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Sample records for attenuated aids virus

  1. Computer-aided codon-pairs deoptimization of the major envelope GP5 gene attenuates porcine reproductive and respiratory syndrome virus.

    Science.gov (United States)

    Ni, Yan-Yan; Zhao, Zhao; Opriessnig, Tanja; Subramaniam, Sakthivel; Zhou, Lei; Cao, Dianjun; Cao, Qian; Yang, Hanchun; Meng, Xiang-Jin

    2014-02-01

    Synthetic attenuated virus engineering (SAVE) is an emerging technology that enables rapid attenuation of viruses. In this study, by using SAVE we demonstrated rapid attenuation of an arterivirus, porcine reproductive and respiratory syndrome virus (PRRSV). The major envelope GP5 gene of PRRSV was codon-pair deoptimized aided by a computer algorithm. The codon-pair deoptimized virus, designated as SAVE5 with a deoptimized GP5 gene, was successfully rescued in vitro. The SAVE5 virus replicated at a lower level in vitro with a significant decrease of GP5 protein expression compared to the wild-type PRRSV VR2385 virus. Pigs experimentally infected with the SAVE5 virus had significantly lower viremia level up to 14 days post-infection as well as significantly reduced gross and histological lung lesions when compared to wild-type PRRSV VR2385 virus-infected pigs, indicating the attenuation of the SAVE5 virus. This study proved the feasibility of rapidly attenuating PRRSV by SAVE. Copyright © 2013 Elsevier Inc. All rights reserved.

  2. Recoding of the vesicular stomatitis virus L gene by computer-aided design provides a live, attenuated vaccine candidate.

    Science.gov (United States)

    Wang, Bingyin; Yang, Chen; Tekes, Gergely; Mueller, Steffen; Paul, Aniko; Whelan, Sean P J; Wimmer, Eckard

    2015-03-31

    Codon pair bias (CPB), which has been observed in all organisms, is a neglected genomic phenomenon that affects gene expression. CPB results from synonymous codons that are paired more or less frequently in ORFeomes regardless of codon bias. The effect of an individual codon pair change is usually small, but when it is amplified by large-scale genome recoding, strikingly altered biological phenotypes are observed. The utility of codon pair bias in the development of live attenuated vaccines was recently demonstrated by recodings of poliovirus (a positive-strand RNA virus) and influenza virus (a negative-strand segmented RNA virus). Here, the L gene of vesicular stomatitis virus (VSV), a nonsegmented negative-sense RNA virus, was partially recoded based on codon pair bias. Totals of 858 and 623 silent mutations were introduced into a 5'-terminal segment of the viral L gene (designated L1) to create sequences containing either overrepresented or underrepresented codon pairs, designated L1(sdmax) and L1(min), respectively. Analysis revealed that recombinant VSV containing the L1(min) sequence could not be recovered, whereas the virus with the sdmax sequence showed a modest level of attenuation in cell culture. More strikingly, in mice the L1(sdmax) virus was almost as immunogenic as the parental strain but highly attenuated. Taken together, these results open a new road to attain a balance between VSV virulence and immunogenicity, which could serve as an example for the attenuation of other negative-strand, nonsegmented RNA viruses. Vesicular stomatitis virus (VSV) is the prototypic rhabdovirus in the order Mononegavirales. A wide range of human pathogens belong to this family. Using a unique computer algorithm and large-scale genome synthesis, we attempted to develop a live attenuated vaccine strain for VSV, which could be used as an antigen delivery platform for humans. Recombinant VSVs with distinct codon pair biases were rationally designed, constructed, and

  3. Conditional virus replication as an approach to a safe live attenuated human immunodeficiency virus vaccine

    NARCIS (Netherlands)

    Berkhout, Ben; Verhoef, Koen; Marzio, Giuseppe; Klaver, Bep; Vink, Monique; Zhou, Xue; Das, Atze T.

    2002-01-01

    Despite intensive efforts, no safe and effective vaccine has been developed for the prophylaxis of human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS). Studies with the simian immunodeficiency virus (SIV)/macaque model demonstrated that live attenuated viruses are the most

  4. Depo-provera treatment does not abrogate protection from intravenous SIV challenge in female macaques immunized with an attenuated AIDS virus.

    Directory of Open Access Journals (Sweden)

    Meritxell Genescà

    Full Text Available BACKGROUND: In a previous study, progesterone treatment of female monkeys immunized with live, attenuated SHIV89.6 abrogated the generally consistent protection from vaginal simian immunodeficiency virus (SIV challenge. The mechanisms responsible for the loss of protection remain to be defined. The objective of the present study was to determine whether Depo-Provera administration alters protection from intravenous SIV challenge in SHIV-immunized female macaques. METHODS AND FINDINGS: Two groups of female macaques were immunized with attenuated SHIV89.6 and then challenged intravenously with SIVmac239. Four weeks before challenge, one animal group was treated with Depo-Provera, a commonly used injectable contraceptive progestin. As expected, SHIV-immunized monkeys had significantly lower peak and set-point plasma viral RNA levels compared to naïve controls, but in contrast to previously published findings with vaginal SIV challenge, the Depo-Provera SHIV-immunized animals controlled SIV replication to a similar, or even slightly greater, degree than did the untreated SHIV-immunized animals. Control of viral replication from week 4 to week 20 after challenge was more consistent in the progesterone-treated, SHIV-immunized animals than in untreated, SHIV-immunized animals. Although levels of interferon-gamma production were similar, the SIV-specific CD8(+ T cells of progesterone-treated animals expressed more functions than the anti-viral CD8(+ T cells from untreated animals. CONCLUSIONS: Depo-Provera did not diminish the control of viral replication after intravenous SIV challenge in female macaques immunized with a live-attenuated lentivirus. This result contrasts with the previously reported effect of Depo-Provera(R on protection from vaginal SIV challenge and strongly implies that the decreased protection from vaginal challenge is due to effects of progesterone on the genital tract rather than to systemic effects. Further, these results

  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. Virus infections in patients with AIDS.

    Science.gov (United States)

    Griffiths, P D

    1990-01-01

    Virus infections are common in patients with acquired immune deficiency syndrome (AIDS). Viruses can have two distinct relationships with human immunodeficiency virus (HIV); they can be opportunists if the second virus takes advantage of decreased immune function in the host or they can act as co-factors to accelerate the rate at which AIDS develops. Viruses acting as opportunists may cause no symptoms or may be life-threatening. Several, including herpes simplex, varicella zoster, cytomegalovirus and Epstein-Barr virus, can be treated with antiviral agents. Before concluding that a virus can act as a co-factor for HIV, several other possible relationships must be excluded including opportunism, co-parameters of lifestyle and prognostic markers. Studies in vitro may suggest which viruses are potential co-factors but clear evidence can come only from carefully defined cohorts of patients. Recent evidence showing that cytomegalovirus can meet these criteria is presented.

  7. Evolutionary history and attenuation of myxoma virus on two continents

    National Research Council Canada - National Science Library

    Kerr, Peter J; Ghedin, Elodie; DePasse, Jay V; Fitch, Adam; Cattadori, Isabella M; Hudson, Peter J; Tscharke, David C; Read, Andrew F; Holmes, Edward C

    2012-01-01

    The attenuation of myxoma virus (MYXV) following its introduction as a biological control into the European rabbit populations of Australia and Europe is the canonical study of the evolution of virulence...

  8. Mechanisms of temperature sensitivity of attenuated Urabe mumps virus.

    Science.gov (United States)

    Schinkel, Stephanie C Burke; Rubin, Steven; Wright, Kathryn E

    2017-01-02

    Temperature sensitivity is a phenotype often associated with attenuation of viruses. Previously, we purified several mumps variants from an incompletely attenuated Urabe strain live attenuated vaccine. Here we characterize one isolate that is sensitive to growth at high temperature. This virus was attenuated in a small animal model of mumps virulence, and we identified unique coding substitutions in the hemagglutinin-neuraminidase (HN), the viral polymerase (L) gene, and a non-coding substitution close to the anti-genome promoter sequences. At the non-permissive temperature, transcription of viral mRNAs and production of the replication intermediate were reduced compared to events at the permissive temperature and to a non-ts virulent Urabe virus. As well, synthesis of viral proteins was also reduced at the higher temperature. While the actual sequence substitutions in the ts virus were unique, the pattern of substitutions in HN, L and genome end sequences is similar to another attenuated Urabe virus previously described by us. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. 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.

  10. Studies on attenuation of rotavirus. A comparison in piglets between virulent virus and its attenuated derivative.

    Science.gov (United States)

    Tzipori, S; Unicomb, L; Bishop, R; Montenaro, J; Vaelioja, L M

    1989-01-01

    The development of rotavirus vaccines against acute gastroenteritis for human infants has been accorded a very high priority. Several vaccine candidates all of which are live cultivated strains of animal origin have been tested in humans. However the nature of attenuation of these viruses for humans is unknown. In this study we have attenuated a pig rotavirus by 15 sequential passages in cell culture after which the virus no longer causes diarrhoea in piglets. The pathogenesis of infection of the attenuated rotavirus strain (AT/76 P15) in gnotobiotic piglets was compared with that of the virulent parent strain (AT/76). The pattern of virus replication in the small intestine was judged by histology, disaccharidase assay, immunoperoxidase labelling of gut sections using group A specific rotavirus antibody, and rotavirus antigen assay of gut contents. The parent strain caused variable but extensive infection that resulted in the complete destruction of mature small intestinal enterocytes and villous contraction within 3 days. Membrane bound digestive enzymes were lost, and profound watery diarrhoea and dehydration resulted in causing piglets to become moribund. In contrast attenuated virus appeared to propagate at a much slower pace. Fewer infected epithelial cells were detected at any one time. Destruction of enterocytes was never extensive enough to cause marked mucosal changes in histology. Membrane bound digestive enzymes remained near normal levels and there was little or no diarrhoea. Virus replication ceased after 6 days. It is concluded that attenuation of the porcine rotavirus strain studied was associated with its decreased ability to propagate in enterocytes after adaption to culture.

  11. 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.

  12. 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.

  13. Evolutionary history and attenuation of myxoma virus on two continents.

    Science.gov (United States)

    Kerr, Peter J; Ghedin, Elodie; DePasse, Jay V; Fitch, Adam; Cattadori, Isabella M; Hudson, Peter J; Tscharke, David C; Read, Andrew F; Holmes, Edward C

    2012-01-01

    The attenuation of myxoma virus (MYXV) following its introduction as a biological control into the European rabbit populations of Australia and Europe is the canonical study of the evolution of virulence. However, the evolutionary genetics of this profound change in host-pathogen relationship is unknown. We describe the genome-scale evolution of MYXV covering a range of virulence grades sampled over 49 years from the parallel Australian and European epidemics, including the high-virulence progenitor strains released in the early 1950s. MYXV evolved rapidly over the sampling period, exhibiting one of the highest nucleotide substitution rates ever reported for a double-stranded DNA virus, and indicative of a relatively high mutation rate and/or a continually changing selective environment. Our comparative sequence data reveal that changes in virulence involved multiple genes, likely losses of gene function due to insertion-deletion events, and no mutations common to specific virulence grades. Hence, despite the similarity in selection pressures there are multiple genetic routes to attain either highly virulent or attenuated phenotypes in MYXV, resulting in convergence for phenotype but not genotype.

  14. Evolutionary history and attenuation of myxoma virus on two continents.

    Directory of Open Access Journals (Sweden)

    Peter J Kerr

    Full Text Available The attenuation of myxoma virus (MYXV following its introduction as a biological control into the European rabbit populations of Australia and Europe is the canonical study of the evolution of virulence. However, the evolutionary genetics of this profound change in host-pathogen relationship is unknown. We describe the genome-scale evolution of MYXV covering a range of virulence grades sampled over 49 years from the parallel Australian and European epidemics, including the high-virulence progenitor strains released in the early 1950s. MYXV evolved rapidly over the sampling period, exhibiting one of the highest nucleotide substitution rates ever reported for a double-stranded DNA virus, and indicative of a relatively high mutation rate and/or a continually changing selective environment. Our comparative sequence data reveal that changes in virulence involved multiple genes, likely losses of gene function due to insertion-deletion events, and no mutations common to specific virulence grades. Hence, despite the similarity in selection pressures there are multiple genetic routes to attain either highly virulent or attenuated phenotypes in MYXV, resulting in convergence for phenotype but not genotype.

  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. Mechanisms of Cytotoxicity of the Aids Virus

    Science.gov (United States)

    1992-10-10

    the above experiments was a significant pcoblem in data interpretation. To mare clearly define the cellular localizaticn of vpr by imarflurrescence, we...Department of Pathology , George Washington University, Washington D.C. 200372; and Henry M. Jackson Foundation for the Advancement of Military Medicine and the...cellular transcriptional factors. (mouse mammary tumour virus) LTR-linked nef Specific targets of PKC, PKA, cAMP-dependent transgenic lines expressed Nef

  17. 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

  18. Comparison of immune responses to attenuated rabies virus and street virus in mouse brain.

    Science.gov (United States)

    Miao, Fa-Ming; Zhang, Shou-Feng; Wang, Shu-Chao; Liu, Ye; Zhang, Fei; Hu, Rong-Liang

    2017-01-01

    Rabies is a lethal neurological disease caused by the neurotropic rabies virus (RABV). To investigate the innate immune response in the brain during rabies infection, key gene transcripts indicative of innate immunity in a mouse model system were measured using real-time RT-PCR. Mice were infected via the intracerebral or intramuscular route with either attenuated rabies virus (SRV9) or pathogenic rabies virus (BD06). Infection with SRV9 resulted in the early detection of viral replication and the rapid induction of innate immune response gene expression in the brain. BD06 infection elicited innate immune response gene expression during only the late stage of infection. We measured Na-fluorescein uptake to assess blood-brain barrier (BBB) permeability, which was enhanced during the early stage of SRV9 infection and significantly enhanced during the late stage of BD06 infection. Furthermore, early SRV9 replication increased the maturation and differentiation of dendritic cells (DCs) and B cells in the inguinal lymph nodes and initiated the generation of virus-neutralizing antibodies (VNAs), which cooperate with the innate immune response to eliminate virus from the CNS. However, BD06 infection did not stimulate VNA production; thus, the virus was able to evade the host immune response and cause encephalitis. The rabies virus phosphoprotein has been reported to counteract IFN activation. In an in vitro study of the relationship between IFN antagonism and RABV pathogenicity, we demonstrated that SRV9 more strongly antagonized IFN activity than did BD06. Therefore, there is no positive relationship between the IFN antagonist activity of the virus and its pathogenicity.

  19. Management of varicella zoster virus retinitis in AIDS

    OpenAIRE

    Moorthy, R; Weinberg, D.; Teich, S.; Berger, B; Minturn, J.; Kumar, S.; Rao, N; Fowell, S.; Loose, I; Jampol, L

    1997-01-01

    AIMS/BACKGROUND—Varicella zoster virus retinitis (VZVR) in patients with AIDS, also called progressive outer retinal necrosis (PORN), is a necrotising viral retinitis which has resulted in blindness in most patients. The purposes of this study were to investigate the clinical course and visual outcome, and to determine if the choice of a systemic antiviral therapy affected the final visual outcome in patients with VZVR and AIDS.
METHODS—A review of the clinical records of 20 patients with VZV...

  20. AIDS

    Science.gov (United States)

    ... smear to check for cancer of the anus Treatment HIV/AIDS is treated with medicines that stop the virus ... having a long-term illness. Outlook (Prognosis) With treatment, most people with HIV/AIDS can live a healthy and normal life. Current ...

  1. Hepatitis B and C virus infection and liver function in aids patients ...

    African Journals Online (AJOL)

    Hepatitis B and C virus infection and liver function in aids patients: research. ... in aids patients: research. H Lodenyo, B Schoub, R Ally, S Kairu, L Segal ... Objective: To asses liver function and prevalence of co-infection with hepatitis B and hepatitis C viruses in AIDS patients at Chris Hani Baragwanath Hospital. Design: A ...

  2. Genetic instability of live, attenuated human immunodeficiency virus type 1 vaccine strains

    NARCIS (Netherlands)

    Berkhout, B.; Verhoef, K.; van Wamel, J. L.; Back, N. K.

    1999-01-01

    Live, attenuated viruses have been the most successful vaccines in monkey models of human immunodeficiency virus type 1 (HIV-1) infection. However, there are several safety concerns about using such an anti-HIV vaccine in humans, including reversion of the vaccine strain to virulence and

  3. Contamination of live attenuated vaccines with an infectious feline endogenous retrovirus (RD-114 virus).

    Science.gov (United States)

    Yoshikawa, Rokusuke; Shimode, Sayumi; Sakaguchi, Shoichi; Miyazawa, Takayuki

    2014-03-01

    Retroviruses are classified as exogenous and endogenous retroviruses according to the mode of transmission. Endogenous retroviruses (ERVs) are retroviruses which have been integrated into germ-line cells and inherited from parents to offspring. Most ERVs are inactivated by deletions and mutations; however, certain ERVs maintain their infectivity and infect the same host and new hosts as exogenous retroviruses. All domestic cats have infectious ERVs, termed RD-114 virus. Several canine and feline attenuated vaccines are manufactured using RD-114 virus-producing cell lines such as Crandell-Rees feline kidney cells; therefore, it is possible that infectious RD-114 virus contaminates live attenuated vaccines. Recently, Japanese and UK research groups found that several feline and canine vaccines were indeed contaminated with infectious RD-114 virus. This was the first incidence of contamination of 'infectious' ERVs in live attenuated vaccines. RD-114 virus replicates efficiently in canine cell lines and primary cells. Therefore, it is possible that RD-114 virus infects dogs following inoculation with contaminated vaccines and induces proliferative diseases and immune suppression, if it adapts to grow efficiently in dogs. In this review, we summarize the incidence of contamination of RD-114 virus in live attenuated vaccines and potential risks of infection with RD-114 virus in dogs.

  4. Highly Attenuated Recombinant Vesicular Stomatitis Virus VSV-12′GFP Displays Immunogenic and Oncolytic Activity

    Science.gov (United States)

    Davis, John N.

    2013-01-01

    Vesicular stomatitis virus (VSV) has shown considerable promise both as an immunization vector and as an oncolytic virus. In both applications, an important concern is the safety profile of the virus. To generate a highly attenuated virus, we added two reporter genes to the 3′ end of the VSV genome, thereby shifting the NPMGL genes from positions 1 to 5 to positions 3 to 7. The resulting virus (VSV-12′GFP) was highly attenuated, generating smaller plaques than four other attenuated VSVs. In one-step growth curves, VSV-12′GFP displayed the slowest growth kinetics. The mechanism of attenuation appears to be due to reduced expression of VSV genes downstream of the reporter genes, as suggested by a 10.4-fold reduction in L-protein RNA transcript. Although attenuated, VSV-12′GFP was highly effective at generating an immune response, indicated by a high-titer antibody response against the green fluorescent protein (GFP) expressed by the virus. Although VSV-12′GFP was more attenuated than other VSVs on both normal and cancer cells, it nonetheless showed a greater level of infection of human cancer cells (glioma and melanoma) than of normal cells, and this effect was magnified in glioma by interferon application, indicating selective oncolysis. Intravenous VSV-12′GFP selectively infected human gliomas implanted into SCID mice subcutaneously or intracranially. All postnatal day 16 mice given intranasal VSV-12′GFP survived, whereas only 10% of those given VSV-G/GFP survived, indicating reduced neurotoxicity. Intratumoral injection of tumors with VSV-12′GFP dramatically suppressed tumor growth and enhanced survival. Together these data suggest this recombinant virus merits further study for its oncolytic and vaccine potential. PMID:23135719

  5. Highly attenuated recombinant vesicular stomatitis virus VSV-12'GFP displays immunogenic and oncolytic activity.

    Science.gov (United States)

    van den Pol, Anthony N; Davis, John N

    2013-01-01

    Vesicular stomatitis virus (VSV) has shown considerable promise both as an immunization vector and as an oncolytic virus. In both applications, an important concern is the safety profile of the virus. To generate a highly attenuated virus, we added two reporter genes to the 3' end of the VSV genome, thereby shifting the NPMGL genes from positions 1 to 5 to positions 3 to 7. The resulting virus (VSV-12'GFP) was highly attenuated, generating smaller plaques than four other attenuated VSVs. In one-step growth curves, VSV-12'GFP displayed the slowest growth kinetics. The mechanism of attenuation appears to be due to reduced expression of VSV genes downstream of the reporter genes, as suggested by a 10.4-fold reduction in L-protein RNA transcript. Although attenuated, VSV-12'GFP was highly effective at generating an immune response, indicated by a high-titer antibody response against the green fluorescent protein (GFP) expressed by the virus. Although VSV-12'GFP was more attenuated than other VSVs on both normal and cancer cells, it nonetheless showed a greater level of infection of human cancer cells (glioma and melanoma) than of normal cells, and this effect was magnified in glioma by interferon application, indicating selective oncolysis. Intravenous VSV-12'GFP selectively infected human gliomas implanted into SCID mice subcutaneously or intracranially. All postnatal day 16 mice given intranasal VSV-12'GFP survived, whereas only 10% of those given VSV-G/GFP survived, indicating reduced neurotoxicity. Intratumoral injection of tumors with VSV-12'GFP dramatically suppressed tumor growth and enhanced survival. Together these data suggest this recombinant virus merits further study for its oncolytic and vaccine potential.

  6. Complete Genome Sequences of Four African Horse Sickness Virus Strains from a Commercial Tetravalent Live Attenuated Vaccine

    Science.gov (United States)

    Coetzee, Peter; Martin, Darren P.; Lourens, Carina W.; Venter, Estelle H.; Weyer, Camilla T.; Joone, Christopher; le Grange, Misha; Harper, Cindy K.; Howell, Peter G.; MacLachlan, N. James

    2015-01-01

    This is a report of the complete genome sequences of plaque-selected isolates of each of the four virus strains included in a South African commercial tetravalent African horse sickness attenuated live virus vaccine. PMID:26607890

  7. Complete Genome Sequences of the Three African Horse Sickness Virus Strains from a Commercial Trivalent Live Attenuated Vaccine

    Science.gov (United States)

    Coetzee, Peter; Martin, Darren P.; Lourens, Carina W.; Venter, Estelle H.; Weyer, Camilla T.; Joone, Christopher; le Grange, Misha; Harper, Cindy K.; Howell, Peter G.; MacLachlan, N. James

    2015-01-01

    This is a report of the complete genome sequences of plaque-selected isolates of each of the three virus strains included in a South African commercial trivalent African horse sickness attenuated live virus vaccine. PMID:26294618

  8. 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.

  9. The safety of the hepatitis B vaccine. Inactivation of the AIDS virus during routine vaccine manufacture.

    Science.gov (United States)

    Francis, D P; Feorino, P M; McDougal, S; Warfield, D; Getchell, J; Cabradilla, C; Tong, M; Miller, W J; Schultz, L D; Bailey, F J

    1986-08-15

    In the United States, one hepatitis B vaccine (Heptavax-B) has been licensed for the prevention of hepatitis B virus infections. Even though this vaccine has been shown to be highly effective and well tolerated in controlled trials and has been recommended for use in those at risk for acquiring infection by hepatitis B virus, many individuals have been reluctant to be immunized for fear of contracting acquired immunodeficiency syndrome (AIDS). In this study, we demonstrate that each of the three inactivation steps used in the manufacture of Heptavax-B independently will inactivate the infectivity of high-titered preparations of the AIDS virus; recipients of the hepatitis B vaccine do not develop antibodies to the AIDS virus; the hepatitis B vaccine does not contain detectable levels of nucleic acids related to the AIDS virus. These observations clearly demonstrate that vaccination with the currently available hepatitis B vaccine poses no demonstrable risk for acquiring AIDS.

  10. Influenza A virus attenuation by codon deoptimization of the NS gene for vaccine development.

    Science.gov (United States)

    Nogales, Aitor; Baker, Steven F; Ortiz-Riaño, Emilio; Dewhurst, Stephen; Topham, David J; Martínez-Sobrido, Luis

    2014-09-01

    Influenza viral infection represents a serious public health problem that causes contagious respiratory disease, which is most effectively prevented through vaccination to reduce transmission and future infection. The nonstructural (NS) gene of influenza A virus encodes an mRNA transcript that is alternatively spliced to express two viral proteins, the nonstructural protein 1 (NS1) and the nuclear export protein (NEP). The importance of the NS gene of influenza A virus for viral replication and virulence has been well described and represents an attractive target to generate live attenuated influenza viruses with vaccine potential. Considering that most amino acids can be synthesized from several synonymous codons, this study employed the use of misrepresented mammalian codons (codon deoptimization) for the de novo synthesis of a viral NS RNA segment based on influenza A/Puerto Rico/8/1934 (H1N1) (PR8) virus. We generated three different recombinant influenza PR8 viruses containing codon-deoptimized synonymous mutations in coding regions comprising the entire NS gene or the mRNA corresponding to the individual viral protein NS1 or NEP, without modifying the respective splicing and packaging signals of the viral segment. The fitness of these synthetic viruses was attenuated in vivo, while they retained immunogenicity, conferring both homologous and heterologous protection against influenza A virus challenges. These results indicate that influenza viruses can be effectively attenuated by synonymous codon deoptimization of the NS gene and open the possibility of their use as a safe vaccine to prevent infections with these important human pathogens. Vaccination serves as the best therapeutic option to protect humans against influenza viral infections. However, the efficacy of current influenza vaccines is suboptimal, and novel approaches are necessary for the prevention of disease cause by this important human respiratory pathogen. The nonstructural (NS) gene of

  11. 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.

  12. 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 (CΔ170). 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

  13. 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) (3Dpol) 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 3Dpol 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) A24 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 (W237FHF) mutant virus was more resistant to the mutagenic nucleoside analogs ribavirin and 5-fluorouracil than the WT virus, whereas the lower-fidelity W237I (W237ILF) and W237LLF 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 3Dpol mutations that affect polymerase fidelity

  14. 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

    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......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...

  15. Type III interferon attenuates a vesicular stomatitis virus-based vaccine vector.

    Science.gov (United States)

    Guayasamin, Ryann C; Reynolds, Tracy D; Wei, Xin; Fujiwara, Mai; Robek, Michael D

    2014-09-01

    Vesicular stomatitis virus (VSV) has been extensively studied as a vaccine vector and oncolytic agent. Nevertheless, safety concerns have limited its widespread use in humans. The type III lambda interferon (IFN-λ) family of cytokines shares common signaling pathways with the IFN-α/β family and thus evokes similar antiviral activities. However, IFN-λ signals through a distinct receptor complex that is expressed in a cell type-specific manner, which restricts its activity to epithelial barriers, particularly those corresponding to the respiratory and gastrointestinal tracts. In this study, we determined how IFN-λ expression from recombinant VSV would influence vector replication, spread, and immunogenicity. We demonstrate that IFN-λ expression severely attenuates VSV in cell culture. In vivo, IFN-λ limits VSV replication in the mouse lung after intranasal administration and reduces virus spread to other organs. Despite this attenuation, however, the vector retains its capacity to induce protective CD8 T cell and antibody responses after a single immunization. These findings demonstrate a novel method of viral vector attenuation that could be used in both vaccine and oncolytic virus applications. Viruses such as VSV that are used as vaccine vectors can induce protective T cell and antibody responses after a single dose. Additionally, IFN-λ is a potent antiviral agent that has certain advantages for clinical use compared to IFN-α/β, such as fewer patient side effects. Here, we demonstrate that IFN-λ attenuates VSV replication and spread following intranasal virus delivery but does not reduce the ability of VSV to induce potent protective immune responses. These findings demonstrate that the type III IFN family may have widespread applicability for improving the safety and efficacy of viral vaccine and oncolytic vectors. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  16. In Vitro and In Vivo Attenuation of Vesicular Stomatitis Virus (VSV) by Phosphoprotein Deletion.

    Science.gov (United States)

    Wongthida, Phonphimon; Jengarn, Juggragarn; Narkpuk, Jaraspim; Koonyosying, Pongpisid; Srisutthisamphan, Kanjana; Wanitchang, Asawin; Leaungwutiwong, Pornsawan; Teeravechyan, Samaporn; Jongkaewwattana, Anan

    2016-01-01

    Vesicular stomatitis virus (VSV) is highly immunogenic and able to stimulate both innate and adaptive immune responses. However, its ability to induce adverse effects has held back the use of VSV as a potential vaccine vector. In this study we developed VSV-ΔP, a safe yet potent replication-defective recombinant VSV in which the phosphoprotein (P) gene was deleted. VSV-ΔP replicated only in supporting cells expressing P (BHK-P cells) and at levels more than 2 logs lower than VSV. In vivo studies indicated that the moderate replication of VSV-ΔP in vitro was associated with the attenuation of this virus in the mouse model, whereas mice intracranially injected with VSV succumbed to neurotoxicity. Furthermore, we constructed VSV and VSV-ΔP expressing a variety of antigens including hemagglutinin-neuraminidase (HN) from Newcastle disease virus (NDV), hemagglutinin (HA) from either a 2009 H1N1 pandemic influenza virus (pdm/09) or the avian H7N9. VSV and VSV-ΔP incorporated the foreign antigens on their surface resulting in induction of robust neutralizing antibody, serum IgG, and hemagglutination inhibition (HAI) titers against their corresponding viruses. These results indicated that VSV with P gene deletion was attenuated in vitro and in vivo, and possibly expressed the foreign antigen on its surface. Therefore, the P gene-deletion strategy may offer a potentially useful and safer approach for attenuating negative-sense RNA viruses which use phosphoprotein as a cofactor for viral replication.

  17. In Vitro and In Vivo Attenuation of Vesicular Stomatitis Virus (VSV by Phosphoprotein Deletion.

    Directory of Open Access Journals (Sweden)

    Phonphimon Wongthida

    Full Text Available Vesicular stomatitis virus (VSV is highly immunogenic and able to stimulate both innate and adaptive immune responses. However, its ability to induce adverse effects has held back the use of VSV as a potential vaccine vector. In this study we developed VSV-ΔP, a safe yet potent replication-defective recombinant VSV in which the phosphoprotein (P gene was deleted. VSV-ΔP replicated only in supporting cells expressing P (BHK-P cells and at levels more than 2 logs lower than VSV. In vivo studies indicated that the moderate replication of VSV-ΔP in vitro was associated with the attenuation of this virus in the mouse model, whereas mice intracranially injected with VSV succumbed to neurotoxicity. Furthermore, we constructed VSV and VSV-ΔP expressing a variety of antigens including hemagglutinin-neuraminidase (HN from Newcastle disease virus (NDV, hemagglutinin (HA from either a 2009 H1N1 pandemic influenza virus (pdm/09 or the avian H7N9. VSV and VSV-ΔP incorporated the foreign antigens on their surface resulting in induction of robust neutralizing antibody, serum IgG, and hemagglutination inhibition (HAI titers against their corresponding viruses. These results indicated that VSV with P gene deletion was attenuated in vitro and in vivo, and possibly expressed the foreign antigen on its surface. Therefore, the P gene-deletion strategy may offer a potentially useful and safer approach for attenuating negative-sense RNA viruses which use phosphoprotein as a cofactor for viral replication.

  18. 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; Van Borm, Steven

    2016-10-13

    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). Copyright © 2016 Mathijs et al.

  19. Computer aided epitope design as a peptide vaccine component against Lassa virus.

    Science.gov (United States)

    Faisal, Ar-Rafi Md; Imtiaz, Syed Hassan; Zerin, Tasnim; Rahman, Tania; Shekhar, Hossain Uddin

    2017-01-01

    Lassa virus (LASV) is an arena virus causing hemorrhagic fever and it is endemic in several regions of West Africa. The disease-causing virus records high mortality rate in endemic regions due to lack of appropriate treatment and prevention strategies. Therefore, it is of interest to design and develop viable vaccine components against the virus. We used the Lassa virus envelope glyco-proteins as a vaccine target to identify linear peptides as potential epitopes with immunogenic properties by computer aided epitope prediction tools. We report a T-cell epitope 'LLGTFTWTL' and a B-cell epitope 'AELKCFGNTAVAKCNE' with predicted potential immunogenicity for further in vivo and in vitro consideration.

  20. Partial Deletion of the L-Segment Intergenic Region Produces an Attenuated Machupo Virus that Protects Guinea Pigs Against Lethal Guanarito Virus Infection

    Science.gov (United States)

    2017-01-11

    1 Golden, J.W. et al. Machupo virus live-attenuated vaccine Partial deletion of the L -segment intergenic region produces an attenuated Machupo...had a 35 nucleotide deletion in the L -segment non-coding intergenic region. Contrary to Car91, Car68 produced a lethal infection in guinea pigs with...BACKGROUND Arenaviruses are enveloped ambisense single-stranded RNA viruses with two segments, small (S) and large ( L ), encoding a 10.7 Kb genome

  1. Live attenuated influenza virus increases pneumococcal translocation and persistence within the middle ear.

    Science.gov (United States)

    Mina, Michael J; Klugman, Keith P; Rosch, Jason W; McCullers, Jonathan A

    2015-07-15

    Infection with influenza A virus (IAV) increases susceptibility to respiratory bacterial infections, resulting in increased bacterial carriage and complications such acute otitis media, pneumonia, bacteremia, and meningitis. Recently, vaccination with live attenuated influenza virus (LAIV) was reported to enhance subclinical bacterial colonization within the nasopharynx, similar to IAV. Although LAIV does not predispose to bacterial pneumonia, whether it may alter bacterial transmigration toward the middle ear, where it could have clinically relevant implications, has not been investigated. BALB/c mice received LAIV or phosphate-buffered saline 1 or 7 days before or during pneumococcal colonization with either of 2 clinical isolates, 19F or 7F. Middle ear bacterial titers were monitored daily via in vivo imaging. LAIV increased bacterial transmigration to and persistence within the middle ear. When colonization followed LAIV inoculation, a minimum LAIV incubation period of 4 days was required before bacterial transmigration commenced. While LAIV vaccination is safe and effective at reducing IAV and coinfection with influenza virus and bacteria, LAIV may increase bacterial transmigration to the middle ear and could thus increase the risk of clinically relevant acute otitis media. These data warrant further investigations into interactions between live attenuated viruses and naturally colonizing bacterial pathogens. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  2. Some Attenuated Variants of Vesicular Stomatitis Virus Show Enhanced Oncolytic Activity against Human Glioblastoma Cells relative to Normal Brain Cells▿

    OpenAIRE

    Wollmann, Guido; Rogulin, Vitaliy; Simon, Ian; Rose, John K.; van den Pol, Anthony N.

    2009-01-01

    Vesicular stomatitis virus (VSV) has been shown in laboratory studies to be effective against a variety of tumors, including malignant brain tumors. However, attenuation of VSV may be necessary to balance the potential toxicity toward normal cells, particularly when targeting brain tumors. Here we compared 10 recombinant VSV variants resulting from different attenuation strategies. Attenuations included gene shifting (VSV-p1-GFP/RFP), M protein mutation (VSV-M51), G protein cytoplasmic tail t...

  3. 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.

  4. 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.

  5. Rabies virus pathogenesis in relationship to intervention with inactivated and attenuated rabies vaccines.

    Science.gov (United States)

    Franka, Richard; Wu, Xianfu; Jackson, Felix R; Velasco-Villa, Andres; Palmer, Dustyn P; Henderson, Heather; Hayat, Wajid; Green, Douglas B; Blanton, Jesse D; Greenberg, Lauren; Rupprecht, Charles E

    2009-11-27

    Despite progress in vaccine development in the past century the mechanisms behind immune responses elicited by rabies biologics or via natural infection remain largely unknown. In this study, we compared protection elicited by standard, early, or delayed prophylaxis with a reduced number of vaccine doses using inactivated and live-attenuated vaccines. Two-month-old Syrian hamsters, 4-week-old ICR mice or adult rhesus macaques were inoculated with canine rabies virus variants. Thereafter, prophylaxis was initiated 6h, 1, 2, 3, 4, 5, 6 or 7 days post-exposure (p.e.). One or several doses of inactivated (HDCV), or reverse genetically attenuated (live), or gamma-irradiated (inactivated)-ERAG333 vaccines were administered intramuscularly. The dynamics of virus spread were measured over time in the rodent models. Rabies virus reached the spinal cord at day 4 and brain at day 6 p.e. All hamsters succumbed in groups in which live ERAG333 was delayed until days 5 and 6 p.e. However, 78%, 44%, 56% and 22% of hamsters survived when one dose of live ERAG333 was administered 6h, 1, 2, 3, and 4 days p.e., respectively. Similarly, 67% survived when inactivated ERAG333 was administered at 24h p.e. All hamsters succumbed when standard prophylaxis (the Essen regimen) was delayed until days 3-6, but 67% and 33% of hamsters survived when PEP began 1 or 2 days p.e., respectively. Macaques were protected by one dose of attenuated ERAG333 at 24h p.e. The highly attenuated (live) and inactivated ERAG333 vaccines elicited potent protective immune responses, even when prophylaxis initiation was delayed. When 2-5 doses of commercial vaccine and HRIG were administered according to the Essen scheme, 89-100% of the animals survived. Reduced vaccine schedules provided efficacious intervention, regardless of the total number of vaccine doses administered.

  6. Attenuation of vaccinia virus by the expression of human Flt3 ligand

    Directory of Open Access Journals (Sweden)

    Sanda Miloslav

    2010-05-01

    Full Text Available Abstract Background Vaccinia virus, one of the best known members of poxvirus family, has a wide host range both in vivo and in vitro. The expression of Flt3 ligand (FL by recombinant vaccinia virus (rVACV highly influenced properties of the virus in dependence on the level of expression. Results High production of FL driven by the strong synthetic promoter decreased the growth of rVACV in macrophage cell line J774.G8 in vitro as well as its multiplication in vivo when inoculated in mice. The inhibition of replication in vivo was mirrored in low levels of antibodies against vaccinia virus (anti-VACV which nearly approached to the negative serum level in non-infected mice. Strong FL expression changed not only the host range of the recombinant but also the basic protein contents of virions. The major proteins - H3L and D8L - which are responsible for the virus binding to the cells, and 28 K protein that serves as a virulence factor, were changed in the membrane portion of P13-E/L-FL viral particles. The core virion fraction contained multiple larger, uncleaved proteins and a higher amount of cellular proteins compared to the control virus. The overexpression of FL also resulted in its incorporation into the viral core of P13-E/L-FL IMV particles. In contrary to the equimolar ratio of glycosylated and nonglycosylated FL forms found in cells transfected with the expression plasmid, the recombinant virus incorporated mainly the smaller, nonglycosylated FL. Conclusions It has been shown that the overexpression of the Flt3L gene in VACV results in the attenuation of the virus in vivo.

