bovine Serum (FBS) and porcine trypsin are one of the essential raw materials used in the manufacturing of cell culture based viral vaccines. Being from animal origin, these raw materials can potentially contaminate the final product by known or unknown adventitious agents. The issue is more serious in case of live attenuated viral vaccines, where there is no inactivation step which can take care of such adventitious agents. It is essential to design production processes which can offer maximum viral clearance potential for animal origin products. Ultraviolet-C irradiation is known to inactivate various adventitious viral agents; however there are limited studies on ultraviolet inactivation of viruses in liquid media. We obtained a recently developed UVivatec ultraviolet-C (UV-C) irradiation based viral clearance system for evaluating its efficacy to inactivate selected model viruses. This system has a unique design with spiral path of liquid allowing maximum exposure to UV-C light of a short wavelength of 254 nm. Five live attenuated vaccine viruses and four other model viruses were spiked in tissue culture media and exposed to UV-C irradiation. The pre and post UV-C irradiation samples were analyzed for virus content to find out the extent of inactivation of various viruses. These experiments showed substantial log reduction for the majority of the viruses with few exceptions based on the characteristics of these viruses. Having known the effect of UV irradiation on protein structure, we also evaluated the post irradiation samples of culture media for growth promoting properties using one of the most fastidious human diploid cells (MRC-5). UV-C exposure did not show any notable impact on the nutritional properties of culture media. The use of an UV-C irradiation based system is considered to be promising approach to mitigate the risk of adventitious agents in cell culture media arising through animal derived products. Copyright © 2018 Elsevier Ltd. All

  9. Gender Differences in AIDS-Relevant Condom Attitudes and Condom Use.

    Science.gov (United States)

    Sacco, William P.; And Others

    Many heterosexuals have not altered their sexual practices in response to the threat of Acquired Immune Deficiency Syndrome (AIDS). Knowledge of risk alone appears to have little effect on altering sexual behavior; more complex psychological factors seem to be involved. Condom use to prevent the spread of Human Immunodeficiency Virus is a unique…

  10. Experience with a pilot plant for sewage sludge: Experiments on the inactivation of viruses in sewage sludge after a radiation treatment

    International Nuclear Information System (INIS)

    Epp, C.

    1975-01-01

    Investigations examining the virus inactivating effect of a Cobalt-60-plant were, till now, limited to the attempts to isolate virus from the sludge samples taken from sewage sludge before and after irradiation with 300 krad. As in those sludge samples virus presence could be proven only on a rather irregular basis, an experiment was devised in which defined virus quantities were packed into capsules and mixed with the digested sludge. At the end of the hygienization process these capsules were removed from the sludge and examined for virus content. Furthermore one radiation volume (5.6 m 3 ) was infected with attenuated polio virus type I and the virus content was determined before and after the radiation treatment. In 33 sludge samples examined before hygienization, presence of one or several viruses occurred in 8 samples. With the 33 capsules examined after hygienization with 300 krad, only 2 showed presence of virus. Suspensions of attenuated polio virus type I packed into synthetic capsules with a medium virus dosis of 10sup(6.92) JD 50/0.1 were immersed into sludge. In 6 experiments it was found that after hygienization, virus dosis was reduced to an average value of 10sup(5.4) JD 50/0.1 ml. Accordingly, the experimental results showed that after the radiation treatment the reduction of the exposed virus was more than 90%. Under natural conditions the investigation of the sewage sludge samples showed presence of virus 4 times less after hygienization than in the samples examined before hygienization. (orig./AK) [de

  11. Production and efficacy of an attenuated live vaccine against contagious ovine ecthyma

    Directory of Open Access Journals (Sweden)

    Attilio Pini

    2008-09-01

    Full Text Available Contagious ecthyma is caused by the orf virus, a member of the family Poxviridae, genus Parapoxvirus. Morbidity in affected sheep flocks is approximately 100%, while mortality varies between 1% and 10%. A live attenuated vaccine was produced by the Istituto Zooprofilattico Sperimentale dell’Abruzzo e del Molise ‘G. Caporale’. Quality control was performed in accordance with the European Pharmacopoeia. A wild virus strain was attenuated through serial passages on primary chicken embryo fibroblast tissue cultures. The virus suspension was treated according to standard procedures and freeze dried. The immunising dose was 1 ml containing 104,5TCID50, administered intramuscularly. The safety of the vaccine was successfully tested by intramuscular inoculation of 20 susceptible sheep and 20 lambs with the routine dose, 10 times the immunising dose and two normal doses administered at seven-day intervals. The efficacy of the vaccine was tested using three groups of susceptible animals. The first group included 10 lambs and the second 10 adult sheep; the animals were immunised intramuscularly with 1 ml of the reconstituted vaccine. The third group, used as controls, included five sheep and five lambs. Serological reactivity was monitored by indirect enzyme-linked immunosorbent assay (ELISA. The animals were challenged 30 days later with a pathogenic strain administered intradermally along the labial area. Vaccinated animals did not show any clinical signs of disease, whereas all the controls developed typical signs of contagious ecthyma. To confirm the efficacy of the vaccine, a field trial was conducted in four flocks affected by the disease. The trial showed that the vaccine was able to block the normal course of the disease and induce rapid recovery.

  12. [Data mining analysis of professor Li Fa-zhi AIDS itchy skin medical record].

    Science.gov (United States)

    Wang, Dan-Ni; Li, Zhen; Xu, Li-Ran; Guo, Hui-Jun

    2013-08-01

    Analysis of professor Li Fa-zhi in the treatment of AIDS drug laws of itchy skin, provide the corresponding drug reference basis for Chinese medicine treatment of AIDS, skin itching. By using the method of analyzing the complex network of Weishi county, Henan in 2007 October to 2011 July during an interview with professor Li Fa-zhi treatment of AIDS patients with skin pruritus, etiology and pathogenesis analysis, skin itching AIDS syndrome differentiation of old Chinese medicine treatment and medication rule. The use of multi-dimensional query analysis, core drug skin itching AIDS treatment in this study as a windbreak, cicada slough, bupleurum, Qufeng solution table drug, licorice detoxification efficacy of drugs, Radix Scutellariae, Kochia scoparia, clearing away heat and promoting diuresis medicine; core prescription for Jingfang San streak virus. Professor Li Fa-zhi treatment of AIDS in the skin itching Qufeng solution table dehumidification antipruritic treatment.

  13. Characteristics of substance abuse treatment programs providing services for HIV/AIDS, hepatitis C virus infection, and sexually transmitted infections: the National Drug Abuse Treatment Clinical Trials Network.

    Science.gov (United States)

    Brown, Lawrence S; Kritz, Steven Allan; Goldsmith, R Jeffrey; Bini, Edmund J; Rotrosen, John; Baker, Sherryl; Robinson, Jim; McAuliffe, Patrick

    2006-06-01

    Illicit drug users sustain the epidemics of human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS), hepatitis C (HCV), and sexually transmitted infections (STIs). Substance abuse treatment programs present a major intervention point in stemming these epidemics. As a part of the "Infections and Substance Abuse" study, established by the National Drug Abuse Treatment Clinical Trials Network, sponsored by National Institute on Drug Abuse, three surveys were developed; for treatment program administrators, for clinicians, and for state and District of Columbia health and substance abuse department administrators, capturing service availability, government mandates, funding, and other key elements related to the three infection groups. Treatment programs varied in corporate structure, source of revenue, patient census, and medical and non-medical staffing; medical services, counseling services, and staff education targeted HIV/AIDS more often than HCV or STIs. The results from this study have the potential to generate hypotheses for further health services research to inform public policy.