  7. Protective essential oil attenuates influenza virus infection: An in vitro study in MDCK cells

    Directory of Open Access Journals (Sweden)

    Metcalf Jordan P

    2010-11-01

    viability was only seen with concentrations of oil that were 2 to 6 times greater than the doses that inhibited viral infectivity. RT-PCR and western blotting demonstrated that oil treatment of the virus inhibited viral NP and NS1 protein, but not mRNA expression. Conclusions An essential oil blend significantly attenuates influenza virus PR8 infectivity in vitro without affecting viral binding or cellular internalization in MDCK cells. Oil treated virus continued to express viral mRNAs but had minimal expression of viral proteins, suggesting that the antiviral effect may be due to inhibition of viral protein translation.

  8. Temperature-Sensitive Live-Attenuated Canine Influenza Virus H3N8 Vaccine.

    Science.gov (United States)

    Nogales, Aitor; Rodriguez, Laura; Chauché, Caroline; Huang, Kai; Reilly, Emma C; Topham, David J; Murcia, Pablo R; Parrish, Colin R; Martínez-Sobrido, Luis

    2017-02-15

    Canine influenza is a respiratory disease of dogs caused by canine influenza virus (CIV). CIV subtypes responsible for influenza in dogs include H3N8, which originated from the transfer of H3N8 equine influenza virus to dogs; and the H3N2 CIV, which is an avian-origin virus that adapted to infect dogs. Influenza infections are most effectively prevented through vaccination to reduce transmission and future infection. Currently, only inactivated influenza vaccines (IIVs) are available for the prevention of CIV in dogs. However, the efficacy of IIVs is suboptimal, and novel approaches are necessary for the prevention of disease caused by this canine respiratory pathogen. Using reverse genetics techniques, we have developed a live-attenuated CIV vaccine (LACIV) for the prevention of H3N8 CIV. The H3N8 LACIV replicates efficiently in canine cells at 33°C but is impaired at temperatures of 37 to 39°C and was attenuated compared to wild-type H3N8 CIV in vivo and ex vivo The LACIV was able to induce protection against H3N8 CIV challenge with a single intranasal inoculation in mice. Immunogenicity and protection efficacy were better than that observed with a commercial CIV H3N8 IIV but provided limited cross-reactive immunity and heterologous protection against H3N2 CIV. These results demonstrate the feasibility of implementing a LAIV approach for the prevention and control of H3N8 CIV in dogs and suggest the need for a new LAIV for the control of H3N2 CIV. Two influenza A virus subtypes has been reported in dogs in the last 16 years: the canine influenza viruses (CIV) H3N8 and H3N2 of equine and avian origins, respectively. To date, only inactivated influenza vaccines (IIVs) are available to prevent CIV infections. Here, we report the generation of a recombinant, temperature-sensitive H3N8 CIV as a live-attenuated influenza vaccine (LAIV), which was attenuated in mice and dog tracheal, explants compared to CIV H3N8 wild type. A single dose of H3N8 LACIV showed

  9. Application of reverse genetics for producing attenuated vaccine strains against highly pathogenic avian influenza viruses.

    Science.gov (United States)

    Uchida, Yuko; Takemae, Nobuhiro; Saito, Takehiko

    2014-08-01

    In this study, reverse genetics was applied to produce vaccine candidate strains against highly pathogenic avian influenza viruses (HPAIVs) of the H5N1 subtype. The H5 subtype vaccine strains were generated by a reverse genetics method in a biosafety level 2 facility. The strain contained the HA gene from the H5N1 subtype HPAIV attenuated by genetic modification at the cleavage site, the NA gene derived from the H5N1 subtype HPAI or the H5N3 subtype of avian influenza virus and internal genes from A/Puerto Rico/8/34. Vaccination with an inactivated recombinant virus with oil-emulsion completely protected chickens from a homologous viral challenge with a 640 HAU or 3,200 HAU/vaccination dose. Vaccination with a higher dose of antigen, 3,200 HAU, was effective at increasing survival and efficiently reduced viral shedding even when challenged by a virus of a different HA clade. The feasibility of differentiation of infected from vaccinated animals (DIVA) was demonstrated against a challenge with H5N1 HPAIVs when the recombinant H5N3 subtype viruses were used as the antigens of the vaccine. Our study demonstrated that the use of reverse genetics would be an option to promptly produce an inactivated vaccine with better matching of antigenicity to a circulating strain.

  10. 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.

  11. Deep Sequencing of Distinct Preparations of the Live Attenuated Varicella-Zoster Virus Vaccine Reveals a Conserved Core of Attenuating Single-Nucleotide Polymorphisms.

    Science.gov (United States)

    Depledge, Daniel P; Yamanishi, Koichi; Gomi, Yasuyuki; Gershon, Anne A; Breuer, Judith

    2016-10-01

    The continued success of the live attenuated varicella-zoster virus vaccine in preventing varicella-zoster and herpes zoster is well documented, as are many of the mutations that contribute to the attenuation of the vOka virus for replication in skin. At least three different preparations of vOka are marketed. Here, we show using deep sequencing of seven batches of vOka vaccine (including ZostaVax, VariVax, VarilRix, and the Oka/Biken working seed) from three different manufacturers (VariVax, GSK, and Biken) that 137 single-nucleotide polymorphism (SNP) mutations are present in all vaccine batches. This includes six sites at which the vaccine allele is fixed or near fixation, which we speculate are likely to be important for attenuation. We also show that despite differences in the vaccine populations between preparations, batch-to-batch variation is minimal, as is the number and frequency of mutations unique to individual batches. This suggests that the vaccine manufacturing processes are not introducing new mutations and that, notwithstanding the mixture of variants present, VZV live vaccines are extremely stable. The continued success of vaccinations to prevent chickenpox and shingles, combined with the extremely low incidence of adverse reactions, indicates the quality of these vaccines. The vaccine itself is comprised of a heterogeneous live attenuated virus population and thus requires deep-sequencing technologies to explore the differences and similarities in the virus populations between different preparations and batches of the vaccines. Our data demonstrate minimal variation between batches, an important safety feature, and provide new insights into the extent of the mutations present in this attenuated virus. Copyright © 2016 Depledge et al.

  12. Sequence-Specific Fidelity Alterations Associated with West Nile Virus Attenuation in Mosquitoes.

    Directory of Open Access Journals (Sweden)

    Greta A Van Slyke

    2015-06-01

    Full Text Available High rates of error-prone replication result in the rapid accumulation of genetic diversity of RNA viruses. Recent studies suggest that mutation rates are selected for optimal viral fitness and that modest variations in replicase fidelity may be associated with viral attenuation. Arthropod-borne viruses (arboviruses are unique in their requirement for host cycling and may necessitate substantial genetic and phenotypic plasticity. In order to more thoroughly investigate the correlates, mechanisms and consequences of arbovirus fidelity, we selected fidelity variants of West Nile virus (WNV; Flaviviridae, Flavivirus utilizing selection in the presence of a mutagen. We identified two mutations in the WNV RNA-dependent RNA polymerase associated with increased fidelity, V793I and G806R, and a single mutation in the WNV methyltransferase, T248I, associated with decreased fidelity. Both deep-sequencing and in vitro biochemical assays confirmed strain-specific differences in both fidelity and mutational bias. WNV fidelity variants demonstrated host-specific alterations to replicative fitness in vitro, with modest attenuation in mosquito but not vertebrate cell culture. Experimental infections of colonized and field populations of Cx. quinquefaciatus demonstrated that WNV fidelity alterations are associated with a significantly impaired capacity to establish viable infections in mosquitoes. Taken together, these studies (i demonstrate the importance of allosteric interactions in regulating mutation rates, (ii establish that mutational spectra can be both sequence and strain-dependent, and (iii display the profound phenotypic consequences associated with altered replication complex function of flaviviruses.

  13. Zika Virus Encoding Non-Glycosylated Envelope Protein is Attenuated and Defective in Neuroinvasion.

    Science.gov (United States)

    Annamalai, Arun S; Pattnaik, Aryamav; Sahoo, Bikash R; Muthukrishnan, Ezhumalai; Natarajan, Sathish Kumar; Steffen, David; Vu, Hiep L X; Delhon, Gustavo; Osorio, Fernando A; Petro, Thomas M; Xiang, Shi-Hua; Pattnaik, Asit K

    2017-09-20

    Zika virus (ZIKV), a mosquito-transmitted flavivirus, responsible for sporadic outbreaks of mild and febrile illness in Africa and Asia, re-emerged in the last decade causing serious human diseases including microcephaly, congenital malformations, and Guillain-Barré syndrome. Although genomic and phylogenetic analyses suggest that genetic evolution may have led to enhanced virulence of ZIKV, experimental evidence supporting the role of specific genetic changes in virulence is currently outstanding. One sequence motif, VNDT, containing an N-linked glycosylation site in the envelope (E) protein, is polymorphic, being absent in many of the African isolates while present in all isolates from the recent outbreaks. In the present study, we interrogated the role of this sequence motif and glycosylation of the E protein in pathogenicity of ZIKV. We first constructed a stable full-length cDNA clone of ZIKV in a novel linear vector from which infectious virus was recovered. The recombinant ZIKV generated from the infectious clone, which contains the VNDT motif, is highly pathogenic and causes lethality in a mouse model. In contrast, recombinant viruses from which the VNDT motif is deleted or from which N-linked glycosylation site is mutated by single amino acid substitution, are highly attenuated and non-lethal. The mutant viruses replicate poorly in the brain of infected mice when inoculated subcutaneously but replicate well following intracranial inoculation. Our findings provide the first evidence that N-linked glycosylation of the E protein is an important determinant of ZIKV virulence and neuroinvasion.IMPORTANCE Recent emergence of Zika virus (ZIKV) in the Americas has caused major worldwide public health concern. The virus appears to have gained significant pathogenicity, causing serious human diseases including microcephaly and Guillain-Barré syndrome. The factors responsible for the emergence of pathogenic ZIKV are not understood at this time, although genetic

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

    Science.gov (United States)

    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 phenotype for growth in tissue culture at 39°C and was attenuated in the lungs of Syrian golden hamsters. In order to test whether r-bPIV3 could serve as a vector, the fusion and hemagglutinin-neuraminidase genes of bPIV3 were replaced with those of hPIV3. The resulting bovine/human PIV3 was temperature sensitive for growth in Vero cells at 37°C. The replication of bovine/human PIV3 was also restricted in the lungs of hamsters, albeit not as severely as was observed for r-bPIV3. Despite the attenuation phenotypes observed for r-bPIV3 and bovine/human PIV3, both of these viruses protected hamsters completely upon challenge with hPIV3. In summary, bPIV3 was shown to function as a virus vector that may be especially suitable for vaccination of infants and children against PIV3 and other viruses. PMID:11090161

  15. 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

  16. 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.

  17. Deliberate attenuation of chikungunya virus by adaptation to heparan sulfate-dependent infectivity: a model for rational arboviral vaccine design.

    Directory of Open Access Journals (Sweden)

    Christina L Gardner

    2014-02-01

    Full Text Available Mosquito-borne chikungunya virus (CHIKV is a positive-sense, single-stranded RNA virus from the genus Alphavirus, family Togaviridae, which causes fever, rash and severe persistent polyarthralgia in humans. Since there are currently no FDA licensed vaccines or antiviral therapies for CHIKV, the development of vaccine candidates is of critical importance. Historically, live-attenuated vaccines (LAVs for protection against arthropod-borne viruses have been created by blind cell culture passage leading to attenuation of disease, while maintaining immunogenicity. Attenuation may occur via multiple mechanisms. However, all examined arbovirus LAVs have in common the acquisition of positively charged amino acid substitutions in cell-surface attachment proteins that render virus infection partially dependent upon heparan sulfate (HS, a ubiquitously expressed sulfated polysaccharide, and appear to attenuate by retarding dissemination of virus particles in vivo. We previously reported that, like other wild-type Old World alphaviruses, CHIKV strain, La Réunion, (CHIKV-LR, does not depend upon HS for infectivity. To deliberately identify CHIKV attachment protein mutations that could be combined with other attenuating processes in a LAV candidate, we passaged CHIKV-LR on evolutionarily divergent cell-types. A panel of single amino acid substitutions was identified in the E2 glycoprotein of passaged virus populations that were predicted to increase electrostatic potential. Each of these substitutions was made in the CHIKV-LR cDNA clone and comparisons of the mutant viruses revealed surface exposure of the mutated residue on the spike and sensitivity to competition with the HS analog, heparin, to be primary correlates of attenuation in vivo. Furthermore, we have identified a mutation at E2 position 79 as a promising candidate for inclusion in a CHIKV LAV.

  18. Incidence of Herpes Simplex Virus Keratitis in HIV/AIDS patients compared with the general population

    OpenAIRE

    Burcea, M; Gheorghe, A.; Pop, M

    2015-01-01

    Acquired immune deficiency syndrome (AIDS) is associated with a wide spectrum of systemic and ocular infectious diseases. Little information is known about Herpes Simplex Virus type 1 (HSV-1) keratoconjunctivitis in association with AIDS. Because HSV-1 is becoming, day by day, a common eye disease (nearly 100% patients of over 60 years old harbor HSV in their trigeminal ganglia at autopsy), this article discussing a worldwide public health problem. Aim. The purpose of this paper is to compare...

  19. A live-attenuated influenza vaccine for H3N2 canine influenza virus.

    Science.gov (United States)

    Rodriguez, Laura; Nogales, Aitor; Reilly, Emma C; Topham, David J; Murcia, Pablo R; Parrish, Colin R; Martinez Sobrido, Luis

    2017-04-01

    Canine influenza is a contagious respiratory disease in dogs caused by two subtypes (H3N2 and H3N8) of canine influenza virus (CIV). Currently, only inactivated influenza vaccines (IIVs) are available for the prevention of CIVs. Historically, live-attenuated influenza vaccines (LAIVs) have been shown to produce better immunogenicity and protection efficacy than IIVs. Here, we have engineered a CIV H3N2 LAIV by using the internal genes of a previously described CIV H3N8 LAIV as a master donor virus (MDV) and the surface HA and NA genes of a circulating CIV H3N2 strain. Our findings show that CIV H3N2 LAIV replicates efficiently at low temperature but its replication is impaired at higher temperatures. The CIV H3N2 LAIV was attenuated in vivo but induced better protection efficacy in mice against challenge with wild-type CIV H3N2 than a commercial CIV H3N2 IIV. This is the first description of a LAIV for the prevention of CIV H3N2 in dogs. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. A highly attenuated recombinant human respiratory syncytial virus lacking the G protein induces long-lasting protection in cotton rats.

    Science.gov (United States)

    Widjojoatmodjo, Myra N; Boes, Jolande; van Bers, Marleen; van Remmerden, Yvonne; Roholl, Paul J M; Luytjes, Willem

    2010-06-02

    Respiratory syncytial virus (RSV) is a primary cause of serious lower respiratory tract illness for which there is still no safe and effective vaccine available. Using reverse genetics, recombinant (r)RSV and an rRSV lacking the G gene (DeltaG) were constructed based on a clinical RSV isolate (strain 98-25147-X). Growth of both recombinant viruses was equivalent to that of wild type virus in Vero cells, but was reduced in human epithelial cells like Hep-2. Replication in cotton rat lungs could not be detected for DeltaG, while rRSV was 100-fold attenuated compared to wild type virus. Upon single dose intranasal administration in cotton rats, both recombinant viruses developed high levels of neutralizing antibodies and conferred comparable long-lasting protection against RSV challenge; protection against replication in the lungs lasted at least 147 days and protection against pulmonary inflammation lasted at least 75 days. Collectively, the data indicate that a single dose immunization with the highly attenuated DeltaG as well as the attenuated rRSV conferred long term protection in the cotton rat against subsequent RSV challenge, without inducing vaccine enhanced pathology. Since DeltaG is not likely to revert to a less attenuated phenotype, we plan to evaluate this deletion mutant further and to investigate its potential as a vaccine candidate against RSV infection.

  1. Wild and attenuated vaccine RS-12 strains of mumps virus exhibit differences in amino acid sequences of their proteins.

    Science.gov (United States)

    Alirezaie, B; Shahbazi, R; Safavieh, S S; Mohammad, A

    2014-01-01

    Attenuated mumps virus (MuV) RS-12 strain-based vaccine is one of several effective vaccines available in the prevention of mumps. Since previous studies have unveiled only about one-third of the attenuated vaccine RS-12 strain genome sequence, the rest of sequence and molecular basis for attenuation remained unsolved. Therefore, in this study, the full-length genome sequences of wild and attenuated RS-12 strains were determined and compared. The comparison revealed nucleotide substitutions at 9 positions leading to amino acid substitutions at 6 positions in P, V, I, M, and L proteins, while the remaining substitutions were silent. This result indicates that the observed mutations in P, V, I, M, and L proteins of MuV might be responsible for the attenuation of the RS-12 vaccine strain.

  2. Inactivation of the AIDS-causing retrovirus and other human viruses in antihemophilic plasma protein preparations by pasteurization.

    Science.gov (United States)

    Hilfenhaus, J; Herrmann, A; Mauler, R; Prince, A M

    1986-01-01

    Heat treatment at 60 degrees C for 10 h in solution (pasteurization) was introduced into the manufacturing process of antihemophilic cryoprecipitate (AHC) and factor VIII concentrates (F VIII) to reduce the risk of transmission of hepatitis to hemophiliacs. Since the acquired immunodeficiency syndrome (AIDS) may also be transmitted to hemophiliacs by antihemophilic plasma protein preparations, we have investigated inactivation of the AIDS virus HTLV III by pasteurization in AHC or F VIII and included in this study cytomegalovirus (CMV), Epstein-Barr virus (EBV), herpes simplex virus (HSV), poliovirus and vaccinia virus. Each of these viruses was efficiently inactivated by pasteurization although considerable differences were observed between the different viruses HTLV III was rapidly inactivated, becoming nondetectable within 30-60 min. Our findings indicate that pasteurized AHC or F VIII should have a high margin of safety regarding the transmission of AIDS or any other infectious disease caused by viruses such as those tested.

  3. Chronic spinal cord injury attenuates influenza virus-specific antiviral immunity.

    Science.gov (United States)

    Bracchi-Ricard, Valerie; Zha, Ji; Smith, Annalise; Lopez-Rodriguez, Darlah M; Bethea, John R; Andreansky, Samita

    2016-05-31

    Individuals suffering from spinal cord injury (SCI) are at higher risk for respiratory-related viral infections such as influenza. In a previous study (Zha et al., J Neuroinflammation 11:65, 2014), we demonstrated that chronic spinal cord injury caused impairment in CD8(+)T cell function with increased expression of the immunosuppressive protein, programmed cell death 1 (PD-1). The present study was undertaken to establish whether chronic SCI-induced immune deficits would affect antiviral immunity directed against primary and secondary infections. Six to seven weeks following a SCI contusion at thoracic level T9, mice were infected intranasally with influenza virus. Virus-specific immunity was analyzed at various time points post-infection and compared to uninjured controls. We report that chronic thoracic SCI impairs the ability of the animals to mount an adequate antiviral immune response. While all uninjured control mice cleared the virus from their lungs by day 10 post-infection, a significant number (approximately 70 %) of chronic SCI mice did not clear the virus and succumbed to infection-induced mortality. This was attributed to severe deficits in both virus-specific antibody production and CD8(+) T cell response in injured mice after primary infection. We also determined that previously acquired humoral immunity was maintained after spinal cord injury as vaccination against influenza A prior to injury-protected mice from a homologous viral challenge. In contrast, prior immunization did not protect mice from a heterotypic challenge with a different strain of influenza virus. Taken together, our data demonstrate that chronic SCI attenuates virus-specific humoral and cellular immunity during the establishment of primary response and impairs the development of memory CD8(+) T cells. In contrast, B cell memory acquired through vaccination prior to SCI is preserved after injury which demonstrates that antigen-specific memory cells are refractory following injury

  4. Efficiency of live attenuated and inactivated rabies viruses in prophylactic and post exposure vaccination against the street virus strain.

    Science.gov (United States)

    Huang, F; Ahmad, W; Duan, M; Liu, Z; Guan, Z; Zhang, M; Qiao, B; Li, Y; Song, Y; Song, Y; Chen, Y; Amjad Ali, M

    2015-06-01

    Rabies remains an enigmatic and widely discussed global infectious disease and causes an increasing number of deaths. The currently used highly effective prophylactic and post exposure (p.e.) vaccination depends solely upon inexpensive, effective and safe vaccines to counteract the spread of the disease. In this study, the potential of an attenuated Chinese rabies vaccine (SRV9) strain in prophylactic and p.e. vaccination against the street strain of rabies virus (RV) was evaluated in mice. Prophylactic vaccination consisting of one intramuscular (i.m.) dose of SRV9 protected 100% of mice from intracerebral (i.c.) challenge with a lethal dose of the street virus. The latter was detected in the brain of mice at day 6 post challenge by RT-PCR. Post exposure vaccination was performed at days 1, 2, 3, 4, 5 and 6 post infection (p.i.) with either SRV9 or inactivated rabies vaccine. The survival rates after i.m. inoculation of SRV9 at the indicated days were 70%, 50%, 30%, 20%, 10%, and 0%, respectively; the corresponding survival rates for the inactivated rabies vaccine were 30%, 20%, 10%, 0%, 0%, and 0%, respectively. However, 100%, 90%, 70%, 50%, 20%, 10%, and 10% of mice survived after i.c. inoculation of SRV9 at the indicated days. The increased permeability of the blood-brain barrier and the infiltration of CD19+ B cells into the central nervous system after i.c. inoculation of SRV9 are regarded as prerequisites for the clearance of the street virus. The obtained data suggest that SRV9 is a promising candidate for prophylactic and p.e. vaccination against rabies infection and that it exhibits a potential for the control of rabies in China.

  5. Expression of interferon gamma by a recombinant rabies virus strongly attenuates the pathogenicity of the virus via induction of type I interferon.

    Science.gov (United States)

    Barkhouse, Darryll A; Garcia, Samantha A; Bongiorno, Emily K; Lebrun, Aurore; Faber, Milosz; Hooper, D Craig

    2015-01-01

    Previous animal model experiments have shown a correlation between interferon gamma (IFN-γ) expression and both survival from infection with attenuated rabies virus (RABV) and reduction of neurological sequelae. Therefore, we hypothesized that rapid production of murine IFN-γ by the rabies virus itself would induce a more robust antiviral response than would occur naturally in mice. To test this hypothesis, we used reverse engineering to clone the mouse IFN-γ gene into a pathogenic rabies virus backbone, SPBN, to produce the recombinant rabies virus designated SPBNγ. Morbidity and mortality were monitored in mice infected intranasally with SPBNγ or SPBN(-) control virus to determine the degree of attenuation caused by the expression of IFN-γ. Incorporation of IFN-γ into the rabies virus genome highly attenuated the virus. SPBNγ has a 50% lethal dose (LD50) more than 100-fold greater than SPBN(-). In vitro and in vivo mouse experiments show that SPBNγ infection enhances the production of type I interferons. Furthermore, knockout mice lacking the ability to signal through the type I interferon receptor (IFNAR(-/-)) cannot control the SPBNγ infection and rapidly die. These data suggest that IFN-γ production has antiviral effects in rabies, largely due to the induction of type I interferons. Survival from rabies is dependent upon the early control of virus replication and spread. Once the virus reaches the central nervous system (CNS), this becomes highly problematic. Studies of CNS immunity to RABV have shown that control of replication begins at the onset of T cell entry and IFN-γ production in the CNS prior to the appearance of virus-neutralizing antibodies. Moreover, antibody-deficient mice are able to control but not clear attenuated RABV from the CNS. We find here that IFN-γ triggers the early production of type I interferons with the expected antiviral effects. We also show that engineering a lethal rabies virus to express IFN-γ directly in the

  6. 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.

  7. 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...

  8. 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.

  9. Attenuation of seizures and neuronal death by adeno-associated virus vector galanin expression and secretion.

    Science.gov (United States)

    Haberman, Rebecca P; Samulski, R Jude; McCown, Thomas J

    2003-08-01

    Seizure disorders present an attractive gene therapy target, particularly because viral vectors such as adeno-associated virus (AAV) and lentivirus can stably transduce neurons. When we targeted the N-methyl-D-aspartic acid (NMDA) excitatory amino acid receptor with an AAV-delivered antisense oligonucleotide, however, the promoter determined whether focal seizure sensitivity was significantly attenuated or facilitated. One potential means to circumvent this liability would be to express an inhibitory neuroactive peptide and constitutively secrete the peptide from the transduced cell. The neuropeptide galanin can modulate seizure activity in vivo, and the laminar protein fibronectin is usually secreted through a constitutive pathway. Initially, inclusion of the fibronectin secretory signal sequence (FIB) in an AAV vector caused significant gene product secretion in vitro. More importantly, the combination of this secretory signal with the coding sequence for the active galanin peptide significantly attenuated in vivo focal seizure sensitivity, even with different promoters, and prevented kainic acid-induced hilar cell death. Thus, neuroactive peptide expression and local secretion provides a new gene therapy platform for the treatment of neurological disorders.

  10. Accumulation of defective interfering viral particles in only a few passages in Vero cells attenuates mumps virus neurovirulence.

    Science.gov (United States)

    Šantak, Maja; Markušić, Maja; Balija, Maja Lang; Kopač, Sandra Keć; Jug, Renata; Örvell, Claes; Tomac, Jelena; Forčić, Dubravko

    2015-03-01

    Immunization programs have implemented live attenuated mumps vaccines which reduced mumps incidence ≥97%. Some of the vaccine strains were abandoned due to unwanted side effects and the genetic marker of attenuation has not been identified so far. Our hypothesis was that non-infectious viral particles, in particular defective interfering particles (DIPs), contribute to neuroattenuation. We showed that non-infectious particles of the mumps vaccine L-Zagreb attenuated neurovirulence of wild type mumps virus 9218/Zg98. Then, we attenuated recent wild type mumps virus MuVi/Zagreb.HRV/28.12 in Vero cells through 16 passages but already the fifth passage (p5) showed accumulation of DIPs and attenuated neurovirulence in a newborn rat model when compared to the second passage (p2). Sequence analysis of the p2 and p5 revealed a single mutation in the 5' untranslated region of the HN gene. Analysis of the expression level of the HN protein showed that this mutation does not affect the expression of the protein. We conclude that the passages of MuVi/Zagreb.HRV/28.12 in Vero cells for only three passages accumulated DIPs which attenuate neurovirulence. These findings reveal DIPs as a very promising and general neuroattenuating factor which should be considered in the rational design of the new mumps vaccine. Copyright © 2014 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

  11. 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

  12. Cultivation of attenuated hepatitis A virus antigen in a titanium static mixer reactor.

    Science.gov (United States)

    Junker, B H; Seamans, T C; Ramasubramanyan, K; Aunins, J; Paul, E; Buckland, B C

    1994-12-01

    The titanium static mixer reactor, demonstrated for a variety of vaccine processes during the late 197s, was investigated for the production of attenuated hepatitis A virus antigen from anchorage-dependent MRC-5 cells. This reactor system used Charles River Biotechnological Services cabinets for monitoring and process control. Cell inoculation protocols, using 6000-10,000 cells/cm(2), resulted on over 95% attachment at both the laboratory and pilot scales. Indirect monitoring techniques using oxygen, glucose, L-serine, and L-glutamine uptake rates were indicative of cell growth prior to virus inoculation as well as environmental and/or nutrient limitations. Seven laboratory-scale (3900 cm(2)) runs and one pilotscale (265,000 cm(2)) run were conducted to investigate refeeding regiments, parallel versus perpendicular element orientation, increased element surface area per unit volume, and scale-up performance. In general, lysate antigen yields achieved were similar to those of parallel T-flasks cultivated under similar conditions.

  13. 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

  14. 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.

  15. 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.

  16. Attenuating the ear canal feedback pressure of a laser-driven hearing aid.

    Science.gov (United States)

    Khaleghi, Morteza; Puria, Sunil

    2017-03-01

    Microphone placement behind the pinna, which minimizes feedback but also reduces perception of the high-frequency pinna cues needed for sound localization, is one reason why hearing-aid users often complain of poor sound quality and difficulty understanding speech in noisy situations. In this paper, two strategies are investigated for minimizing the feedback pressure (thereby increasing the maximum stable gain, MSG) of a wide-bandwidth light-activated contact hearing aid (CHA) to facilitate microphone placement in the ear canal (EC): (1) changing the location of the drive force and its direction at the umbo, and (2) placing an acoustic damper within the EC to reduce the feedback pressure at the microphone location. The MSG and equivalent pressure output (EPO) are calculated in a 3D finite element model of a human middle ear based on micro computed tomography (micro-CT) images. The model calculations indicate that changing the umbo-force direction can decrease feedback pressure, but at the expense of decreased EPO. However the model shows improvements in MSG without sacrificing EPO when an acoustic damper is placed in the EC. This was verified through benchtop experimentation and in human cadaver temporal bones. The results pave the path towards a wide-bandwidth hearing aid that incorporates an EC-microphone design.

  17. Genetic Determinants of Japanese Encephalitis Virus Vaccine Strain SA14-14-2 That Govern Attenuation of Virulence in Mice.

    Science.gov (United States)

    Gromowski, Gregory D; Firestone, Cai-Yen; Whitehead, Stephen S

    2015-06-01

    The safety and efficacy of the live-attenuated Japanese encephalitis virus (JEV) SA14-14-2 vaccine are attributed to mutations that accumulated in the viral genome during its derivation. However, little is known about the contribution that is made by most of these mutations to virulence attenuation and vaccine immunogenicity. Here, we generated recombinant JEV (rJEV) strains containing JEV SA14-14-2 vaccine-specific mutations that are located in the untranslated regions (UTRs) and seven protein genes or are introduced from PCR-amplified regions of the JEV SA14-14-2 genome. The resulting mutant viruses were evaluated in tissue culture and in mice. The authentic JEV SA14-14-2 (E) protein, with amino acid substitutions L107F, E138K, I176V, T177A, E244G, Q264H, K279M, A315V, S366A, and K439R relative to the wild-type rJEV clone, was essential and sufficient for complete attenuation of neurovirulence. Individually, the nucleotide substitution T39A in the 5' UTR (5'-UTR-T39A), the capsid (C) protein amino acid substitution L66S (C-L66S), and the complete NS1/2A genome region containing 10 mutations each significantly reduced virus neuroinvasion but not neurovirulence. The levels of peripheral virulence attenuation imposed by the 5'-UTR-T39A and C-L66S mutations, individually, were somewhat mitigated in combination with other vaccine strain-specific mutations, which might be compensatory, and together did not affect immunogenicity. However, a marked reduction in immunogenicity was observed with the addition of the NS1/2A and NS5 vaccine virus genome regions. These results suggest that a second-generation recombinant vaccine can be rationally engineered to maximize levels of immunogenicity without compromising safety. The live-attenuated JEV SA14-14-2 vaccine has been vital for controlling the incidence of disease caused by JEV, particularly in rural areas of Asia where it is endemic. The vaccine was developed >25 years ago by passaging wild-type JEV strain SA14 in tissue

  18. Pandemic preparedness with live attenuated influenza vaccines based on A/Leningrad/134/17/57 master donor virus.

    Science.gov (United States)

    Rudenko, Larisa; Isakova-Sivak, Irina

    2015-03-01

    Continuously evolving avian influenza viruses pose a constant threat to the human public health. In response to this threat, a number of pandemic vaccine candidates have been prepared and evaluated in animal models and clinical trials. This review summarizes the data from the development and preclinical and clinical evaluation of pandemic live attenuated influenza vaccines (LAIV) based on Russian master donor virus A/Leningrad/134/17/57. LAIV candidates of H5N1, H5N2, H7N3, H1N1 and H2N2 subtypes were safe, immunogenic and protected animals from challenge with homologous and heterologous viruses. Clinical trials of the pandemic LAIVs demonstrated their safety and immunogenicity for healthy adult volunteers. The vaccine viruses were infectious, genetically stable and did not transmit to unvaccinated contacts. In addition, here we discuss criteria for the assessment of pandemic LAIV immunogenicity and efficacy necessary for their licensure.

  19. Attenuated Human Parainfluenza Virus Type 1 (HPIV1) Expressing the Fusion Glycoprotein of Human Respiratory Syncytial Virus (RSV) as a Bivalent HPIV1/RSV Vaccine

    Science.gov (United States)

    Mackow, Natalie; Amaro-Carambot, Emérito; Liang, Bo; Surman, Sonja; Lingemann, Matthias; Yang, Lijuan; Collins, Peter L.

    2015-01-01

    ABSTRACT Live attenuated recombinant human parainfluenza virus type 1 (rHPIV1) was investigated as a vector to express the respiratory syncytial virus (RSV) fusion (F) glycoprotein, to provide a bivalent vaccine against RSV and HPIV1. The RSV F gene was engineered to include HPIV1 transcription signals and inserted individually into three gene locations in each of the two attenuated rHPIV1 backbones. Each backbone contained a single previously described attenuating mutation that was stabilized against deattenuation, specifically, a non-temperature-sensitive deletion mutation involving 6 nucleotides in the overlapping P/C open reading frames (ORFs) (CΔ170) or a temperature-sensitive missense mutation in the L ORF (LY942A). The insertion sites in the genome were pre-N (F1), N-P (F2), or P-M (F3) and were identical for both backbones. In vitro, the presence of the F insert reduced the rate of virus replication, but the final titers were the same as the final titer of wild-type (wt) HPIV1. High levels of RSV F expression in cultured cells were observed with rHPIV1-CΔ170-F1, -F2, and -F3 and rHPIV1-LY942A-F1. In hamsters, the rHPIV1-CΔ170-F1, -F2, and -F3 vectors were moderately restricted in the nasal turbinates, highly restricted in lungs, and genetically stable in vivo. Among the CΔ170 vectors, the F1 virus was the most immunogenic and protective against wt RSV challenge. The rHPIV1-LY942A vectors were highly restricted in vivo and were not detectably immunogenic or protective, indicative of overattenuation. The CΔ170-F1 construct appears to be suitably attenuated and immunogenic for further development as a bivalent intranasal pediatric vaccine. IMPORTANCE There are no vaccines for the pediatric respiratory pathogens RSV and HPIV. We are developing live attenuated RSV and HPIV vaccines for use in virus-naive infants. Live attenuated RSV strains in particular are difficult to develop due to their poor growth and physical instability, but these obstacles could be

  20. Studies of Genetic Variation in the AIDS Virus: Relevance to Disease Pathogenesis Anti-Viral Therapy, and Vaccine Development

    Science.gov (United States)

    1990-06-30

    virus carrier), different modes of virus transmission (perinatal, heterosexual , and homosexual ), and widely different numbers of exposures to the AIDS...PCR derived HIV-1 molecular clones from two different frozen specimens of brain tissue that were processed one year apart prove conclusively that the...DAMD1 7-87-C-7038) were to define the extent and nature of HIV-1 and HIV- 2 genetic variability in independent virus isolates from different

  1. Nasal lavage natural killer cell function is suppressed in smokers after live attenuated influenza virus

    Directory of Open Access Journals (Sweden)

    Zhou Haibo

    2011-08-01

    Full Text Available Abstract Background Modified function of immune cells in nasal secretions may play a role in the enhanced susceptibility to respiratory viruses that is seen in smokers. Innate immune cells in nasal secretions have largely been characterized by cellular differentials using morphologic criteria alone, which have successfully identified neutrophils as a significant cell population within nasal lavage fluid (NLF cells. However, flow cytometry may be a superior method to fully characterize NLF immune cells. We therefore characterized immune cells in NLF by flow cytometry, determined the effects of live attenuated influenza virus (LAIV on NLF and peripheral blood immune cells, and compared responses in samples obtained from smokers and nonsmokers. Methods In a prospective observational study, we characterized immune cells in NLF of nonsmokers at baseline using flow cytometry and immunohistochemistry. Nonsmokers and smokers were inoculated with LAIV on day 0 and serial nasal lavages were collected on days 1-4 and day 9 post-LAIV. LAIV-induced changes of NLF cells were characterized using flow cytometry. Cell-free NLF was analyzed for immune mediators by bioassay. Peripheral blood natural killer (NK cells from nonsmokers and smokers at baseline were stimulated in vitro with LAIV followed by flow cytometric and mediator analyses. Results CD45(+CD56(-CD16(+ neutrophils and CD45(+CD56(+ NK cells comprised median 4.62% (range 0.33-14.52 and 23.27% (18.29-33.97, respectively, of non-squamous NLF cells in nonsmokers at baseline. LAIV did not induce changes in total NK cell or neutrophil percentages in either nonsmokers or smokers. Following LAIV inoculation, CD16(+ NK cell percentages and granzyme B levels increased in nonsmokers, and these effects were suppressed in smokers. LAIV inoculation enhanced expression of activating receptor NKG2D and chemokine receptor CXCR3 on peripheral blood NK cells from both nonsmokers and smokers in vitro but did not induce

  2. Live attenuated nephropathogenic infectious bronchitis virus vaccine provides broad cross protection against new variant strains.

    Science.gov (United States)

    Lim, T-H; Kim, M-S; Jang, J-H; Lee, D-H; Park, J-K; Youn, H-N; Lee, J-B; Park, S-Y; Choi, I-S; Song, C-S

    2012-01-01

    Infectious bronchitis virus (IBV) infections cause great economic losses to the poultry industry worldwide, and the emergence of new variant strains complicates disease control. The present study investigated the genetic and protectotypic features of newly emerged Korean IBV strains. A phylogenetic analysis showed that several recent isolates formed 2 different clusters (new cluster 1 and 2), which were distinct from other preexisting clusters. New cluster 1 IBV strains represented recombinants between Korean nephropathogenic strain KM91 and the QXIBV strain. New cluster 2 IBV strains showed low amino acid homology (vaccines (H120 and K2 strain) against these new isolates. In cross-protection studies, the H120 strain did not provide sufficient protection against these variants. However, highly attenuated nephropathogenic IBV vaccine, K2 strain, provided significantly higher levels of protection against variants compared with chickens vaccinated with H120 (P vaccine could be helpful for the reduction of economic losses caused by newly evolving IBV recombinants (new cluster 1) and variants (new cluster 2).

  3. TRIM5α Promotes Ubiquitination of Rta from Epstein–Barr Virus to Attenuate Lytic Progression

    Science.gov (United States)

    Huang, Hsiang-Hung; Chen, Chien-Sin; Wang, Wen-Hung; Hsu, Shih-Wei; Tsai, Hsiao-Han; Liu, Shih-Tung; Chang, Li-Kwan

    2017-01-01

    Replication and transcription activator (Rta), a key protein expressed by Epstein–Barr virus (EBV) during the immediate-early stage of the lytic cycle, is responsible for the activation of viral lytic genes. In this study, GST-pulldown and coimmunoprecipitation assays showed that Rta interacts in vitro and in vivo with TRIM5α, a host factor known to be involved in the restriction of retroviral infections. Confocal microscopy results revealed that Rta colocalizes with TRIM5α in the nucleus during lytic progression. The interaction involves 190 amino acids in the N-terminal of Rta and the RING domain in TRIM5α, and it was further found that TRIM5α acts as an E3 ubiquitin ligase to promote Rta ubiquitination. Overexpression of TRIM5α reduced the transactivating capabilities of Rta, while reducing TRIM5α expression enhanced EBV lytic protein expression and DNA replication. Taken together, these results point to a critical role for TRIM5α in attenuating EBV lytic progression through the targeting of Rta for ubiquitination, and suggest that the restrictive capabilities of TRIM5α may go beyond retroviral infections. PMID:28105027

  4. Watsonianone A from Rhodomyrtus tomentosa Fruit Attenuates Respiratory-Syncytial-Virus-Induced Inflammation In Vitro.

    Science.gov (United States)

    Zhuang, Ling; Chen, Li-Feng; Zhang, Yu-Bo; Liu, Zhong; Xiao, Xu-Hui; Tang, Wei; Wang, Guo-Cai; Song, Wen-Jun; Li, Yao-Lan; Li, Man-Mei

    2017-05-03

    Respiratory syncytial virus (RSV) is one of the most common respiratory pathogens. Immoderate inflammation plays a great role in causing RSV-induced diseases. In the present study, watsonianone A, isolated from the fruit of Rhodomyrtus tomentosa (Ait.) Hassk, was found to show a good inhibitory effect on RSV-induced NO production, with a half-maximal inhibitory concentration of 37.2 ± 1.6 μM. Enzyme-linked immunosorbent assay and fluorescence quantitative polymerase chain reaction analyses indicated that watsonianone A markedly reduced both mRNA and protein levels of tumor necrosis factor α, interleukin 6, and monocyte chemoattractant protein 1 in RSV-infected RAW264.7 cells. Mechanistically, watsonianone A inhibited nuclear factor κB (NF-κB) activation by suppressing IκBα phosphorylation. Further analysis revealed that watsonianone A activated the thioredoxin system and decreased intracellular reactive oxygen species (ROS) levels, which are closely associated with NF-κB activation in RSV-infected cells. These results reveal that watsonianone A can attenuate RSV-induced inflammation via the suppression of ROS-sensitive inflammatory signaling.

  5. Protection Against Dengue Virus by Non-Replicating and Live Attenuated Vaccines Used Together in a Prime Boost Vaccination Strategy

    Science.gov (United States)

    2010-01-01

    inactivated virus (TPIV), and terr ,walenr DNA (TDNA) vaccines and then challenged at month 8 with live. non-attenuated DENV 3. Reciprocal geometric...method modified from that originally described (Russell er al .. 1967). Vero cell mono layers were seeded in six-well plates (Falcon; Becton...Briefly, microtiter plate wells were coated with purified DENV 2 virions in PBS at 4 oc overnight followed by blocking with 5% non-fat dry milk in PBS

  6. Incidence of Herpes Simplex Virus Keratitis in HIV/AIDS patients compared with the general population.

    Science.gov (United States)

    Burcea, M; Gheorghe, A; Pop, M

    2015-01-01

    Acquired immune deficiency syndrome (AIDS) is associated with a wide spectrum of systemic and ocular infectious diseases. Little information is known about Herpes Simplex Virus type 1 (HSV-1) keratoconjunctivitis in association with AIDS. Because HSV-1 is becoming, day by day, a common eye disease (nearly 100% patients of over 60 years old harbor HSV in their trigeminal ganglia at autopsy), this article discussing a worldwide public health problem. The purpose of this paper is to compare the incidence and clinical aspects of HSV-1 Keratitis in HIV/ AIDS patients compared with the general population who develops HSV- 1 Keratitis. The study is retrospective and comparative. Each patient was examined thoroughly at the biomicroscope ocular slit after corneal staining with fluorescein or rose bengal. Visual acuity, intraocular pressure and corneal sensitivity were also examined. From 170 patients with HIV and ocular anterior segment disorders, 47 patients had viral etiology. 58 patients had keratitis; 14 of them were HSV-1 keratitis. Doctors should be aware of the existence of the ocular damage in HIV/ AIDS and emphasize the importance of regular ophthalmologic examination of patients with HIV/ AIDS as HSV infection is common nowadays among the general population.

  7. 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.

  8. 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.

  9. Characterization of immune responses induced by inactivated, live attenuated and DNA vaccines against Japanese encephalitis virus in mice.

    Science.gov (United States)

    Li, Jieqiong; Chen, Hui; Wu, Na; Fan, Dongying; Liang, Guodong; Gao, Na; An, Jing

    2013-08-28

    Vaccination is the most effective countermeasure for protecting individuals from Japanese encephalitis virus (JEV) infection. There are two types of JEV vaccines currently used in China: the Vero cell-derived inactivated vaccine and the live attenuated vaccine. In this study, we characterized the immune response and protective efficacy induced in mice by the inactivated vaccine, live attenuated vaccine and the DNA vaccine candidate pCAG-JME, which expresses JEV prM-E proteins. We found that the live attenuated vaccine conferred 100% protection and resulted in the generation of high levels of specific anti-JEV antibodies and cytokines. The pCAG-JME vaccine induced protective immunity as well as the live attenuated vaccine. Unexpectedly, immunization with the inactivated vaccine only induced a limited immune response and partial protection, which may be due to the decreased activity of dendritic cells and the expansion of CD4+CD25+Foxp3+ regulatory T cells observed in these mice. Altogether, our results suggest that the live attenuated vaccine is more effective in providing protection against JEV infection than the inactivated vaccine and that pCAG-JME will be a potential JEV vaccine candidate. Copyright © 2013 Elsevier Ltd. All rights reserved.

  10. Prospective on multiscale simulation of virus-like particles: Application to computer-aided vaccine design.

    Science.gov (United States)

    Abi Mansour, Andrew; Sereda, Yuriy V; Yang, Jing; Ortoleva, Peter J

    2015-11-04

    Simulations of virus-like particles needed for computer-aided vaccine design highlight the need for new algorithms that accelerate molecular dynamics. Such simulations via conventional molecular dynamics present a practical challenge due to the millions of atoms involved and the long timescales of the phenomena of interest. These phenomena include structural transitions, self-assembly, and interaction with a cell surface. A promising approach for addressing this challenge is multiscale factorization. The approach is distinct from coarse-graining techniques in that it (1) avoids the need for conjecturing phenomenological governing equations for coarse-grained variables, (2) provides simulations with atomic resolution, (3) captures the cross-talk between disturbances at the atomic and the whole virus-like particle scale, and (4) achieves significant speedup over molecular dynamics. A brief review of multiscale factorization method is provided, as is a prospective on its development. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. New pandemics: HIV and AIDS, HCV and chronic hepatitis, Influenza virus and flu

    Directory of Open Access Journals (Sweden)

    Cohen Éric A

    2007-02-01

    Full Text Available Abstract New pandemics are a serious threat to the health of the entire world. They are essentially of viral origin and spread at large speed. A meeting on this topic was held in Lyon, France, within the XIXth Jacques Cartier Symposia, a series of France-Québec meetings held every year. New findings on HIV and AIDS, on HCV and chronic hepatitis, and an update on influenza virus and flu were covered during this meeting on December 4 and 5, 2006. Aspects of viral structure, virus-host interactions, antiviral defenses, drugs and vaccinations, and epidemiological aspects were discussed for HIV and HCV. Old and recent data on the flu epidemics ended this meeting.

  12. Bilateral Retrobulbar Optic Neuritis Caused by Varicella Zoster Virus in a Patient with AIDS.

    Science.gov (United States)

    Duda, Jose F; Castro, Jose G

    To report on a case of bilateral retrobulbar optic neuritis in a patient with acquired immune deficiency syndrome (AIDS) caused by varicella-zoster virus (VZV); and to review the literature focusing on: cases reported, epidemiology, pathophysiology, diagnosis and treatment. A 38-year-old woman with AIDS presented with a 10-day history of progressive bilateral visual loss and ocular pain. She had bilateral dilated pupils with no light perception; the fundoscopic examination was normal. Facial herpes zoster lesions appeared on the second day of hospitalization Magnetic resonance imaging (MRI) findings were compatible with a bilateral optic neuritis; the cerebrospinal fluid (CSF) showed pleocytosis, increased proteins and a positive VZV-DNA PCR. She was treated with intravenous acyclovir and corticosteroids and was able, when discharged 2 weeks after admission, to carry out activities of daily living. VZV retrobulbar optic neuritis has previously been reported in 12 patients with AIDS, more than half of the cases had concomitant herpes zoster and an associated retinopathy. A positive VZV-DNA in the CSF is indicative of VZV infection, initial use of intravenous acyclovir is recommended, and the concomitant use of corticosteroids would be a prudent choice; the duration of antiviral therapy remains undefined. VZV retrobulbar optic neuritis in AIDS patients can occur with or without herpes zoster. It is a sight-threatening infectious and inflammatory process requiring the advice of specialists in infectious diseases, ophthalmology, neurology and viral microbiology.

  13. T-bet Is Required for the Rapid Clearance of Attenuated Rabies Virus from Central Nervous System Tissue.

    Science.gov (United States)

    Lebrun, Aurore; Portocarrero, Carla; Kean, Rhonda B; Barkhouse, Darryll A; Faber, Milosz; Hooper, D Craig

    2015-11-01

    Much of our understanding of CNS immunity has been gained from models involving pathological inflammation. Attenuated rabies viruses (RABV) are unique tools to study CNS immunity in the absence of conventional inflammatory mechanisms, as they spread from the site of inoculation to the CNS transaxonally, thereby bypassing the blood-brain barrier (BBB), and are cleared without neutrophil or monocyte infiltration. To better understand the role of CD4 T cell subsets in the clearance of the virus from CNS tissues, we examined the development of antiviral immunity in wild-type (WT) and T-bet knockout mice (T-bet(-/-)), which lack Th1 cells. Early control of RABV replication in the CNS tissues of WT mice is associated with the production of IFN-γ, with antiviral effects likely mediated through the enhanced expression of type I IFNs. Of interest, IFN-α and -γ are overexpressed in the infected T-bet(-/-) by comparison with WT CNS tissues, and the initial control of RABV infection is similar. Ultimately, attenuated RABV are cleared from the CNS tissues of WT mice by Ab locally produced by the activities of infiltrating T and B cells. Although T and B cell infiltration into the CNS of infected T-bet(-/-) mice is comparable, their activities are not, the consequence being delayed, low-level Ab production and prolonged RABV replication. More importantly, neither T-bet(-/-) mice immunized with an attenuated virus, nor WT mice with Th2 RABV-specific immunity induced by immunization with inactivated virus, are protected in the long term against challenge with a pathogenic RABV. Copyright © 2015 by The American Association of Immunologists, Inc.

  14. African Swine Fever Virus Georgia Isolate Harboring Deletions of MGF360 and MGF505 Genes Is Attenuated in Swine and Confers Protection against Challenge with Virulent Parental Virus.

    Science.gov (United States)

    O'Donnell, Vivian; Holinka, Lauren G; Gladue, Douglas P; Sanford, Brenton; Krug, Peter W; Lu, Xiqiang; Arzt, Jonathan; Reese, Bo; Carrillo, Consuelo; Risatti, Guillermo R; Borca, Manuel V

    2015-06-01

    African swine fever virus (ASFV) is the etiological agent of a contagious and often lethal disease of domestic pigs that has significant economic consequences for the swine industry. The control of African swine fever (ASF) has been hampered by the unavailability of vaccines. Experimental vaccines have been developed using genetically modified live attenuated ASFVs where viral genes involved in virus virulence were removed from the genome. Multigene family 360 (MGF360) and MGF505 represent a group of genes sharing partial sequence and structural identities that have been connected with ASFV host range specificity, blocking of the host innate response, and virus virulence. Here we report the construction of a recombinant virus (ASFV-G-ΔMGF) derived from the highly virulent ASFV Georgia 2007 isolate (ASFV-G) by specifically deleting six genes belonging to MGF360 or MGF505: MGF505-1R, MGF360-12L, MGF360-13L, MGF360-14L, MGF505-2R, and MGF505-3R. ASFV-G-ΔMGF replicates as efficiently in primary swine macrophage cell cultures as the parental virus. In vivo, ASFV-G-ΔMGF is completely attenuated in swine, since pigs inoculated intramuscularly (i.m.) with either 10(2) or 10(4) 50% hemadsorbing doses (HAD50) remained healthy, without signs of the disease. Importantly, when these animals were subsequently exposed to highly virulent parental ASFV-G, no signs of the disease were observed, although a proportion of these animals harbored the challenge virus. This is the first report demonstrating the role of MGF genes acting as independent determinants of ASFV virulence. Additionally, ASFV-G-ΔMGF is the first experimental vaccine reported to induce protection in pigs challenged with highly virulent and epidemiologically relevant ASFV-G. The main problem for controlling ASF is the lack of vaccines. Studies focusing on understanding ASFV virulence led to the production of genetically modified recombinant viruses that, while attenuated, are able to confer protection in pigs

  15. 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.

  16. 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...

  17. Attenuation of Semliki Forest Virus Neurovirulence by MicroRNA-Mediated Detargeting

    OpenAIRE

    Ylösmäki, Erkko; Martikainen, Miika; Hinkkanen, Ari; Saksela, Kalle

    2013-01-01

    Artificial target sequences for tissue-specific miRNAs have recently been introduced as a new means for altering the tissue tropism of viral replication. This approach can be used to improve the safety of oncolytic viruses for cancer virotherapy by restricting their replication in unwanted tissues, such as the liver. Semliki Forest virus (SFV) is a positive-strand RNA virus and, similar to the related alphaviruses, like Sindbis virus, has potential as a gene therapy vector and an oncolytic vi...

  18. Quantitative PCR: a quality control assay for estimation of viable virus content in live attenuated goat pox vaccine.

    Science.gov (United States)

    Kallesh, D J; Hosamani, M; Balamurugan, V; Bhanuprakash, V; Yadav, V; Singh, R K

    2009-11-01

    Efficacy of live viral vaccine and vaccine-induced sero-conversion depends on the optimum number of live virus particles in a vaccine dose, which is one of the important aspects of quality control. In the present study, TaqMan probe quantitative polymerase chain reaction (QPCR) based on conserved DNA pol gene of capripoxvirus was developed for the quality control of attenuated monovalent goatpox and/or combined attenuated goatpox and peste des petits ruminants (PPR) vaccines. Cells infected with vaccine virus were harvested at critical time point and subjected to QPCR. A critical time point for harvest of Vero cells infected with various log10 dilutions of reference virus was determined to be 36 h (highest slope 3.062), by comparison of slopes of standard curves established with harvests at different time intervals. The assay method was evaluated using different batches of goatpox vaccine, and bivalent goatpox and PPR vaccine. The titers estimated by QPCR and TCID50 method were comparable to each other. The QPCR assay thus, could be used as an alternate method or supplementary tool for estimation of live GTPV particles in monovalent goatpox or bivalent goatpox and PPR vaccines.

  19. Comparison of the genome sequence of FP9, an attenuated, tissue culture-adapted European strain of Fowlpox virus, with those of virulent American and European viruses.

    Science.gov (United States)

    Laidlaw, Stephen M; Skinner, Michael A

    2004-02-01

    The 266 kbp genome sequence of plaque-purified, tissue culture-adapted, attenuated European Fowlpox virus FP9 has been determined and compared with the 288 kbp sequence of a pathogenic US strain (FPVUS). FP9 carries 244 of the 260 reported FPVUS ORFs (both viruses also have an unreported orthologue of conserved poxvirus gene A14.5L). Relative to FPVUS, FP9 differed by 118 mutations (26 deletions, 15 insertions and 77 base substitutions), affecting FP9 equivalents of 71 FPVUS ORFs. To help to identify mutations involved in adaptation and attenuation, the virulent parent of FP9, HP1, was sequenced at positions where FP9 differed from FPVUS. At 68 positions, FP9 and HP1 sequences were identical, reflecting differences between American and European lineages. Mutations at the remaining 50 positions in FP9 relative to FPVUS and HP1, involving 46 ORFs, therefore accounted for adaptation and attenuation. ORFs deleted during passage included those encoding members of multigene families: 12 ankyrin repeat proteins, three C-type lectin-like proteins, two C4L/C10L-like proteins, one G-protein coupled receptor protein, one V-type Ig domain protein, two N1R/p28 proteins and one EFc family protein. Tandem ORFs encoding Variola virus B22R orthologues were fused by a 5.8 kbp deletion. Single-copy genes disrupted or deleted during passage included those encoding a homologue of murine T10, a conserved DNA/pantothenate metabolism flavoprotein, photolyase, the A-type inclusion protein and an orthologue of vaccinia A47L. Gene assignments have been updated for DNase II/DLAD, binding proteins for IL-18 and interferon-gamma, phospholipid hydroperoxide glutathione peroxidase (PHGPX/GPX-4) and for a highly conserved homologue of ELOVL4.

  20. 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.

  1. Attenuation of Recombinant Vesicular Stomatitis Virus-Human Immunodeficiency Virus Type 1 Vaccine Vectors by Gene Translocations and G Gene Truncation Reduces Neurovirulence and Enhances Immunogenicity in Mice▿

    Science.gov (United States)

    Cooper, David; Wright, Kevin J.; Calderon, Priscilla C.; Guo, Min; Nasar, Farooq; Johnson, J. Erik; Coleman, John W.; Lee, Margaret; Kotash, Cheryl; Yurgelonis, Irene; Natuk, Robert J.; Hendry, R. Michael; Udem, Stephen A.; Clarke, David K.

    2008-01-01

    Recombinant vesicular stomatitis virus (rVSV) has shown great potential as a new viral vector for vaccination. However, the prototypic rVSV vector described previously was found to be insufficiently attenuated for clinical evaluation when assessed for neurovirulence in nonhuman primates. Here, we describe the attenuation, neurovirulence, and immunogenicity of rVSV vectors expressing human immunodeficiency virus type 1 Gag. These rVSV vectors were attenuated by combinations of the following manipulations: N gene translocations (N4), G gene truncations (CT1 or CT9), noncytopathic M gene mutations (Mncp), and positioning of the gag gene into the first position of the viral genome (gag1). The resulting N4CT1-gag1, N4CT9-gag1, and MncpCT1-gag1 vectors demonstrated dramatically reduced neurovirulence in mice following direct intracranial inoculation. Surprisingly, in spite of a very high level of attenuation, the N4CT1-gag1 and N4CT9-gag1 vectors generated robust Gag-specific immune responses following intramuscular immunization that were equivalent to or greater than immune responses generated by the more virulent prototypic vectors. MncpCT1-gag1 also induced Gag-specific immune responses following intramuscular immunization that were equivalent to immune responses generated by the prototypic rVSV vector. Placement of the gag gene in the first position of the VSV genome was associated with increased in vitro expression of Gag protein, in vivo expression of Gag mRNA, and enhanced immunogenicity of the vector. These findings demonstrate that through directed manipulation of the rVSV genome, vectors that have reduced neurovirulence and enhanced immunogenicity can be made. PMID:17942549

  2. The Burden of Smoking in the Health-Disease Process in People with Human Immunodeficiency Virus and AIDS

    Directory of Open Access Journals (Sweden)

    Yoenny Peña García

    2017-09-01

    Full Text Available Foundation: smoking affects individual, familial and social health of people living with the human immunodeficiency virus and AIDS. The effects of the habit on these patients influence morbidity and mortality and increase the risk of various diseases and affect the immune response to antiretroviral treatment. Objective: to determine the burden of smoking on the disease health process in patients living with human immunodeficiency virus and AIDS. Methods: an analytical cohort study was performed. It was analyzed as a dependent variable for smoking in people living with the human immunodeficiency virus and AIDS, and as independent variables: age, years of exposure (as a smoker, diseases that have suffered in the last 5 years, immunological condition, and response to antiretroviral therapy. The relative risk and the etiologic risk fraction were calculated, as well as the Chi2 test to estimate the strength of association between the independent and dependent variables. Results: smoking in patients living with human immunodeficiency virus and AIDS had a significant statistical association with different related effects, which in order of strength of association increases the risk of deterioration of the immune system and the incidence of malignant tumours and pneumonia Pneumocystis jirovecii. Conclusion: there was a causal relationship between smoking and the immunodeficiency virus in addition to the incidence of Pneumocystis jirovecii pneumonia. It was show that smoking impairs the immune condition of these patients and affects the adequate response to antiretroviral treatment.

  3. 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...... as a live vaccine in Poland, and the Hungarian isolates were related to the Bartha K-61 vaccine strain widely used in Hungary. Pigs experimentally infected with derivatives of BUK-TK-900 or BUK-TK-900 itself were found to develop gI-antibodies, while pigs infected with derivatives of Bartha K-61 showed a g...

  4. 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.

  5. Attenuation mechanism of virulent infectious bronchitis virus strain with QX genotype by continuous passage in chicken embryos.

    Science.gov (United States)

    Huo, Ya-fei; Huang, Qing-hua; Lu, Mei; Wu, Jia-qiang; Lin, Shu-qian; Zhu, Fengzhu; Zhang, Xiu-mei; Huang, Yan-yan; Yang, Shao-hua; Xu, Chuan-tian

    2016-01-02

    The virulent isolate SDZB0808 of QX-type infectious bronchitis virus (IBV) was continuously passaged in chicken embryos for 110 generations. The safety and immune efficacy of the 110th generation of IBVs (P110) were evaluated. Damage was not found in the appearance of the 3-day-old specific-pathogen-free (SPF) chicks immunized with 10(4.5) EID50 (median embryo infective dose) of P110 by intranasal and ocular administration. At 14 d after the vaccination with 10(4.5) EID50 of P110, all the 3-day-old SPF chicks were immune from the attack of the homologous virulent strain SDZB0808 and the heterologous virulent strain SDIB821/2012. The whole genome sequencing of SDZB0808 of different generations (P1-P110) indicated that the replicase 1a sequences of P60-P110 all lost a length of 30bp in the same region. Specific primers were designed according to the differences in the genomes of P1-P110. SYBR Green I real-time quantitative PCR was adopted to analyze the proportion of the viruses with 30bp deletion in P60, P100, and P110. Results showed that with the passage in chicken embryos, the proportion of the viruses with 30bp deletion gradually increased. Almost 100% of the viruses in the P110 had 30bp deletion in the replicase 1a sequence. Therefore, the attenuation of IBV's virulence may be the outcome of directional screening in the chicken embryos. This work confirmed the high safety and immune efficacy of P110 in SPF chickens. Thus, P110 can serve as an attenuated IBV vaccine candidate. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

    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. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. Attenuation of foot-and-mouth disease virus by engineered viral polymerase fidelity

    Science.gov (United States)

    The foot-and-mouth disease virus (FMDV) RNA dependent RNA polymerase (RdRp or 3Dpol) catalyzes viral RNA synthesis. The 3Dpol is a low fidelity enzyme incapable of proofreading which results in a high mutation frequencies that allow the virus to rapidly adapt to different environments. In this study...

  8. 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...

  9. 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...

  10. Regulation of interferon signaling by the C and V proteins from attenuated and wild-type strains of measles virus.

    Science.gov (United States)

    Fontana, Judith M; Bankamp, Bettina; Bellini, William J; Rota, Paul A

    2008-04-25

    The C and V proteins of the measles virus (MV) have been shown to block the signaling of type I and II interferon (IFN-alpha/beta and IFN-gamma). The relative contribution of the C and V proteins to the inhibition of IFN signaling and the extent to which this activity differs in attenuated or wild-type strains of MV remains undefined. This study presents a comparison of the IFN-antagonist activities of C and V proteins from four attenuated and two wild-type strains of MV. The V proteins were more potent inhibitors of IFN-inducible reporter gene expression than the C proteins, and this effect was unrelated to whether the protein originated from an attenuated or wild-type strain. The results also demonstrated the importance of the tyrosine at position 110 in the inhibition of IFN-alpha/beta and IFN-gamma signaling by the V protein, and identified a non-recombinant MV expressing a V protein that was impaired due to a mutation at this residue.

  11. 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.

  12. 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. ...

  13. Histoplasmosis in Patients With Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome (HIV/AIDS)

    Science.gov (United States)

    Anderson, Albert M.; Sanchez, Alejandro; Farabi, Alireza; Hage, Chadi; Baddley, John W.; Jhaveri, Malhar; Greenberg, Richard N.; Bamberger, David M.; Rodgers, Mark; Crawford, Timothy N.; Wheat, L. Joseph

    2014-01-01

    Abstract Although discontinuation of suppressive antifungal therapy for acquired immunodeficiency syndrome (AIDS)-associated histoplasmosis is accepted for patients with immunologic recovery, there have been no published studies of this approach in clinical practice, and minimal characterization of individuals who relapse with this disease. We performed a multicenter retrospective cohort study to determine the outcome in AIDS patients following discontinuation of suppressive antifungal therapy for histoplasmosis. Ninety-seven patients were divided into a physician-discontinued suppressive therapy group (PD) (38 patients) and a physician-continued suppressive therapy group (PC) (59 patients). The 2 groups were not statistically different at baseline, but at discontinuation of therapy and at the most recent follow-up there were significant differences in adherence to therapy, human immunodeficiency virus (HIV) RNA, and urinary Histoplasma antigen concentration. There was no relapse or death attributed to histoplasmosis in the PD group compared with 36% relapse (p 150 cells/mL, HIV RNA <400 c/mL, Histoplasma antigenuria <2 ng/mL (equivalent to <4.0 units in second-generation method), and no CNS histoplasmosis. PMID:24378739

  14. Attenuated hepatitis A virus: genetic determinants of adaptation to growth in MRC-5 cells.

    OpenAIRE

    Funkhouser, A W; Purcell, R H; D'hondt, E.; Emerson, S. U.

    1994-01-01

    A live candidate hepatitis A virus vaccine, developed from the HM-175 strain and adapted to growth in primary African green monkey kidney (AGMK) cells, was adapted to growth in MRC-5 cells. The nucleotide sequence of the MRC-5 cell-adapted virus was determined and compared with the known sequence of the AGMK cell-adapted virus. Thirteen unique mutations, which occurred during passage in MRC-5 cells, were identified. Four of the unique mutations were located in a cluster in the 5' noncoding re...

  15. Attenuation of vesicular stomatitis virus infection of brain using antiviral drugs and an adeno-associated virus-interferon vector

    Science.gov (United States)

    Wollmann, Guido; Paglino, Justin C.; Maloney, Patrick R; Ahmadi, Sebastian A; van den Pol, Anthony N

    2015-01-01

    Vesicular stomatitis virus (VSV) shows promise as vaccine-vector and oncolytic virus. However, reports of neurotoxicity of VSV remain a concern. We compared 12 antiviral compounds to control infection of VSV-CT9-M51 and VSV-rp30 using murine and human brain cultures, and in vivo mouse models. Inhibition of replication, cytotoxicity and infectivity was strongest with ribavirin and IFN-α and to some extent with mycophenolic acid, chloroquine, and adenine 9-β-D-arabinofuranoside. To generate continuous IFN exposure, we made an adeno-associated virus vector expressing murine IFN; AAV-mIFN-β protected mouse brain cells from VSV, as did a combination of ribavirin and chloroquine. Intracranial AAV-mIFN-β protected the brain against VSV-CT9-M51. In SCID mice bearing human glioblastoma, AAV-mIFN-β moderately enhanced survival. VSV-CT9-M51 doubled median survival when administered after AAV-mIFN-β; some surviving mice showed complete tumor destruction. Together, these data suggest that AAV-IFN or IFN with ribavirin and chloroquine provide an optimal anti-virus combination against VSV in the brain. PMID:25462341

  16. Attenuation of vesicular stomatitis virus infection of brain using antiviral drugs and an adeno-associated virus-interferon vector.

    Science.gov (United States)

    Wollmann, Guido; Paglino, Justin C; Maloney, Patrick R; Ahmadi, Sebastian A; van den Pol, Anthony N

    2015-01-15

    Vesicular stomatitis virus (VSV) shows promise as a vaccine-vector and oncolytic virus. However, reports of neurotoxicity of VSV remain a concern. We compared 12 antiviral compounds to control infection of VSV-CT9-M51 and VSV-rp30 using murine and human brain cultures, and in vivo mouse models. Inhibition of replication, cytotoxicity and infectivity was strongest with ribavirin and IFN-α and to some extent with mycophenolic acid, chloroquine, and adenine 9-β-d-arabinofuranoside. To generate continuous IFN exposure, we made an adeno-associated virus vector expressing murine IFN; AAV-mIFN-β protected mouse brain cells from VSV, as did a combination of IFN, ribavirin and chloroquine. Intracranial AAV-mIFN-β protected the brain against VSV-CT9-M51. In SCID mice bearing human glioblastoma, AAV-mIFN-β moderately enhanced survival. VSV-CT9-M51 doubled median survival when administered after AAV-mIFN-β; some surviving mice showed complete tumor destruction. Together, these data suggest that AAV-IFN or IFN with ribavirin and chloroquine provide an optimal anti-virus combination against VSV in the brain. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. The arbuscular mycorrhizal symbiosis attenuates symptom severity and reduces virus concentration in tomato infected by Tomato yellow leaf curl Sardinia virus (TYLCSV).

    Science.gov (United States)

    Maffei, Giulia; Miozzi, Laura; Fiorilli, Valentina; Novero, Mara; Lanfranco, Luisa; Accotto, Gian Paolo

    2014-04-01

    The arbuscular mycorrhizal (AM) symbiosis is considered a natural instrument to improve plant health and productivity since mycorrhizal plants often show higher tolerance to abiotic and biotic stresses. However, the impact of the AM symbiosis on infection by viral pathogens is still largely uncertain and little explored. In the present study, tomato plants were grown under controlled conditions and inoculated with the AM fungus Funneliformis mosseae. Once the mycorrhizal colonization had developed, plants were inoculated with the Tomato yellow leaf curl Sardinia virus (TYLCSV), a geminivirus causing one of the most serious viral diseases of tomatoes in Mediterranean areas. Biological conditions consisted of control plants (C), TYLCSV-infected plants (V), mycorrhizal plants (M), and TYLCSV-infected mycorrhizal plants (MV). At the time of analysis, the level of mycorrhiza development and the expression profiles of mycorrhiza-responsive selected genes were not significantly modified by virus infection, thus indicating that the AM symbiosis was unaffected by the presence and spread of the virus. Viral symptoms were milder, and both shoot and root concentrations of viral DNA were lower in MV plants than in V plants. Overall F. mosseae colonization appears to exert a beneficial effect on tomato plants in attenuating the disease caused by TYLCSV.

  18. miR-144 attenuates the host response to influenza virus by targeting the TRAF6-IRF7 signaling axis.

    Directory of Open Access Journals (Sweden)

    Carrie M Rosenberger

    2017-04-01

    Full Text Available Antiviral responses must rapidly defend against infection while minimizing inflammatory damage, but the mechanisms that regulate the magnitude of response within an infected cell are not well understood. miRNAs are small non-coding RNAs that suppress protein levels by binding target sequences on their cognate mRNA. Here, we identify miR-144 as a negative regulator of the host antiviral response. Ectopic expression of miR-144 resulted in increased replication of three RNA viruses in primary mouse lung epithelial cells: influenza virus, EMCV, and VSV. We identified the transcriptional network regulated by miR-144 and demonstrate that miR-144 post-transcriptionally suppresses TRAF6 levels. In vivo ablation of miR-144 reduced influenza virus replication in the lung and disease severity. These data suggest that miR-144 reduces the antiviral response by attenuating the TRAF6-IRF7 pathway to alter the cellular antiviral transcriptional landscape.

  19. 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...

  20. Attenuated Human Parainfluenza Virus Type 1 Expressing the Respiratory Syncytial Virus (RSV) Fusion (F) Glycoprotein from an Added Gene: Effects of Prefusion Stabilization and Packaging of RSV F.

    Science.gov (United States)

    Liu, Xiang; Liang, Bo; Ngwuta, Joan; Liu, Xueqiao; Surman, Sonja; Lingemann, Matthias; Kwong, Peter D; Graham, Barney S; Collins, Peter L; Munir, Shirin

    2017-11-15

    Human respiratory syncytial virus (RSV) is the most prevalent worldwide cause of severe respiratory tract infection in infants and young children. Human parainfluenza virus type 1 (HPIV1) also causes severe pediatric respiratory illness, especially croup. Both viruses lack vaccines. Here, we describe the preclinical development of a bivalent RSV/HPIV1 vaccine based on a recombinant HPIV1 vector, attenuated by a stabilized mutation, that expresses RSV F protein modified for increased stability in the prefusion (pre-F) conformation by previously described disulfide bond (DS) and hydrophobic cavity-filling (Cav1) mutations. RSV F was expressed from the first or second gene position as the full-length protein or as a chimeric protein with its transmembrane and cytoplasmic tail (TMCT) domains substituted with those of HPIV1 F in an effort to direct packaging in the vector particles. All constructs were recovered by reverse genetics. The TMCT versions of RSV F were packaged in the rHPIV1 particles much more efficiently than their full-length counterparts. In hamsters, the presence of the RSV F gene, and in particular the TMCT versions, was attenuating and resulted in reduced immunogenicity. However, the vector expressing full-length RSV F from the pre-N position was immunogenic for RSV and HPIV1. It conferred complement-independent high-quality RSV-neutralizing antibodies at titers similar to those of wild-type RSV and provided protection against RSV challenge. The vectors exhibited stable RSV F expression in vitro and in vivo In conclusion, an attenuated rHPIV1 vector expressing a pre-F-stabilized form of RSV F demonstrated promising immunogenicity and should be further developed as an intranasal pediatric vaccine.IMPORTANCE RSV and HPIV1 are major viral causes of acute pediatric respiratory illness for which no vaccines or suitable antiviral drugs are available. The RSV F glycoprotein is the major RSV neutralization antigen. We used a rHPIV1 vector, bearing a

  1. Enhancement or Attenuation of Disease by Deletion of Genes from Citrus Tristeza Virus

    Science.gov (United States)

    Tatineni, Satyanarayana

    2012-01-01

    Stem pitting is a common virus-induced disease of perennial woody plants induced by a range of different viruses. The phenotype results from sporadic areas of the stem in which normal xylem and phloem development is prevented during growth of stems. These alterations interfere with carbohydrate transport, resulting in reduced plant growth and yield. Citrus tristeza virus (CTV), a phloem-limited closterovirus, induces economically important stem-pitting diseases of citrus. CTV has three nonconserved genes (p33, p18, and p13) that are not related to genes of other viruses and that are not required for systemic infection of some species of citrus, which allowed us to examine the effect of deletions of these genes on symptom phenotypes. In the most susceptible experimental host, Citrus macrophylla, the full-length virus causes only very mild stem-pitting symptoms. Surprisingly, we found that certain deletion combinations (p33 and p18 and/or p13) induced greatly increased stem-pitting symptoms, while other combinations (p13 or p13 plus p18) resulted in reduced stem pitting. These results suggest that the stem-pitting phenotype, which is one of more economically important disease phenotypes, can result not from a specific sequence or protein but from a balance between the expression of different viral genes. Unexpectedly, using green fluorescent protein-tagged full-length virus and deletion mutants (CTV9Δp33 and CTV9Δp33Δp18Δp13), the virus was found at pitted areas in abnormal locations outside the normal ring of phloem. Thus, increased stem pitting was associated not only with a prevention of xylem production but also with a proliferation of cells that supported viral replication, suggesting that at random areas of stems the virus can elicit changes in cellular differentiation and development. PMID:22593155

  2. Enhancement or attenuation of disease by deletion of genes from Citrus tristeza virus.

    Science.gov (United States)

    Tatineni, Satyanarayana; Dawson, William O

    2012-08-01

    Stem pitting is a common virus-induced disease of perennial woody plants induced by a range of different viruses. The phenotype results from sporadic areas of the stem in which normal xylem and phloem development is prevented during growth of stems. These alterations interfere with carbohydrate transport, resulting in reduced plant growth and yield. Citrus tristeza virus (CTV), a phloem-limited closterovirus, induces economically important stem-pitting diseases of citrus. CTV has three nonconserved genes (p33, p18, and p13) that are not related to genes of other viruses and that are not required for systemic infection of some species of citrus, which allowed us to examine the effect of deletions of these genes on symptom phenotypes. In the most susceptible experimental host, Citrus macrophylla, the full-length virus causes only very mild stem-pitting symptoms. Surprisingly, we found that certain deletion combinations (p33 and p18 and/or p13) induced greatly increased stem-pitting symptoms, while other combinations (p13 or p13 plus p18) resulted in reduced stem pitting. These results suggest that the stem-pitting phenotype, which is one of more economically important disease phenotypes, can result not from a specific sequence or protein but from a balance between the expression of different viral genes. Unexpectedly, using green fluorescent protein-tagged full-length virus and deletion mutants (CTV9Δp33 and CTV9Δp33Δp18Δp13), the virus was found at pitted areas in abnormal locations outside the normal ring of phloem. Thus, increased stem pitting was associated not only with a prevention of xylem production but also with a proliferation of cells that supported viral replication, suggesting that at random areas of stems the virus can elicit changes in cellular differentiation and development.

  3. Characterisation of virus transport and attenuation in epikarst using short pulse and prolonged injection multi-tracer testing.