  14. Tingkat Pengetahuan dan Sikap Pelajar SMA Negeri Siabu Mandailing Natal Angkatan 2011 tentang HIV/ AIDS Tahun

    OpenAIRE

    Nasution, Yusda Rahayu

    2012-01-01

    HIV is a retrovirus that damage the immune system while AIDS (Acquired Immune Deficiency Syndrome) is a set of symptoms that caused by the lower of body immune system caused by HIV (Human Immunodeficiency virus) infection. HIV/AIDS is one of diseases that cause the higher mortality rate and the number of patient is increase over time. Therefore, the student must has knowledge and good understanding about HIV/AIDS. This research aims to study the knowledge level and attitude of student abou...

  15. Brazil's fight against AIDS and its implications for global health governance.

    Science.gov (United States)

    Wogart, J P; Calcagnotto, G

    2006-01-01

    The paper traces Brazil's efforts to fight AIDS in the last 20 years. The analysis concentrates on the efforts to combat and prevent the deadly infectious disease through ingenious efforts of private citizens, government agencies, national and international NGOs, which challenged multinational companies, international organizations and foreign governments. While the investigation led to a positive evaluation of the joint efforts in managing the threat, it is made clear that the fight against the HIV/AIDS virus is far from over in Brazil and will have to be strengthened on the local, national and international level.

  16. AIDS Kaposi sarcoma-derived cells produce and respond to interleukin 6

    International Nuclear Information System (INIS)

    Miles, S.A.; Rezai, A.R.; Salazar-Gonzalez, J.F.; Meyden, M.V.; Stevens, R.H.; Mitsuyasu, R.T.; Martinez-Maza, O.; Logan, D.M.; Taga, Tetsuya; Hirano, Toshio; Kishimoto, Tadamitsu

    1990-01-01

    Cell lines derived from Kaposi sarcoma lesions of patients with AIDS (AIDS-KS cells) produce several cytokines, including an endothelial cell growth factor, interleukin 1β, and basic fibroblast growth factor. Since exposure to human immunodeficiency virus increases interleukin 6 (IL-6) production in monocytes and endothelial cells produce IL-6, the authors examined IL-6 expression and response in AIDS-KS cell lines and IL-6 expression in AIDS Kaposi sarcoma tissue. The AIDS-KS cell lines (N521J and EKS3) secreted large amounts of immunoreactive and biologically active IL-6. The authors found both IL-6 and IL-6 receptor (IL-6-R) RNA by slot blot hybridization analysis of AIDS-KS cells. The IL-6-R was functional, as [ 3 H]thymidine incorporation by AIDS-KS cells increased significantly after exposure to human recombinant IL-6 (hrIL-6) at >10 units/ml. When AIDS-KS cells (EKS3) were exposed to IL-6 antisense oligonucleotide, cellular proliferation decreased by nearly two-thirds, with a corresponding decrease in the production of IL-6. These results show that both IL-6 and IL-6-R are produced by AIDS-KS cells and that IL-6 is required for optimal AIDS-KS cell proliferation, and they suggest that IL-6 is an autocrine growth factor for AIDS-KS cells

  17. Vaccine and Wild-Type Strains of Yellow Fever Virus Engage Distinct Entry Mechanisms and Differentially Stimulate Antiviral Immune Responses

    Directory of Open Access Journals (Sweden)

    Maria Dolores Fernandez-Garcia

    2016-02-01

    Full Text Available The live attenuated yellow fever virus (YFV vaccine 17D stands as a “gold standard” for a successful vaccine. 17D was developed empirically by passaging the wild-type Asibi strain in mouse and chicken embryo tissues. Despite its immense success, the molecular determinants for virulence attenuation and immunogenicity of the 17D vaccine are poorly understood. 17D evolved several mutations in its genome, most of which lie within the envelope (E protein. Given the major role played by the YFV E protein during virus entry, it has been hypothesized that the residues that diverge between the Asibi and 17D E proteins may be key determinants of attenuation. In this study, we define the process of YFV entry into target cells and investigate its implication in the activation of the antiviral cytokine response. We found that Asibi infects host cells exclusively via the classical clathrin-mediated endocytosis, while 17D exploits a clathrin-independent pathway for infectious entry. We demonstrate that the mutations in the 17D E protein acquired during the attenuation process are sufficient to explain the differential entry of Asibi versus 17D. Interestingly, we show that 17D binds to and infects host cells more efficiently than Asibi, which culminates in increased delivery of viral RNA into the cytosol and robust activation of the cytokine-mediated antiviral response. Overall, our study reveals that 17D vaccine and Asibi enter target cells through distinct mechanisms and highlights a link between 17D attenuation, virus entry, and immune activation.

  18. [Rejecting or prioritizing life? The ambiguities of AIDS biopolitics in Uruguay].

    Science.gov (United States)

    Reihling, Hanspeter

    2010-06-01

    The biopolitics of aids in Uruguay could be seen between two big poles: the investment and the rejection of life. The productive mode can be expressed in the treatment of children who contracted HIV through mother to child transmission. For these children the infection in many cases becomes an asset until they reach adolescence. Except of some efforts of forced detention and mandatory testing, the public health system as well as NGOs show little interest in assisting adolescence infected or affected by HIV/aids. This is the result of a moral economy which marks people who are able to transmit the virus sexually or who have contracted it through sexual intercourse. Especially HIV positive mothers are seen as irresponsible and dangerous in contraposition to their "pure" offspring. However, this moral discourse hardly takes into account the larger social and economic context in which those mothers contracted the virus and as they faced Antiretroviral Therapy (ART). The life history of an adolescent boy will be told in order to reflect upon the modes of inclusion and exclusion of people living with HIV/aids since the beginning of the epidemic in Uruguay. Although the case is not representative, it identifies dynamics within the Uruguayan health system which are difficult to discern through conventional statistical methods.

  19. An analysis of FDA-approved drugs for infectious disease: HIV/AIDS drugs.

    Science.gov (United States)

    Kinch, Michael S; Patridge, Eric

    2014-10-01

    HIV/AIDS is one of the worst pandemics in history. According to the World Health Organization, 26 million people have died since 1981 - 1.6 million in 2012 alone. The dramatic rise in HIV/AIDS mobilized a swift and impressive coordination among governmental, academic and private sector organizations to identify the virus and develop new treatments. Herein, we assess the arsenal of 28 new molecular entities (NMEs) targeting HIV/AIDS. These data demonstrate that the first approval of zidovudine presaged an expansion of the antiviral repertoire over the following years. Whereas the rate of HIV/AIDS NMEs is rapidly declining, so is the number of organizations developing NMEs. We speculate that decisions to abandon further research reflect, in part, growing costs and time required for development. Copyright © 2014 Elsevier Ltd. All rights reserved.