    Science.gov (United States)

    Flynn, Raymond M; Sinreich, Michael

    2010-02-01

    Attenuation processes controlling virus fate and transport in the vadose zone of karstified systems can strongly influence groundwater quality. This research compares the breakthrough of two bacteriophage tracers (H40/1 and T7), with contrasting properties, at subsurface monitoring points following application onto an overlying composite sequence of thin organic soil and weathered limestone (epikarst). Short pulse multi-tracer test results revealed that T7 (Source concentration, Co=1.8x10(6)pfu/mL) and H40/1 (Co=5.9x10(6)pfu/mL) could reach sampling points 10 m below ground less than 30 min after tracer application. Contrasting deposition rates, determined from simulated tracer responses, reflected the potential of the ground to differentially attenuate viruses. Prolonged application of both T7 (Co=2.3x10(4)pfu/mL) and H40/1 (Co=1.3x10(5)pfu/mL) over a five hour period during a subsequent test, in which ionic strength levels observed at monitoring points rose consistently, corresponded to a rapid rise in T7 levels, followed by a gradual decline before the end of tracer injection; this reflected reaction-limited deposition in the system. T7's response contrasted with that of H40/1, whose concentration remained constant over a three hour period before declining dramatically prior to the end of tracer injection. Subsequent application of lower ionic strength tracer-free flush water generated a rapid rise in H40/1 levels and a more gradual release of T7. Results highlight the benefits of employing prolonged injection multi-tracer tests for identifying processes not apparent from conventional short pulse tests. Study findings demonstrate that despite rapid transport rates, the epikarst is capable of physicochemical filtration of viruses and their remobilization, depending on virus type and hydrochemical conditions. Crown Copyright 2009. Published by Elsevier Ltd. All rights reserved.

  4. 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.

  5. Innate anti-viral immunity is associated with the protection elicited by the simian immunodeficiency virus (SIV) live attenuated virus vaccine in cynomolgus monkeys.

    Science.gov (United States)

    Goletti, Delia; Macchia, Iole; Leone, Pasqualina; Pace, Monica; Sernicola, Leonardo; Pavone-Cossut, Maria Rosaria; Maggiorella, Maria Teresa; Cafaro, Aurelio; Ensoli, Barbara; Titti, Fausto

    2006-10-01

    The Delta-nef live attenuated virus vaccine approach offered in the SIV-macaque model the opportunity to identify humoral and cell-mediated immune responses associated with protection against viral infections. In addition, soluble factors different from those related to specific immune responses appear to correlate with the establishment and maintenance of the protective status. Investigated were: 1) the ability of CD8+ T cells from cynomolgus monkeys vaccinated with SIV Delta-nef and long-term protected against sequential SIVs and SHIV challenges to inhibit in vitro SHIV replication in an acute infection cell system, 2) the ability of cell-free supernatants from CD8+ T cell cultures to inhibit replication of HIV in chronically infected cells, and 3) whether the antiviral activity of CD8+ T cells correlated with IFNgamma production. Soluble factor(s) secreted by CD8+ T cells from Delta-nef vaccinated monkeys significantly inhibited SHIV replication in an autologous cell system. This effect was not dependent on beta-chemokine secretion and correlated with an increased IFNgamma production. In addition, since supernatants from CD8+ T cells inhibited HIV production in chronically infected monocytic cells, the suppressive activity was not related to the viral strain. Vaccination with the live attenuated virus induces both a CD8+ T cell-dependent antiviral activity and IFNgamma responses potentially responsible for the protection from challenge with heterologous highly pathogenic SHIV89.6P. It is conceivable that boosting the "natural" along with the antigen-specific immunity is a desirable outcome to improve the protective efficacy of any vaccine approach.

  6. Immunogenicity and virulence of attenuated vaccinia virus Tian Tan encoding HIV-1 muti-epitope genes, p24 and cholera toxin B subunit in mice.

    Science.gov (United States)

    Du, Shouwen; Wang, Yuhang; Liu, Cunxia; Wang, Maopeng; Zhu, Yilong; Tan, Peng; Ren, Dayong; Li, Xiao; Tian, Mingyao; Yin, Ronglan; Li, Chang; Jin, Ningyi

    2015-07-01

    No effective prophylactic or therapeutic vaccine against HIV-1 in humans is currently available. This study analyzes the immunogenicity and safety of a recombinant attenuated vaccinia virus. A chimeric gene of HIV-1 multi-epitope genes containing CpG ODN and cholera toxin B subunit (CTB) was inserted into Chinese vaccinia virus Tian Tan strain (VTT) mutant strain. The recombinant virus rddVTT(-CCMp24) was assessed for immunogenicity and safety in mice. Results showed that the protein CCMp24 was expressed stably in BHK-21 infected with rddVTT(-CCMp24). And the recombinant virus induced the production of HIV-1 p24 specific immunoglobulin G (IgG), IL-2 and IL-4. The recombinant vaccine induced γ-interferon secretion against HIV peptides, and elicited a certain levels of immunological memory. Results indicated that the recombinant virus had certain immunogenicity to HIV-1. Additionally, the virulence of the recombinant virus was been attenuated in vivo of mice compared with wild type VTT (wtVTT), and the introduction of CTB and HIV Mp24 did not alter the infectivity and virulence of defective vaccinia virus. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. Immune Regulatory Effects of Enteromorphaclathrata Polysaccharides on Nd Attenuated Vaccine in a Chicken Model Infected with Reticuloendotheliosis Virus

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    Q Sun

    Full Text Available ABSTRACT Reticuloendotheliosis virus (REV infection has frequently affected the poultry industry in recent years. The infection with REV weakens the immune responses of the infected poultry. It is reported that Enteromorphaclathrata polysaccharides are capable of regulating immune function. In order to investigate the immuno regulatory effects of Enteromorphaclathrata polysaccharides (EPS on the response of REV-infected broilers to a live attenuated Newcastle disease (ND vaccine. Broilers were intraperitoneally injected with REV at one day of age, subcutaneously infected with EPS at 2 days of age, and vaccinated by nasal drip with a live attenuated ND (Lasota strain vaccine at 5 days of age. Immune organ index, secretory immunoglobulinA (SIgA, peripheral blood heterophil to lymphocyte ratios (H/L ratio, peripheral blood lymphocyte transformation rates, and interferon-gamma (IFN-γ and interleukin-2 (IL-2 levels were measured at 3, 7, 14, 21, 28, 35, 42, and 56 days of age. The results showed that EPS increased the immune organ index, and the secretion of small intestine secretory immunoglobulin A, serum ND antibody titers, blood H/L ratio, peripheral blood lymphocyte transformation rates, and IL-2 and IFN-γ levels. These results indicate that EPS are able to enhance the immune responses of chickens both to REV infection and to ND vaccination. Therefore, Enteromorphaclathrata polysaccharides can be considered as an immune regulator in the future.

  8. Nasal lavage natural killer cell function is suppressed in smokers after live attenuated influenza virus

    Science.gov (United States)

    Background Modified function of immune cells in nasal secretions may playa role in the enhanced susceptibility to resp iratory viruses that is seen in smokers. Innate immune cells in nasal secretions have largely been characterized by cellular differentials using morphologic c...

  9. Attenuation of Marek's disease virus lacking the Meq oncogene in cell culture

    Science.gov (United States)

    Marek’s disease virus (MDV) encodes a basic leucine zipper oncoprotein, meq, which structurally resembles the jun/fos family of transcriptional activators. It has been clearly demonstrated that deletion of meq results in loss of transformation and oncogenic capacity of MDV. Chickens vaccinated with ...

  10. 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

  11. 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 como......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...... hazard rates for both non-AIDS comorbidities (cardiovascular disease, chronic kidney disease, chronic lung disease, liver disease, and cancer) and all-cause mortality....

  12. In vivo Biodistribution of a Highly Attenuated Recombinant Vesicular Stomatitis Virus Expressing HIV-1 Gag Following Intramuscular, Intranasal, or Intravenous Inoculation

    Science.gov (United States)

    Johnson, J. Erik; Coleman, John W.; Kalyan, Narender K.; Calderon, Priscilla; Wright, Kevin J.; Obregon, Jennifer; Ogin-Wilson, Eleanor; Natuk, Robert J.; Clarke, David K.; Udem, Stephen A.; Cooper, David; Hendry, R. Michael

    2009-01-01

    Recombinant vesicular stomatitis viruses (rVSVs) are being developed as potential HIV-1 vaccine candidates. To characterize the in vivo replication and dissemination of rVSV vectors in mice, high doses of a highly attenuated vector expressing HIV-1 Gag, rVSVIN- N4CT9-Gag1, and a prototypic reference virus, rVSVIN-HIVGag5, were delivered intramuscularly (IM), intranasally (IN), or intravenously (IV). We used quantitative, real-time RT-PCR (Q-PCR) and standard plaque assays to measure the temporal dissemination of these viruses to various tissues. Following IM inoculation, both viruses were detected primarily at the injection site as well as in draining lymph nodes; neither virus induced significant weight loss, pathologic signs, or evidence of neuroinvasion. In contrast, following IN inoculation, the prototypic virus was detected in all tissues tested and caused significant weight loss leading to death. IN administration of rVSVIN- N4CT9-Gag1 resulted in detection in numerous tissues (brain, lung, nasal turbinates, and lymph nodes) albeit in significantly reduced levels, which caused little or no weight loss nor any mortality. Following IV inoculation, both prototypic and attenuated viruses were detected by Q-PCR in all tissues tested. In contrast to the prototype, rVSVIN-N4CT9-Gag1 viral loads were significantly lower in all organs tested, and no infectious virus was detected in the brain following IV inoculation, despite the presence of viral RNA. These studies demonstrated significant differences in the biodistribution patterns of and the associated pathogenicity engendered by the prototypic and attenuated vectors in a highly susceptible host. PMID:19428903

  13. Recombinant Adeno-Associated Virus-Mediated Expression of Methamphetamine Antibody Attenuates Methamphetamine-Induced Hyperactivity in Mice.

    Science.gov (United States)

    Chen, Yun-Hsiang; Wu, Kuo-Jen; Wu, Kuang-Lun; Wu, Kun-Lieh; Tsai, Ho-Min; Chen, Mao-Liang; Chen, Yi-Wei; Hsieh, Wei; Lin, Chun-Ming; Wang, Yun

    2017-04-07

    Methamphetamine (Meth) is one of the most frequently abused drugs worldwide. Recent studies have indicated that antibodies with high affinity for Meth reduce its pharmacological effects. The purpose of this study was to develop a technique for virus-based passive immunization against Meth effects. We generated a recombinant adeno-associated virus serotype-8 vector (AAV-MethAb) carrying the gene for a Meth-specific monoclonal antibody (MethAb). Infection of 293 cells with AAV-MethAb resulted in the expression and secretion of antibodies which bind to Meth. The viral vector was then examined in adult ICR mice. Systemic administration of AAV-MethAb resulted in long-term expression of MethAb in the serum for up to 29 weeks. Serum collected from the animals receiving AAV-MethAb retained a high specificity for (+)-Meth. Animals were challenged with Meth five weeks after viral injection. Meth levels in the brain and serum were reduced while Meth-induced locomotor activity was significantly attenuated. In conclusion, AAV-MethAb administration effectively depletes Meth from brain and serum while reducing the behavioral response to Meth, and thus is a potential therapeutic approach for Meth abuse.

  14. [Human immunodeficiency virus and AIDS in terms of reverse transcriptase and molecular evolution].

    Science.gov (United States)

    Doi, H

    1998-03-01

    Human immunodeficiency virus type 1 (HIV-1) evolves rapidly in the host. The computer analysis of the HIV-1 genome has shown that the mutation manner is dependent on oligonucleotide sequences (in particular, six bases long); thus HIV-1 adaptively evolves. The six-base-long interaction between template-primer oligonucleotide and the reverse transcriptase (RT) has been revealed by the crystal structure of RT, in vitro termination assay of plymerization, and hydroxyl radical footprint analysis. It has been thought that AIDS is caused by the large numbers of HIV-1 quasispecies yielded by the adaptive and rapid evolution in the host. However, the slow evolution and the high levels of viral RNA in the progressive HIV-1 infected individuals (progressives) were recently reported; in contrast, the adaptive and rapid evolution and the low viral-RNA levels were reported in the non-progressives. This suggests that the physiological environment, e.g. pH and dNTP balance, in which RT works in the progressives is different from that in the non-progressives.

  15. SHIV-1157i and passaged progeny viruses encoding R5 HIV-1 clade C env cause AIDS in rhesus monkeys

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    Siddappa Nagadenahalli B

    2008-10-01

    Full Text Available Abstract Background Infection of nonhuman primates with simian immunodeficiency virus (SIV or chimeric simian-human immunodeficiency virus (SHIV strains is widely used to study lentiviral pathogenesis, antiviral immunity and the efficacy of AIDS vaccine candidates. SHIV challenges allow assessment of anti-HIV-1 envelope responses in primates. As such, SHIVs should mimic natural HIV-1 infection in humans and, to address the pandemic, encode HIV-1 Env components representing major viral subtypes worldwide. Results We have developed a panel of clade C R5-tropic SHIVs based upon env of a Zambian pediatric isolate of HIV-1 clade C, the world's most prevalent HIV-1 subtype. The parental infectious proviral clone, SHIV-1157i, was rapidly passaged through five rhesus monkeys. After AIDS developed in the first animal at week 123 post-inoculation, infected blood was infused into a sixth monkey. Virus reisolated at this late stage was still exclusively R5 tropic and mucosally transmissible. Here we describe the long-term follow-up of this initial cohort of six monkeys. Two have remained non-progressors, whereas the other four gradually progressed to AIDS within 123–270 weeks post-exposure. Two progressors succumbed to opportunistic infections, including a case of SV40 encephalitis. Conclusion These data document the disease progression induced by the first mucosally transmissible, pathogenic R5 non-clade B SHIV and suggest that SHIV-1157i-derived viruses, including the late-stage, highly replication-competent SHIV-1157ipd3N4 previously described (Song et al., 2006, display biological characteristics that mirror those of HIV-1 clade C and support their expanded use for AIDS vaccine studies in nonhuman primates.

  16. NS1-Truncated Live Attenuated Virus Vaccine Provides Robust Protection to Aged Mice from Viral Challenge

    Science.gov (United States)

    Pica, Natalie; Langlois, Ryan A.; Krammer, Florian; Margine, Irina

    2012-01-01

    Immunological changes associated with age contribute to the high rates of influenza virus morbidity and mortality in the elderly. Compounding this problem, aged individuals do not respond to vaccination as well as younger, healthy adults. Efforts to increase protection to this demographic group are of utmost importance, as the proportion of the population above the age of 65 is projected to increase in the coming decade. Using a live influenza virus with a truncated nonstructural protein 1 (NS1), we are able to stimulate cellular and humoral immune responses of aged mice comparable to levels seen in young mice. Impressively, a single vaccination provided protection following stringent lethal challenge in aged mice. PMID:22787224

  17. Evaluation of cancer virotherapy with attenuated replicative Semliki forest virus in different rodent tumor models.

    Science.gov (United States)

    Määttä, Ann-Marie; Liimatainen, Timo; Wahlfors, Tiina; Wirth, Thomas; Vähä-Koskela, Markus; Jansson, Linda; Valonen, Piia; Häkkinen, Katja; Rautsi, Outi; Pellinen, Riikka; Mäkinen, Kimmo; Hakumäki, Juhana; Hinkkanen, Ari; Wahlfors, Jarmo

    2007-08-15

    Semliki Forest virus (SFV) is one of the latest candidates for a virotherapeutic agent against cancer, and recent studies have demonstrated its efficacy in tumor models. In the present study, we examined the antitumor efficacy of an avirulent SFV strain A7(74) and its derivative, a replication-competent SFV vector VA7-EGFP, in a partially immunodeficient mouse tumor model (subcutaneous A549 human lung adenocarcinoma in NMRI nu/nu mouse) and in an immunocompetent rat tumor model (intracranial BT4C glioma in BDIX rat). When subcutaneous mouse tumors were injected 3 times with VA7-EGFP, intratumorally treated animals showed almost complete inhibition of tumor growth, while systemically treated mice displayed only delayed tumor growth (intravenous injection) or no response at all (intraperitoneal injection). This was at least partially due to a strong type I interferon (IFN) response in the tumors. The animals did not display any signs of abnormal behavior or encephalitis, even though SFV-positive foci were detected in the brain after the initial blood viremia. Intracranial rat tumors were injected directly with SFV A7(74) virus and monitored with magnetic resonance imaging. Tumor growth was significantly reduced (p virotherapy induced extensive production of neutralizing anti-SFV antibodies that most likely contributed to the insufficient treatment efficacy. In conclusion, we show here that SFV A7(74) is a potential oncolytic agent for cancer virotherapy, but major immunological hurdles may need to be overcome before the virus can be clinically tested.

  18. Attenuation of pathogenic immune responses during infection with human and simian immunodeficiency virus (HIV/SIV by the tetracycline derivative minocycline.

    Directory of Open Access Journals (Sweden)

    Julia L Drewes

    Full Text Available 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.

  19. 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

  20. Evaluation of the attenuation, immunogenicity, and efficacy of a live virus vaccine generated by codon-pair bias de-optimization of the 2009 pandemic H1N1 influenza virus, in ferrets.

    Science.gov (United States)

    Broadbent, Andrew J; Santos, Celia P; Anafu, Amanda; Wimmer, Eckard; Mueller, Steffen; Subbarao, Kanta

    2016-01-20

    Codon-pair bias de-optimization (CPBD) of viruses involves re-writing viral genes using statistically underrepresented codon pairs, without any changes to the amino acid sequence or codon usage. Previously, this technology has been used to attenuate the influenza A/Puerto Rico/8/34 (H1N1) virus. The de-optimized virus was immunogenic and protected inbred mice from challenge. In order to assess whether CPBD could be used to produce a live vaccine against a clinically relevant influenza virus, we generated an influenza A/California/07/2009 pandemic H1N1 (2009 pH1N1) virus with de-optimized HA and NA gene segments (2009 pH1N1-(HA+NA)(Min)), and evaluated viral replication and protein expression in MDCK cells, and attenuation, immunogenicity, and efficacy in outbred ferrets. The 2009 pH1N1-(HA+NA)(Min) virus grew to a similar titer as the 2009 pH1N1 wild type (wt) virus in MDCK cells (∼10(6)TCID50/ml), despite reduced HA and NA protein expression on western blot. In ferrets, intranasal inoculation of 2009 pH1N1-(HA+NA)(Min) virus at doses ranging from 10(3) to 10(5) TCID50 led to seroconversion in all animals and protection from challenge with the 2009 pH1N1 wt virus 28 days later. The 2009 pH1N1-(HA+NA)(Min) virus did not cause clinical illness in ferrets, but replicated to a similar titer as the wt virus in the upper and lower respiratory tract, suggesting that de-optimization of additional gene segments may be warranted for improved attenuation. Taken together, our data demonstrate the potential of using CPBD technology for the development of a live influenza virus vaccine if the level of attenuation is optimized. Published by Elsevier Ltd.

  1. Immune clearance of attenuated rabies virus results in neuronal survival with altered gene expression.

    Directory of Open Access Journals (Sweden)

    Emily A Gomme

    Full Text Available Rabies virus (RABV is a highly neurotropic pathogen that typically leads to mortality of infected animals and humans. The precise etiology of rabies neuropathogenesis is unknown, though it is hypothesized to be due either to neuronal death or dysfunction. Analysis of human brains post-mortem reveals surprisingly little tissue damage and neuropathology considering the dramatic clinical symptomology, supporting the neuronal dysfunction model. However, whether or not neurons survive infection and clearance and, provided they do, whether they are functionally restored to their pre-infection phenotype has not been determined in vivo for RABV, or any neurotropic virus. This is due, in part, to the absence of a permanent "mark" on once-infected cells that allow their identification long after viral clearance. Our approach to study the survival and integrity of RABV-infected neurons was to infect Cre reporter mice with recombinant RABV expressing Cre-recombinase (RABV-Cre to switch neurons constitutively expressing tdTomato (red to expression of a Cre-inducible EGFP (green, permanently marking neurons that had been infected in vivo. We used fluorescence microscopy and quantitative real-time PCR to measure the survival of neurons after viral clearance; we found that the vast majority of RABV-infected neurons survive both infection and immunological clearance. We were able to isolate these previously infected neurons by flow cytometry and assay their gene expression profiles compared to uninfected cells. We observed transcriptional changes in these "cured" neurons, predictive of decreased neurite growth and dysregulated microtubule dynamics. This suggests that viral clearance, though allowing for survival of neurons, may not restore them to their pre-infection functionality. Our data provide a proof-of-principle foundation to re-evaluate the etiology of human central nervous system diseases of unknown etiology: viruses may trigger permanent neuronal

  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.

  3. Dislipidemia y virus de inmunodeficiencia adquirida/sida Dyslipemia and the HIV/AIDS

    Directory of Open Access Journals (Sweden)

    Lizet Castelo Elías-Calles

    2010-08-01

    Full Text Available La epidemia por el virus de inmunodeficiencia adquirida (VIH constituye un problema de la salud pública a nivel mundial. La morbilidad y mortalidad asociada al síndrome de inmunodeficiencia adquirida (sida ha variado de forma significativa con el empleo de la terapia antirretroviral. Sin embargo, se ha visto afectada por los cambios que ocasiona en el metabolismo lipoproteico. Estos se caracterizan por la elevación de los niveles de lipoproteína de muy baja densidad y triglicéridos, el incremento del colesterol total, lipoproteína de baja densidad, y la disminución de los niveles de lipoproteína de alta densidad. La infección por VIH, asociada a otros factores inflamatorios, es un modelo de progresión de la aterosclerosis. El perfil lipídico proaterogénico en personas con VIH/sida constituye un alto riesgo para el desarrollo de enfermedad coronaria. En este trabajo se revisó la contribución tanto de la infección por VIH como del efecto de la terapia antirretroviral en el metabolismo lipídico y su procedimiento terapéutico.The HIV epidemic is a public health problem at worldwide. The morbidity and mortality associated with AIDS have change in a significant way with the use of anti-retroviral therapy. However, it has been affected by the changes provoked in the lipoprotein metabolism, which are characterized by a rise of the very low-density lipoprotein (VLDL levels and triglycerides, an increase of total cholesterol, low-density lipoprotein (LDL. HIV-infection associated with other inflammatory factors, is a progression model of atherosclerosis. The proatherogenic lipid profile in HIV/AIDS persons is a high risk for the development of the coronary disease. In present paper we analyzed the contribution of both the HIV-infection and the antiretroviral therapy effect on the lipid metabolism and its therapeutical procedure.

  4. Numbers of CD4+ cells and the levels of core antigens of and antibodies to the human immunodeficiency virus as predictors of AIDS among seropositive homosexual men

    NARCIS (Netherlands)

    de Wolf, F.; Lange, J. M.; Houweling, J. T.; Coutinho, R. A.; Schellekens, P. T.; van der Noordaa, J.; Goudsmit, J.

    1988-01-01

    The relation between serological and immunologic profiles and the risk of developing AIDS was assessed in 306 initially asymptomatic, human immunodeficiency virus-infected homosexual men studied for 30 mo. Twenty-nine men developed AIDS (attack rate, 16.8%). The attack rate in core antibody-negative

  5. Effect of functionalization of polymeric nanoparticles incorporated with whole attenuated rabies virus antigen on sustained release and efficacy

    Directory of Open Access Journals (Sweden)

    Kiran Nivedh

    2016-12-01

    Full Text Available Nanovaccines introduced a new dimension to prevent or cure diseases in an efficient and sustained manner. Various polymers have been used for the drug delivery to increase the therapeutic value with minimal side effects. Thus the present study incorporates both nanotechnology and polymers for the drug delivery. Poly(d,l-lactic-co-glycolic acid-b-poly(ethylene glycol was incorporated with the rabies whole attenuated viral antigen using double emulsion (W/O/W method and characterized by Scanning Electron Microscopy (SEM and Atomic Force Microscopy (AFM. Chitosan-PEG nanoparticles incorporated with the rabies whole attenuated virus antigen (CS-PEG NP-RV Ag. were prepared using Ionic Gelation method. The CS-PEG NP-RV Ag. was surface modified with biocompatible polymers such as Acacia, Bovine Serum Albumin (BSA, Casein, Ovalbumin and Starch by Ionic Gelation method. The morphology was confirmed by SEM and Transmission Electron Microscopy (TEM. The surface modification was confirmed by Fourier Transform Infrared Spectroscopy (FTIR, Zeta potential. The size distribution of CS-PEG-RV Ag. and surface modified CS-PEG-RV Ag. by respective biocompatible polymers was assessed by Zetasizer. Release profile of both stabilized nanoparticles was carried out by modified centrifugal ultrafiltration method which showed the sustained release pattern of the Rabies Ag. Immune stimulation under in-vitro condition was studied using rosette assay and phagocytosis assay. In-vitro toxicity using human blood and genotoxicity using human blood DNA was also studied to assess the toxicity of the nanoformulations. The results of these studies infer that PLGA-b-PEG nanoparticles, CS-PEG and surface modified CS-PEG nanoparticles may be an efficient nanocarrier for the RV Ag. to elicit immune response sustainably with negligible toxic effect to the human system.

  6. Comparison of virus shedding after lived attenuated and pentavalent reassortant rotavirus vaccine.

    Science.gov (United States)

    Hsieh, Yu-Chia; Wu, Fang-Tzy; Hsiung, Chao A; Wu, Ho-Sheng; Chang, Kuang-Yi; Huang, Yhu-Chering

    2014-02-26

    Transmission of rotavirus vaccine or vaccine-reassortant strains to unvaccinated contacts has been reported. Therefore, it is essential to evaluate and characterize the nature of vaccine-virus shedding among rotavirus vaccine recipients. Two groups of healthy infants who received a complete course of RotaTeq (RV5) or Rotarix (RV2) were enrolled (between March 2010 and June 2011) to compare fecal shedding for one month after each vaccine dose. Shedding was assessed using both enzyme immunoassay (EIA) and real-time reverse transcription-polymerase chain reaction (RT-PCR). Eighty-seven infants (34 girls and 53 boys) were enrolled in the study. After the first vaccine dose, the peak time of virus shedding occurred between day 4 and day 7, with positive detection rates of 80-90% by real-time RT-PCR and 20-30% by EIA. In both groups, vaccine shedding occurred as early as one day and as late as 25-28 days. Mixed effects logistic regression analysis of real-time RT-PCR data showed no significant differences between two groups when shedding rates were compared after the first vaccine dose (odds ratio [OR] 1.26; P=0.71) or after the second vaccine dose (odds ratio [OR] 1.26; P=0.99). However, infants receiving RV2 shed significantly higher viral loads than those receiving RV5 when compared after the first vaccine dose (P=0.001) and after the second dose (P=0.039). In terms of shedding rates detected by real-time RT-PCR, vaccine uptake of RV5 or RV2 among infants in Taiwan was comparable. Clinical significance of higher shedding viral loads in RV2 should be further observed. Copyright © 2014 Elsevier Ltd. All rights reserved.

  7. The latex condom, an efficient barrier against sexual transmission of AIDS-related viruses.

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    Van de Perre, P; Jacobs, D; Sprecher-Goldberger, S

    1987-05-01

    Using a mechanical model, we studied human immunodeficiency virus (HIV) leakage through six different trademark condoms. The presence of the recovered virus was determined after passage to MT-2 cells and to cultured mitogen-stimulated normal human peripheral blood mononuclear cells (PMC). Only the natural membrane condom showed virus leakage after inside pressure. In addition, the kinetics of virus inactivation at 37 degrees C were followed inside and outside the condom. The virus was partially inactivated after 10 min at 37 degrees C inside the condom, but the degree of inactivation seemed higher in some of the trademark condoms.

  8. Characterization of a novel mutation in NS1 protein of influenza A virus induced by a chemical substance for the attenuation of pathogenicity.

    Directory of Open Access Journals (Sweden)

    Kohei Sasaki

    Full Text Available It is generally accepted that live attenuated influenza vaccine (LAIV has the potential for use as a vaccination against flu. In this study, we demonstrated the nature of an influenza A virus (IAV mutant induced by treating the IAV with a stable furan derivative, (1R,2R-1-(5'-methylfur-3'-ylpropane-1,2,3-triol (MFPT, which had been isolated from Streptomyces sp. strain FV60 with the objective of it being an LAIV candidate. The resulting MFPT-resistant (MFPTr IAVs possessed attenuated pathogenicity in vitro and in vivo when compared with that of the parent virus (H1N1 subtype, NWS strain. Sequencing analysis revealed that a novel mutation, C490U in ns gene (P164S in NS1, was detected in all MFPTr virus clones tested. Therefore, NS1 might be a main target of MFPT, and it was suggested that the P164S mutation contributed to the attenuated pathogenicity of the mutants. Although the phosphatidylinositol 3-kinase (PI3K/Akt signaling pathway is one of the targets of NS1, the MFPTr virus suppressed the phosphorylation of Akt when compared with the wild-type (WT virus. It was suggested that this might lead to the subsequent inhibition of the cleavage of PARP-1 and caspase-3, which is important for the progression of apoptosis. At the same time, nucleoprotein (NP was found to be retained in the nuclei in MFPTr virus-infected cells while nuclear export of NP was detected in WT virus-infected cells. In addition, the expression levels of interferon-β transcripts were significantly decreased in MFPTr virus-infected cells. From these results it can be shown that the mutation, NS1P164S, might be one of the key residues to control NS1 function concerning the induction of apoptosis. In conclusion, MFPT induced favorable mutation in the ns gene for the attenuation of IAV, and therefore might provide the novel methodology for preparing LAIVs.

  9. Critical Role for Monocytes/Macrophages in Rapid Progression to AIDS in Pediatric Simian Immunodeficiency Virus-Infected Rhesus Macaques.

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    Sugimoto, Chie; Merino, Kristen M; Hasegawa, Atsuhiko; Wang, Xiaolei; Alvarez, Xavier A; Wakao, Hiroshi; Mori, Kazuyasu; Kim, Woong-Ki; Veazey, Ronald S; Didier, Elizabeth S; Kuroda, Marcelo J

    2017-09-01

    Infant humans and rhesus macaques infected with the human or simian immunodeficiency virus (HIV or SIV), respectively, express higher viral loads and progress more rapidly to AIDS than infected adults. Activated memory CD4(+) T cells in intestinal tissues are major primary target cells for SIV/HIV infection, and massive depletion of these cells is considered a major cause of immunodeficiency. Monocytes and macrophages are important cells of innate immunity and also are targets of HIV/SIV infection. We reported previously that a high peripheral blood monocyte turnover rate was predictive for the onset of disease progression to AIDS in SIV-infected adult macaques. The purpose of this study was to determine if earlier or higher infection of monocytes/macrophages contributes to the more rapid progression to AIDS in infants. We observed that uninfected infant rhesus macaques exhibited higher physiologic baseline monocyte turnover than adults. Early after SIV infection, the monocyte turnover further increased, and it remained high during progression to AIDS. A high percentage of terminal deoxynucleotidyltransferase dUTP nick end label (TUNEL)-positive macrophages in the lymph nodes (LNs) and intestine corresponded with an increasing number of macrophages derived from circulating monocytes (bromodeoxyuridine positive [BrdU(+)] CD163(+)), suggesting that the increased blood monocyte turnover was required to rapidly replenish destroyed tissue macrophages. Immunofluorescence analysis further demonstrated that macrophages were a significant portion of the virus-producing cells found in LNs, intestinal tissues, and lungs. The higher baseline monocyte turnover in infant macaques and subsequent macrophage damage by SIV infection may help explain the basis of more rapid disease progression to AIDS in infants.IMPORTANCE HIV infection progresses much more rapidly in pediatric cases than in adults; however, the mechanism for this difference is unclear. Using the rhesus macaque model

  10. Systemic and mucosal immunity induced by attenuated Salmonella enterica serovar Typhimurium expressing ORF7 of porcine reproductive and respiratory syndrome virus.

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    Han, Young Woo; Kim, Seong Bum; Rahman, Masudur; Uyangaa, Erdenebileg; Lee, Byung Min; Kim, Jin Hyoung; Park, Ki In; Hong, Jin Tae; Han, Sang-Bae; Eo, Seong Kug

    2011-07-01

    Oral administration of attenuated Salmonella vaccine may provide valuable advantages such as low cost, easy preparation, and safety. Attenuated Salmonella vaccines also serve as carriers of foreign antigens and immunomodulatory cytokines. Presently, an attenuated Salmonella enterica serovar Typhimurium strain was used as a carrier for open reading frame 7 (ORF7) protein of porcine reproductive and respiratory syndrome virus (PRRSV), a swine pathogen of significant global economic importance. Initially, an attenuated S. enterica serovar Typhimurium expressing ORF7 gene derived from PRRSV Korean isolate was constructed. Following oral administration of a single dose of the attenuated Salmonella vaccine expressing PRRSV ORF7, humoral and cell-mediated immune responses specific for ORF7 were induced at both systemic and mucosal sites including spleen, mesenteric lymph node, Peyer's patch, and laminar propria, as evaluated by determining serum ORF7-specific IgG and mucosal IgA responses, as well as Th1- and Th2-type cytokine production from antigen-stimulated T cells. The induced humoral responses were sustained for at least 12weeks post-immunization. In particular, the immunized mice displayed immune responses to both the foreign ORF7 antigen and Salmonella itself. The results indicate the value of attenuated S. enterica serovar Typhimurium as an oral carrier of PRRSV antigenic proteins to induce effective systemic and mucosal immunity. Copyright © 2011 Elsevier Ltd. All rights reserved.

  11. Construction of a bivalent DNA vaccine co-expressing S genes of transmissible gastroenteritis virus and porcine epidemic diarrhea virus delivered by attenuated Salmonella typhimurium.

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    Zhang, Yudi; Zhang, Xiaohui; Liao, Xiaodan; Huang, Xiaobo; Cao, Sanjie; Wen, Xintian; Wen, Yiping; Wu, Rui; Liu, Wumei

    2016-06-01

    Porcine transmissible gastroenteritis virus (TGEV) and porcine epidemic diarrhea virus (PEDV) can cause severe diarrhea in newborn piglets and led to significant economic losses. The S proteins are the main structural proteins of PEDV and TGEV capable of inducing neutralizing antibodies in vivo. In this study, a DNA vaccine SL7207 (pVAXD-PS1-TS) co-expressing S proteins of TGEV and PEDV delivered by attenuated Salmonella typhimurium was constructed and its immunogenicity in piglets was investigated. Twenty-day-old piglets were orally immunized with SL7207 (pVAXD-PS1-TS) at a dosage of 1.6 × 10(11) CFU per piglet and then booster immunized with 2.0 × 10(11) CFU after 2 weeks. Humoral immune responses, as reflected by virus neutralizing antibodies and specific IgG and sIgA, and cellular immune responses, as reflected by IFN-γ, IL-4, and lymphocyte proliferation, were evaluated. SL7207 (pVAXD-PS1-TS) simultaneously elicited immune responses against TGEV and PEDV after oral immunization. The immune levels started to increase at 2 weeks after immunization and increased to levels statistically significantly different than controls at 4 weeks post-immunization, peaking at 6 weeks and declined at 8 weeks. The humoral, mucosal, and cellular immune responses induced by SL7207 (pAXD-PS1-TS) were significantly higher than those of the PBS and SL7207 (pVAXD) (p < 0.01). In particular, the levels of IFN-γ and IL-4 were higher than those induced by the single-gene vaccine SL7207 (pVAXD-PS1) (p < 0.05). These results demonstrated that SL7207 (pVAXD-PS1-TS) possess the immunological functions of the two S proteins of TGEV and PEDV, indicating that SL7207 (pVAXD-PS1-TS) is a candidate oral vaccine for TGE and PED.

  12. Differential Host Immune Responses after Infection with Wild-Type or Lab-Attenuated Rabies Viruses in Dogs

    Science.gov (United States)

    Huang, Ying; Li, Zhenguang; Leyson, Christina M.; Cooper, Tanya L.; Platt, Simon R.; Harvey, Stephen B.; Hooper, Douglas C.; Faber, Milosz; Fu, Zhen F.

    2015-01-01

    Rabies virus (RABV) induces encephalomyelitis in humans and animals. One of the major problems with rabies is that the infected individuals most often do not develop virus neutralizing antibodies (VNA). In this study we have investigated the host immune response to RABV infection in dogs, using a live-attenuated (TriGAS) or a wild-type (wt) (DRV-NG11) RABV isolated from a rabid dog. Methodology/Principal Findings The experimental infection of dogs with TriGAS induced high levels of VNA in the serum, whereas wt RABV infection did not. Dogs infected with TriGAS developed antibodies against the virus including its glycoprotein, whereas dogs infected with DRV-NG11 only developed rabies antibodies that are presumably specific for the nucleoprotein, (N) and not the glycoprotein (G). We show that infection with TriGAS induces early activation of B cells in the draining lymph nodes and persistent activation of DCs and B cells in the blood. On the other hand, infection with DRV-NG11 fails to induce the activation of DCs and B cells and further reduces CD4 T cell production. Further, we show that intrathecal (IT) immunization of TriGAS not only induced high levels of VNA in the serum but also in the CSF while intramuscular (IM) immunization of TriGAS induced VNA only in the serum. In addition, high levels of total protein and WBC were detected in the CSF of IT immunized dogs, indicating the transient enhancement of blood-brain barrier (BBB) permeability, which is relevant to the passage of immune effectors from periphery into the CNS. Conclusions/Significance IM infection of dogs with TriGAS induced the production of serum VNA whereas, IT immunization of TriGAS in dogs induces high levels of VNA in the periphery as well as in the CSF and transiently enhances BBB permeability. In contrast, infection with wt DRV-NG11 resulted in the production of RABV-reactive antibodies but VNA and antibodies specific for G were absent. As a consequence, all of the dogs infected with wt DRV

  13. Partial Attenuation of Respiratory Syncytial Virus with a Deletion of a Small Hydrophobic Gene Is Associated with Elevated Interleukin-1β Responses.

    Science.gov (United States)

    Russell, Ryan F; McDonald, Jacqueline U; Ivanova, Maria; Zhong, Ziyun; Bukreyev, Alexander; Tregoning, John S

    2015-09-01

    The small hydrophobic (SH) gene of respiratory syncytial virus (RSV), a major cause of infant hospitalization, encodes a viroporin of unknown function. SH gene knockout virus (RSV ΔSH) is partially attenuated in vivo, but not in vitro, suggesting that the SH protein may have an immunomodulatory role. RSV ΔSH has been tested as a live attenuated vaccine in humans and cattle, and here we demonstrate that it protected against viral rechallenge in mice. We compared the immune response to infection with RSV wild type and RSV ΔSH in vivo using BALB/c mice and in vitro using epithelial cells, neutrophils, and macrophages. Strikingly, the interleukin-1β (IL-1β) response to RSV ΔSH infection was greater than to wild-type RSV, in spite of a decreased viral load, and when IL-1β was blocked in vivo, the viral load returned to wild-type levels. A significantly greater IL-1β response to RSV ΔSH was also detected in vitro, with higher-magnitude responses in neutrophils and macrophages than in epithelial cells. Depleting macrophages (with clodronate liposome) and neutrophils (with anti-Ly6G/1A8) demonstrated the contribution of these cells to the IL-1β response in vivo, the first demonstration of neutrophilic IL-1β production in response to viral lung infection. In this study, we describe an increased IL-1β response to RSV ΔSH, which may explain the attenuation in vivo and supports targeting the SH gene in live attenuated vaccines. There is a pressing need for a vaccine for respiratory syncytial virus (RSV). A number of live attenuated RSV vaccine strains have been developed in which the small hydrophobic (SH) gene has been deleted, even though the function of the SH protein is unknown. The structure of the SH protein has recently been solved, showing it is a pore-forming protein (viroporin). Here, we demonstrate that the IL-1β response to RSV ΔSH is greater in spite of a lower viral load, which contributes to the attenuation in vivo. This potentially suggests a

  14. MAVS Is Essential for Primary CD4+ T Cell Immunity but Not for Recall T Cell Responses following an Attenuated West Nile Virus Infection.

    Science.gov (United States)

    Luo, Huanle; Winkelmann, Evandro; Xie, Guorui; Fang, Rong; Peng, Bi-Hung; Li, Li; Lazear, Helen M; Paessler, Slobodan; Diamond, Michael S; Gale, Michael; Barrett, Alan D; Wang, Tian

    2017-03-15

    focus in individual vaccine development. Here, we determined the role of mitochondrial antiviral-signaling protein (MAVS), the adaptor protein for RIG-I like receptor in regulating host immunity against the live attenuated West Nile virus (WNV) vaccine strain, the nonstructural (NS) 4B-P38G mutant. We found that MAVS is important for boosting optimal primary CD4+ T cell response during NS4B-P38G vaccination. However, MAVS is dispensable for memory T cell development and host protection during secondary wild-type WNV infection. Overall, these results may be utilized as a paradigm to aid in the rational development of other efficacious live attenuated flavivirus vaccines. Copyright © 2017 American Society for Microbiology.

  15. miR-124 attenuates Japanese encephalitis virus replication by targeting DNM2.

    Science.gov (United States)

    Yang, Songbai; Pei, Yue; Li, Xinyun; Zhao, Shuhong; Zhu, Mengjin; Zhao, Ayong

    2016-06-21

    Japanese encephalitis virus (JEV) is a mosquito-borne flavivirus that causes acute viral encephalitis in humans. Pigs are important amplifier hosts of JEV. Emerging evidence indicates that host microRNAs (miRNAs) play key roles in modulating viral infection and pathogenesis. However, mechanistic studies delineating the roles of miRNAs in regulating host-JEV interactions remain scarce. In this study, we demonstrated that miR-124 inhibited JEV replication in porcine kidney epithelial PK15 cells. Furthermore, using bioinformatics tools, we identified dynamin2 (DNM2), a GTPase responsible for vesicle scission, as a target of miR-124. Small interfering RNA (siRNA) depletion studies inicated that dynamin2 was required for efficient JEV replication. We also demonstrated that upregulation of miR-124 expression corresponded to decreased expression of its target, DNM2, in the JEV-infected PK15 cells. Overall, these results suggest the importance of miR-124 in modulating JEV replication and provide a scientific basis for using cellular miRNAs in anti-JEV therapies.

  16. Dengue type 4 live-attenuated vaccine viruses passaged in vero cells affect genetic stability and dengue-induced hemorrhaging in mice.

    Science.gov (United States)

    Lee, Hsiang-Chi; Yen, Yu-Ting; Chen, Wen-Yu; Wu-Hsieh, Betty A; Wu, Suh-Chin

    2011-01-01

    Most live-attenuated tetravalent dengue virus vaccines in current clinical trials are produced from Vero cells. In a previous study we demonstrated that an infectious cDNA clone-derived dengue type 4 (DEN-4) virus retains higher genetic stability in MRC-5 cells than in Vero cells. For this study we investigated two DEN-4 viruses: the infectious cDNA clone-derived DEN-4 2A and its derived 3' NCR 30-nucleotide deletion mutant DEN-4 2AΔ30, a vaccine candidate. Mutations in the C-prM-E, NS2B-NS3, and NS4B-NS5 regions of the DEN genome were sequenced and compared following cell passages in Vero and MRC-5 cells. Our results indicate stronger genetic stability in both viruses following MRC-5 cell passages, leading to significantly lower RNA polymerase error rates when the DEN-4 virus is used for genome replication. Although no significant increases in virus titers were observed following cell passages, DEN-4 2A and DEN-4 2AΔ30 virus titers following Vero cell passages were 17-fold to 25-fold higher than titers following MRC-5 cell passages. Neurovirulence for DEN-4 2A and DEN-4 2AΔ30 viruses increased significantly following passages in Vero cells compared to passages in MRC-5 cells. In addition, more severe DEN-induced hemorrhaging in mice was noted following DEN-4 2A and DEN-4 2AΔ30 passages in Vero cells compared to passages in MRC-5 cells. Target mutagenesis performed on the DEN-4 2A infectious clone indicated that single point mutation of E-Q(438)H, E-V(463)L, NS2B-Q(78)H, and NS2B-A(113)T imperatively increased mouse hemorrhaging severity. The relationship between amino acid mutations acquired during Vero cell passage and enhanced DEN-induced hemorrhages in mice may be important for understanding DHF pathogenesis, as well as for the development of live-attenuated dengue vaccines. Taken together, the genetic stability, virus yield, and DEN-induced hemorrhaging all require further investigation in the context of live-attenuated DEN vaccine development.

  17. 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.

  18. Chronic Δ9-Tetrahydrocannabinol Administration May Not Attenuate Simian Immunodeficiency Virus Disease Progression in Female Rhesus Macaques

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    Amedee, Angela M.; Nichols, Whitney A.; LeCapitaine, Nicole J.; Stouwe, Curtis Vande; Birke, Leslie L.; Lacour, Nedra; Winsauer, Peter J.

    2014-01-01

    Abstract Persons living with HIV/AIDS (PLWHA) frequently use cannabinoids, either recreationally by smoking marijuana or therapeutically (delta-9-tetrahydrocannabinol; Δ9-THC dronabinol). Previously, we demonstrated that chronic Δ9-THC administration decreases early mortality in male simian immunodeficiency virus (SIV)-infected macaques. In this study, we sought to examine whether similar protective effects resulted from chronic cannabinoid administration in SIV-infected female rhesus macaques. Clinical and viral parameters were evaluated in eight female rhesus macaques that received either Δ9-THC (0.18–0.32 mg/kg, intramuscularly, twice daily) or vehicle (VEH) starting 28 days prior to intravenous inoculation with SIVmac251. SIV disease progression was assessed by changes in body weight, mortality, viral levels in plasma and mucosal sites, and lymphocyte subsets. In contrast to our results in male animals, chronic Δ9-THC did not protect SIV-infected female rhesus macaques from early mortality. Markers of SIV disease, including viral load and CD4+/CD8+ ratio, were not altered by Δ9-THC compared to control females; however, females that received chronic Δ9-THC did not gain as much weight as control animals. In addition, Δ9-THC administration increased total CXCR4 expression in both peripheral and duodenal CD4+ and CD8+ T lymphocytes prior to SIV inoculation. Although protection from early mortality was not evident, chronic Δ9-THC did not affect clinical markers of SIV disease progression. The contrasting effects of chronic Δ9-THC in males versus females remain to be explained, but highlight the need for further studies to explore the sex-dependent effects of Δ9-THC and other cannabinoids on the HIV disease course and their implications for virus transmission. PMID:25113915

  19. Gastroenteritis: First Aid

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    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 ...

  20. 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 ...

  1. A significant productive in vivo infection of resting cells with simian immunodeficiency virus in a macaque with AIDS.

    Science.gov (United States)

    Pahar, Bapi; Lala, Wendy; Kuebler, Dot; Liu, David

    2017-04-01

    Identifying the cells that can be infected with HIV in vivo and thus potentially persist as latent reservoirs is of high priority. Here, we report the major infected cells in a chronically simian immunodeficiency virus (SIV)-infected macaque that developed AIDS and encephalitis. A majority of the infected cells were detected as non-proliferating resting cells. SIV-infected non-proliferating resting cells were found to be playing an important role in viral pathogenesis, persistence, or reservoir formation. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  2. Live-attenuated auxotrophic mutant of Salmonella Typhimurium expressing immunogenic HA1 protein enhances immunity and protective efficacy against H1N1 influenza virus infection.

    Science.gov (United States)

    Kamble, Nitin Machindra; Hyoung, Kim Je; Lee, John Hwa

    2017-07-01

    To evaluate the efficacy of attenuated Salmonella Typhimurium (JOL912) as a live bacterial vaccine vector. The JOL912 engineered to deliver HA1 protein from influenza A/Puerto Rico/8/1934 (H1N1; PR8) virus was coined as JOL1635 and further evaluated for immunogenicity and protective efficacy. The JOL1635 stably harbored the HA1 gene within pMMP65 plasmid with periplasmic expression and effective delivery of HA1 protein to RAW264.7 cells. The JOL1635 immunized chickens showed the significant increase in HA1-specific IgG, sIgA antibody, IFN-γ, IL-6 cytokine and cellular immune responses. The postoral challenge, the JOL1635-immunized chickens showed a faster clearance of PR8 virus cloacal shedding than the control group. Generated JOL1635 can establish specific immunogenicity and protection against the PR8 virus in chickens.

  3. Epstein-Barr virus BPLF1 deubiquitinates PCNA and attenuates polymerase η recruitment to DNA damage sites.

    Science.gov (United States)

    Whitehurst, Christopher B; Vaziri, Cyrus; Shackelford, Julia; Pagano, Joseph S

    2012-08-01

    PCNA is monoubiquitinated in response to DNA damage and fork stalling and then initiates recruitment of specialized polymerases in the DNA damage tolerance pathway, translesion synthesis (TLS). Since PCNA is reported to associate with Epstein-Barr virus (EBV) DNA during its replication, we investigated whether the EBV deubiquitinating (DUB) enzyme encoded by BPLF1 targets ubiquitinated PCNA and disrupts TLS. An N-terminal BPLF1 fragment (a BPLF1 construct containing the first 246 amino acids [BPLF1 1-246]) associated with PCNA and attenuated its ubiquitination in response to fork-stalling agents UV and hydroxyurea in cultured cells. Moreover, monoubiquitinated PCNA was deubiquitinated after incubation with purified BPLF1 1-246 in vitro. BPLF1 1-246 dysregulated TLS by reducing recruitment of the specialized repair polymerase polymerase η (Polη) to the detergent-resistant chromatin compartment and virtually abolished localization of Polη to nuclear repair foci, both hallmarks of TLS. Expression of BPLF1 1-246 decreased viability of UV-treated cells and led to cell death, presumably through deubiquitination of PCNA and the inability to repair damaged DNA. Importantly, deubiquitination of PCNA could be detected endogenously in EBV-infected cells in comparison with samples expressing short hairpin RNA (shRNA) against BPLF1. Further, the specificity of the interaction between BPLF1 and PCNA was dependent upon a PCNA-interacting peptide (PIP) domain within the N-terminal region of BPLF1. Both DUB activity and PIP sequence are conserved in the members of the family Herpesviridae. Thus, deubiquitination of PCNA, normally deubiquitinated by cellular USP1, by the viral DUB can disrupt repair of DNA damage by compromising recruitment of TLS polymerase to stalled replication forks. PCNA is the first cellular target identified for BPLF1 and its deubiquitinating activity.

  4. Varicella-Zoster Virus-Specific Cellular Immune Responses to the Live Attenuated Zoster Vaccine in Young and Older Adults.

    Science.gov (United States)

    Weinberg, Adriana; Canniff, Jennifer; Rouphael, Nadine; Mehta, Aneesh; Mulligan, Mark; Whitaker, Jennifer A; Levin, Myron J

    2017-07-15

    The incidence and severity of herpes zoster (HZ) increases with age. The live attenuated zoster vaccine generates immune responses similar to HZ. We compared the immune responses to zoster vaccine in young and older to adults to increase our understanding of the immune characteristics that may contribute to the increased susceptibility to HZ in older adults. Young (25-40 y; n = 25) and older (60-80 y; n = 33) adults had similar magnitude memory responses to varicella-zoster virus (VZV) ex vivo restimulation measured by responder cell-frequency and flow cytometry, but the responses were delayed in older compared with young adults. Only young adults had an increase in dual-function VZV-specific CD4+ and CD8+ T cell effectors defined by coexpression of IFN-γ, IL-2, and CD107a after vaccination. In contrast, older adults showed marginal increases in VZV-specific CD8+CD57+ senescent T cells after vaccination, which were already higher than those of young adults before vaccination. An increase in VZV-stimulated CD4+CD69+CD57+PD1+ and CD8+CD69+CD57+PD1+ T cells from baseline to postvaccination was associated with concurrent decreased VZV-memory and CD8+ effector responses, respectively, in older adults. Blocking the PD1 pathway during ex vivo VZV restimulation increased the CD4+ and CD8+ proliferation, but not the effector cytokine production, which modestly increased with TIM-3 blockade. We conclude that high proportions of senescent and exhausted VZV-specific T cells in the older adults contribute to their poor effector responses to a VZV challenge. This may underlie their inability to contain VZV reactivation and prevent the development of HZ. Copyright © 2017 by The American Association of Immunologists, Inc.

  5. Oral Delivery of a Novel Attenuated Salmonella Vaccine Expressing Influenza A Virus Proteins Protects Mice against H5N1 and H1N1 Viral Infection.

    Directory of Open Access Journals (Sweden)

    Zenglin Pei

    Full Text Available Attenuated strains of invasive enteric bacteria, such as Salmonella, represent promising gene delivery agents for nucleic acid-based vaccines as they can be administrated orally. In this study, we constructed a novel attenuated strain of Salmonella for the delivery and expression of the hemagglutinin (HA and neuraminidase (NA of a highly pathogenic H5N1 influenza virus. We showed that the constructed Salmonella strain exhibited efficient gene transfer activity for HA and NA expression and little cytotoxicity and pathogenicity in mice. Using BALB/c mice as the model, we evaluated the immune responses and protection induced by the constructed Salmonella-based vaccine. Our study showed that the Salmonella-based vaccine induced significant production of anti-HA serum IgG and mucosal IgA, and of anti-HA interferon-γ producing T cells in orally vaccinated mice. Furthermore, mice orally vaccinated with the Salmonella vaccine expressing viral HA and NA proteins were completely protected from lethal challenge of highly pathogenic H5N1 as well as H1N1 influenza viruses while none of the animals treated with the Salmonella vaccine carrying the empty expression vector with no viral antigen expression was protected. These results suggest that the Salmonella-based vaccine elicits strong antigen-specific humoral and cellular immune responses and provides effective immune protection against multiple strains of influenza viruses. Furthermore, our study demonstrates the feasibility of developing novel attenuated Salmonella strains as new oral vaccine vectors against influenza viruses.

  6. [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 < .05 to .001) in multivariate analysis. To reduce the 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.

  7. 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.

  8. Improved immune response to an attenuated pseudorabies virus vaccine by ginseng stem-leaf saponins (GSLS) in combination with thimerosal (TS).

    Science.gov (United States)

    Ni, Jingxuan; Bi, Shicheng; Xu, Wei; Zhang, Cenrong; Lu, Yisong; Zhai, Lijuan; Hu, Songhua

    2016-08-01

    Vaccination using attenuated vaccines remains an important method to control animal infectious diseases. The present study evaluated ginseng stem-leaf saponins (GSLS) and thimerosal (TS) for their adjuvant effect on an attenuated pseudorabies virus (aPrV) vaccine in mice. Compared to the group immunized with aPrV alone, the co-inoculation of GSLS and/or TS induced a higher antibody response. Particularly, when administered together with GSLS-TS, the aPrV vaccine provoked a higher serum gB-specific antibody, IgG1 and IgG2a levels, lymphocyte proliferative responses, as well as production of cytokines (IFN-γ, IL-12, IL-5 and IL-10) from lymphocytes, and more importantly provided an enhanced cytotoxicity of NK cells and protection against virulent field pseudorabies virus challenge. Additionally, the increased expression of miR-132, miR-146a, miR-147 and miR-155 was found in murine macrophages cultured with GSLS and/or TS. These data suggest that GSLS-TS as adjuvant improve the efficacy of aPrV vaccine in mouse model and have potential for the development of attenuated viral vaccines. Copyright © 2016 Elsevier B.V. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Jones Philip H

    2012-06-01

    Full Text Available Abstract 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.

  10. Detoxification activity and energy cost is attenuated in whiteflies feeding on tomato yellow leaf curl China virus-infected tobacco plants.

    Science.gov (United States)

    Luan, J-B; Wang, Y-L; Wang, J; Wang, X-W; Liu, S-S

    2013-10-01

    The begomovirus Tomato yellow leaf curl China virus (TYLCCNV) can benefit its vector, the whitefly Bemisia tabaci, through suppressing the defences of their shared host plants. However, the mechanisms of this vector-virus mutualism remain largely unknown on the insect side of the interaction. Here, we compared the transcriptional profiles of female adult whiteflies of B. tabaci Middle East-Asia Minor 1 feeding on TYLCCNV-free and TYLCCNV-infected tobacco plants using the next-generation sequencing technique and quantitative real-time PCR. Interestingly, the genes involved in the oxidative phosphorylation (OXPHOS) pathway and detoxification enzyme were down-regulated in whiteflies feeding on virus-infected plants. Decreased detoxification activity costs less energy, which may reduce OXPHOS activity. Moreover, the genes involved in redox activity were also down-regulated, which may indicate that the reduced OXPHOS activity decreased reactive oxygen species production. Reduced detoxification activity is likely to attenuate energy costs, thereby enhancing the performance of whiteflies on virus-infected plants. These results provide further insight into the mechanisms of the plant-mediated whitefly-virus mutualism. Moreover, our study suggests that investigating the transcriptional profiles on the insect side of the interaction can advance our understanding of the tripartite interactions. © 2013 Royal Entomological Society.

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

    OpenAIRE

    Tengan, Fatima Mitiko; Ibrahim, Karim Yakub; Dantas, Bianca Peixoto; Manchiero, Caroline; Magri, Mariana Cavalheiro; Bernardo, Wanderley Marques

    2016-01-01

    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 t...

  12. Vaccination with Live Attenuated Simian Immunodeficiency Virus (SIV) Protects from Mucosal, but Not Necessarily Intravenous, Challenge with a Minimally Heterologous SIV.

    Science.gov (United States)

    Sutton, Matthew S; Burns, Charles M; Weiler, Andrea M; Balgeman, Alexis J; Braasch, Andrew; Lehrer-Brey, Gabrielle; Friedrich, Thomas C; O'Connor, Shelby L

    2016-06-15

    Few studies have evaluated the impact of the viral challenge route on protection against a heterologous simian immunodeficiency virus (SIV) challenge. We vaccinated seven macaques with a live attenuated SIV that differed from SIVmac239Δnef by 24 amino acids, called m3KOΔnef. All animals were protected from an intrarectal SIVmac239 challenge, whereas only four animals were protected from subsequent intravenous SIVmac239 challenge. These data suggest that immune responses elicited by vaccination with live attenuated SIV in an individual animal can confer protection from intrarectal challenge while remaining insufficient for protection from intravenous challenge. Our study is important because we show that vaccinated animals can be protected from a mucosal challenge with a heterologous SIV, but the same animals are not necessarily protected from intravenous challenge with the same virus. This is unique because in most studies, either vaccinated animals are challenged multiple times by the same route or only a single challenge is performed. An individually vaccinated animal is rarely challenged multiple times by different routes, so protection from different challenge routes cannot be measured in the same animal. Our data imply that vaccine-elicited responses in an individual animal may be insufficient for protection from intravenous challenge but may be suitable for protection from a mucosal challenge that better approximates human immunodeficiency virus (HIV) exposure. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  13. 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.

  14. A Recombinant Respiratory Syncytial Virus Vaccine Candidate Attenuated by a Low-Fusion F Protein Is Immunogenic and Protective against Challenge in Cotton Rats.

    Science.gov (United States)

    Rostad, Christina A; Stobart, Christopher C; Gilbert, Brian E; Pickles, Ray J; Hotard, Anne L; Meng, Jia; Blanco, Jorge C G; Moin, Syed M; Graham, Barney S; Piedra, Pedro A; Moore, Martin L

    2016-08-15

    Although respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infections in infants, a safe and effective vaccine is not yet available. Live-attenuated vaccines (LAVs) are the most advanced vaccine candidates in RSV-naive infants. However, designing an LAV with appropriate attenuation yet sufficient immunogenicity has proven challenging. In this study, we implemented reverse genetics to address these obstacles with a multifaceted LAV design that combined the codon deoptimization of genes for nonstructural proteins NS1 and NS2 (dNS), deletion of the small hydrophobic protein (ΔSH) gene, and replacement of the wild-type fusion (F) protein gene with a low-fusion RSV subgroup B F consensus sequence of the Buenos Aires clade (BAF). This vaccine candidate, RSV-A2-dNS-ΔSH-BAF (DB1), was attenuated in two models of primary human airway epithelial cells and in the upper and lower airways of cotton rats. DB1 was also highly immunogenic in cotton rats and elicited broadly neutralizing antibodies against a diverse panel of recombinant RSV strains. When vaccinated cotton rats were challenged with wild-type RSV A, DB1 reduced viral titers in the upper and lower airways by 3.8 log10 total PFU and 2.7 log10 PFU/g of tissue, respectively, compared to those in unvaccinated animals (P < 0.0001). DB1 was thus attenuated, highly immunogenic, and protective against RSV challenge in cotton rats. DB1 is the first RSV LAV to incorporate a low-fusion F protein as a strategy to attenuate viral replication and preserve immunogenicity. RSV is a leading cause of infant hospitalizations and deaths. The development of an effective vaccine for this high-risk population is therefore a public health priority. Although live-attenuated vaccines have been safely administered to RSV-naive infants, strategies to balance vaccine attenuation with immunogenicity have been elusive. In this study, we introduced a novel strategy to attenuate a recombinant RSV vaccine by

  15. 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

  16. Human immunodeficiency virus infection and AIDS in east Africa: challenges and possibilities for prevention and control.

    Science.gov (United States)

    Mhalu, F S; Lyamuya, E

    1996-01-01

    Human immunodeficiency infection and AIDS are a major recent microbial infection in east Africa with serious health and socioeconomic impacts in the region. At present HIV infection and AIDS account for more than 50% of adult medical admissions into some of the national and provincial hospitals as well as for 10-15% of paediatric admissions. AIDS is also at present the commonest cause of death among those aged 15-45 years. Tuberculosis, a closely associated disease to HIV infection, has increased more than three fold in some countries in the region. The prevalence of HIV infection currently ranges from 10-30% among adults in urban areas and from less than 1% to 25% in adults in rural areas; since this prevalence is still rising, the full impact of the AIDS problem in east Africa is yet to be realised. This is different from the situation in many developed countries where AIDS is no longer a priority health issue and where peak prevalences of the infection have been reached. The differences in HIV prevalences between east Africa and developed countries are due to poverty, ignorance, high prevalence of other STDs and associated cultural and traditional practices which prevail and facilitate HIV transmission in the region. While more than 80% of HIV infection in east Africa is transmitted through heterosexual intercourse, 5-15% of cases are perinatally transmitted and the remaining cases are transmitted through blood and blood products. While a lot of scientific advances have been made in immunopathology of AIDS, diagnostics and in social behavioural studies, we are still a long way towards getting curative therapy and or effective preventive vaccines. Recent discovery that use of zidovudine can significantly reduce perinatal HIV transmission is an additional breakthrough. While knowledge and tools for preventing HIV transmission are available in the world, prospects for AIDS control in east Africa appear gloomy unless major efforts are made in the reduction of

  17. 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

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

    Science.gov (United States)

    Feng, Ming-Chu; Feng, Jui-Ying; Yu, Chien-Tai; Chen, Li-Hua; Yang, Pei-Hsuan; Shih, Chung-Ching; Lu, Po-Liang

    2015-09-01

    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. Copyright © 2015. Published by Elsevier Taiwan.

  19. Envelope Protein Mutations L107F and E138K Are Important for Neurovirulence Attenuation for Japanese Encephalitis Virus SA14-14-2 Strain.

    Science.gov (United States)

    Yang, Jian; Yang, Huiqiang; Li, Zhushi; Wang, Wei; Lin, Hua; Liu, Lina; Ni, Qianzhi; Liu, Xinyu; Zeng, Xianwu; Wu, Yonglin; Li, Yuhua

    2017-01-21

    The attenuated Japanese encephalitis virus (JEV) strain SA14-14-2 has been successfully utilized to prevent JEV infection; however, the attenuation determinants have not been fully elucidated. The envelope (E) protein of the attenuated JEV SA14-14-2 strain differs from that of the virulent parental SA14 strain at eight amino acid positions (E107, E138, E176, E177, E264, E279, E315, and E439). Here, we investigated the SA14-14-2-attenuation determinants by mutating E107, E138, E176, E177, and E279 in SA14-14-2 to their status in the parental virulent strain and tested the replication capacity, neurovirulence, neuroinvasiveness, and mortality associated with the mutated viruses in mice, as compared with those of JEV SA14-14-2 and SA14. Our findings indicated that revertant mutations at the E138 or E107 position significantly increased SA14-14-2 virulence, whereas other revertant mutations exhibited significant increases in neurovirulence only when combined with E138, E107, and other mutations. Revertant mutations at all eight positions in the E protein resulted in the highest degree of SA14-14-2 virulence, although this was still lower than that observed in SA14. These results demonstrated the critical role of the viral E protein in controlling JEV virulence and identified the amino acids at the E107 and E138 positions as the key determinants of SA14-14-2 neurovirulence.

  20. Transmission of simian immunodeficiency virus carrying multiple cytotoxic T-lymphocyte escape mutations with diminished replicative ability can result in AIDS progression in rhesus macaques.

    Science.gov (United States)

    Seki, Sayuri; Kawada, Miki; Takeda, Akiko; Igarashi, Hiroko; Sata, Tetsutaro; Matano, Tetsuro

    2008-05-01

    Cytotoxic T-lymphocyte (CTL) responses frequently select for immunodeficiency virus mutations that result in escape from CTL recognition with viral fitness costs. The replication in vivo of such viruses carrying not single but multiple escape mutations in the absence of the CTL pressure has remained undetermined. Here, we have examined the replication of simian immunodeficiency virus (SIV) with five gag mutations selected in a macaque possessing the major histocompatibility complex haplotype 90-120-Ia after its transmission into 90-120-Ia-negative macaques. Our results showed that even such a "crippled" SIV infection can result in persistent viral replication, multiple reversions, and AIDS progression.

  1. Evaluation of the Efficacy, Potential for Vector Transmission, and Duration of Immunity of MP-12, an Attenuated Rift Valley Fever Virus Vaccine Candidate, in Sheep

    Science.gov (United States)

    2015-08-01

    pathogen by the National Institute for Allergy and Infectious Diseases and is dual listed as a U.S. Department of Agriculture (USDA) select agent due to...12 serial passages of the wild-type ZH548 strain of RVFV in the presence of a chemical mutagen (22) and selected based on attenuation of virulence in...1743-422X-8-532. 22. Caplen H, Peters CJ, Bishop DH. 1985. Mutagen -directed attenua- tion of Rift Valley fever virus as a method for vaccine

  2. A Phase II, Randomized, Safety and Immunogenicity Trial of a Re-Derived, Live-Attenuated Dengue Virus Vaccine in Healthy Children and Adults Living in Puerto Rico.

    Science.gov (United States)

    Bauer, Kristen; Esquilin, Ines O; Cornier, Alberto Santiago; Thomas, Stephen J; Quintero Del Rio, Ana I; Bertran-Pasarell, Jorge; Morales Ramirez, Javier O; Diaz, Clemente; Carlo, Simon; Eckels, Kenneth H; Tournay, Elodie; Toussaint, Jean-Francois; De La Barrera, Rafael; Fernandez, Stefan; Lyons, Arthur; Sun, Wellington; Innis, Bruce L

    2015-09-01

    This was a double-blind, randomized, controlled, phase II clinical trial, two dose study of re-derived, live-attenuated, tetravalent dengue virus (TDEN) vaccine (two formulations) or placebo in subjects 1-50 years of age. Among the 636 subjects enrolled, 331 (52%) were primed, that is, baseline seropositive to at least one dengue virus (DENV) type. Baseline seropositivity prevalence increased with age (10% [vaccines were similar to placebo regardless of priming status. No vaccine-related serious adverse events (SAEs) were reported. Among unprimed subjects, immunogenicity (geometric mean antibody titers [GMT] and seropositivity rates) for each DENV increased substantially in both TDEN vaccine groups with at least 74.6% seropositive for four DENV types. The TDEN vaccine candidate showed an acceptable safety and immunogenicity profile in children and adults ranging from 1 to 50 years of age, regardless of priming status. ClinicalTrials.gov: NCT00468858. © The American Society of Tropical Medicine and Hygiene.

  3. VP2-serotyped live-attenuated bluetongue virus without NS3/NS3a expression provides serotype-specific protection and enables DIVA.

    Science.gov (United States)

    Feenstra, Femke; Maris-Veldhuis, Mieke; Daus, Franz J; Tacken, Mirriam G J; Moormann, Rob J M; van Gennip, René G P; van Rijn, Piet A

    2014-12-12

    Bluetongue virus (BTV) causes Bluetongue in ruminants and is transmitted by Culicoides biting midges. Vaccination is the most effective measure to control vector borne diseases; however, there are 26 known BTV serotypes showing little cross protection. The BTV serotype is mainly determined by genome segment 2 encoding the VP2 protein. Currently, inactivated and live-attenuated Bluetongue vaccines are available for a limited number of serotypes, but each of these have their specific disadvantages, including the inability to differentiate infected from vaccinated animals (DIVA). BTV non-structural proteins NS3 and NS3a are not essential for virus replication in vitro, but are important for cytopathogenic effect in mammalian cells and for virus release from insect cells in vitro. Recently, we have shown that virulent BTV8 without NS3/NS3a is non-virulent and viremia in sheep is strongly reduced, whereas local in vivo replication leads to seroconversion. Live-attenuated BTV6 without NS3/NS3a expression protected sheep against BTV challenge. Altogether, NS3/NS3a knockout BTV6 is a promising vaccine candidate and has been named Disabled Infectious Single Animal (DISA) vaccine. Here, we show serotype-specific protection in sheep by DISA vaccine in which only genome segment 2 of serotype 8 was exchanged. Similarly, DISA vaccines against other serotypes could be developed, by exchange of only segment 2, and could therefore safely be combined in multi-serotype cocktail vaccines with respect to reassortment between vaccine viruses. Additionally, NS3 antibody responses are raised after natural BTV infection and NS3-based ELISAs are therefore appropriate tools for DIVA testing accompanying the DISA vaccine. To enable DIVA, we developed an experimental NS3 ELISA. Indeed, vaccinated sheep remained negative for NS3 antibodies, whereas seroconversion for NS3 antibodies was associated with viremia after heterologous BTV challenge. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. Selection of attenuated dengue 4 viruses by serial passage in primary kidney cells. V. Human response to immunization with a candidate vaccine prepared in fetal rhesus lung cells.

    Science.gov (United States)

    Eckels, K H; Scott, R M; Bancroft, W H; Brown, J; Dubois, D R; Summers, P L; Russell, P K; Halstead, S B

    1984-07-01

    A dengue 4 (strain H241, PDK35-TD3 FRhL p3) vaccine attenuated by passage in primary dog kidney cells followed by passage and final vaccine preparation in DBS-FRhL-2 cells was tested in five yellow fever-immune volunteers. Only two volunteers seroconverted by producing hemagglutination-inhibiting and neutralizing antibodies. Mild illness, compatible with dengue infection was found only in the individuals who later developed antibodies. Both volunteers developed a rash by the 8th day following vaccination, coinciding with a slight elevation in temperature and leukopenia. Additionally, several serum enzymes were elevated during the observation period. Dengue 4 virus was isolated from the blood of the two infected volunteers starting as early as day 5 post vaccination. During the viremic period, which lasted 5 days, phenotypically-changed virus was recovered, indicating genetic instability of the vaccine virus. The clinical disease and immune response in the two infected individuals was probably related to replication of the variant virus. Further testing of this vaccine in its present form is not indicated.

  5. Neutralizing Antibody Responses to Antigenically Drifted Influenza A(H3N2) Viruses among Children and Adolescents following 2014-2015 Inactivated and Live Attenuated Influenza Vaccination

    Science.gov (United States)

    Martin, Judith M.; Gross, F. Liaini; Jefferson, Stacie; Cole, Kelly Stefano; Archibald, Crystal Ann; Nowalk, Mary Patricia; Susick, Michael; Moehling, Krissy; Spencer, Sarah; Chung, Jessie R.; Flannery, Brendan; Zimmerman, Richard K.

    2016-01-01

    Human influenza A(H3N2) viruses that predominated during the moderately severe 2014-2015 influenza season differed antigenically from the vaccine component, resulting in reduced vaccine effectiveness (VE). To examine antibody responses to 2014-2015 inactivated influenza vaccine (IIV) and live-attenuated influenza vaccine (LAIV) among children and adolescents, we collected sera before and after vaccination from 150 children aged 3 to 17 years enrolled at health care facilities. Hemagglutination inhibition (HI) assays were used to assess the antibody responses to vaccine strains. We evaluated cross-reactive antibody responses against two representative A(H3N2) viruses that had antigenically drifted from the A(H3N2) vaccine component using microneutralization (MN) assays. Postvaccination antibody titers to drifted A(H3N2) viruses were higher following receipt of IIV (MN geometric mean titers [GMTs], 63 to 68; 38 to 45% achieved seroconversion) versus LAIV (MN GMT, 22; only 3 to 5% achieved seroconversion). In 9- to 17-year-olds, the highest MN titers were observed among IIV-vaccinated individuals who had received LAIV in the previous season. Among all IIV recipients aged 3 to 17 years, the strongest predictor of antibody responses to the drifted viruses was the prevaccination titers to the vaccine strain. The results of our study suggest that in an antigenically drifted influenza season, vaccination still induced cross-reactive antibody responses to drifted circulating A(H3N2) viruses, although higher antibody titers may be required for protection. Antibody responses to drifted A(H3N2) viruses following vaccination were influenced by multiple factors, including vaccine type and preexisting immunity from prior exposure. PMID:27558294

  6. The preferred nucleotide contexts of the AID/APOBEC cytidine deaminases have differential effects when mutating retrotransposon and virus sequences compared to host genes.

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    Jeffrey Chen

    2017-03-01

    Full Text Available The AID / APOBEC genes are a family of cytidine deaminases that have evolved in vertebrates, and particularly mammals, to mutate RNA and DNA at distinct preferred nucleotide contexts (or "hotspots" on foreign genomes such as viruses and retrotransposons. These enzymes play a pivotal role in intrinsic immunity defense mechanisms, often deleteriously mutating invading retroviruses or retrotransposons and, in the case of AID, changing antibody sequences to drive affinity maturation. We investigate the strength of various hotspots on their known biological targets by evaluating the potential impact of mutations on the DNA coding sequences of these targets, and compare these results to hypothetical hotspots that did not evolve. We find that the existing AID / APOBEC hotspots have a large impact on retrotransposons and non-mammalian viruses while having a much smaller effect on vital mammalian genes, suggesting co-evolution with AID / APOBECs may have had an impact on the genomes of the viruses we analyzed. We determine that GC content appears to be a significant, but not sole, factor in resistance to deaminase activity. We discuss possible mechanisms AID and APOBEC viral targets have adopted to escape the impacts of deamination activity, including changing the GC content of the genome.

  7. Addiction and sexually transmitted disease (STD), human immunodeficiency virus, (HIV), and acquired immune deficiency syndrome (AIDS): their mutual interactions.

    Science.gov (United States)

    Adrian, Manuella

    2006-01-01

    We explore the links between substance use, misuse, addiction, and dependency1 and sexuality, sexually transmitted diseases (STD), human immunodeficiency virus (HIV), and acquired immune deficiency syndrome (AIDS) to increase our awareness of their interdependence and to identify new ways to perceive, judge, and intervene (or not to) with associated problems. We consider the sociocultural and economic context in which these behaviors occur; the impact these behaviors have on one another; the personal opinions and attitudes; the religious, moral, or political beliefs and agendas; the physiological and fiscal constraints; and theories of rational decision-making and psychological motivation that act to increase or reduce the incidence of these behaviors and their sequellae, while hindering or facilitating prevention, harm reduction, and treatment interventions. Mechanisms of epidemic spread of STDS/HIV/AIDS are presented in the Appendix. Each of these terms are loaded "container concepts" that are culture-bound and stakeholder-driven and whose dimensions are less than consensus-based. They represent a range of meanings, uses, and misuses in an ongoing politicalized area of human and systemic functioning and adaptations.

  8. Rapid spread of tomato yellow leaf curl virus in China is aided differentially by two invasive whiteflies.

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    Huipeng Pan

    Full Text Available BACKGROUND: Tomato yellow leaf curl virus (TYLCV was introduced into China in 2006, approximately 10 years after the introduction of an invasive whitefly, Bemisia tabaci (Genn. B biotype. Even so the distribution and prevalence of TYLCV remained limited, and the economic damage was minimal. Following the introduction of Q biotype into China in 2003, the prevalence and spread of TYLCV started to accelerate. This has lead to the hypothesis that the two biotypes might not be equally competent vectors of TYLCV. METHODOLOGY/PRINCIPAL FINDINGS: The infection frequency of TYLCV in the field-collected B. tabaci populations was investigated, the acquisition and transmission capability of TYLCV by B and Q biotypes were compared under the laboratory conditions. Analysis of B. tabaci populations from 55 field sites revealed the existence of 12 B and 43 Q biotypes across 18 provinces in China. The acquisition and transmission experiments showed that both B and Q biotypes can acquire and transmit the virus, however, Q biotype demonstrated superior acquisition and transmission capability than its B counterparts. Specifically, Q biotype acquired significantly more viral DNA than the B biotype, and reached the maximum viral load in a substantially shorter period of time. Although TYLCV was shown to be transmitted horizontally by both biotypes, Q biotype exhibited significantly higher viral transmission frequency than B biotype. Vertical transmission result, on the other hand, indicated that TYLCV DNA can be detected in eggs and nymphs, but not in pupae and adults of the first generation progeny. CONCLUSIONS/SIGNIFICANCE: These combined results suggested that the epidemiology of TYLCV was aided differentially by the two invasive whiteflies (B and Q biotypes through horizontal but not vertical transmission of the virus. This is consistent with the concomitant eruption of TYLCV in tomato fields following the recent rapid invasion of Q biotype whitefly in China.