  20. A mouse model for studying viscerotropic disease caused by yellow fever virus infection.

    Directory of Open Access Journals (Sweden)

    Kathryn C Meier

    2009-10-01

    Full Text Available Mosquito-borne yellow fever virus (YFV causes highly lethal, viscerotropic disease in humans and non-human primates. Despite the availability of efficacious live-attenuated vaccine strains, 17D-204 and 17DD, derived by serial passage of pathogenic YFV strain Asibi, YFV continues to pose a significant threat to human health. Neither the disease caused by wild-type YFV, nor the molecular determinants of vaccine attenuation and immunogenicity, have been well characterized, in large part due to the lack of a small animal model for viscerotropic YFV infection. Here, we describe a small animal model for wild-type YFV that manifests clinical disease representative of that seen in primates without adaptation of the virus to the host, which was required for the current hamster YF model. Investigation of the role of type I interferon (IFN-alpha/beta in protection of mice from viscerotropic YFV infection revealed that mice deficient in the IFN-alpha/beta receptor (A129 or the STAT1 signaling molecule (STAT129 were highly susceptible to infection and disease, succumbing within 6-7 days. Importantly, these animals developed viscerotropic disease reminiscent of human YF, instead of the encephalitic signs typically observed in mice. Rapid viremic dissemination and extensive replication in visceral organs, spleen and liver, was associated with severe pathologies in these tissues and dramatically elevated MCP-1 and IL-6 levels, suggestive of a cytokine storm. In striking contrast, infection of A129 and STAT129 mice with the 17D-204 vaccine virus was subclinical, similar to immunization in humans. Although, like wild-type YFV, 17D-204 virus amplified within regional lymph nodes and seeded a serum viremia in A129 mice, infection of visceral organs was rarely established and rapidly cleared, possibly by type II IFN-dependent mechanisms. The ability to establish systemic infection and cause viscerotropic disease in A129 mice correlated with infectivity for A129

  1. A mouse model for studying viscerotropic disease caused by yellow fever virus infection.

    Science.gov (United States)

    Meier, Kathryn C; Gardner, Christina L; Khoretonenko, Mikhail V; Klimstra, William B; Ryman, Kate D

    2009-10-01

    Mosquito-borne yellow fever virus (YFV) causes highly lethal, viscerotropic disease in humans and non-human primates. Despite the availability of efficacious live-attenuated vaccine strains, 17D-204 and 17DD, derived by serial passage of pathogenic YFV strain Asibi, YFV continues to pose a significant threat to human health. Neither the disease caused by wild-type YFV, nor the molecular determinants of vaccine attenuation and immunogenicity, have been well characterized, in large part due to the lack of a small animal model for viscerotropic YFV infection. Here, we describe a small animal model for wild-type YFV that manifests clinical disease representative of that seen in primates without adaptation of the virus to the host, which was required for the current hamster YF model. Investigation of the role of type I interferon (IFN-alpha/beta) in protection of mice from viscerotropic YFV infection revealed that mice deficient in the IFN-alpha/beta receptor (A129) or the STAT1 signaling molecule (STAT129) were highly susceptible to infection and disease, succumbing within 6-7 days. Importantly, these animals developed viscerotropic disease reminiscent of human YF, instead of the encephalitic signs typically observed in mice. Rapid viremic dissemination and extensive replication in visceral organs, spleen and liver, was associated with severe pathologies in these tissues and dramatically elevated MCP-1 and IL-6 levels, suggestive of a cytokine storm. In striking contrast, infection of A129 and STAT129 mice with the 17D-204 vaccine virus was subclinical, similar to immunization in humans. Although, like wild-type YFV, 17D-204 virus amplified within regional lymph nodes and seeded a serum viremia in A129 mice, infection of visceral organs was rarely established and rapidly cleared, possibly by type II IFN-dependent mechanisms. The ability to establish systemic infection and cause viscerotropic disease in A129 mice correlated with infectivity for A129-derived, but not WT

  2. Determinants of HIV/AIDS in armed conflict populations.

    Science.gov (United States)

    Omare, Danvas; Kanekar, Amar

    2011-03-01

    More than 40 million people worldwide have been infected with human immunodeficiency virus (HIV) since it was first reported in 1981. Over 25 million of these have lost their lives to the disease. Most of the studies related to HIV/AIDS have been conducted in stable populations across the globe. Few of these studies have been devoted to displaced populations, particularly those in areas of conflict. Displaced populations that are forced to leave their homes in most cases find themselves in unfamiliar territories, often poor and hungry. Many of them become refugees and internally displaced people (IDPs). The objective of this review was to address a number of different social determinants of HIV/AIDS in displaced populations in areas of conflict. A comprehensive review of peer reviewed literature published in English between 1990 and 2010 obtained through an open search of PUBMED database using key words such as HIV and war , HIV/AIDS and conflict , AIDS and security was conducted. Twelve different studies that looked at the implications of HIV/AIDS in conflict or displaced populations were retrieved. The review revealed that there were various factors influencing conflict and HIV/AIDS such as forced population displacement, breakdown of traditional sexual norms, lack of health infrastructure, and poverty and powerlessness of women and children. Social determinants of increased HIV/AIDS prevalence in displaced populations are scarcity of food, poverty, insecurity of displaced populations and gender power differentials.

  3. Determinants of HIV/AIDS in armed conflict populations

    Directory of Open Access Journals (Sweden)

    Danvas Omare

    2011-02-01

    Full Text Available More than 40 million people worldwide have been infected with human immunodeficiency virus (HIV since it was first reported in 1981. Over 25 million of these have lost their lives to the disease. Most of the studies related to HIV/AIDS have been conducted in stable populations across the globe. Few of these studies have been devoted to displaced populations, particularly those in areas of conflict. Displaced populations that are forced to leave their homes in most cases find themselves in unfamiliar territories, often poor and hungry. Many of them become refugees and internally displaced people (IDPs. The objective of this review was to address a number of different social determinants of HIV/AIDS in displaced populations in areas of conflict. A comprehensive review of peer reviewed literature published in English between 1990 and 2010 obtained through an open search of PUBMED database using key words such as “HIV and war”, “HIV/AIDS and conflict”, “AIDS and security” was conducted. Twelve different studies that looked at the implications of HIV/AIDS in conflict or displaced populations were retrieved. The review revealed that there were various factors influencing conflict and HIV/AIDS such as forced population displacement, breakdown of traditional sexual norms, lack of health infrastructure, and poverty and powerlessness of women and children. Social determinants of increased HIV/AIDS prevalence in displaced populations are scarcity of food, poverty, insecurity of displaced populations and gender power differentials.

  4. Examination of virus shedding in semen from vaccinated and from previously infected boars after experimental challenge with porcine reproductive and respiratory syndrome virus

    DEFF Research Database (Denmark)

    Nielsen, Thomas L.; Nielsen, Jens; Have, Per

    1997-01-01

    to the Danish pig industry. The use of a vaccination-program may be a way to avoid or reduce the problem, This study evaluates the use of two vaccines: One live, attenuated vaccine and one inactivated vaccine, A pronounced reduction in viremia and shedding of virus in semen was demonstrated by use of the live...

  5. Virus-Like-Vaccines against HIV.

    Science.gov (United States)

    Andersson, Anne-Marie C; Schwerdtfeger, Melanie; Holst, Peter J

    2018-02-11

    Protection against chronic infections has necessitated the development of ever-more potent vaccination tools. HIV seems to be the most challenging foe, with a remarkable, poorly immunogenic and fragile surface glycoprotein and the ability to overpower the cell immune system. Virus-like-particle (VLP) vaccines have emerged as potent inducers of antibody and helper T cell responses, while replication-deficient viral vectors have yielded potent cytotoxic T cell responses. Here, we review the emerging concept of merging these two technologies into virus-like-vaccines (VLVs) for the targeting of HIV. Such vaccines are immunologically perceived as viruses, as they infect cells and produce VLPs in situ, but they only resemble viruses, as the replication defective vectors and VLPs cannot propagate an infection. The inherent safety of such a platform, despite robust particle production, is a distinct advantage over live-attenuated vaccines that must balance safety and immunogenicity. Previous studies have delivered VLVs encoded in modified Vaccinia Ankara vectors and we have developed the concept into a single-reading adenovirus-based technology capable of eliciting robust CD8⁺ and CD4⁺ T cells responses and trimer binding antibody responses. Such vaccines offer the potential to display the naturally produced immunogen directly and induce an integrated humoral and cellular immune response.