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

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    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.

  10. [Consensus statement on assistance to women with human immunodeficiency virus infection in the health care sector. National AIDS Plan (PNS) and AIDS Study Group (GeSIDA)].

    Science.gov (United States)

    2014-02-01

    To develop a consensus document on clinical recommendations for the health care of women with human immunodeficiency virus (HIV) infection. We assembled a panel of experts appointed by the Secretariat of the National AIDS Plan and GeSIDA that included internal medicine physicians with expertise in the field of HIV infection, gynecologists, pediatricians and psychologists, and two panel members acting as coordinators. Scientific information was reviewed in publications and conference reports up to October 2012. In keeping with the criteria of the Infectious Disease Society of America, two levels of evidence were applied to support the proposed recommendations: the strength of the recommendation according to expert opinion (A, B, C), and the level of empirical evidence (i, ii, iii), already used in previous documents from SPNS/GeSIDA. We provide multiple recommendations for the clinical management of women with HIV infection, considering both the diagnostic and possible therapeutic strategies. The consensus recommends gender mainstreaming in health care, and promoting training for healthcare professionals in order to avoid gender bias. With currently available data it seems that the effectiveness of the treatment is the same in both men and women, there being no limitation as to the use of any antiretroviral for this reason. Women have more treatments suspended for reasons other than virological failure, thus they require better monitoring. This document presents recommendations for addressing women with HIV infection. This must be multidisciplinary, taking into account the differences that can be found in the diagnosis, disease development, and treatment between men and women. Copyright © 2012 Elsevier España, S.L. All rights reserved.

  11. Immunogenicity of viral vector, prime-boost SIV vaccine regimens in infant rhesus macaques: attenuated vesicular stomatitis virus (VSV) and modified vaccinia Ankara (MVA) recombinant SIV vaccines compared to live-attenuated SIV.

    Science.gov (United States)

    Van Rompay, Koen K A; Abel, Kristina; Earl, Patricia; Kozlowski, Pamela A; Easlick, Juliet; Moore, Joseph; Buonocore-Buzzelli, Linda; Schmidt, Kimberli A; Wilson, Robert L; Simon, Ian; Moss, Bernard; Rose, Nina; Rose, John; Marthas, Marta L

    2010-02-10

    In a previously developed infant macaque model mimicking HIV infection by breast-feeding, we demonstrated that intramuscular immunization with recombinant poxvirus vaccines expressing simian immunodeficiency virus (SIV) structural proteins provided partial protection against infection following oral inoculation with virulent SIV. In an attempt to further increase systemic but also local antiviral immune responses at the site of viral entry, we tested the immunogenicity of different orally administered, replicating vaccines. One group of newborn macaques received an oral prime immunization with a recombinant vesicular stomatitis virus expressing SIVmac239 gag, pol and env (VSV-SIVgpe), followed 2 weeks later by an intramuscular boost immunization with MVA-SIV. Another group received two immunizations with live-attenuated SIVmac1A11, administered each time both orally and intravenously. Control animals received mock immunizations or non-SIV VSV and MVA control vectors. Analysis of SIV-specific immune responses in blood and lymphoid tissues at 4 weeks of age demonstrated that both vaccine regimens induced systemic antibody responses and both systemic and local cell-mediated immune responses. The safety and immunogenicity of the VSV-SIVgpe+MVA-SIV immunization regimen described in this report provide the scientific incentive to explore the efficacy of this vaccine regimen against virulent SIV exposure in the infant macaque model. Copyright (c) 2009 Elsevier Ltd. All rights reserved.

  12. Balancing Trained Immunity with Persistent Immune Activation and the Risk of Simian Immunodeficiency Virus Infection in Infant Macaques Vaccinated with Attenuated Mycobacterium tuberculosis or Mycobacterium bovis BCG Vaccine

    Science.gov (United States)

    Jensen, Kara; dela Pena-Ponce, Myra Grace; Piatak, Michael; Shoemaker, Rebecca; Oswald, Kelli; Jacobs, William R.; Fennelly, Glenn; Lucero, Carissa; Mollan, Katie R.; Hudgens, Michael G.; Amedee, Angela; Kozlowski, Pamela A.; Estes, Jacob D.; Lifson, Jeffrey D.; Van Rompay, Koen K. A.; Larsen, Michelle

    2016-01-01

    ABSTRACT Our goal is to develop a pediatric combination vaccine to protect the vulnerable infant population against human immunodeficiency virus type 1 (HIV-1) and tuberculosis (TB) infections. The vaccine consists of an auxotroph Mycobacterium tuberculosis strain that coexpresses HIV antigens. Utilizing an infant rhesus macaque model, we have previously shown that this attenuated M. tuberculosis (AMtb)-simian immunodeficiency virus (SIV) vaccine is immunogenic, and although the vaccine did not prevent oral SIV infection, a subset of vaccinated animals was able to partially control virus replication. However, unexpectedly, vaccinated infants required fewer SIV exposures to become infected compared to naive controls. Considering that the current TB vaccine, Mycobacterium bovis bacillus Calmette-Guérin (BCG), can induce potent innate immune responses and confer pathogen-unspecific trained immunity, we hypothesized that an imbalance between enhanced myeloid cell function and immune activation might have influenced the outcome of oral SIV challenge in AMtb-SIV-vaccinated infants. To address this question, we used archived samples from unchallenged animals from our previous AMtb-SIV vaccine studies and vaccinated additional infant macaques with BCG or AMtb only. Our results show that vaccinated infants, regardless of vaccine strain or regimen, had enhanced myeloid cell responses. However, CD4+ T cells were concurrently activated, and the persistence of these activated target cells in oral and/or gastrointestinal tissues may have facilitated oral SIV infection. Immune activation was more pronounced in BCG-vaccinated infant macaques than in AMtb-vaccinated infant macaques, indicating a role for vaccine attenuation. These findings underline the importance of understanding the interplay of vaccine-induced immunity and immune activation and its effect on HIV acquisition risk and outcome in infants. PMID:27655885

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

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    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

  14. Balancing Trained Immunity with Persistent Immune Activation and the Risk of Simian Immunodeficiency Virus Infection in Infant Macaques Vaccinated with Attenuated Mycobacterium tuberculosis or Mycobacterium bovis BCG Vaccine.

    Science.gov (United States)

    Jensen, Kara; Dela Pena-Ponce, Myra Grace; Piatak, Michael; Shoemaker, Rebecca; Oswald, Kelli; Jacobs, William R; Fennelly, Glenn; Lucero, Carissa; Mollan, Katie R; Hudgens, Michael G; Amedee, Angela; Kozlowski, Pamela A; Estes, Jacob D; Lifson, Jeffrey D; Van Rompay, Koen K A; Larsen, Michelle; De Paris, Kristina

    2017-01-01

    Our goal is to develop a pediatric combination vaccine to protect the vulnerable infant population against human immunodeficiency virus type 1 (HIV-1) and tuberculosis (TB) infections. The vaccine consists of an auxotroph Mycobacterium tuberculosis strain that coexpresses HIV antigens. Utilizing an infant rhesus macaque model, we have previously shown that this attenuated M. tuberculosis (AMtb)-simian immunodeficiency virus (SIV) vaccine is immunogenic, and although the vaccine did not prevent oral SIV infection, a subset of vaccinated animals was able to partially control virus replication. However, unexpectedly, vaccinated infants required fewer SIV exposures to become infected compared to naive controls. Considering that the current TB vaccine, Mycobacterium bovis bacillus Calmette-Guérin (BCG), can induce potent innate immune responses and confer pathogen-unspecific trained immunity, we hypothesized that an imbalance between enhanced myeloid cell function and immune activation might have influenced the outcome of oral SIV challenge in AMtb-SIV-vaccinated infants. To address this question, we used archived samples from unchallenged animals from our previous AMtb-SIV vaccine studies and vaccinated additional infant macaques with BCG or AMtb only. Our results show that vaccinated infants, regardless of vaccine strain or regimen, had enhanced myeloid cell responses. However, CD4+ T cells were concurrently activated, and the persistence of these activated target cells in oral and/or gastrointestinal tissues may have facilitated oral SIV infection. Immune activation was more pronounced in BCG-vaccinated infant macaques than in AMtb-vaccinated infant macaques, indicating a role for vaccine attenuation. These findings underline the importance of understanding the interplay of vaccine-induced immunity and immune activation and its effect on HIV acquisition risk and outcome in infants. Copyright © 2017 American Society for Microbiology.

  15. Immunoglobulin G, Plasma Cells, and Lymphocytes in the Murine Vagina after Vaginal or Parenteral Immunization with Attenuated Herpes Simplex Virus Type 2

    Science.gov (United States)

    Parr, Earl L.; Parr, Margaret B.

    1998-01-01

    This investigation evaluated immunity to vaginal herpes simplex virus type 2 (HSV-2) infection after local or parenteral immunization with attenuated HSV-2. Vaginal immunization induced sterilizing immunity against challenge with a high dose of wild-type virus, whereas parenteral immunizations protected against neurologic disease but did not entirely prevent infection of the vagina. Vaginal immunization caused 86- and 31-fold increases in the numbers of immunoglobulin G (IgG) plasma cells in the vagina at 6 weeks and 10 months after immunization, whereas parenteral immunizations did not increase plasma cell numbers in the vagina. Vaginal secretion/serum titer ratios and specific antibody activities in vaginal secretions and serum indicated that IgG viral antibody was produced in the vagina and released into vaginal secretions at 6 weeks and 10 months after vaginal immunization but not after parenteral immunizations. In contrast to the case for plasma cells, the numbers of T and B lymphocytes in the vagina were similar in vaginally and parenterally immunized mice. Also, lymphocyte numbers in the vagina were markedly but similarly increased by vaginal challenge with HSV-2 in both vaginally and parenterally immunized mice. Lymphocyte recruitment to the vagina after virus challenge appeared to involve memory lymphocytes, because it was not observed in nonimmunized mice. Thus, local vaginal immunization with attenuated HSV-2 increased the number of IgG plasma cells in the vagina and increased vaginal secretion/serum titer ratios to 3.0- to 4.7-fold higher than in parenterally immunized groups but caused little if any selective homing of T and B lymphocytes to the vagina. PMID:9573285

  16. African swine fever virus Georgia isolate harboring deletions of 9GL and MGF360/505 genes is highly attenuated in swine but does not confer protection against parental virus challenge.

    Science.gov (United States)

    O'Donnell, Vivian; Holinka, Lauren G; Sanford, Brenton; Krug, Peter W; Carlson, Jolene; Pacheco, Juan M; Reese, Bo; Risatti, Guillermo R; Gladue, Douglas P; Borca, Manuel V

    2016-08-02

    African swine fever virus (ASFV) produces a contagious disease of domestic pigs that results in severe economic consequences to the swine industry. Control of the disease has been hampered by the unavailability of vaccines. We recently reported the development of two experimental vaccine strains (ASFV-G-Δ9GL and ASFV-G-ΔMGF) based on the attenuation of the highly virulent and epidemiologically relevant Georgia2007 isolate. Deletion of the 9GL gene or six genes of the MGF360/505 group produced two attenuated ASFV strains which were able to confer protection to animals when challenged with the virulent parental virus. Both viruses, although efficient in inducing protection, present concerns regarding their safety. In an attempt to solve this problem we developed a novel virus strain, ASFV-G-Δ9GL/ΔMGF, based on the deletion of all genes deleted in ASFV-G-Δ9GL and ASFV-G-ΔMGF. ASFV-G-Δ9GL/ΔMGF is the first derivative of a highly virulent ASFV field strain subjected to a double round of recombination events seeking to sequentially delete specific genes. ASFV-G-Δ9GL/ΔMGF showed a decreased ability to replicate in primary swine macrophage cultures relative to that of ASFV-G and ASFV-G-ΔMGF but similar to that of ASFV-G-Δ9GL. ASFV-G-Δ9GL/ΔMGF was attenuated when intramuscularly inoculated into swine, even at doses as high as 10(6) HAD50. Animals infected with doses ranging from 10(2) to 10(6) HAD50 did not present detectable levels of virus in blood at any time post-infection and they did not develop detectable levels of anti-ASFV antibodies. Importantly, ASFV-G-Δ9GL/ΔMGF does not induce protection against challenge with the virulent parental ASFV-G isolate. Results presented here suggest caution towards approaches involving genomic manipulations when developing rationally designed ASFV vaccine strains. Published by Elsevier B.V.

  17. A novel, live-attenuated vesicular stomatitis virus vector displaying conformationally intact, functional HIV-1 envelope trimers that elicits potent cellular and humoral responses in mice.

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    Svetlana Rabinovich

    Full Text Available Though vaccination with live-attenuated SIV provides the greatest protection from progressive disease caused by SIV challenge in rhesus macaques, attenuated HIV presents safety concerns as a vaccine; therefore, live viral vectors carrying HIV immunogens must be considered. We have designed a replication-competent vesicular stomatitis virus (VSV displaying immunogenic HIV-1 Env trimers and attenuating quantities of the native surface glycoprotein (G. The clade B Env immunogen is an Env-VSV G hybrid (EnvG in which the transmembrane and cytoplasmic tail regions are derived from G. Relocation of the G gene to the 5'terminus of the genome and insertion of EnvG into the natural G position induced a ∼1 log reduction in surface G, significant growth attenuation compared to wild-type, and incorporation of abundant EnvG. Western blot analysis indicated that ∼75% of incorporated EnvG was a mature proteolytically processed form. Flow cytometry showed that surface EnvG bound various conformationally- and trimer-specific antibodies (Abs, and in-vitro growth assays on CD4+CCR5+ cells demonstrated EnvG functionality. Neither intranasal (IN or intramuscular (IM administration in mice induced any observable pathology and all regimens tested generated potent Env-specific ELISA titers of 10(4-10(5, with an IM VSV prime/IN VSV boost regimen eliciting the highest binding and neutralizing Ab titers. Significant quantities of Env-specific CD4+ T cells were also detected, which were augmented as much as 70-fold by priming with IM electroporated plasmids encoding EnvG and IL-12. These data suggest that our novel vector can achieve balanced safety and immunogenicity and should be considered as an HIV vaccine platform.

  18. Differential gene expression in chicken primary B cells infected ex vivo with attenuated and very virulent strains of infectious bursal disease virus (IBDV).

    Science.gov (United States)

    Dulwich, Katherine L; Giotis, Efstathios S; Gray, Alice; Nair, Venugopal; Skinner, Michael A; Broadbent, Andrew J

    2017-11-20

    Infectious bursal disease virus (IBDV) belongs to the family Birnaviridae and is economically important to the poultry industry worldwide. IBDV infects B cells in the bursa of Fabricius (BF), causing immunosuppression and morbidity in young chickens. In addition to strains that cause classical Gumboro disease, the so-called 'very virulent' (vv) strain, also in circulation, causes more severe disease and increased mortality. IBDV has traditionally been controlled through the use of live attenuated vaccines, with attenuation resulting from serial passage in non-lymphoid cells. However, the factors that contribute to the vv or attenuated phenotypes are poorly understood. In order to address this, we aimed to investigate host cell-IBDV interactions using a recently described chicken primary B-cell model, where chicken B cells are harvested from the BF and cultured ex vivo in the presence of chicken CD40L. We demonstrated that these cells could support the replication of IBDV when infected ex vivo in the laboratory. Furthermore, we evaluated the gene expression profiles of B cells infected with an attenuated strain (D78) and a very virulent strain (UK661) by microarray. We found that key genes involved in B-cell activation and signalling (TNFSF13B, CD72 and GRAP) were down-regulated following infection relative to mock, which we speculate could contribute to IBDV-mediated immunosuppression. Moreover, cells responded to infection by expressing antiviral type I IFNs and IFN-stimulated genes, but the induction was far less pronounced upon infection with UK661, which we speculate could contribute to its virulence.

  19. [Transmission of AIDS virus by transfusion and blood products. Risks and preventive strategies].

    Science.gov (United States)

    Habibi, B

    1986-01-01

    This article reviews some of the epidemiologic aspects of transmission of LAV through transfusion of blood and blood products in the light of data available until late December 1985 in France, Europe and the United States. As of December 1985, blood transfusion has been considered the etiologic factor in 2.58% of the 15,172 cases of AIDS reported in the USA and in 5.6% of 1,573 cases of AIDS registered in Europe. Whole blood, cellular blood components and plasma derivatives except Albumin and immunoglobulins have been incriminated in 1.75 to 2.22 of the above percentages. Hemophiliacs under long term therapy by factor VIII and factor IX concentrates (0.83 to 3.36 of the above percentages) represent a highly exposed group when one considers the small proportion of these individuals in the general population (1/10,000 inhabitants). Three preventive measures have been officially implemented in the French transfusion network: self refrainment and deferral of prospective donors belonging to risk factor groups, systematic screening of donated blood for the presence of anti-LAV antibodies and elimination of seropositive units, heat treatment of coagulation factor concentrates to achieve viral inactivation. Information and medical follow up of LAV-contaminated donors thus identified and of their partners represent an important issue among the current public health problems.

  20. 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.

  1. A bivalent live-attenuated influenza vaccine for the control and prevention of H3N8 and H3N2 canine influenza viruses.

    Science.gov (United States)

    Rodriguez, Laura; Nogales, Aitor; Murcia, Pablo R; Parrish, Colin R; Martínez-Sobrido, Luis

    2017-08-03

    Canine influenza viruses (CIVs) cause a contagious respiratory disease in dogs. CIV subtypes include H3N8, which originated from the transfer of H3N8 equine influenza virus (EIV) to dogs; and the H3N2, which is an avian-origin virus adapted to infect dogs. Only inactivated influenza vaccines (IIVs) are currently available against the different CIV subtypes. However, the efficacy of these CIV IIVs is not optimal and improved vaccines are necessary for the efficient prevention of disease caused by CIVs in dogs. Since live-attenuated influenza vaccines (LAIVs) induce better immunogenicity and protection efficacy than IIVs, we have combined our previously described H3N8 and H3N2 CIV LAIVs to create a bivalent vaccine against both CIV subtypes. Our findings show that, in a mouse model of infection, the bivalent CIV LAIV is safe and able to induce, upon a single intranasal immunization, better protection than that induced by a bivalent CIV IIV against subsequent challenge with H3N8 or H3N2 CIVs. These protection results also correlated with the ability of the bivalent CIV LAIV to induce better humoral immune responses. This is the first description of a bivalent LAIV for the control and prevention of H3N8 and H3N2 CIV infections in dogs. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Mucosal immunization of rhesus monkeys against respiratory syncytial virus subgroups A and B and human parainfluenza virus type 3 by using a live cDNA-derived vaccine based on a host range-attenuated bovine parainfluenza virus type 3 vector backbone.

    Science.gov (United States)

    Schmidt, Alexander C; Wenzke, Daniel R; McAuliffe, Josephine M; St Claire, Marisa; Elkins, William R; Murphy, Brian R; Collins, Peter L

    2002-02-01

    Reverse genetics was used to develop a two-component, trivalent live attenuated vaccine against human parainfluenza virus type 3 (HPIV3) and respiratory syncytial virus (RSV) subgroups A and B. The backbone for each of the two components of this vaccine was the attenuated recombinant bovine/human PIV3 (rB/HPIV3), a recombinant BPIV3 in which the bovine HN and F protective antigens are replaced by their HPIV3 counterparts (48). This chimera retains the well-characterized host range attenuation phenotype of BPIV3, which appears to be appropriate for immunization of young infants. The open reading frames (ORFs) for the G and F major protective antigens of RSV subgroup A and B were each placed under the control of PIV3 transcription signals and inserted individually or in homologous pairs as supernumerary genes in the promoter proximal position of rB/HPIV3. The level of replication of rB/HPIV3-RSV chimeric viruses in the respiratory tract of rhesus monkeys was similar to that of their parent virus rB/HPIV3, and each of the chimeras induced a robust immune response to both RSV and HPIV3. RSV-neutralizing antibody titers induced by rB/HPIV3-RSV chimeric viruses were equivalent to those induced by infection with wild-type RSV, and HPIV3-specific antibody responses were similar to, or slightly less than, after infection with the rB/HPIV3 vector itself. This study describes a novel vaccine strategy against RSV in which vaccine viruses with a common attenuated backbone, specifically rB/HPIV3 derivatives expressing the G and/or F major protective antigens of RSV subgroup A and of RSV subgroup B, are used to immunize by the intranasal route against RSV and HPIV3, which are the first and second most important viral agents of pediatric respiratory tract disease worldwide.

  3. The Prevalence of Different Human Immunodeficiency Virus Transmission Routes and Knowledge about AIDS in Infected People with HIV in Sirjan

    Directory of Open Access Journals (Sweden)

    Mahin Behzadpour

    2012-06-01

    Full Text Available Background & Objective: The immune system of Patients with Acquired Immune Deficiency Syndrome (AIDS is weekend because of Human immunodeficiency virus (HIV infection, and they become vulnerable to several opportunistic and non-opportunistic pathogens and different carcinomas. IV drug abuse, sexual contact, occupational transmission, blood transfusion and maternal-fetal transmission are well known transmission routes for HIV infection. This study was under taken to investigate the prevalence of HIV transmission routs in the HIV infected population of Sirjan, and their knowledge about the disease, in order to plan better preventive strategies. Materials & Methods: A cross sectional study was planned. During a 6-month period in 2010, all of the HIV infected people in Sirjan (old and new cases who had a file at the consultation center for high risk behavior, completed a valid and reliable questionnaire. Results: The definite route of transmission was not clear in any of the patients because they had more than one suspicious route. Injected drug abusers were the most common (88.4% followed by those who got tattoos (79.1%, invasive therapeutic procedures, dentistry, surgery and endoscopy (56.1%, high risk sexual behavior (62.8%, bloodletting (9.3%, injuries in the barbershop (9.3% and blood transfusion (2.3%. Conclusion: All of the HIV infected cases in Sirjan were involved with several high risk behaviors, but the major route of transmission, similar to other parts of the country was injected drug abuse. Educational programs for prevention of AIDS should be followed seriously and special attention should be paid to groups with multiple high risk behaviors.

  4. Relationship between Human Immunodeficiency Virus Neuroretinal Disorder and Vision-Specific Quality of Life among People with AIDS.

    Science.gov (United States)

    Ashraf, Davin C; May, K Patrick; Holland, Gary N; Van Natta, Mark L; Wu, Albert W; Thorne, Jennifer E; Jabs, Douglas A

    2015-12-01

    Some human immunodeficiency virus (HIV)-infected individuals have evidence of optic nerve or retinal dysfunction that manifests as decreased contrast sensitivity, even with good best-corrected visual acuity (BCVA). This condition, termed HIV-related neuroretinal disorder (HIV-NRD), is a risk factor for vision impairment (BCVA AIDS cohort who completed the National Eye Institute 25-item Visual Function Questionnaire (VFQ-25), had BCVA of 20/40 or better, and had no evidence of ocular opportunistic infection or cataract. We compared QOL by HIV-NRD status, adjusting for potential confounding variables, using multiple linear regression. Among those with HIV-NRD, we assessed the relationship between VFQ-25 and the logarithm of contrast sensitivity (logCS), using Spearman correlation. We defined a minimum clinically important difference (MCID) as 1 standard error of measurement from a well-characterized, historical population of individuals with a variety of ophthalmic disorders. Subscales and composite VFQ-25 scores (0 = worst, 100 = best). A total of 813 individuals met study criteria. Those with HIV-NRD (n = 39 [4.8%]) had a lower mean composite score than those without HIV-NRD (81 vs. 89; P = 0.0002) and lower mean scores in the following subscales: near activities (77 vs. 86; P = 0.004), distance activities (85 vs. 91; P = 0.01), social functioning (89 vs. 96; P = 0.0005), mental health (75 vs. 87; P = 0.0001), dependency (81 vs. 94; P AIDS and good BCVA. Published by Elsevier Inc.

  5. 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

  6. African Horse Sickness Caused by Genome Reassortment and Reversion to Virulence of Live, Attenuated Vaccine Viruses, South Africa, 2004–2014

    Science.gov (United States)

    Weyer, Camilla T.; Grewar, John D.; Burger, Phillippa; Rossouw, Esthea; Lourens, Carina; Joone, Christopher; le Grange, Misha; Coetzee, Peter; Venter, Estelle; Martin, Darren P.; MacLachlan, N. James

    2016-01-01

    African horse sickness (AHS) is a hemorrhagic viral fever of horses. It is the only equine disease for which the World Organization for Animal Health has introduced specific guidelines for member countries seeking official recognition of disease-free status. Since 1997, South Africa has maintained an AHS controlled area; however, sporadic outbreaks of AHS have occurred in this area. We compared the whole genome sequences of 39 AHS viruses (AHSVs) from field AHS cases to determine the source of 3 such outbreaks. Our analysis confirmed that individual outbreaks were caused by virulent revertants of AHSV type 1 live, attenuated vaccine (LAV) and reassortants with genome segments derived from AHSV types 1, 3, and 4 from a LAV used in South Africa. These findings show that despite effective protection of vaccinated horses, polyvalent LAV may, paradoxically, place susceptible horses at risk for AHS. PMID:27442883

  7. Hepatitis A virus-encoded miRNAs attenuate the accumulation of viral genomic RNAs in infected cells.

    Science.gov (United States)

    Shi, Jiandong; Sun, Jing; Wu, Meini; Hu, Ningzhu; Hu, Yunzhang

    2016-06-01

    The establishment of persistent infection with hepatitis A virus (HAV) is the common result of most HAV/cell culture systems. Previous observations show that the synthesis of viral RNAs is reduced during infection. However, the underlying mechanism is poorly understood. We characterized three HAV-encoded miRNAs in our previous study. In this study, we aim to investigate the impact of these miRNAs on the accumulation of viral RNAs. The results indicated that the synthesis of viral genomic RNAs was dramatically reduced (more than 75 % reduction, P virus-derived miRNA could serve as a self-mediated feedback regulator during infection.

  8. Recombinant Adeno-Associated Virus-Mediated Expression of Methamphetamine Antibody Attenuates Methamphetamine-Induced Hyperactivity in Mice

    OpenAIRE

    Yun-Hsiang Chen; Kuo-Jen Wu; Kuang-Lun Wu; Kun-Lieh Wu; Ho-Min Tsai; Mao-Liang Chen; Yi-Wei Chen; Wei Hsieh; Chun-Ming Lin; Yun Wang

    2017-01-01

    Methamphetamine (Meth) is one of the most frequently abused drugs worldwide. Recent studies have indicated that antibodies with high affinity for Meth reduce its pharmacological effects. The purpose of this study was to develop a technique for virus-based passive immunization against Meth effects. We generated a recombinant adeno-associated virus serotype-8 vector (AAV-MethAb) carrying the gene for a Meth-specific monoclonal antibody (MethAb). Infection of 293 cells with AAV-MethAb resulted i...

  9. Computer-aided design of novel HIV-1 entry inhibitors blocking the virus envelope gp120 V3 loop

    Directory of Open Access Journals (Sweden)

    Tuzikov A. V.

    2012-12-01

    Full Text Available Aim. The object of this study was to implement computer-aided design of the water-soluble analog of glycolipid β -galactosylceramide (β-GalCer, which presents a potential HIV-1 entry inhibitor, by the analysis of intermolecular interactions of β-GalCer with the central region of the virus envelope gp120 V3 loop followed by synthesis of this glycolipid derivative and testing for antiviral activity. Methods. To reach the object of view, computer modeling procedures, such as quantum chemical calculations, molecular docking, molecular dynamics and free energy simulations, were involved in the studies in conjunction with chemical synthesis and anti-HIV-1 assay methods. Results. As a result, the high probability of exhibiting of antiviral activity was predicted for the designed β-GalCer analog. The data of molecular modeling were confirmed by those of primary medical trials of the synthesized compound. Conclusions. In the light of the findings obtained, the designed analog of β-GalCer may be considered as the basic structure for simulation of its more potent structural forms and for posterior selection of drug candidates most promising for synthesis and anti-HIV-1 assays.

  10. Attenuated Salmonella typhimurium delivering DNA vaccine encoding duck enteritis virus UL24 induced systemic and mucosal immune responses and conferred good protection against challenge

    Directory of Open Access Journals (Sweden)

    Yu Xia

    2012-07-01

    Full Text Available Abstract Orally delivered DNA vaccines against duck enteritis virus (DEV were developed using live attenuated Salmonella typhimurium (SL7207 as a carrier and Escherichia coli heat labile enterotoxin B subunit (LTB as a mucosal adjuvant. DNA vaccine plasmids pVAX-UL24 and pVAX-LTB-UL24 were constructed and transformed into attenuated Salmonella typhimurium SL7207 resulting SL7207 (pVAX-UL24 and SL7207 (pVAX-LTB-UL24 respectively. After ducklings were orally inoculated with SL7207 (pVAX-UL24 or SL7207 (pVAX-LTB-UL24, the anti-DEV mucosal and systemic immune responses were recorded. To identify the optimum dose that confers maximum protection, we used different doses of the candidate vaccine SL7207 (pVAX-LTB-UL24 during oral immunization. The strongest mucosal and systemic immune responses developed in the SL7207 (pVAX-LTB-UL24 (1011 CFU immunized group. Accordingly, oral immunization of ducklings with SL7207 (pVAX-LTB-UL24 showed superior efficacy of protection (60-80% against a lethal DEV challenge (1000 LD50, compared with the limited survival rate (40% of ducklings immunized with SL7207 (pVAX-UL24. Our study suggests that the SL7207 (pVAX-LTB-UL24 can be a candidate DEV vaccine.

  11. Pseudodiploid genome organization AIDS full-length human immunodeficiency virus type 1 DNA synthesis.

    Science.gov (United States)

    King, Steven R; Duggal, Nisha K; Ndongmo, Clement B; Pacut, Crystal; Telesnitsky, Alice

    2008-03-01

    Template switching between copackaged human immunodeficiency virus type 1 (HIV-1) genomic RNAs is genetically silent when identical RNAs are copackaged but yields recombinants when virions contain two distinct RNAs. Sequencing has revealed that errors at retroviral recombination junctions are infrequent, suggesting that template switching is not intrinsically mutagenic. Here, we tested the hypothesis that template switching may instead contribute to replication fidelity. This hypothesis predicts that reverse transcription of a single-copy gene will be more error prone than replication in the presence of a second copy. To test this, HIV-1-based vectors containing both lacZ and the puromycin resistance marker were expressed either alone or with an excess of an "empty" vector lacking lacZ and puro. This resulted in virions with either RNA homodimers or haploid genomes with only a single lacZ-puro RNA. In untreated cells, lacZ inactivation rates suggested that haploid vector reverse transcription was slightly more error prone than that of homodimerized pseudodiploid vectors. Haploid reverse transcription was at least threefold more error prone than pseudodiploid-templated synthesis when slowed by hydroxyurea treatment or stopped prematurely with zidovudine. Individual products of one- and two-copy genes revealed both nucleotide substitutions and deletions, with deletions more frequent than point mutations among haploid genome products. Similar spectra of defective products were observed at early reverse transcription time points and among products of haploid virions. These results indicate that faithful, full-length reverse transcription products were underrepresented in the absence of a reserve of genetic information and suggest that template switching contributes to HIV-1 genomic integrity.

  12. Induction of feline immunodeficiency virus specific antibodies in cats with an attenuated Salmonella strain expressing the Gag protein.

    NARCIS (Netherlands)

    E.J. Tijhaar (Edwin); C.H.J. Siebelink (Kees); J.A. Karlas (Jos); M.C. Burger; F.R. Mooi (Frits); A.D.M.E. Osterhaus (Albert)

    1997-01-01

    textabstractSalmonella typhimurium aroA strains (SL3261), expressing high levels of the Gag protein of feline immunodeficiency virus (FIV) fused with maltose binding protein (SL3261-MFG), were constructed using an invertible promoter system that allows the stable expression of heterologous antigens

  13. Polo-like Kinase 1 Activated by the Hepatitis B Virus X Protein Attenuates Both the DNA Damage Checkpoint and DNA Repair Resulting in Partial Polyploidy*

    Science.gov (United States)

    Studach, Leo; Wang, Wen-Horng; Weber, Gregory; Tang, Jiabin; Hullinger, Ronald L.; Malbrue, Raphael; Liu, Xiaoqi; Andrisani, Ourania

    2010-01-01

    Hepatitis B virus X protein (pX), implicated in hepatocarcinogenesis, induces DNA damage because of re-replication and allows propagation of damaged DNA, resulting in partial polyploidy and oncogenic transformation. The mechanism by which pX allows cells with DNA damage to continue proliferating is unknown. Herein, we show pX activates Polo-like kinase 1 (Plk1) in the G2 phase, thereby attenuating the DNA damage checkpoint. Specifically, in the G2 phase of pX-expressing cells, the checkpoint kinase Chk1 was inactive despite DNA damage, and protein levels of claspin, an adaptor of ataxia telangiectasia-mutated and Rad3-related protein-mediated Chk1 phosphorylation, were reduced. Pharmacologic inhibition or knockdown of Plk1 restored claspin protein levels, Chk1 activation, and p53 stabilization. Also, protein levels of DNA repair protein Mre11 were decreased in the G2 phase of pX-expressing cells but not with Plk1 knockdown. Interestingly, in pX-expressing cells, Mre11 co-immunoprecipitated with transfected Plk1 Polo-box domain, and inhibition of Plk1 increased Mre11 stability in cycloheximide-treated cells. These results suggest that pX-activated Plk1 by down-regulating Mre11 attenuates DNA repair. Importantly, concurrent inhibition of Plk1, p53, and Mre11 increased the number of pX-expressing cells with DNA damage entering mitosis, relative to Plk1 inhibition alone. By contrast, inhibition or knockdown of Plk1 reduced pX-induced polyploidy while increasing apoptosis. We conclude Plk1, activated by pX, allows propagation of DNA damage by concurrently attenuating the DNA damage checkpoint and DNA repair, resulting in polyploidy. We propose this novel Plk1 mechanism initiates pX-mediated hepatocyte transformation. PMID:20624918

  14. Polo-like kinase 1 activated by the hepatitis B virus X protein attenuates both the DNA damage checkpoint and DNA repair resulting in partial polyploidy.

    Science.gov (United States)

    Studach, Leo; Wang, Wen-Horng; Weber, Gregory; Tang, Jiabin; Hullinger, Ronald L; Malbrue, Raphael; Liu, Xiaoqi; Andrisani, Ourania

    2010-09-24

    Hepatitis B virus X protein (pX), implicated in hepatocarcinogenesis, induces DNA damage because of re-replication and allows propagation of damaged DNA, resulting in partial polyploidy and oncogenic transformation. The mechanism by which pX allows cells with DNA damage to continue proliferating is unknown. Herein, we show pX activates Polo-like kinase 1 (Plk1) in the G(2) phase, thereby attenuating the DNA damage checkpoint. Specifically, in the G(2) phase of pX-expressing cells, the checkpoint kinase Chk1 was inactive despite DNA damage, and protein levels of claspin, an adaptor of ataxia telangiectasia-mutated and Rad3-related protein-mediated Chk1 phosphorylation, were reduced. Pharmacologic inhibition or knockdown of Plk1 restored claspin protein levels, Chk1 activation, and p53 stabilization. Also, protein levels of DNA repair protein Mre11 were decreased in the G(2) phase of pX-expressing cells but not with Plk1 knockdown. Interestingly, in pX-expressing cells, Mre11 co-immunoprecipitated with transfected Plk1 Polo-box domain, and inhibition of Plk1 increased Mre11 stability in cycloheximide-treated cells. These results suggest that pX-activated Plk1 by down-regulating Mre11 attenuates DNA repair. Importantly, concurrent inhibition of Plk1, p53, and Mre11 increased the number of pX-expressing cells with DNA damage entering mitosis, relative to Plk1 inhibition alone. By contrast, inhibition or knockdown of Plk1 reduced pX-induced polyploidy while increasing apoptosis. We conclude Plk1, activated by pX, allows propagation of DNA damage by concurrently attenuating the DNA damage checkpoint and DNA repair, resulting in polyploidy. We propose this novel Plk1 mechanism initiates pX-mediated hepatocyte transformation.

  15. Curative effect of split low dosage total-body irradiation on murine AIDS induced by Friend virus: the results and the possible mechanism.

    Science.gov (United States)

    Shen, R N; Lu, L; Kaiser, H E; Broxmeyer, H E

    1996-01-01

    Mice infected with Friend Leukemia Virus (FLV) rapidly develop erythroleukemia and severe immune deficiency which resembles human AIDS. We have reported that mice infected with a lethal dose of FLV can be 100% cured by 150 cGy total body irradiation (TBI). This curative effect was associated with restoration of cellular immunity which was compromised by the virus. This restoration may result from activation of the IFN-gamma system and IL-2 production. Our research work further demonstrated that no spleen focus-forming virus (SFFV) specific mRNAs, no 6.0kb SFFV fragments and SFFV envelope glycoproteins were detectable in FLV-infected mice treated with low dose TBI. Predicated on our report, del Regato has initiated clinical trials to treat AIDS patients with low dose TBI. The preliminary results are encouraging and the study is continuing. We have also studied the effects of low dose TBI on the expression of the P53 gene. The results show loss or inactivation of P53 tumor suppressor genes in FLV-infected mice, but P53 expression was restored in FLV-infected mice treated by low dose TBI. It is intriguing to speculate that in the curative effect of low dose TBI on mice infected with retrovirus, the P53 tumor suppressor gene may play an important role. It would be of interest to see if this type of treatment, which was well tolerated by mice, would be beneficial in other types of virally induced disease, including AIDS.

  16. Enhanced CD8+ T cell immune responses and protection elicited against Plasmodium berghei malaria by prime boost immunization regimens using a novel attenuated fowlpox virus.