  6. What Can a Teacher Do with a Cellphone? Using Participatory Visual Research to Speak Back in Addressing HIV & AIDS

    Science.gov (United States)

    Mitchell, Claudia; de Lange, Naydene

    2013-01-01

    The ubiquity of cellphones in South Africa, a country ravaged by HIV and AIDS, makes cellphones an easily accessible tool to use in participatory approaches to addressing HIV (Human Immunodeficiency Virus) and AIDS (Acquired Immunodeficiency Syndrome)issues, particularly in school contexts. In this article we explore a participatory visual…

  7. Magnetic resonance imaging findings of the brain in adult HIV and AIDS patients

    International Nuclear Information System (INIS)

    Kloska, S.P.; Schlegel, P.M.; Fischbach, R.; Heindel, W.; Husstedt, I.W.; Anneken, K.; Evers, S.

    2008-01-01

    The spectrum of pathology affecting the central nervous system (CNS) in patients suffering from acquired immunodeficiency syndrome (AIDS) includes not only the human immunodeficiency virus (HIV) infection itself but also opportunistic infections and tumors secondary to AIDS. Despite progress in antiretroviral therapy and the subsequent decrease in the incidence of associated diseases, opportunistic infections and tumors secondary to the HIV infection continue to be the limiting factor in terms of survival with AIDS. Therefore, the therapeutic aim is permanent antiretroviral therapy as well as early diagnosis and treatment of opportunistic infections. Magnetic resonance imaging is often the diagnostic method of choice in suspected CNS pathology of HIV patients. In the following, the typical clinical and radiological features of several AIDS-related pathologies are presented and discussed. (orig.)

  8. Forging Collaborative Relationships in Brazil: From AIDS to ZIKV.

    Science.gov (United States)

    O'Connor, David H; Osorio, Jorge E; Tanuri, Amilcar; Kallas, Esper G

    2016-06-30

    The Zika virus (ZIKV) outbreak has stimulated collaborations between Brazilians, researchers from other South American countries, and scientists from around the world. The Brazilian response to the HIV/AIDS epidemic demonstrates capabilities that can be applied to the study of ZIKV and provides lessons for developing effective international infectious disease research collaborations. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Epidemiological patterns of human immunodeficiency virus and ...

    African Journals Online (AJOL)

    There is no doubt that the greatest health problem threatening the human race these times is the HIV/AIDS pandemic. The greatest burden of this scourge is in sub-saharan African. This has undoubtedly increased the incidence of opportunistic infection like herpes simplex virus infection. This study investigated the ...

  10. Deep sequencing reveals persistence of cell-associated mumps vaccine virus in chronic encephalitis.

    Science.gov (United States)

    Morfopoulou, Sofia; Mee, Edward T; Connaughton, Sarah M; Brown, Julianne R; Gilmour, Kimberly; Chong, W K 'Kling'; Duprex, W Paul; Ferguson, Deborah; Hubank, Mike; Hutchinson, Ciaran; Kaliakatsos, Marios; McQuaid, Stephen; Paine, Simon; Plagnol, Vincent; Ruis, Christopher; Virasami, Alex; Zhan, Hong; Jacques, Thomas S; Schepelmann, Silke; Qasim, Waseem; Breuer, Judith

    2017-01-01

    Routine childhood vaccination against measles, mumps and rubella has virtually abolished virus-related morbidity and mortality. Notwithstanding this, we describe here devastating neurological complications associated with the detection of live-attenuated mumps virus Jeryl Lynn (MuV JL5 ) in the brain of a child who had undergone successful allogeneic transplantation for severe combined immunodeficiency (SCID). This is the first confirmed report of MuV JL5 associated with chronic encephalitis and highlights the need to exclude immunodeficient individuals from immunisation with live-attenuated vaccines. The diagnosis was only possible by deep sequencing of the brain biopsy. Sequence comparison of the vaccine batch to the MuV JL5 isolated from brain identified biased hypermutation, particularly in the matrix gene, similar to those found in measles from cases of SSPE. The findings provide unique insights into the pathogenesis of paramyxovirus brain infections.

  11. The use of attenuated isolates of Pepino mosaic virus for cross-protection

    NARCIS (Netherlands)

    Schenk, M.F.; Hamelink, R.; Vlugt, van der R.A.A.; Vermunt, A.M.W.; Kaarsemaker, R.C.; Stijger, C.C.M.M.

    2010-01-01

    Pepino mosaic virus (PepMV) has recently emerged as a highly infectious viral pathogen in tomato crops. Greenhouse trials were conducted under conditions similar to commercial tomato production. These trials examined whether tomato plants can be protected against PepMV by a preceding infection with

  12. Oncolytic Herpes Simplex Virus Vectors Fully Retargeted to Tumor- Associated Antigens.

    Science.gov (United States)

    Uchida, Hiroaki; Hamada, Hirofumi; Nakano, Kenji; Kwon, Heechung; Tahara, Hideaki; Cohen, Justus B; Glorioso, Joseph C

    2018-01-01

    Oncolytic virotherapy is a novel therapeutic modality for malignant diseases that exploits selective viral replication in cancer cells. Herpes simplex virus (HSV) is a promising agent for oncolytic virotherapy due to its broad cell tropism and the identification of mutations that favor its replication in tumor over normal cells. However, these attenuating mutations also tend to limit the potency of current oncolytic HSV vectors that have entered clinical studies. As an alternative, vector retargeting to novel entry receptors has the potential to achieve tumor specificity at the stage of virus entry, eliminating the need for replication-attenuating mutations. Here, we summarize the molecular mechanism of HSV entry and recent advances in the development of fully retargeted HSV vectors for oncolytic virotherapy. Retargeted HSV vectors offer an attractive platform for the creation of a new generation of oncolytic HSV with improved efficacy and specificity. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  13. Lost but Not Forgotten - The Economics of Improving Patient Retention in AIDS Treatment Programs

    OpenAIRE

    Losina, Elena; Tour?, Hapsatou; Uhler, Lauren M.; Anglaret, Xavier; Paltiel, A. David; Balestre, Eric; Walensky, Rochelle P.; Messou, Eug?ne; Weinstein, Milton C.; Dabis, Fran?ois; Freedberg, Kenneth A.

    2009-01-01

    Editors' Summary Background Acquired immunodeficiency syndrome (AIDS) has killed more than 25 million people since the first reported case in 1981. Currently, about 33 million people are infected with the human immunodeficiency virus (HIV), which causes AIDS. Two-thirds of people infected with HIV live in sub-Saharan Africa. HIV infects and destroys immune system cells, thereby weakening the immune system and rendering infected individuals susceptible to infection. There is no cure for HIV/AI...

  14. Respiratory viruses in airline travellers with influenza symptoms: Results of an airport screening study.

    Science.gov (United States)

    Jennings, Lance C; Priest, Patricia C; Psutka, Rebecca A; Duncan, Alasdair R; Anderson, Trevor; Mahagamasekera, Patalee; Strathdee, Andrew; Baker, Michael G

    2015-06-01

    There is very little known about the prevalence and distribution of respiratory viruses, other than influenza, in international air travellers and whether symptom screening would aid in the prediction of which travellers are more likely to be infected with specific respiratory viruses. In this study, we investigate whether, the use of a respiratory symptom screening tool at the border would aid in predicting which travellers are more likely to be infected with specific respiratory viruses. Data were collected from travellers arriving at Christchurch International Airport, New Zealand, during the winter 2008, via a symptom questionnaire, temperature testing, and respiratory sampling. Respiratory viruses were detected in 342 (26.0%) of 1313 samples obtained from 2714 symptomatic travellers. The most frequently identified viruses were rhinoviruses (128), enteroviruses (77) and influenza B (48). The most frequently reported symptoms were stuffy or runny nose (60%), cough (47%), sore throat (27%) and sneezing (24%). Influenza B infections were associated with the highest number of symptoms (mean of 3.4) followed by rhinoviruses (mean of 2.2) and enteroviruses (mean of 1.9). The positive predictive value (PPV) of any symptom for any respiratory virus infection was low at 26%. The high prevalence of respiratory virus infections caused by viruses other than influenza in this study, many with overlapping symptotology to influenza, has important implications for any screening strategies for the prediction of influenza in airline travellers. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. Magnetic resonance imaging of brain involvement in aids

    International Nuclear Information System (INIS)

    Cordoliani, Y.S.; Pharaboz, C.; Jeanbourquin, D.; Le Gall, R.; Derosier, C.; Cosnard, G.

    1991-01-01

    Magnetic resonance imaging is the most sensitive and the most specific technique for the study of the neurological complications of AIDS. The analysis of the images must be aimed at recognizing the specific lesions produced by the human immunodeficiency virus (HIV), in order to identify the opportunistic lesions, which are often multiple. For each major opportunistic disease, a number of arguments likely to guide the treatment can be pointed out [fr

  16. Pharmacological inhibition of feline immunodeficiency virus (FIV).

    Science.gov (United States)

    Mohammadi, Hakimeh; Bienzle, Dorothee

    2012-05-01

    Feline immunodeficiency virus (FIV) is a member of the retroviridae family of viruses and causes an acquired immunodeficiency syndrome (AIDS) in domestic and non-domestic cats worldwide. Genome organization of FIV and clinical characteristics of the disease caused by the virus are similar to those of human immunodeficiency virus (HIV). Both viruses infect T lymphocytes, monocytes and macrophages, and their replication cycle in infected cells is analogous. Due to marked similarity in genomic organization, virus structure, virus replication and disease pathogenesis of FIV and HIV, infection of cats with FIV is a useful tool to study and develop novel drugs and vaccines for HIV. Anti-retroviral drugs studied extensively in HIV infection have targeted different steps of the virus replication cycle: (1) inhibition of virus entry into susceptible cells at the level of attachment to host cell surface receptors and co-receptors; (2) inhibition of fusion of the virus membrane with the cell membrane; (3) blockade of reverse transcription of viral genomic RNA; (4) interruption of nuclear translocation and viral DNA integration into host genomes; (5) prevention of viral transcript processing and nuclear export; and (6) inhibition of virion assembly and maturation. Despite much success of anti-retroviral therapy slowing disease progression in people, similar therapy has not been thoroughly investigated in cats. In this article we review current pharmacological approaches and novel targets for anti-lentiviral therapy, and critically assess potentially suitable applications against FIV infection in cats.

  17. Functional Analysis of Glycosylation of Zika Virus Envelope Protein.

    Science.gov (United States)

    Fontes-Garfias, Camila R; Shan, Chao; Luo, Huanle; Muruato, Antonio E; Medeiros, Daniele B A; Mays, Elizabeth; Xie, Xuping; Zou, Jing; Roundy, Christopher M; Wakamiya, Maki; Rossi, Shannan L; Wang, Tian; Weaver, Scott C; Shi, Pei-Yong

    2017-10-31

    Zika virus (ZIKV) infection causes devastating congenital abnormities and Guillain-Barré syndrome. The ZIKV envelope (E) protein is responsible for viral entry and represents a major determinant for viral pathogenesis. Like other flaviviruses, the ZIKV E protein is glycosylated at amino acid N154. To study the function of E glycosylation, we generated a recombinant N154Q ZIKV that lacks the E glycosylation and analyzed the mutant virus in mammalian and mosquito hosts. In mouse models, the mutant was attenuated, as evidenced by lower viremia, decreased weight loss, and no mortality; however, knockout of E glycosylation did not significantly affect neurovirulence. Mice immunized with the mutant virus developed a robust neutralizing antibody response and were completely protected from wild-type ZIKV challenge. In mosquitoes, the mutant virus exhibited diminished oral infectivity for the Aedes aegypti vector. Collectively, the results demonstrate that E glycosylation is critical for ZIKV infection of mammalian and mosquito hosts. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  18. [Immune Response of Recombinant Pseudorabies Virus rPRV-VP2 Expressing VP2 Gene of Porcine Parvovirus in Mice].

    Science.gov (United States)

    Fu, Pengfei; Pan, Xinlong; Han, Qiao; Yang, Xingwu; Zhu, Qianlei; Guo, Xiaoqing; Zhang, Yu; Chen, Hongying

    2016-03-01

    In order to develop a combined live vaccine that will be used to prevent against porcine parvovirus (PPV) and Pseudorabies virus (PRV) infection, the VP2 gene of PPV was inserted into the transfer vector plasmid pG to produce the recombinant plasmid pGVP2. The plasmid pGVP2 and the genome of PRV HB98 attenuated vaccine were transfected by using lipofectamine into swine testis cells for the homologous recombination. The recombinant virus rPRV-VP2 was purified by selection of green fluorescence plaques for five cycles. 6-week-old female Kunming mice were immunized intramuscularly with attenuated PRV parent HB98 strain, commercial inactivated vaccine against PPV, recombinant virus, DMEM culture solution. The injections were repeated with an equivalent dose after 2 weeks in all of the groups, and then challenged with the virulent PRV NY strain at 7 weeks after the first immunization. The recombinant virus rPRV-VP2 was successfully generated, and the recombinant virus could effectively elicite anti-PPV and PRV antibody and significant cellular immune response as indicated by anti-PPV ELISA and HI, PRV-neutralizing assay and flow cytometry. The challenge assay indicated that recombinant virus could protect the mice against the virulent PRV challenge. These results demonstrated that the recombinant virus can be a candidate recombinant vaccine strain for the prevention of PRV and PPV.

  19. Effects of attenuation map accuracy on attenuation-corrected micro-SPECT images

    NARCIS (Netherlands)

    Wu, C.; Gratama van Andel, H.A.; Laverman, P.; Boerman, O.C.; Beekman, F.J.

    2013-01-01

    Background In single-photon emission computed tomography (SPECT), attenuation of photon flux in tissue affects quantitative accuracy of reconstructed images. Attenuation maps derived from X-ray computed tomography (CT) can be employed for attenuation correction. The attenuation coefficients as well

  20. Cross-Protection against Marburg Virus Strains by Using a Live, Attenuated Recombinant Vaccine

    National Research Council Canada - National Science Library

    Daddario-DiCaprio, Kathleen M; Geisbert, Thomas W; Geisbert, Joan B; Stroeher, Ute; Hensley, Lisa E; Grolla, Allen; Fritz, Elizabeth A; Feldmann, Friederike; Feldmann, Heinz; Jones, Steven M

    2006-01-01

    Marburg virus (MARV) has been associated with sporadic episodes of hemorrhagic fever, including a recent highly publicized outbreak in Angola that produced severe disease and significant mortality in infected patients...

  1. What the perspective of the elderly in relation to HIV / AIDS?

    Directory of Open Access Journals (Sweden)

    Claudia Lysia Oliveira de Araújo

    2012-06-01

    Full Text Available The epidemic of human immunodeficiency virus / acquired immunodeficiency syndrome (HIV / AIDS in the elderly in Brazil has emerged a public health problem. When we refer to aging and AIDS we must consider the sexuality of older people. Research aimed to characterize and identify through the viewpoint of senior knowledge and sentiment against the HIV / AIDS. The methodology of the study was descriptive and quantitative descriptiveanalysis. The results of this study have said that older people have knowledge about HIV / AIDS. Only 22.2% use condoms. We conclude that prevention campaigns are not reaching the elderly. For we know that many seniors have active sex life, with more than one partner. Prevention campaigns and actions of the nursing staff should pay special attention to this fact and increase the information, so that older people can understand and adhere to the means of prevention of this disease.