    Science.gov (United States)

    Anderson, Richard J; Hannan, Carolyn M; Gilbert, Sarah C; Laidlaw, Stephen M; Sheu, Eric G; Korten, Simone; Sinden, Robert; Butcher, Geoffrey A; Skinner, Michael A; Hill, Adrian V S

    2004-03-01

    Sterile immunity can be provided against the pre-erythrocytic stages of malaria by IFN-gamma-secreting CD8(+) T cells that recognize parasite-infected hepatocytes. In this study, we have investigated the use of attenuated fowlpox virus (FPV) strains as recombinant vaccine vectors for eliciting CD8(+) T cells against Plasmodium berghei. The gene encoding the P. berghei circumsporozoite (PbCS) protein was inserted into an FPV vaccine strain licensed for use in chickens, Webster's FPV, and the novel FPV vaccine strain FP9 by homologous recombination. The novel FP9 strain proved more potent as a vaccine for eliciting CD8(+) T cell responses against the PbCS Ag. Sequential immunization with rFP9 and recombinant modified vaccinia virus Anakara (MVA) encoding the PbCS protein, administered by clinically acceptable routes, elicited potent CD8(+) T cell responses against the PbCS protein. This immunization regimen elicited substantial protection against a stringent liver-stage challenge with P. berghei and was more immunogenic and protective than DNA/MVA prime/boost immunization. However, further improvement was not achieved by sequential (triple) immunization with a DNA vaccine, FP9, and MVA.

  17. Adeno-associated virus mediated delivery of a non-membrane targeted human soluble CD59 attenuates some aspects of diabetic retinopathy in mice.

    Directory of Open Access Journals (Sweden)

    Mehreen Adhi

    Full Text Available Diabetic retinopathy is the leading cause of visual dysfunction in working adults and is attributed to retinal vascular and neural cell damage. Recent studies have described elevated levels of membrane attack complex (MAC and reduced levels of membrane associated complement regulators including CD55 and CD59 in the retina of diabetic retinopathy patients as well as in animal models of this disease. We have previously described the development of a soluble membrane-independent form of CD59 (sCD59 that when delivered via a gene therapy approach using an adeno-associated virus vector (AAV2/8-sCD59 to the eyes of mice, can block MAC deposition and choroidal neovascularization. Here, we examine AAV2/8-sCD59 mediated attenuation of MAC deposition and ensuing complement mediated damage to the retina of mice following streptozotocin (STZ induced diabetes. We observed a 60% reduction in leakage of retinal blood vessels in diabetic eyes pre-injected with AAV2/8-sCD59 relative to negative control virus injected diabetic eyes. AAV2/8-sCD59 injected eyes also exhibited protection from non-perfusion of retinal blood vessels. In addition, a 200% reduction in retinal ganglion cell apoptosis and a 40% reduction in MAC deposition were documented in diabetic eyes pre-injected with AAV2/8-sCD59 relative to diabetic eyes pre-injected with the control virus. This is the first study characterizing a viral gene therapy intervention that targets MAC in a model of diabetic retinopathy. Use of AAV2/8-sCD59 warrants further exploration as a potential therapy for advanced stages of diabetic retinopathy.

  18. An attenuated Lassa vaccine in SIV-infected rhesus macaques does not persist or cause arenavirus disease but does elicit Lassa virus-specific immunity.

    Science.gov (United States)

    Zapata, Juan C; Poonia, Bhawna; Bryant, Joseph; Davis, Harry; Ateh, Eugene; George, Lanea; Crasta, Oswald; Zhang, Yan; Slezak, Tom; Jaing, Crystal; Pauza, C David; Goicochea, Marco; Moshkoff, Dmitry; Lukashevich, Igor S; Salvato, Maria S

    2013-02-12

    Lassa hemorrhagic fever (LHF) is a rodent-borne viral disease that can be fatal for human beings. In this study, an attenuated Lassa vaccine candidate, ML29, was tested in SIV-infected rhesus macaques for its ability to elicit immune responses without instigating signs pathognomonic for arenavirus disease. ML29 is a reassortant between Lassa and Mopeia viruses that causes a transient infection in non-human primates and confers sterilizing protection from lethal Lassa viral challenge. However, since the LHF endemic area of West Africa also has high HIV seroprevalence, it is important to determine whether vaccination could be safe in the context of HIV infection. SIV-infected and uninfected rhesus macaques were vaccinated with the ML29 virus and monitored for specific humoral and cellular immune responses, as well as for classical and non-classical signs of arenavirus disease. Classical disease signs included viremia, rash, respiratory distress, malaise, high liver enzyme levels, and virus invasion of the central nervous system. Non-classical signs, derived from profiling the blood transcriptome of virulent and non-virulent arenavirus infections, included increased expression of interferon-stimulated genes (ISG) and decreased expression of COX2, IL-1β, coagulation intermediates and nuclear receptors needed for stress signaling. All vaccinated monkeys showed ML29-specific antibody responses and ML29-specific cell-mediated immunity. SIV-infected and uninfected rhesus macaques responded similarly to ML29 vaccination, and none developed chronic arenavirus infection. Importantly, none of the macaques developed signs, classical or non-classical, of arenavirus disease.

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

    Science.gov (United States)

    Tengan, Fatima Mitiko; Ibrahim, Karim Yakub; Dantas, Bianca Peixoto; Manchiero, Caroline; Magri, Mariana Cavalheiro; Bernardo, Wanderley Marques

    2016-11-09

    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. 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. 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. Investigation of HCV infection among PLHA and of HIV infection among people living with HCV is highly recommended because it allows for better follow up, counseling and treatment of HIV

  20. 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

  1. Attenuation of influenza virus infectivity with herbal-marine compound (HESA-A: an in vitro study in MDCK cells

    Directory of Open Access Journals (Sweden)

    Mehrbod Parvaneh

    2012-02-01

    Full Text Available Abstract Background The influenza virus is still one of the most important respiratory risks affecting humans which require effective treatments. In this case, traditional medications are of interest. HESA-A is an active natural biological compound from herbal-marine origin. Previous studies have reported that the therapeutic properties of HESA-A are able to treat psoriasis vulgaris and cancers. However, no antiviral properties have been reported. Methods This study was designed to investigate the potential antiviral properties of HESA-A and its effects in modulating TNF-α and IL-6 cytokine levels. HESA-A was prepared in normal saline as a stock solution (0.8 mg/ml, pH = 7.4. Percentages of cell survival when exposed to different concentrations of HESA-A at different time intervals was determined by MTT assay. To study the potential antiviral activity of HESA-A, Madin-Darby Canine Kidney (MDCK cells were treated with the effective concentration (EC50 of HESA-A (0.025 mg/ml and 100 TCID50/0.1 ml of virus sample under different types of exposure. Results Based on the MTT method and hemagglutination assay (HA, HESA-A is capable of improving cell viability to 31% and decreasing HA titre to almost 99% in co-penetration exposures. In addition, based on quantitative real-time PCR (qRT-PCR and enzyme-linked immunosorbent assay (ELISA, it was found that HESA-A causes decrements in TNF-α and IL-6 cytokine expressions, which was significant for TNF-α (p ≤ 0.05 but not for IL-6. Conclusion In conclusion, HESA-A was effective against influenza infection through suppressing cytokine expression.

  2. Effect of Broccoli Sprouts and Live Attenuated Influenza Virus on Peripheral Blood Natural Killer Cells: A Randomized, Double-Blind Study.

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    Loretta Müller

    Full Text Available Enhancing antiviral host defense responses through nutritional supplementation would be an attractive strategy in the fight against influenza. Using inoculation with live attenuated influenza virus (LAIV as an infection model, we have recently shown that ingestion of sulforaphane-containing broccoli sprout homogenates (BSH reduces markers of viral load in the nose. To investigate the systemic effects of short-term BSH supplementation in the context of LAIV-inoculation, we examined peripheral blood immune cell populations in non-smoking subjects from this study, with a particular focus on NK cells. We carried out a randomized, double-blinded, placebo-controlled study measuring the effects of BSH (N = 13 or placebo (alfalfa sprout homogenate, ASH; N = 16 on peripheral blood mononuclear cell responses to a standard nasal vaccine dose of LAIV in healthy volunteers. Blood was drawn prior to (day-1 and post (day2, day21 LAIV inoculation and analyzed for neutrophils, monocytes, macrophages, T cells, NKT cells, and NK cells. In addition, NK cells were enriched, stimulated, and assessed for surface markers, intracellular markers, and cytotoxic potential by flow cytometry. Overall, LAIV significantly reduced NKT (day2 and day21 and T cell (day2 populations. LAIV decreased NK cell CD56 and CD158b expression, while significantly increasing CD16 expression and cytotoxic potential (on day2. BSH supplementation further increased LAIV-induced granzyme B production (day2 in NK cells compared to ASH and in the BSH group granzyme B levels appeared to be negatively associated with influenza RNA levels in nasal lavage fluid cells. We conclude that nasal influenza infection may induce complex changes in peripheral blood NK cell activation, and that BSH increases virus-induced peripheral blood NK cell granzyme B production, an effect that may be important for enhanced antiviral defense responses.ClinicalTrials.gov NCT01269723.

  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. 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.

  5. In vivo evolution of the gp90 gene and consistently low plasma viral load during transient immune suppression demonstrate the safety of an attenuated equine infectious anemia virus (EIAV) vaccine.

    Science.gov (United States)

    Ma, Jian; Jiang, Chenggang; Lin, Yuezhi; Wang, Xuefeng; Zhao, Liping; Xiang, Wenhua; Shao, Yiming; Shen, Rongxian; Kong, Xiangang; Zhou, Jianhua

    2009-01-01

    To study the in vivo evolution of the attenuated Chinese equine infectious anemia virus (EIAV) vaccine, viral gp90 gene variation and virus replication in immunosuppressed hosts were investigated. The results showed that after vaccination, the gp90 gene followed an evolutionary trend of declining diversity. The trend coincided with the maturation of immunity to EIAV, and eventually, the gp90 gene became highly homologous. The sequences of these predominant quasispecies were consistently detected up to 18 months after vaccination. Furthermore, after transient immune suppression with dexamethasone, the plasma viral RNA copy number of the vaccine strain in three vaccinated ponies remained consistently below the "pathogenic threshold" level, while the viral load increased by 25,000-fold in the positive control of an inapparent carrier of the parental virulent strain. This study is the first to provide evidence for the safety of an attenuated lentiviral vaccine with decreased genomic diversity and consistently low viral replication under suppressed immunity.

  6. 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 10(9) CFU of p3D-NT56/S. cho and challenged 36 h later with 50 ID(50) 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 x 10(9) CFU of p3D-NT56/S. cho were protected in 9 days. INRA, EDP Sciences, 2010.

  7. [Private companies: an opportunity for hepatitis B virus (HBV) prevention and care in Ivory Coast in the wake of HIV/AIDS?].

    Science.gov (United States)

    Bekelynck, A

    2015-02-01

    In the 1990s, defenders of "aids exceptionnalism" have promised that the inequities caused by HIV/AIDS could provide leverage in the care of other health issues later. Fifteen years later, this argument can be rethought at the light of the current context of hepatitis B virus (HBV) in Ivory Coast. In fact, in this country, the challenges caused by HBVecho those of HIV/AIDS fifteen years ago: high prevalence (8-10%), ignorance of the disease, and high cost of care. To this end, this article compares the role of private companies in the fights against HIV/AIDS in the 2000s and its role in the fight against HBV today. Although some private firms played a critical role in the promotion of universal access to ART, today, they are one of the few places where HBV screening, vaccination and treatment are offered in the country. HIV/AIDS opened the door for private companies to address other diseases through their health care systems. However, many challenges still need to be met: the absence of qualitative ongoing training for health professionals, illness representations and the costs of treatments, which are all related to the lack of international and national collective action. In Ivory Coast, at the early stage of the HIV/AIDS epidemic, national authorities took up the leadership in the fight against AIDS in West Africa, by developing extraverted strategies (Xth ICASA's organization, Unaids initiative hosting). The exceptional international mobilization and the creation of innovative funding mechanisms [International Therapeutic Solidarity Fund (ITSF), Global Fund (GM), and President's Emergency Plan for AIDS Relief (PEPFAR)] have facilitated easy access to ARV. Although 380 million people are infected by chronic HBV in the world, even so, international and national collective actions are fledgling and remained weak. Moreover, private firms have represented leverage for testing, treatment, and the provision of universal access to medication in the context of the HIV/AIDS

  8. Safety of Live Attenuated High-Titer Varicella-Zoster Virus Vaccine in Pediatric Allogeneic Hematopoietic Stem Cell Transplantation Recipients.

    Science.gov (United States)

    Aoki, Takahiro; Koh, Katsuyoshi; Kawano, Yutaka; Mori, Makiko; Arakawa, Yuki; Kato, Motohiro; Hanada, Ryoji

    2016-04-01

    Hematopoietic stem cell transplantation (HSCT) recipients have a high risk of varicella-zoster virus (VZV) infections. Although VZV vaccination may be beneficial in preventing VZV infections, data on safety and efficacy of VZV vaccines in HSCT recipients, particularly of zoster vaccine, are limited. We report our experience with the use of a single dose of an Oka strain high-titer zoster-equivalent varicella vaccine in pediatric allogeneic HSCT recipients. We administered the high-titer VZV vaccine to 31 pediatric allogeneic HSCT recipients without vaccine-type VZV infections. One patient developed varicella due to wild-type VZV 13 days after vaccination. No zoster developed after vaccination during a median follow-up period of 4.8 years from vaccination. No other adverse effects were observed. Eighteen of the 31 patients (58.1%) were seropositive after vaccination. Seventeen patients were vaccinated within 24 months after HSCT; the seropositivity of these patients did not significantly differ from that of patients vaccinated > 24 months after HSCT. VZV vaccination may be a safe and beneficial approach in preventing VZV infections after HSCT. Copyright © 2016 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  9. Tick-Borne Langat/Mosquito-Borne Dengue Flavivirus Chimera, a Candidate Live Attenuated Vaccine for Protection against Disease Caused by Members of the Tick-Borne Encephalitis Virus Complex: Evaluation in Rhesus Monkeys and in Mosquitoes

    Science.gov (United States)

    Pletnev, Alexander G.; Bray, Michael; Hanley, Kathryn A.; Speicher, Jim; Elkins, Randy

    2001-01-01

    Langat virus (LGT), strain TP21, a naturally avirulent tick-borne flavivirus, was used to construct a chimeric candidate virus vaccine which contained LGT genes for premembrane (preM) and envelope (E) glycoprotein and all other sequences derived from dengue type 4 virus (DEN4). The live virus vaccine was developed to provide resistance to the highly virulent, closely related tick-borne flaviviruses that share protective E epitopes among themselves and with LGT. Toward that end the chimera, initially recovered in mosquito cells, was adapted to grow to high titer in qualified simian Vero cells. When inoculated intraperitoneally (i.p.), the Vero cell-adapted LGT TP21/DEN4 chimera remained completely attenuated for SCID mice. Significantly, the chimera protected immunocompetent mice against the most virulent tick-borne encephalitis virus (TBEV). Subsequently, rhesus monkeys were immunized in groups of 4 with 105 or 107 PFU of LGT strain TP21, with 105 PFU of DEN4, or with 103, 105, or 107 PFU of the chimera. Each of the monkeys inoculated with DEN4 or LGT TP21 became viremic, and the duration of viremia ranged from 1 to 5 days. In contrast, viremia was detected in only 1 of 12 monkeys inoculated with the LGT TP21/DEN4 chimera; in this instance the level of viremia was at the limit of detection. All monkeys immunized with the chimera or LGT TP21 virus developed a moderate to high level of neutralizing antibodies against LGT TP21 as well as TBEV and were completely protected against subsequent LGT TP21 challenge, whereas monkeys previously immunized with DEN4 virus became viremic when challenged with LGT TP21. These observations suggest that the chimera is attenuated, immunogenic, and able to induce a protective immune response. Furthermore, passive transfer of serum from monkeys immunized with chimera conferred significant protection to mice subsequently challenged with 100 i.p. 50% lethal doses of the highly virulent TBEV. The issue of transmissibility of the chimera

  10. Differences in human immunodeficiency virus type 1 V3 sequences from patients with and without AIDS dementia complex

    NARCIS (Netherlands)

    Kuiken, C. L.; Goudsmit, J.; Weiller, G. F.; Armstrong, J. S.; Hartman, S.; Portegies, P.; Dekker, J.; Cornelissen, M.

    1995-01-01

    Paired serum and cerebrospinal fluid (CSF) samples from 10 AIDS patients with and 10 without AIDS dementia complex (ADC) were studied, in an attempt to uncover ADC-associated variation in V3 sequences. Sequences were obtained from four of the patients with and eight of those without ADC. Comparison

  11. Differential Host Immune Responses after Infection with Wild-Type or Lab-Attenuated Rabies Viruses in Dogs.

    Directory of Open Access Journals (Sweden)

    Clement W Gnanadurai

    Full Text Available The experimental infection of dogs with TriGAS induced high levels of VNA in the serum, whereas wt RABV infection did not. Dogs infected with TriGAS developed antibodies against the virus including its glycoprotein, whereas dogs infected with DRV-NG11 only developed rabies antibodies that are presumably specific for the nucleoprotein, (N and not the glycoprotein (G. We show that infection with TriGAS induces early activation of B cells in the draining lymph nodes and persistent activation of DCs and B cells in the blood. On the other hand, infection with DRV-NG11 fails to induce the activation of DCs and B cells and further reduces CD4 T cell production. Further, we show that intrathecal (IT immunization of TriGAS not only induced high levels of VNA in the serum but also in the CSF while intramuscular (IM immunization of TriGAS induced VNA only in the serum. In addition, high levels of total protein and WBC were detected in the CSF of IT immunized dogs, indicating the transient enhancement of blood-brain barrier (BBB permeability, which is relevant to the passage of immune effectors from periphery into the CNS.IM infection of dogs with TriGAS induced the production of serum VNA whereas, IT immunization of TriGAS in dogs induces high levels of VNA in the periphery as well as in the CSF and transiently enhances BBB permeability. In contrast, infection with wt DRV-NG11 resulted in the production of RABV-reactive antibodies but VNA and antibodies specific for G were absent. As a consequence, all of the dogs infected with wt DRV-NG11 succumbed to rabies. Thus the failure to activate protective immunity is one of the important features of RABV pathogenesis in dogs.

  12. Differential Host Immune Responses after Infection with Wild-Type or Lab-Attenuated Rabies Viruses in Dogs.

    Science.gov (United States)

    Gnanadurai, Clement W; Yang, Yang; Huang, Ying; Li, Zhenguang; Leyson, Christina M; Cooper, Tanya L; Platt, Simon R; Harvey, Stephen B; Hooper, Douglas C; Faber, Milosz; Fu, Zhen F

    2015-01-01

    The experimental infection of dogs with TriGAS induced high levels of VNA in the serum, whereas wt RABV infection did not. Dogs infected with TriGAS developed antibodies against the virus including its glycoprotein, whereas dogs infected with DRV-NG11 only developed rabies antibodies that are presumably specific for the nucleoprotein, (N) and not the glycoprotein (G). We show that infection with TriGAS induces early activation of B cells in the draining lymph nodes and persistent activation of DCs and B cells in the blood. On the other hand, infection with DRV-NG11 fails to induce the activation of DCs and B cells and further reduces CD4 T cell production. Further, we show that intrathecal (IT) immunization of TriGAS not only induced high levels of VNA in the serum but also in the CSF while intramuscular (IM) immunization of TriGAS induced VNA only in the serum. In addition, high levels of total protein and WBC were detected in the CSF of IT immunized dogs, indicating the transient enhancement of blood-brain barrier (BBB) permeability, which is relevant to the passage of immune effectors from periphery into the CNS. IM infection of dogs with TriGAS induced the production of serum VNA whereas, IT immunization of TriGAS in dogs induces high levels of VNA in the periphery as well as in the CSF and transiently enhances BBB permeability. In contrast, infection with wt DRV-NG11 resulted in the production of RABV-reactive antibodies but VNA and antibodies specific for G were absent. As a consequence, all of the dogs infected with wt DRV-NG11 succumbed to rabies. Thus the failure to activate protective immunity is one of the important features of RABV pathogenesis in dogs.

  13. Quantitative computer-aided diagnostic algorithm for automated detection of peak lesion attenuation in differentiating clear cell from papillary and chromophobe renal cell carcinoma, oncocytoma, and fat-poor angiomyolipoma on multiphasic multidetector computed tomography.

    Science.gov (United States)

    Coy, Heidi; Young, Jonathan R; Douek, Michael L; Brown, Matthew S; Sayre, James; Raman, Steven S

    2017-07-01

    To evaluate the performance of a novel, quantitative computer-aided diagnostic (CAD) algorithm on four-phase multidetector computed tomography (MDCT) to detect peak lesion attenuation to enable differentiation of clear cell renal cell carcinoma (ccRCC) from chromophobe RCC (chRCC), papillary RCC (pRCC), oncocytoma, and fat-poor angiomyolipoma (fp-AML). We queried our clinical databases to obtain a cohort of histologically proven renal masses with preoperative MDCT with four phases [unenhanced (U), corticomedullary (CM), nephrographic (NP), and excretory (E)]. A whole lesion 3D contour was obtained in all four phases. The CAD algorithm determined a region of interest (ROI) of peak lesion attenuation within the 3D lesion contour. For comparison, a manual ROI was separately placed in the most enhancing portion of the lesion by visual inspection for a reference standard, and in uninvolved renal cortex. Relative lesion attenuation for both CAD and manual methods was obtained by normalizing the CAD peak lesion attenuation ROI (and the reference standard manually placed ROI) to uninvolved renal cortex with the formula [(peak lesion attenuation ROI - cortex ROI)/cortex ROI] × 100%. ROC analysis and area under the curve (AUC) were used to assess diagnostic performance. Bland-Altman analysis was used to compare peak ROI between CAD and manual method. The study cohort comprised 200 patients with 200 unique renal masses: 106 (53%) ccRCC, 32 (16%) oncocytomas, 18 (9%) chRCCs, 34 (17%) pRCCs, and 10 (5%) fp-AMLs. In the CM phase, CAD-derived ROI enabled characterization of ccRCC from chRCC, pRCC, oncocytoma, and fp-AML with AUCs of 0.850 (95% CI 0.732-0.968), 0.959 (95% CI 0.930-0.989), 0.792 (95% CI 0.716-0.869), and 0.825 (95% CI 0.703-0.948), respectively. On Bland-Altman analysis, there was excellent agreement of CAD and manual methods with mean differences between 14 and 26 HU in each phase. A novel, quantitative CAD algorithm enabled robust peak HU lesion detection

  14. VIRUSES

    Indian Academy of Sciences (India)

    and-mouth disease in livestock was an infectious particle smaller than any bacteria. This was the first clue to the nature of viruses, genetic entities that lie somewhere in the gray area between living and non-living states.

  15. An approach to a FMD vaccine based on genetic engineered attenuated pseudorabies virus: one experiment using VP1 gene alone generates an antibody responds on FMD and pseudorabies in swine.

    Science.gov (United States)

    Qian, Ping; Li, Xiang-Min; Jin, Mei-Lin; Peng, Gui-Qing; Chen, Huan-Chun

    2004-06-02

    Foot-and-mouth disease (FMD) and pseudorabies (PR) are two important infectious diseases in swine. An attenuated pseudorabies virus (PRV) has been successfully used as a gene delivery vector for the development of live-viral vaccines. In this study, a recombinant PRV-VP1 virus was constructed by fusioning the VP1 gene of FMD virus in frame to the N-terminal sequence of the gG gene of PRV. To test the protective immunity, 15 FMDV sero-negative white swine were divided into three groups and immunized with the recombinant PRV-VP1 virus, commercial FMD vaccine and vector virus (TK(-)/gG(-)/LacZ(+)), respectively, and challenged intramuscularly with 20 minimal infecting doses (MID) of virulent type O FMDV 4 weeks after booster immunization. Swine vaccinated with PRV-VP1 acquired antibodies against both FMDV and PRV, however, anti-FMDV antibodies were much lower than those vaccinated with the commercial FMD vaccine. Our results suggested that the recombinant PRV-VP1 virus, which only expressed FMDV VP1 gene controlled by PRV gG promoter, could not protect swine from the challenge of 20 MID type O FMDV, but could delay and reduce the clinical symptoms of FMD.

  16. Evaluation of attenuation, immunogenicity and efficacy of a bovine parainfluenza virus type 3 (PIV-3) vaccine and a recombinant chimeric bovine/human PIV-3 vaccine vector in rhesus monkeys.

    Science.gov (United States)

    Pennathur, Sridhar; Haller, Aurelia A; MacPhail, Mia; Rizzi, Tom; Kaderi, Sepideh; Fernandes, Fiona; Bicha, Leenas; Schickli, Jeanne H; Tang, Roderick S; Chen, Wendy; Nguyen, Nick; Mathie, Sharon; Mehta, Hersh; Coelingh, Kathleen L

    2003-12-01

    Restricted replication in the respiratory tract of rhesus monkeys is an intrinsic property of bovine parainfluenza virus type 3 (bPIV-3) strains. This host range phenotype of bPIV-3 has been utilized as a marker to evaluate the attenuation of bPIV-3 vaccines for human use. Two safety, immunogenicity and efficacy studies in primates evaluated and compared three human parainfluenza virus type 3 (hPIV-3) vaccine candidates: biologically derived bPIV-3, a plasmid-derived bPIV-3 (r-bPIV-3) and a chimeric bovine/human PIV-3 (b/hPIV-3). These studies also examined the feasibility of substituting Vero cells, cultured in the presence or absence of foetal bovine serum, for foetal rhesus lung-2 (FRhL-2) cells as the tissue culture substrate for the production of bPIV-3 vaccine. The results demonstrated that (i) Vero cell-produced bPIV-3 was as attenuated, immunogenic and efficacious as bPIV-3 vaccine grown in FRhL-2 cells, (ii) plasmid-derived bPIV-3 was as attenuated, immunogenic and efficacious as the biologically derived bPIV-3 and (iii) the b/hPIV-3 chimera displayed an intermediate attenuation phenotype and protected animals completely from hPIV-3 challenge. These results support the use of bPIV-3 vaccines propagated in Vero cells in human clinical trials and the use of b/hPIV-3 as a virus vaccine vector to express foreign viral antigens.

  17. bta-miR-29b attenuates apoptosis by directly targeting caspase-7 and NAIF1 and suppresses bovine viral diarrhea virus replication in MDBK cells.

    Science.gov (United States)

    Fu, Qiang; Shi, Huijun; Shi, Mengting; Meng, Luping; Zhang, Hui; Ren, Yan; Guo, Fei; Jia, Bin; Wang, Pengyan; Ni, Wei; Chen, Chuangfu

    2014-07-01

    MicroRNAs (miRNAs) are small, endogenous, noncoding RNA molecules that serve as powerful regulators of multiple cellular processes, including apoptosis, differentiation, growth, and proliferation. Bovine viral diarrhea virus (BVDV) contributes significantly to health-related economic losses in the beef and dairy industries. Although BVDV-induced apoptosis correlates with increased intracellular viral RNA accumulation and with bta-miR-29b (miR-29b) expression upregulation in Madin-Darby bovine kidney (MDBK) cells infected with BVDV strain NADL, the role of miR-29b in regulating BVDV-infection-related apoptosis remains unexplored. Here, we report that miR-29b serves as a new miRNA regulating apoptosis. We showed that miR-29b target sequences were present in the 3' untranslated regions of 2 key apoptosis regulators mRNAs, cysteine aspartases-7 (caspase-7) and nuclear apoptosis-inducing factor 1 (NAIF1). Indeed, upon miRNA overexpression, both mRNA and protein levels of caspase-7 and NAIF1 were decreased. We further found that miR-29b attenuated apoptosis by directly regulating intracellular levels of caspase-7 and NAIF1. Moreover, apoptosis blockage by miR-29b was rescued upon co-infection of MDBK cells with lentiviruses expressing caspase-7 and NAIF1. Importantly, miR-29b decreased BVDV NADL envelope glycoprotein E1 mRNA levels and suppressed viral replication. These studies advance our understanding of the mechanisms of miRNAs in mediating the cells combating viral infections.

  18. In-depth genome analyses of viruses from vaccine-derived rabies cases and corresponding live-attenuated oral rabies vaccines.

    Science.gov (United States)

    Pfaff, Florian; Müller, Thomas; Freuling, Conrad M; Fehlner-Gardiner, Christine; Nadin-Davis, Susan; Robardet, Emmanuelle; Cliquet, Florence; Vuta, Vlad; Hostnik, Peter; Mettenleiter, Thomas C; Beer, Martin; Höper, Dirk

    2018-02-10

    Live-attenuated rabies virus strains such as those derived from the field isolate Street Alabama Dufferin (SAD) have been used extensively and very effectively as oral rabies vaccines for the control of fox rabies in both Europe and Canada. Although these vaccines are safe, some cases of vaccine-derived rabies have been detected during rabies surveillance accompanying these campaigns. In recent analysis it was shown that some commercial SAD vaccines consist of diverse viral populations, rather than clonal genotypes. For cases of vaccine-derived rabies, only consensus sequence data have been available to date and information concerning their population diversity was thus lacking. In our study, we used high-throughput sequencing to analyze 11 cases of vaccine-derived rabies, and compared their viral population diversity to the related oral rabies vaccines using pairwise Manhattan distances. This extensive deep sequencing analysis of vaccine-derived rabies cases observed during oral vaccination programs provided deeper insights into the effect of accidental in vivo replication of genetically diverse vaccine strains in the central nervous system of target and non-target species under field conditions. The viral population in vaccine-derived cases appeared to be clonal in contrast to their parental vaccines. The change from a state of high population diversity present in the vaccine batches to a clonal genotype in the affected animal may indicate the presence of a strong bottleneck during infection. In conclusion, it is very likely that these few cases are the consequence of host factors and not the result of the selection of a more virulent genotype. Furthermore, this type of vaccine-derived rabies leads to the selection of clonal genotypes and the selected variants were genetically very similar to potent SAD vaccines that have undergone a history of in vitro selection. Copyright © 2018. Published by Elsevier Ltd.

  19. 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 ...

  20. Peru-15 (Choleragarde(®)), a live attenuated oral cholera vaccine, is safe and immunogenic in human immunodeficiency virus (HIV)-seropositive adults in Thailand.

    Science.gov (United States)

    Ratanasuwan, W; Kim, Y H; Sah, B K; Suwanagool, S; Kim, D R; Anekthananon, A; Lopez, A L; Techasathit, W; Grahek, S L; Clemens, J D; Wierzba, T F

    2015-09-11

    Many areas with endemic and epidemic cholera report significant levels of HIV transmission. According to the World Health Organization (WHO), over 95% of reported cholera cases occur in Africa, which also accounts for nearly 70% of people living with HIV/AIDS globally. Peru-15, a promising single dose live attenuated oral cholera vaccine (LA-OCV), was previously found to be safe and immunogenic in cholera endemic areas. However, no data on the vaccine's safety among HIV-seropositive adults had been collected. This study was a double-blinded, individually randomized, placebo-controlled trial enrolling HIV-seropositive adults, 18-45 years of age, conducted in Bangkok, Thailand, to assess the safety of Peru-15 in a HIV-seropositive cohort. 32 HIV infected subjects were randomized to receive either a single oral dose of the Peru-15 vaccine with a buffer or a placebo (buffer only). No serious adverse events were reported during the follow-up period in either group. The geometric mean fold (GMF) rise in V. cholerae O1 El Tor specific antibody titers between baseline and 7 days after dosing was 32.0 (pcholerae was isolated from the stool of one vaccinee, and found to be genetically identical to the Peru-15 vaccine strain. There were no significant changes in HIV viral load or CD4 T-cell counts between vaccine and placebo groups. Peru-15 was shown to be safe and immunogenic in HIV-seropositive Thai adults. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. Theoretical study of the Usutu virus helicase 3D structure, by means of computer-aided homology modelling

    Directory of Open Access Journals (Sweden)

    Vlachakis Dimitrios

    2009-06-01

    Full Text Available Abstract Background Usutu virus belongs to the Flaviviridae viral family and constitutes an important pathogen. The viral helicase is an ideal target for inhibitor design, since this enzyme is essential for the survival, proliferation and transmission of the virus. Results Towards a drug-design approach, the 3D model of the Usutu virus helicase structure has been designed, using conventional homology modelling techniques and the known 3D-structure of the Murray Valley Encephalitis virus helicase, of the same viral family, as template. The model was then subjected to extended molecular dynamics simulations in a periodic box, filled with explicit water molecules for 10 nanoseconds. The reliability of the model was confirmed by obtaining acceptable scores from a variety of in silico scoring tools, including Procheck and Verify3D. Conlcusion The 3D model of the Usutu virus helicase exhibits in silico all known structural characteristics of the Flaviviridae viral family helicase enzymes and could provide the platform for further de novo structure-based design of novel anti-Usutu agents.

  2. Type 1 Immune Mechanisms Driven by the Response to Infection with Attenuated Rabies Virus Result in Changes in the Immune Bias of the Tumor Microenvironment and Necrosis of Mouse GL261 Brain Tumors.

    Science.gov (United States)

    Bongiorno, Emily K; Garcia, Samantha A; Sauma, Sami; Hooper, D Craig

    2017-06-01

    Immunotherapeutic strategies for malignant glioma have to overcome the immunomodulatory activities of M2 monocytes that appear in the circulation and as tumor-associated macrophages (TAMs). M2 cell products contribute to the growth-promoting attributes of the tumor microenvironment (TME) and bias immunity toward type 2, away from the type 1 mechanisms with antitumor properties. To drive type 1 immunity in CNS tissues, we infected GL261 tumor-bearing mice with attenuated rabies virus (RABV). These neurotropic viruses spread to CNS tissues trans-axonally, where they induce a strong type 1 immune response that involves Th1, CD8, and B cell entry across the blood-brain barrier and virus clearance in the absence of overt sequelae. Intranasal infection with attenuated RABV prolonged the survival of mice bearing established GL261 brain tumors. Despite the failure of virus spread to the tumor, infection resulted in significantly enhanced tumor necrosis, extensive CD4 T cell accumulation, and high levels of the proinflammatory factors IFN-γ, TNF-α, and inducible NO synthase in the TME merely 4 d postinfection, before significant virus spread or the appearance of RABV-specific immune mechanisms in CNS tissues. Although the majority of infiltrating CD4 cells appeared functionally inactive, the proinflammatory changes in the TME later resulted in the loss of accumulating M2 and increased M1 TAMs. Mice deficient in the Th1 transcription factor T-bet did not gain any survival advantage from RABV infection, exhibiting only limited tumor necrosis and no change in TME cytokines or TAM phenotype and highlighting the importance of type 1 mechanisms in this process. Copyright © 2017 by The American Association of Immunologists, Inc.

  3. Lipid-based nutrient supplements containing vitamins and minerals attenuate renal electrolyte loss in HIV/AIDS patients starting antiretroviral therapy: A randomized controlled trial in Zambia.

    Science.gov (United States)

    Munkombwe, D; Muungo, T L; Michelo, C; Kelly, P; Chirwa, S; Filteau, S

    2016-06-01

    Advanced HIV infection combined with undernutrition and antiretroviral therapy (ART) places HIV/AIDS patients at high risk of electrolyte abnormalities and increased morbidity and mortality. Here, in a sub-study of a large published randomized trial, we evaluated if nutritional supplements will help curtail renal electrolyte loss in HIV/AIDS patients starting ART. 130 malnourished HIV-positive patients referred for ART received lipid-based nutrient supplements alone (LNS, n = 63) or together with vitamins and minerals (LNS-VM, n = 67). Serum and spot urine samples were collected and assayed for creatinine, potassium, magnesium and phosphate concentrations at baseline and after 12 weeks of ART, and fractional excretion and reabsorption were calculated using standard equations. Eighteen (28.6%) patients from the LNS and 16 (23.9%) from LNS-VM groups died, most during the referral interval before starting ART. Phosphate excretion at baseline, was high in both LNS (mean ± SD: 1.2 ± 0.6 mg/mg creatinine) and LNS-VM (1.1 ± 0.8 mg/mg creatinine) groups relative to normal physiological ranges. Phosphate excretion remained high in the LNS group (1.1 ± 0.41 mg/mg creatinine) but significantly decreased in the LNS-VM group (0.6 ± 0.28 mg/mg creatinine; p 6.4%) reflecting renal potassium wasting. However, FEK was significantly lowered in the LNS-VM group (6.2 ± 3.4%) but not in the LNS group (12.8 ± 4.7%) after 12 weeks of ART (p < 0.001). Finally, the fractional excretion of magnesium was not significantly different between the two groups at baseline (p = 0.68) and remained unchanged within normal physiological ranges at 12 weeks of ART (p = 0.82) in both groups. The LNS-VM regimen appeared to offer protection against phosphate and potassium loss during HIV/AIDS treatment. This offers potential opportunities to improve care and support of poorly nourished HIV-infected patients in resource-limited settings. www.pactr.org ID number: PACTR

  4. Mycobacterium tuberculosis osteomyelitis in a patient with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS): a case report

    Science.gov (United States)

    2010-01-01

    The incidence of tuberculosis is increasing in the United States. Extra-pulmonary involvement is more common in patients with HIV/AIDS. The diagnosis of Tuberculosis osteomyelitis requires a high degree of suspicion for accurate and timely diagnosis. We present a case of a 49 year old Caucasian male with HIV/AIDS who presented with a four-month history of soft tissue swelling in the left proximal thigh unresponsive to various broad spectrum antibiotics who was eventually diagnosed with Mycobacterium tuberculosis osteomyelitis of the left proximal femur. PMID:20178567

  5. Genetic and phenotypic properties of vero cell-adapted Japanese encephalitis virus SA14-14-2 vaccine strain variants and a recombinant clone, which demonstrates attenuation and immunogenicity in mice.

    Science.gov (United States)

    Gromowski, Gregory D; Firestone, Cai-Yen; Bustos-Arriaga, José; Whitehead, Stephen S

    2015-01-01

    The live-attenuated Japanese encephalitis virus (JEV) SA14-14-2 vaccine, produced in primary hamster kidney cells, is safe and effective. Past attempts to adapt this virus to replicate in cells that are more favorable for vaccine production resulted in mutations that significantly reduced immunogenicity. In this study, 10 genetically distinct Vero cell-adapted JEV SA14-14-2 variants were isolated and a recombinant wild-type JEV clone, modified to contain the JEV SA14-14-2 polyprotein amino acid sequence, was recovered in Vero cells. A single capsid protein mutation (S66L) was important for Vero cell-adaptation. Mutations were also identified that modulated virus sensitivity to type I interferon-stimulation in Vero cells. A subset of JEV SA14-14-2 variants and the recombinant clone were evaluated in vivo and exhibited levels of attenuation that varied significantly in suckling mice, but were avirulent and highly immunogenic in weanling mice and are promising candidates for the development of a second-generation, recombinant vaccine. © The American Society of Tropical Medicine and Hygiene.