  2. What the perspective of the elderly in relation to HIV / AIDS?

    Directory of Open Access Journals (Sweden)

    Claudia Lysia Oliveira de Araújo

    2013-12-01

    Full Text Available The epidemic of human immunodeficiency virus / acquired immunodeficiency syndrome (HIV / AIDS in the elderly in Brazil has emerged a public health problem. When we refer to aging and AIDS we must consider the sexuality of older people. Research aimed to characterize and identify through the viewpoint of senior knowledge and sentiment against the HIV / AIDS. The methodology of the study was descriptive and quantitative descriptive analysis. The results of this study have said that older people have knowledge about HIV / AIDS. Only 22.2% use condoms. We conclude that prevention campaigns are not reaching the elderly. For we know that many seniors have active sex life, with more than one partner. Prevention campaigns and actions of the nursing staff should pay special attention to this fact and increase the information, so that older people can understand and adhere to the means of prevention of this disease.

  3. Knowledge of HIV/AIDS among adolescents in Chillán, Chile.

    Science.gov (United States)

    Pérez V, Ruth; Barrales C, Ingrid; Jara P, Jenny; Palma R, Virla; Ceballos M, Alejandra

    2008-12-01

    to analyse adolescents' knowledge of preventive sexual practices related to human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS) by means of a questionnaire recommended by the Joint United Nations Programme on HIV/AIDS (UNAIDS). non-experimental, cross-sectional, descriptive and analytical investigation. four schools in Chillán, Chile, 2005. a total of 480 adolescents aged between 15 and 19 years. Students completed a questionnaire recommended by UNAIDS in order to develop basic indicators. the indicator of preventive sexual practices related to HIV/AIDS was 32.5%; forms of prevention (62.5%) were better known than erroneous ideas about transmission (46%). Adolescents from the only private school in the study demonstrated greater knowledge (43.3%) than students from the public schools (25%) (psexual practices related to HIV and AIDS. It is necessary to implement an indicator of knowledge that allows for the creation and monitoring of sexual education programmes.

  4. My secret: The social meaning of HIV/AIDS stigma

    Science.gov (United States)

    Judgeo, N.; Moalusi, K.P.

    2014-01-01

    Abstract This study uses Goffman's [1963. Stigma: Notes on the Management of Spoiled Identity, New Jersey, Prentice-Hall] theory of stigma as an intellectual scaffold to help understand the social meaning of HIV/AIDS stigma from People Living with HIV/AIDS. The study adopts a qualitative approach because of its appropriateness for unravelling subjective phenomena such as the experiences of HIV/AIDS stigma. In-depth interviews were conducted with 10 HIV-positive employees of a retailing company located in the Western Cape province of South Africa who volunteered to participate in the study. The participants with the discreditable stigma internalised society's prejudice towards those living with the virus. As a result, the participants relied on self-isolation and social withdrawal to cope with enacted stigma. Managing information about one's status and deciding whether, who, when, etc., to tell are crucial questions. The participants feared being devalued by family, friends, co-workers and the community. In concurrence with Goffman [1963. Stigma: Notes on the Management of Spoiled Identity, New Jersey, Prentice-Hall] the HIV/AIDS stigma is seen as about relationships. PMID:24980478

  5. Defining Moments in MMWR History: The AIDS Epidemic, Pneumocystis Pneumonia --- Los Angeles 1981

    Centers for Disease Control (CDC) Podcasts

    On June 5, 1981, MMWR published a report of Pneumocystis pneumonia in five previously healthy young gay men in Los Angeles, California. This report was later acknowledged as the first published account of what would become known as human immunodeficiency virus, or HIV, and acquired immunodeficiency syndrome, or AIDS. It was the first of many MMWR reports that led to a better understanding of this new condition. In this podcast, Dr. Harold Jaffe recalls CDC's investigation and response to the AIDS Epidemic.

  6. Immunogenicity and efficacy of immunodeficiency virus-like particles pseudotyped with the G protein of vesicular stomatitis virus

    International Nuclear Information System (INIS)

    Kuate, Seraphin; Stahl-Hennig, Christiane; Stoiber, Heribert; Nchinda, Godwin; Floto, Anja; Franz, Monika; Sauermann, Ulrike; Bredl, Simon; Deml, Ludwig; Ignatius, Ralf; Norley, Steve; Racz, Paul; Tenner-Racz, Klara; Steinman, Ralph M.; Wagner, Ralf; Uberla, Klaus

    2006-01-01

    Vaccination with exogenous antigens such as recombinant viral proteins, immunodeficiency virus-derived whole inactivated virus particles, or virus-like particles (VLP) has generally failed to provide sufficient protection in animal models for AIDS. Pseudotyping VLPs with the vesicular stomatitis virus G protein (VSV-G), which is known to mediate entry into dendritic cells, might allow more efficient stimulation of immune responses. Therefore, we pseudotyped noninfectious immunodeficiency virus-like particles with VSV-G and carried out a preliminary screen of their immunogenicity and vaccination efficacy. Incorporation of VSV-G into HIV-1 VLPs led to hundred-fold higher antibody titers to HIV-1 Gag and enhancement of T cell responses in mice. Repeated vaccination of rhesus monkeys for 65 weeks with VSV-G pseudotyped simian immunodeficiency virus (SIV)-like particles (VLP[G]) provided initial evidence for efficient suppression of viral load after mucosal challenge with the SIVmac239 virus. Challenge of monkeys after a 28 week vaccination regimen with VLP[G] led to a reduction in peak viremia, but persistent suppression of viral load was not achieved. Due to limitations in the number of animals available for this study, improved efficacy of VSV-G pseudotyped VLPs in nonhuman primates could not be demonstrated. However, mouse experiments revealed that pseudotyping of VLPs with fusion-competent VSV-G clearly improves their immunogenicity. Additional strategies, particularly adjuvants, should be considered to provide greater protection against a challenge with pathogenic immunodeficiency virus

  7. Expression of rabbit IL-4 by recombinant myxoma viruses enhances virulence and overcomes genetic resistance to myxomatosis.

    Science.gov (United States)

    Kerr, P J; Perkins, H D; Inglis, B; Stagg, R; McLaughlin, E; Collins, S V; Van Leeuwen, B H

    2004-06-20

    Rabbit IL-4 was expressed in the virulent standard laboratory strain (SLS) and the attenuated Uriarra (Ur) strain of myxoma virus with the aim of creating a Th2 cytokine environment and inhibiting the development of an antiviral cell-mediated response to myxomatosis in infected rabbits. This allowed testing of a model for genetic resistance to myxomatosis in wild rabbits that have undergone 50 years of natural selection for resistance to myxomatosis. Expression of IL-4 significantly enhanced virulence of both virulent and attenuated virus strains in susceptible (laboratory) and resistant (wild) rabbits. SLS-IL-4 completely overcame genetic resistance in wild rabbits. The pathogenesis of SLS-IL-4 was compared in susceptible and resistant rabbits. The results support a model for resistance to myxomatosis of an enhanced innate immune response controlling virus replication and allowing an effective antiviral cell-mediated immune response to develop in resistant rabbits. Expression of IL-4 did not overcome immunity to myxomatosis induced by immunization.

  8. Protection of pigs against pandemic swine origin H1N1 influenza A virus infection by hemagglutinin- or neuraminidase-expressing attenuated pseudorabies virus recombinants.

    Science.gov (United States)

    Klingbeil, Katharina; Lange, Elke; Blohm, Ulrike; Teifke, Jens P; Mettenleiter, Thomas C; Fuchs, Walter

    2015-03-02

    Influenza is an important respiratory disease of pigs, and may lead to novel human pathogens like the 2009 pandemic H1N1 swine-origin influenza virus (SoIV). Therefore, improved influenza vaccines for pigs are required. Recently, we demonstrated that single intranasal immunization with a hemagglutinin (HA)-expressing pseudorabies virus recombinant of vaccine strain Bartha (PrV-Ba) protected pigs from H1N1 SoIV challenge (Klingbeil et al., 2014). Now we investigated enhancement of efficacy by prime-boost vaccination and/or intramuscular administration. Furthermore, a novel PrV-Ba recombinant expressing codon-optimized N1 neuraminidase (NA) was included. In vitro replication of this virus was only slightly affected compared to parental virus. Unlike HA, the abundantly expressed NA was efficiently incorporated into PrV particles. Immunization of pigs with the two PrV recombinants, either singly or in combination, induced B cell proliferation and the expected SoIV-specific antibodies, whose titers increased substantially after boost vaccination. After immunization of animals with either PrV recombinant H1N1 SoIV challenge virus replication was significantly reduced compared to PrV-Ba vaccinated or naïve controls. Protective efficacy of HA-expressing PrV was higher than of NA-expressing PrV, and not significantly enhanced by combination. Despite higher serum antibody titers obtained after intramuscular immunization, transmission of challenge virus to naïve contact animals was only prevented after intranasal prime-boost vaccination with HA-expressing PrV-Ba. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. ATM supports gammaherpesvirus replication by attenuating type I interferon pathway.

    Science.gov (United States)

    Darrah, Eric J; Stoltz, Kyle P; Ledwith, Mitchell; Tarakanova, Vera L

    2017-10-01

    Ataxia-Telangiectasia mutated (ATM) kinase participates in multiple networks, including DNA damage response, oxidative stress, and mitophagy. ATM also supports replication of diverse DNA and RNA viruses. Gammaherpesviruses are prevalent cancer-associated viruses that benefit from ATM expression during replication. This proviral role of ATM had been ascribed to its signaling within the DNA damage response network; other functions of ATM have not been considered. In this study increased type I interferon (IFN) responses were observed in ATM deficient gammaherpesvirus-infected macrophages. Using a mouse model that combines ATM and type I IFN receptor deficiencies we show that increased type I IFN response in the absence of ATM fully accounts for the proviral role of ATM during gammaherpesvirus replication. Further, increased type I IFN response rendered ATM deficient macrophages more susceptible to antiviral effects of type II IFN. This study identifies attenuation of type I IFN responses as the primary mechanism underlying proviral function of ATM during gammaherpesvirus infection. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. A Herpes Simplex Virus Type 2 Deleted for Glycoprotein D Enables Dendritic Cells to Activate CD4+ and CD8+ T Cells

    Science.gov (United States)

    Retamal-Díaz, Angello R.; Kalergis, Alexis M.; Bueno, Susan M.; González, Pablo A.

    2017-01-01

    Herpes simplex virus type 2 (HSV-2) is highly prevalent in the human population producing significant morbidity, mainly because of the generation of genital ulcers and neonatal encephalitis. Additionally, HSV-2 infection significantly increases the susceptibility of the host to acquire HIV and promotes the shedding of the latter in the coinfected. Despite numerous efforts to create a vaccine against HSV-2, no licensed vaccines are currently available. A long-standing strategy, based on few viral glycoproteins combined with adjuvants, recently displayed poor results in a Phase III clinical study fueling exploration on the development of mutant HSV viruses that are attenuated in vivo and elicit protective adaptive immune components, such as antiviral antibodies and T cells. Importantly, such specialized antiviral immune components are likely induced and modulated by dendritic cells, professional antigen presenting cells that process viral antigens and present them to T cells. However, HSV interferes with several functions of DCs and ultimately induces their death. Here, we propose that for an attenuated mutant virus to confer protective immunity against HSV in vivo based on adaptive immune components, such virus should also be attenuated in dendritic cells to promote a robust and effective antiviral response. We provide a background framework for this idea, considerations, as well as the means to assess this hypothesis. Addressing this hypothesis may provide valuable insights for the development of novel, safe, and effective vaccines against herpes simplex viruses. PMID:28848543

  11. A Herpes Simplex Virus Type 2 Deleted for Glycoprotein D Enables Dendritic Cells to Activate CD4+ and CD8+ T Cells

    Directory of Open Access Journals (Sweden)

    Angello R. Retamal-Díaz

    2017-08-01

    Full Text Available Herpes simplex virus type 2 (HSV-2 is highly prevalent in the human population producing significant morbidity, mainly because of the generation of genital ulcers and neonatal encephalitis. Additionally, HSV-2 infection significantly increases the susceptibility of the host to acquire HIV and promotes the shedding of the latter in the coinfected. Despite numerous efforts to create a vaccine against HSV-2, no licensed vaccines are currently available. A long-standing strategy, based on few viral glycoproteins combined with adjuvants, recently displayed poor results in a Phase III clinical study fueling exploration on the development of mutant HSV viruses that are attenuated in vivo and elicit protective adaptive immune components, such as antiviral antibodies and T cells. Importantly, such specialized antiviral immune components are likely induced and modulated by dendritic cells, professional antigen presenting cells that process viral antigens and present them to T cells. However, HSV interferes with several functions of DCs and ultimately induces their death. Here, we propose that for an attenuated mutant virus to confer protective immunity against HSV in vivo based on adaptive immune components, such virus should also be attenuated in dendritic cells to promote a robust and effective antiviral response. We provide a background framework for this idea, considerations, as well as the means to assess this hypothesis. Addressing this hypothesis may provide valuable insights for the development of novel, safe, and effective vaccines against herpes simplex viruses.

  12. Human immunodeficiency virus contains an epitope immunoreactive with thymosin α1 and the 30-amino acid synthetic p17 group-specific antigen peptide HGP-30

    International Nuclear Information System (INIS)

    Naylor, P.H.; Naylor, C.W.; Badamchian, M.; Wada, S.; Goldstein, A.L.; Wang, S.S.; Sun, D.K.; Thornton, A.H.; Sarin, P.S.

    1987-01-01

    The authors have reported that an antiserum prepared against thymosin α 1 [which shares a region of homology with the p17 protein of the acquired immunodeficiency syndrome (AIDS)-associated human immunodeficiency virus] effectively neutralized the AIDs virus and prevented its replication in H9 cells. Using HPLC and immunoblot analysis, they have identified from a clone B, type III human T-lymphotropic virus (HTLV-IIIB) extracts a protein with a molecular weight of 17,000 that is immunoreactive with thymosin α 1 . In contrast, no immunoreactivity was found in retroviral extracts from a number of nonhuman species including feline, bovine, simian, gibbon, and murine retroviruses. Heterologous antiserum prepared against a 30-amino acid synthetic peptide analogue (HGP-30) does not cross-react with thymosin α 1 but does react specifically with the p17 protein of the AIDS virus in a manner identical to that seen with an HTLV-IIIB p17-specific monoclonal antibody. The demonstration that this synthetic analogue is immunogenic and that antibodies to HGP-30 cross-react not only with synthetic peptide but also with the HTLV-IIIB p17 viral protein provides an additional, and potentially more specific, candidate for development of a synthetic peptide vaccine for AIDS. In addition, the p17 synthetic peptide (HGP-3) may prove to be useful in a diagnostic assay for the detection of AIDS virus infection in seronegative individuals

  13. Human immunodeficiency virus endocrinopathy

    Directory of Open Access Journals (Sweden)

    Uma Sinha

    2011-01-01

    Full Text Available Human immunodeficiency virus (HIV endocrinopathy encompasses a broad spectrum of disorders. Almost all the endocrine organs are virtually affected by HIV infection. HIV can directly alter glandular function. More commonly secondary endocrine dysfunction occurs due to opportunistic infections and neoplasms in immunocompromised state. The complex interaction between HIV infection and endocrine system may be manifested as subtle biochemical and hormonal perturbation to overt glandular failure. Antiretroviral therapy as well as other essential medications often result in adverse endocrinal consequences. Apart from adrenal insufficiency, hypogonadism, diabetes and bone loss, AIDS wasting syndrome and HIV lipodystrophy need special reference. Endocrinal evaluation should proceed as in other patients with suspected endocrine dysfunction. Available treatment options have been shown to improve quality of life and long-term mortality in AIDS patients.

  14. HIV/AIDS: Knowledge, attitudes and practices among adolescents in Nimule, South Sudan

    Directory of Open Access Journals (Sweden)

    Michael Bol Jool Dit

    2018-02-01

    Full Text Available Background: HIV is an infectious virus commonly transmitted through body fluids mostly semen and blood. It causes a serious and non-curable disease with grave consequences especially in sub-Saharan Africa. In South Sudan the prevalence rate of HIV was estimated at 2.6% in 2016. The treatment options are scarce and educational programs limited. This is of great concern since limited knowledge and awareness of HIV is a major risk factor particularly, among young people. Method: A cross-sectional survey using self-administered questionnaires among adolescents was carried out in November 2016. Results: Sixty-five students participated in the study. In general they had good knowledge about HIV/AIDS with the majority having heard of HIV. Majority stated that HIV spreads through sex (82%, blood transfusion (95%, and from mother to child during pregnancy and delivery (66%. Several misconceptions were present with 43% responding that HIV can be transmitted through mosquito bites and 18% stating that the virus can be spread through shaking hands, hugging and living in the same house. Conclusion: Though the respondents showed fair knowledge about HIV/AIDS, there are still some areas in which they lack knowledge especially regarding spread of the disease and practice. More information about HIV/AIDS and sexual education should be made available.

  15. A model for HIV/AIDS pandemic with optimal control

    Science.gov (United States)

    Sule, Amiru; Abdullah, Farah Aini

    2015-05-01

    Human immunodeficiency virus and acquired immune deficiency syndrome (HIV/AIDS) is pandemic. It has affected nearly 60 million people since the detection of the disease in 1981 to date. In this paper basic deterministic HIV/AIDS model with mass action incidence function are developed. Stability analysis is carried out. And the disease free equilibrium of the basic model was found to be locally asymptotically stable whenever the threshold parameter (RO) value is less than one, and unstable otherwise. The model is extended by introducing two optimal control strategies namely, CD4 counts and treatment for the infective using optimal control theory. Numerical simulation was carried out in order to illustrate the analytic results.

  16. Trans-activation of the JC virus late promoter by the tat protein of type 1 human immunodeficiency virus in glial cells

    International Nuclear Information System (INIS)

    Tada, Hiroomi; Lashgari, M.; Amini, S.; Khalili, K.; Rappaport, J.; Wong-Staal, F.

    1990-01-01

    Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the central nervous system caused by the JC virus (JCV), a human papovavirus. PML is a relatively rare disease seen predominantly in immunocompromised individuals and is a frequent complication observed in AIDS patients. The significantly higher incidence of PML in AIDS patients than in other immunosuppressive disorders has suggested that the presence of human immunodeficiency virus type 1 (HIV-1) in the brain may directly or indirectly contribute to the pathogenesis of this disease. In the present study the authors have examined the expression of the JCV genome in both glial and non-glial cells in the presence of HIV-1 regulatory proteins. They find that the HIV-1-encoded trans-regulatory protein tat increases the basal activity of the JCV late promoter, JCV L , in glial cells. They conclude that the presence of the HIV-1-encoded tat protein may positively affect the JCV lytic cycle in glial cells by stimulating JCV gene expression. The results suggest a mechanism for the relatively high incidence of PML in AIDS patients than in other immunosuppressive disorders. Furthermore, the findings indicate that the HIV-1 regulatory protein tat may stimulate other viral and perhaps cellular promoters, in addition to its own

  17. Computed tomography in young children with herpes simplex virus encephalitis

    International Nuclear Information System (INIS)

    Sugimoto, T.; Woo, M.; Okazaki, H.; Nishida, N.; Hara, T.; Yasuhara, A.; Kasahara, M.; Kobayashi, Y.

    1985-01-01

    Computed tomographic (CT) scans were obtained from eight infants and young children with herpes simplex virus encephalitis. In two cases the initial scan showed diffuse edematous changes as a mass effect without laterality. Unilateral localized low attenuation in the initial scan was evident 4 days after the onset in one patient, and high attenuation in the initial scan appeared on the 6th day in another patient, but in general, it was not possible to establish an early diagnosis of herpes simplex virus encephalitis from CT scan. In the longitudinal study the calcification with ventriculomegaly appeared in 3 of 5 survivors, and gyriform calcification in 2 of 3 patients, respectively. The appearance of multicystic encephalomalacia was evident in one patient 6 months after the onset of neonatal herpes simplex encephalitis. It is shown that the CT findings of neonates and young children with herpes simplex encephalitis are different from those of older children and adults, and the importance of longitudinal CT studies was stressed in clarifying the pathophysiology of the central nervous system involvement in survivors. (orig.)

  18. Examination of the selective pressures on a live PRRS vaccine virus

    DEFF Research Database (Denmark)

    Storgaard, Torben; Oleksiewicz, M.; Bøtner, Anette

    1999-01-01

    of the selective pressure this attenuated virus had experienced during reversion. An analysis of nucleotide mutations showed a similar rate of mutations in the two genes (ORF5 and 7). However, non-synonymous mutations in ORF7 were eliminated by purifying selection. In contrast, non-synonymous mutations in ORF5...

  19. Sequence adaptations during growth of rescued classical swine fever viruses in cell culture and within infected pigs

    DEFF Research Database (Denmark)

    Hadsbjerg, Johanne; Friis, Martin Barfred; Fahnøe, Ulrik

    2016-01-01

    RNA could be detected. However, the animals inoculated with these mutant viruses seroconverted against CSFV. Thus, these mutant viruses were highly attenuated in vivo. All 4 rescued viruses were also passaged up to 20 times in cell culture. Using full genome sequencing, the same two adaptations within......Classical swine fever virus (CSFV) causes an economically important disease of swine. Four different viruses were rescued from full-length cloned cDNAs derived from the Paderborn strain of CSFV. Three of these viruses had been modified by mutagenesis (with 7 or 8 nt changes) within stem 2...... each of four independent virus populations were observed that restored the coding sequence to that of the parental field strain. These adaptations occurred with different kinetics. The combination of reverse genetics and in depth, full genome sequencing provides a powerful approach to analyse virus...

  20. The Tuskegee Syphilis Study, 1932 to 1972: Implications for HIV Education and AIDS Risk Education Programs in the Black Community.

    Science.gov (United States)

    Thomas, Stephen B.; Quinn, Sandra Crouse

    1991-01-01

    The Tuskegee study of untreated syphilis in black males caused distrust by blacks of the public health system that has implications for Acquired Immune Deficiency Syndrome (AIDS) and Human Immunodeficiency Virus (HIV) studies. AIDS prevention among blacks may require openness about the Tuskegee study to allay fears of repetition. (SLD)