  6. 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].

  7. Risk assessment of hepatotoxicity among tuberculosis and human immunodeficiency virus/AIDS-coinfected patients under tuberculosis treatment

    Directory of Open Access Journals (Sweden)

    Williams Ngouleun

    2016-01-01

    Conclusion: The results showed that human immunodeficiency virus status and alcohol consumption constitutes aggravating factors for the occurrence of hepatic toxicity. In addition, the consumption of antioxidant foods simultaneously with TB drugs help in reducing the hepatotoxic effects of these drugs.

  8. Researchers See New Patterns in Spread of AIDS Virus; Progress in Development of a Vaccine Sparks Optimism.

    Science.gov (United States)

    Wheeler, David L.

    1990-01-01

    Reports presented at the Sixth International Conference on Aids are summarized including efforts to develop a vaccine, expansion of the epidemic into new areas, the high rate of infection among Romanian children, the crisis in Africa, and evidence of relapsing behaviors among homosexual men in the United States. (MLW)

  9. [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.

  10. [AIDS: the children also].

    Science.gov (United States)

    Kpatinde, F

    1987-10-28

    It is no longer possible for health officials or politicians in Africa to deny the existence of acquired immune deficiency syndrome (AIDS) in their countries in the name of nationalism. Educational and research programs and appeals for international aid to fight the epidemic have become the rule. Almost all sub-Saharan African nations have sought World Health Organization (WHO) assistance for AIDS control. Children contracting the virus transplacentally before birth are among the population groups most affected by AIDS. Half of all AIDS cases in Africa are women, and their high fertility rates have led to a growing incidence of AIDS in children. Although reliable data are lacking, an estimated 6000 children and babies in Zambia are seropositive or ill, and in Rwanda 22% of AIDS victims are children. Some 10% of pregnant women in Zaire may carry the virus. Cases of AIDS in children also occur in Europe and the US, where it is estimated that 10,000-20,000 children under 13 will be AIDS carriers in 1991. Infants of infected mothers in France have a 50% chance of developing the virus, but in Africa the figure is lower. After birth, incubation of the virus is very rapid. The virus destroys not only T4 lymphocytes, but also the B lymphocytes which protect babies against bacteria. Symptoms appear in the first 6 months: cough, diarrhea, respiratory ailments, bacterial or fungal infections, and neurological problems if the virus attacks the brain. In Africa, use of contaminated needles for vaccinations and contaminated blood for transfusions have also been responsible for infecting some children with the AIDS virus. The possibility of infection through the mother's milk for breastfeeding babies has been raised; the evidence is inconclusive, but the WHO recommends pasteurization of human milk received by milk banks as a precaution. Prevention and the search for a cure are the most critical needs for AIDS control. Although moralizing should be avoided, it must be pointed out

  11. Dysfunctional Epstein-Barr virus (EBV)-specific CD8(+) T lymphocytes and increased EBV load in HIV-1 infected individuals progressing to AIDS-related non-Hodgkin lymphoma

    NARCIS (Netherlands)

    van Baarle, D; Hovenkamp, E; Callan, M F; Wolthers, K C; Kostense, S; Tan, L C; Niesters, H G; Osterhaus, A D; McMichael, A J; van Oers, M H; Miedema, F

    2001-01-01

    Acquired immunodeficiency syndrome-related non-Hodgkin lymphomas (AIDS-NHL) are thought to arise because of loss of Epstein-Barr Virus (EBV)-specific cellular immunity. Here, an investigation was done to determine whether cellular immunity to EBV is lost because of physical loss or dysfunction of

  12. 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

  13. Temperature-Sensitive Mutants in the Influenza A Virus RNA Polymerase: Alterations in the PA Linker Reduce Nuclear Targeting of the PB1-PA Dimer and Result in Viral Attenuation.

    Science.gov (United States)

    Da Costa, Bruno; Sausset, Alix; Munier, Sandie; Ghounaris, Alexandre; Naffakh, Nadia; Le Goffic, Ronan; Delmas, Bernard

    2015-06-01

    The influenza virus RNA-dependent RNA polymerase catalyzes genome replication and transcription within the cell nucleus. Efficient nuclear import and assembly of the polymerase subunits PB1, PB2, and PA are critical steps in the virus life cycle. We investigated the structure and function of the PA linker (residues 197 to 256), located between its N-terminal endonuclease domain and its C-terminal structured domain that binds PB1, the polymerase core. Circular dichroism experiments revealed that the PA linker by itself is structurally disordered. A large series of PA linker mutants exhibited a temperature-sensitive (ts) phenotype (reduced viral growth at 39.5°C versus 37°C/33°C), suggesting an alteration of folding kinetic parameters. The ts phenotype was associated with a reduced efficiency of replication/transcription of a pseudoviral reporter RNA in a minireplicon assay. Using a fluorescent-tagged PB1, we observed that ts and lethal PA mutants did not efficiently recruit PB1 to reach the nucleus at 39.5°C. A protein complementation assay using PA mutants, PB1, and β-importin IPO5 tagged with fragments of the Gaussia princeps luciferase showed that increasing the temperature negatively modulated the PA-PB1 and the PA-PB1-IPO5 interactions or complex stability. The selection of revertant viruses allowed the identification of different types of compensatory mutations located in one or the other of the three polymerase subunits. Two ts mutants were shown to be attenuated and able to induce antibodies in mice. Taken together, our results identify a PA domain critical for PB1-PA nuclear import and that is a "hot spot" to engineer ts mutants that could be used to design novel attenuated vaccines. By targeting a discrete domain of the PA polymerase subunit of influenza virus, we were able to identify a series of 9 amino acid positions that are appropriate to engineer temperature-sensitive (ts) mutants. This is the first time that a large number of ts mutations were

  14. Histoplasmosis in patients with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS): multicenter study of outcomes and factors associated with relapse.

    Science.gov (United States)

    Myint, Thein; Anderson, Albert M; Sanchez, Alejandro; Farabi, Alireza; Hage, Chadi; Baddley, John W; Jhaveri, Malhar; Greenberg, Richard N; Bamberger, David M; Rodgers, Mark; Crawford, Timothy N; Wheat, L Joseph

    2014-01-01

    Although discontinuation of suppressive antifungal therapy for acquired immunodeficiency syndrome (AIDS)-associated histoplasmosis is accepted for patients with immunologic recovery, there have been no published studies of this approach in clinical practice, and minimal characterization of individuals who relapse with this disease. We performed a multicenter retrospective cohort study to determine the outcome in AIDS patients following discontinuation of suppressive antifungal therapy for histoplasmosis. Ninety-seven patients were divided into a physician-discontinued suppressive therapy group (PD) (38 patients) and a physician-continued suppressive therapy group (PC) (59 patients). The 2 groups were not statistically different at baseline, but at discontinuation of therapy and at the most recent follow-up there were significant differences in adherence to therapy, human immunodeficiency virus (HIV) RNA, and urinary Histoplasma antigen concentration. There was no relapse or death attributed to histoplasmosis in the PD group compared with 36% relapse (p 150 cells/mL, HIV RNA <400 c/mL, Histoplasma antigenuria <2 ng/mL (equivalent to <4.0 units in second-generation method), and no CNS histoplasmosis.

  15. Epidemiology of human immuno-deficiency virus and quality of life for people living with HIV/AIDS in China.

    Science.gov (United States)

    Mkangara, Ommari Baaliy; Nie, Shaofa; Wang, Chongjian; Xu, Yihua; Mweri, Saumu Tobbi; Kobelo, Theresia M; Bapumiia, Mustaafa

    2008-04-01

    HIV/AIDS is increasing in prevalence in China and spread of infection from highly risk populations to the general populations was recognized. Despite the fact, there are still only few scientific reviews on quality of life (QOL) for people living with HIV/AIDS (PLWHAs). However, many PLWHAs are struggling with social and psychological influences such as substances abuse, cultural beliefs, depression, stigma, poverty, which can affect their QOL. Public unawareness about infection and disease, willingness to seek medical care and motivation to follow therapy are indirectly influencing health outcome. In 2003 Chinese government has established the so-called the "Four Frees and One Care" policy. The policy was officially implemented from 2004 in some areas, yet to date it is not implemented nationwide. This paper discussed the epidemiology of HIV, underlying psychosocial factors affecting PLWHAs and their impact on QOL. We put forward some recommendations for stakeholders, advocacy groups, non-government organizations and Chinese government.

  16. 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.

  17. Computer-aided identification, design and synthesis of a novel series of compounds with selective antiviral activity against chikungunya virus.

    Science.gov (United States)

    Bassetto, Marcella; De Burghgraeve, Tine; Delang, Leen; Massarotti, Alberto; Coluccia, Antonio; Zonta, Nicola; Gatti, Valerio; Colombano, Giampiero; Sorba, Giovanni; Silvestri, Romano; Tron, Gian Cesare; Neyts, Johan; Leyssen, Pieter; Brancale, Andrea

    2013-04-01

    Chikungunya virus (CHIKV) is an Arbovirus that is transmitted to humans primarily by the mosquito species Aedes aegypti. Infection with this pathogen is often associated with fever, rash and arthralgia. Neither a vaccine nor an antiviral drug is available for the prevention or treatment of this disease. Albeit considered a tropical pathogen, adaptation of the virus to the mosquito species Aedes albopictus, which is also very common in temperate zones, has resulted in recent outbreaks in Europe and the US. In the present study, we report on the discovery of a novel series of compounds that inhibit CHIKV replication in the low μM range. In particular, we initially performed a virtual screening simulation of ∼5 million compounds on the CHIKV nsP2, the viral protease, after which we investigated and explored the Structure-Activity Relationships of the hit identified in silico. Overall, a series of 26 compounds, including the original hit, was evaluated in a virus-cell-based CPE reduction assay. The study of such selective inhibitors will contribute to a better understanding of the CHIKV replication cycle and may represents a first step towards the development of a clinical candidate drug for the treatment of this disease. Copyright © 2013 Elsevier B.V. All rights reserved.

  18. Acquired I mmunedeficiency Syndrome (AIDS)

    African Journals Online (AJOL)

    T-lymphotropic virus, type III (HTLV -III), a retrovirus believed to be the causative agent. The virus is also ... In the great debate, excitement and fear which surrounds the origins, mode of transmis- sion and prognosis of AIDS ... hepatitis B virus infections, alcoho- lism and road traffic accidents, none of which have received any.

  19. Interferon-alpha/beta deficiency greatly exacerbates arthritogenic disease in mice infected with wild-type chikungunya virus but not with the cell culture-adapted live-attenuated 181/25 vaccine candidate.

    Science.gov (United States)

    Gardner, Christina L; Burke, Crystal W; Higgs, Stephen T; Klimstra, William B; Ryman, Kate D

    2012-04-10

    In humans, chikungunya virus (CHIKV) infection causes fever, rash, and acute and persisting polyarthralgia/arthritis associated with joint swelling. We report a new CHIKV disease model in adult mice that distinguishes the wild-type CHIKV-LR strain from the live-attenuated vaccine strain (CHIKV-181/25). Although eight-week old normal mice inoculated in the hind footpad developed no hind limb swelling with either virus, CHIKV-LR replicated in musculoskeletal tissues and caused detectable inflammation. In mice deficient in STAT1-dependent interferon (IFN) responses, CHIKV-LR caused significant swelling of the inoculated and contralateral limbs and dramatic inflammatory lesions, while CHIKV-181/25 vaccine and another arthritogenic alphavirus, Sindbis, failed to induce swelling. IFN responses suppressed CHIKV-LR and CHIKV-181/25 replication equally in dendritic cells in vitro whereas macrophages were refractory to infection independently of STAT1-mediated IFN responses. Glycosaminoglycan (GAG) binding may be a CHIKV vaccine attenuation mechanism as CHIKV-LR infectivity was not dependent upon GAG, while CHIKV-181/25 was highly dependent. Copyright © 2012 Elsevier Inc. All rights reserved.

  20. Mutations Driving Airborne Transmission of A/H5N1 Virus in Mammals Cause Substantial Attenuation in Chickens only when combined

    NARCIS (Netherlands)

    M. Richard (Mathilde); S. Herfst (Sander); J.M.A. van den Brand (Judith); D. de Meulder (Dennis); P. Lexmond (Pascal); T.M. Bestebroer (Theo); R.A.M. Fouchier (Ron)

    2017-01-01

    textabstractA/H5N1 influenza viruses pose a threat to human and animal health. A fully avian A/H5N1 influenza virus was previously shown to acquire airborne transmissibility between ferrets upon accumulation of five or six substitutions that affected three traits: polymerase activity,

  1. A molecularly cloned, live-attenuated japanese encephalitis vaccine SA14-14-2 virus: a conserved single amino acid in the ij Hairpin of the Viral E glycoprotein determines neurovirulence in mice.

    Science.gov (United States)

    Yun, Sang-Im; Song, Byung-Hak; Kim, Jin-Kyoung; Yun, Gil-Nam; Lee, Eun-Young; Li, Long; Kuhn, Richard J; Rossmann, Michael G; Morrey, John D; Lee, Young-Min

    2014-07-01

    Japanese encephalitis virus (JEV), a mosquito-borne flavivirus that causes fatal neurological disease in humans, is one of the most important emerging pathogens of public health significance. JEV represents the JE serogroup, which also includes West Nile, Murray Valley encephalitis, and St. Louis encephalitis viruses. Within this serogroup, JEV is a vaccine-preventable pathogen, but the molecular basis of its neurovirulence remains unknown. Here, we constructed an infectious cDNA of the most widely used live-attenuated JE vaccine, SA14-14-2, and rescued from the cDNA a molecularly cloned virus, SA14-14-2MCV, which displayed in vitro growth properties and in vivo attenuation phenotypes identical to those of its parent, SA14-14-2. To elucidate the molecular mechanism of neurovirulence, we selected three independent, highly neurovirulent variants (LD50, 1.5×105 PFU) by serial intracerebral passage in mice. Complete genome sequence comparison revealed a total of eight point mutations, with a common single G1708→A substitution replacing a Gly with Glu at position 244 of the viral E glycoprotein. Using our infectious SA14-14-2 cDNA technology, we showed that this single Gly-to-Glu change at E-244 is sufficient to confer lethal neurovirulence in mice, including rapid development of viral spread and tissue inflammation in the central nervous system. Comprehensive site-directed mutagenesis of E-244, coupled with homology-based structure modeling, demonstrated a novel essential regulatory role in JEV neurovirulence for E-244, within the ij hairpin of the E dimerization domain. In both mouse and human neuronal cells, we further showed that the E-244 mutation altered JEV infectivity in vitro, in direct correlation with the level of neurovirulence in vivo, but had no significant impact on viral RNA replication. Our results provide a crucial step toward developing novel therapeutic and preventive strategies against JEV and possibly other encephalitic flaviviruses.

  2. [GESIDA/National AIDS Plan: Consensus document on antiretroviral therapy in adults infected by the human immunodeficiency virus (Updated January 2015)].

    Science.gov (United States)

    2015-10-01

    This consensus document is an update of combined antiretroviral therapy (cART) guidelines and recommendations for HIV-1 infected adult patients. To formulate these recommendations, a panel composed of members of the AIDS Study Group and the AIDS National Plan (GeSIDA/Plan Nacional sobre el Sida) reviewed the efficacy and safety advances in clinical trials, and cohort and pharmacokinetic studies published in medical journals (PubMed and Embase) or presented in medical scientific meetings. The strength of the recommendations, and the evidence that supports them, are based on modified criteria of the Infectious Diseases Society of America. In this update, cART is recommended for all patients infected by type 1 human immunodeficiency virus (HIV-1). The strength and level of the recommendation depends on the CD4+T-lymphocyte count, the presence of opportunistic diseases or comorbid conditions, age, and prevention of transmission of HIV. The objective of cART is to achieve an undetectable plasma viral load. Initial cART should always comprise a combination of 3 drugs, including 2 nucleoside reverse transcriptase inhibitors, and a third drug from a different family. Three out of the ten recommended regimes are regarded as preferential (all of them with an integrase inhibitor as the third drug), and the other seven (based on a non-nucleoside reverse transcriptase inhibitor, a ritonavir-boosted protease inhibitor, or an integrase inhibitor) as alternatives. This update presents the causes and criteria for switching cART in patients with undetectable plasma viral load, and in cases of virological failure where rescue cART should comprise 3 (or at least 2) drugs that are fully active against the virus. An update is also provided for the specific criteria for cART in special situations (acute infection, HIV-2 infection, and pregnancy) and with comorbid conditions (tuberculosis or other opportunistic infections, kidney disease, liver disease, and cancer). These new guidelines

  3. [Cerebral infarction and intracranial aneurysm related to the reactivation of varicella zoster virus in a Japanese acquired immunodeficiency syndrome (AIDS) patient].

    Science.gov (United States)

    Yasuda, Chiharu; Okada, Kazumasa; Ohnari, Norihiro; Akamatsu, Naoki; Tsuji, Sadatoshi

    2013-01-01

    A 35-years-old right-handed man admitted to our hospital with a worsening of dysarthria, left facial palsy and left hemiparesis for 2 days. Acquired immunodeficiency syndrome (AIDS) was diagnosed when he was 28 years old. At that time, he also was treated for syphilis. After highly active antiretroviral treatment (HAART) was introduced at the age of 35 years old, serum level of human immunodeficiency virus (HIV) was not detected, but the number of CD4+ T cells was still less than 200/μl. He had no risk factors of atherosclerosis including hypertension, diabetes and hyperlipidemia. He had neither coagulation abnormality nor autoimmune disease. Magnetic resonance imaging (MRI) showed acute ischemic infarction spreading from the right corona radiate to the right internal capsule without contrast enhancement. Stenosis and occlusion of intracranial arteries were not detected by MR angiography. Although argatroban and edaravone were administered, his neurological deficits were worsened to be difficult to walk independently. Cerebrospinal fluid (CSF) examination showed a mild mononuclear pleocytosis (16/μl). Oligoclonal band was positive. The titer of anti-varicella zoster virus (VZV) IgG antibodies was increased, that indicated VZV reactivation in the central nervous system (CNS), although VZV DNA PCR was not detected. Therefore, acyclovir (750 mg/day for 2 weeks) and valaciclovir (3,000 mg/day for 1 month) were administered in addition to stroke therapy. He recovered to be able to walk independently 2 month after the admission.Angiography uncovered a saccular aneurysm of 3 mm at the end of branch artery of right anterior cerebral artery, Heubner artery, 28 days after the admission. We speculated that VZV vasculopathy caused by VZV reactivation in CNS was involved in the pathomechanism of cerebral infarction rather than HIV vasculopathy in the case.

  4. Retrospective Species Identification of Microsporidian Spores in Diarrheic Fecal Samples from Human Immunodeficiency Virus/AIDS Patients by Multiplexed Fluorescence In Situ Hybridization▿

    Science.gov (United States)

    Graczyk, Thaddeus K.; Johansson, Michael A.; Tamang, Leena; Visvesvara, Govinda S.; Moura, Laci S.; DaSilva, Alexandre J.; Girouard, Autumn S.; Matos, Olga

    2007-01-01

    In order to assess the applicability of multiplexed fluorescence in situ hybridization (FISH) assay for the clinical setting, we conducted retrospective analysis of 110 formalin-stored diarrheic stool samples from human immunodeficiency virus (HIV)/AIDS patients with intestinal microsporidiosis collected between 1992 and 2003. The multiplexed FISH assay identified microsporidian spores in 94 of 110 (85.5%) samples: 49 (52.1%) were positive for Enterocytozoon bieneusi, 43 (45.8%) were positive for Encephalitozoon intestinalis, 2 (2.1%) were positive for Encephalitozoon hellem, and 9 samples (9.6%) contained both E. bieneusi and E. intestinalis spores. Quantitative spore counts per ml of stool yielded concentration values from 3.5 × 103 to 4.4 × 105 for E. bieneusi (mean, 8.8 × 104/ml), 2.3 × 102 to 7.8 × 104 (mean, 1.5 × 104/ml) for E. intestinalis, and 1.8 × 102 to 3.6 × 102 for E. hellem (mean, 2.7 × 102/ml). Identification of microsporidian spores by multiplex FISH assay was more sensitive than both Chromotrope-2R and CalcoFluor White M2R stains; 85.5% versus 72.7 and 70.9%, respectively. The study demonstrated that microsporidian coinfection in HIV/AIDS patients with intestinal microsporidiosis is not uncommon and that formalin-stored fecal samples older than 10 years may not be suitable for retrospective analysis by techniques targeting rRNA. Multiplexed FISH assay is a reliable, quantitative fluorescence microscopy method for the simultaneous identification of E. bieneusi, E. intestinalis, and E. hellem, as well as Encephalitozoon cuniculi, spores in fecal samples and is a useful tool for assessing spore shedding intensity in intestinal microsporidiosis. The method can be used for epidemiological investigations and applied in clinical settings. PMID:17287331

  5. Replicon-Helper Systems from Attenuated Venezuelan Equine Encephalitis Virus: Expression of Heterologous Genes in Vitro and Immunization Against Heterologous Pathogens in Vivo

    National Research Council Canada - National Science Library

    Pushko, Peter

    1997-01-01

    ...) or the Lassa virus nucleocapsid (N) gene, and upon transfection into eukaryotic cells by electroportation, these replicon RNAs directed the efficient, high-level synthesis of the HA or N proteins...

  6. Human immunodeficiency virus and AIDS and other important predictors of maternal mortality in Mulago Hospital Complex Kampala Uganda

    Directory of Open Access Journals (Sweden)

    Khainza Betty

    2011-07-01

    Full Text Available Abstract Background Women with severe maternal morbidity are at high risk of dying. Quality and prompt management and sometimes luck have been suggested to reduce on the risk of dying. The objective of the study was to identify the direct and indirect causes of severe maternal morbidity, predictors of progression from severe maternal morbidity to maternal mortality in Mulago hospital, Kampala, Uganda. Methods This was a longitudinal follow up study at the Mulago hospital's Department of Obstetrics and Gynaecology. Participants were 499 with severe maternal morbidity admitted in Mulago hospital between 15th November 2001 and 30th November 2002 were identified, recruited and followed up until discharge or death. Potential prognostic factors were HIV status and CD4 cell counts, socio demographic characteristics, medical and gynaecological history, past and present obstetric history and intra- partum and postnatal care. Results Severe pre eclampsia/eclampsia, obstructed labour and ruptured uterus, severe post partum haemorrhage, severe abruptio and placenta praevia, puerperal sepsis, post abortal sepsis and severe anaemia were the causes for the hospitalization of 499 mothers. The mortality incidence rate was 8% (n = 39, maternal mortality ratio of 7815/100,000 live births and the ratio of severe maternal morbidity to mortality was 12.8:1. The independent predictors of maternal mortality were HIV/AIDS (OR 5.1 95% CI 2-12.8, non attendance of antenatal care (OR 4.0, 95% CI 1.3-9.2, non use of oxytocics (OR 4.0, 95% CI 1.7-9.7, lack of essential drugs (OR 3.6, 95% CI 1.1-11.3 and non availability of blood for transfusion (OR 53.7, 95% CI (15.7-183.9 and delivery of amale baby (OR 4.0, 95% CI 1.6-10.1. Conclusion The predictors of progression from severe maternal morbidity to mortalitywere: residing far from hospital, low socio economic status, non attendance of antenatal care, poor intrapartum care, and HIV/AIDS. There is need to improve on the

  7. Human immunodeficiency virus integrase inhibitors efficiently suppress feline immunodeficiency virus replication in vitro and provide a rationale to redesign antiretroviral treatment for feline AIDS

    Directory of Open Access Journals (Sweden)

    Ciervo Alessandra

    2007-10-01

    Full Text Available Abstract Background Treatment of feline immunodeficiency virus (FIV infection has been hampered by the absence of a specific combination antiretroviral treatment (ART. Integrase strand transfer inhibitors (INSTIs are emerging as a promising new drug class for HIV-1 treatment, and we evaluated the possibility of inhibiting FIV replication using INSTIs. Methods Phylogenetic analysis of lentiviral integrase (IN sequences was carried out using the PAUP* software. A theoretical three-dimensional structure of the FIV IN catalytic core domain (CCD was obtained by homology modeling based on a crystal structure of HIV-1 IN CCD. The interaction of the transferred strand of viral DNA with the catalytic cavity of FIV IN was deduced from a crystal structure of a structurally similar transposase complexed with transposable DNA. Molecular docking simulations were conducted using a genetic algorithm (GOLD. Antiviral activity was tested in feline lymphoblastoid MBM cells acutely infected with the FIV Petaluma strain. Circular and total proviral DNA was quantified by real-time PCR. Results The calculated INSTI-binding sites were found to be nearly identical in FIV and HIV-1 IN CCDs. The close similarity of primate and feline lentivirus IN CCDs was also supported by phylogenetic analysis. In line with these bioinformatic analyses, FIV replication was efficiently inhibited in acutely infected cell cultures by three investigational INSTIs, designed for HIV-1 and belonging to different classes. Of note, the naphthyridine carboxamide INSTI, L-870,810 displayed an EC50 in the low nanomolar range. Inhibition of FIV integration in situ was shown by real-time PCR experiments that revealed accumulation of circular forms of FIV DNA within cells treated with L-870,810. Conclusion We report a drug class (other than nucleosidic reverse transcriptase inhibitors that is capable of inhibiting FIV replication in vitro. The present study helped establish L-870,810, a compound

  8. Human immunodeficiency virus type 1 gp120 induces abnormal maturation and functional alterations of dendritic cells: a novel mechanism for AIDS pathogenesis.

    Science.gov (United States)

    Fantuzzi, Laura; Purificato, Cristina; Donato, Karim; Belardelli, Filippo; Gessani, Sandra

    2004-09-01

    Dendritic cells (DCs) play a crucial role in bridging innate and acquired immune responses to pathogens. In human immunodeficiency virus type 1 (HIV-1) infection, immature DCs (iDCs) are also main targets for HIV-1 at the mucosal level. In this study, we evaluated the effects of HIV-1-DC interactions on the maturation and functional activity of these cells. Exposure of human monocyte-derived iDCs to either aldrithiol-2-inactivated HIV-1 or gp120 led to an upmodulation of activation markers indicative of functional maturation. Despite their phenotype, these cells retained antigen uptake capacity and showed an impaired ability to secrete cytokines or chemokines and to induce T-cell proliferation. Although gp120 did not interfere with DC differentiation, the capacity of these cells to produce interleukin-12 (IL-12) upon maturation was markedly reduced. Likewise, iDCs stimulated by classical maturation factors in the presence of gp120 lacked allostimulatory capacity and did not produce IL-12, in spite of their phenotype typical of activated DCs. Exogenous addition of IL-12 restores the allostimulatory capacity of gp120-exposed DCs. The finding that gp120 induces abnormal maturation of DCs linked to profound suppression of their activities unravels a novel mechanism by which HIV can lead to immune dysfunction in AIDS patients. Copyright 2004 American Society for Microbiology

  9. Treatment of multifocal central nervous system AIDS-related Epstein Barr virus-associated malignant myopericytoma with bevacizumab

    Directory of Open Access Journals (Sweden)

    Linda Szymanski

    2017-09-01

    Full Text Available A 31 year-old man with HIV and pulmonary tuberculosis (TB status-post RIPE regimen presented with cough and throbbing headaches. Laboratory results were remarkable for a CD4 count of 2 kcells/L and a viral load of 2.7 million copies/mL. MRI of the brain reported multiple lobulated and cystic intracranial lesions associated with the dura that had thick rinds of enhancement. CT of the chest, abdomen and pelvis demonstrated axillary and inguinal lymphadenopathy, a mass within the right pelvis thought to represent necrotic lymph nodes, prominence of the right psoas muscle, a cystic nodule in the liver, and a right adrenal lesion. The patient was started on dexamethasone, RIPE therapy, and empiric antimicrobial therapy. He subsequently underwent stealth-guided brain biopsy and open craniotomy. Pathology returned a tissue diagnosis of an AIDS related EBV-associated smooth muscle tumor (EBV-SMT best categorized as a malignant myopericytoma. Following surgery, the patient began additional anti-retroviral therapy for HIV and was discharged. Despite treatment, three to four months following discharge the patient's symptoms progressed and he was found to have developed a severe bilateral homonymous hemianopsia. Repeat MRI demonstrated tumor growth and the patient subsequently received whole brain radiation along with sirolimus and pomalidomide. Approximately two months following radiation therapy the patient had increasing headaches along with nausea and vomiting. Repeat MRI was consistent with radiation arrested tumor growth but did not show any decrease in size of his intracranial lesions. Therapy with bevacizumab was initiated and he had marked improvement of his visual field deficits. The patient has since completed 20 cycles of treatment with bevacizumab and is currently 17 months post his initial diagnosis. Repeat imaging has demonstrated decreasing size of his lesions and no new lesions have developed.

  10. 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.

  11. Live, Attenuated Venezuelan Equine Encephalitis Virus Vaccine (TC83) Causes Persistent Brain Infection in Mice with Non-functional αβ T-Cells

    Science.gov (United States)

    Taylor, Katherine; Kolokoltsova, Olga; Ronca, Shannon E.; Estes, Mark; Paessler, Slobodan

    2017-01-01

    Intranasal infection with vaccine strain of Venezuelan equine encephalitis virus (TC83) caused persistent viral infection in the brains of mice without functional αβ T-cells (αβ-TCR -/-). Remarkably, viral kinetics, host response gene transcripts and symptomatic disease are similar between αβ-TCR -/- and wild-type C57BL/6 (WT) mice during acute phase of infection [0–13 days post-infection (dpi)]. While WT mice clear infectious virus in the brain by 13 dpi, αβ-TCR -/- maintain infectious virus in the brain to 92 dpi. Persistent brain infection in αβ-TCR -/- correlated with inflammatory infiltrates and elevated cytokine protein levels in the brain at later time points. Persistent brain infection of αβ-TCR -/- mice provides a novel model to study prolonged alphaviral infection as well as the effects and biomarkers of long-term viral inflammation in the brain. PMID:28184218

  12. Characterization of a new simian immunodeficiency virus strain in a naturally infected Pan troglodytes troglodytes chimpanzee with AIDS related symptoms

    Directory of Open Access Journals (Sweden)

    Aghokeng Avelin F

    2011-01-01

    Full Text Available Abstract Background Data on the evolution of natural SIV infection in chimpanzees (SIVcpz and on the impact of SIV on local ape populations are only available for Eastern African chimpanzee subspecies (Pan troglodytes schweinfurthii, and no data exist for Central chimpanzees (Pan troglodytes troglodytes, the natural reservoir of the ancestors of HIV-1 in humans. Here, we report a case of naturally-acquired SIVcpz infection in a P.t.troglodytes chimpanzee with clinical and biological data and analysis of viral evolution over the course of infection. Results A male chimpanzee (Cam155, 1.5 years, was seized in southern Cameroon in November 2003 and screened SIV positive during quarantine. Clinical follow-up and biological analyses have been performed for 7 years and showed a significant decline of CD4 counts (1,380 cells/mm3 in 2004 vs 287 in 2009, a severe thrombocytopenia (130,000 cells/mm3 in 2004 vs 5,000 cells/mm3 in 2009, a weight loss of 21.8% from August 2009 to January 2010 (16 to 12.5 kg and frequent periods of infections with diverse pathogens. DNA from PBMC, leftover from clinical follow-up samples collected in 2004 and 2009, was used to amplify overlapping fragments and sequence two full-length SIVcpzPtt-Cam155 genomes. SIVcpzPtt-Cam155 was phylogenetically related to other SIVcpzPtt from Cameroon (SIVcpzPtt-Cam13 and Gabon (SIVcpzPtt-Gab1. Ten molecular clones 5 years apart, spanning the V1V4 gp120 env region (1,100 bp, were obtained. Analyses of the env region showed positive selection (dN-dS >0, intra-host length variation and extensive amino acid diversity between clones, greater in 2009. Over 5 years, N-glycosylation site frequency significantly increased (p Conclusions Here, we describe for the first time the clinical history and viral evolution of a naturally SIV infected P.t.troglodytes chimpanzee. The findings show an increasing viral diversity over time and suggest clinical progression to an AIDS-like disease, showing that

  13. 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 ...

  14. Safety profile of the viral vectors of attenuated fowlpox strain FP9 and modified vaccinia virus Ankara recombinant for either of 2 preerythrocytic malaria antigens, ME-TRAP or the circumsporozoite protein, in children and adults in Kenya.

    Science.gov (United States)

    Bejon, Philip; Peshu, Norbert; Gilbert, Sarah C; Lowe, Brett S; Molyneux, Catherine S; Forsdyke, John; Lang, Trudie; Hill, Adrian V S; Marsh, Kevin

    2006-04-15

    We are developing a heterologous prime-boost vaccine strategy against malaria. This approach uses sequential immunization with different vectors to deliver a common preerythrocytic malaria antigen. Preliminary evidence of efficacy and safety has been previously documented in studies from an area where malaria is nonendemic. Additional safety data from an area where malaria is endemic are now required before larger-scale studies are undertaken to determine the efficacy of this vaccine strategy in the field. Other modified vaccinia virus Ankara (MVA) recombinants and prime-boost immunizations are being developed as vaccines against human immunodeficiency virus (HIV) infection, tuberculosis, and cancer, and MVA is a candidate attenuated smallpox vaccine. Candidate vaccines against malaria were intradermally administered to 73 adults (7 of whom were HIV positive) and 22 children in Kenya. These vaccines used the attenuated fowlpox strain FP9 and the MVA recombinant for either of 2 preerythrocytic malaria antigens, multiple preerythrocytic-stage epitopes joined with the preerythrocytic-stage antigen TRAP (ME-TRAP) and the circumsporozoite protein (CS). Adverse events were recorded. Reactogenicity was mild. MVA caused less frequent and less severe cutaneous reaction if given after FP9 priming. Half doses reduced the frequency and the severity of systemic reactogenicity, and particular vaccine lots were associated with different reactogenicities. Unexpectedly, prior immunity to the ME-TRAP antigen appeared to be protective against local reactions after immunization. Where the final intention is to use MVA after FP9 priming, previous testing of MVA alone overestimates reactogenicity. These recombinant vectors appear to be safe and suitable for use in larger-scale studies of children in Africa and of HIV-positive individuals.

  15. Comparative analysis of the acute response of the trout, O. mykiss, head kidney to in vivo challenge with virulent and attenuated infectious hematopoietic necrosis virus and LPS-induced inflammation

    Directory of Open Access Journals (Sweden)

    Roher Nerea

    2008-03-01

    Full Text Available Abstract Background The response of the trout, O. mykiss, head kidney to bacterial lipopolysaccharide (LPS or active and attenuated infectious hematopoietic necrosis virus (IHNV and attINHV respectively intraperitoneal challenge, 24 and 72 hours post-injection, was investigated using a salmonid-specific cDNA microarray. Results The head kidney response to i.p. LPS-induced inflammation in the first instance displays an initial stress reaction involving suppression of major cellular processes, including immune function, followed by a proliferative hematopoietic-type/biogenesis response 3 days after administration. The viral response at the early stage of infection highlights a suppression of hematopoietic and protein biosynthetic function and a stimulation of immune response. In fish infected with IHNV a loss of cellular function including signal transduction, cell cycle and transcriptional activity 72 hours after infection reflects the tissue-specific pathology of IHNV infection. attIHNV treatment on the other hand shows a similar pattern to native IHNV infection at 24 hours however at 72 hours a divergence from the viral response is seen and replace with a recovery response more similar to that observed for LPS is observed. Conclusion In conclusion we have been able to identify and characterise by transcriptomic analysis two different types of responses to two distinct immune agents, a virus, IHNV and a bacterial cell wall component, LPS and a 'mixed' response to an attenuated IHNV. This type of analysis will lead to a greater understanding of the physiological response and the development of effective immune responses in salmonid fish to different pathogenic and pro-inflammatory agents.

  16. Non-hydrolyzed in digestive tract and blood natural L-carnosine peptide ("bioactivated Jewish penicillin") as a panacea of tomorrow for various flu ailments: signaling activity attenuating nitric oxide (NO) production, cytostasis, and NO-dependent inhibition of influenza virus replication in macrophages in the human body infected with the virulent swine influenza A (H1N1) virus.

    Science.gov (United States)

    Babizhayev, Mark A; Deyev, Anatoliy I; Yegorov, Yegor E

    2013-01-01

    in excessive amounts mediate the overreaction of the host's immune response against the organs or tissues in which viruses are replicating, and this may explain the mechanism of tissue injuries observed in influenza virus infection of various types. In this article, the types of protection of carnosine in its bioavailable non-hydrolyzed forms in formulations are considered against reactive oxygen radical species-dependent injury, peroxynitrite damage, and other types of viral injuries in which impaired immune responses to viral pathogens are usually involved. Carnosine (β-alanyl-L-histidine) shows the pharmacological intracellular correction of NO release, which might be one of the important factors of natural immunity in controlling the initial stages of influenza A virus infection (inhibition of virus replication) and virus-induced regulation of cytokine gene expression. The protective effects of orally applied non-hydrolyzed formulated species of carnosine include at least the direct interaction with NO, inhibition of cytotoxic NO-induced proinflammatory condition, and attenuation of the effects of cytokines and chemokines that can exert profound effects on inflammatory cells. These data are consistent with the hypothesis that natural products, such as chicken soup and chicken breast extracts rich in carnosine and its derivative anserine (β-alanyl-1-methyl-L-histidine), could contribute to the pathogenesis and prevention of influenza virus infections and cold but have a limitation due to the susceptibility to enzymatic hydrolysis of dipeptides with serum carnosinase and urine excretion after oral ingestion of a commercial chicken extract. The formulations of non-hydrolyzed in digestive tract and blood natural carnosine peptide and isopeptide (γ-glutamyl-carnosine) products, manufactured at the cGMP-certified facility and patented by the authors, have promise in the control and prevention of influenza A (H1N1) virus infection, cough, and cold.

  17. 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

  18. VP2-serotyped live-attenuated bluetongue virus without NS3/NS3a expression provided serotype-specific protection and enables DIVA.

    NARCIS (Netherlands)

    Feenstra, F.; Maris-Veldhuis, M.A.; Daus, F.J.; Tacken, M.G.J.; Moormann, R.J.M.; Gennip, van H.G.P.; Rijn, van P.A.

    2014-01-01

    Bluetongue virus (BTV) causes Bluetongue in ruminants and is transmitted by Culicoides biting midges. Vaccination is the most effective measure to control vector borne diseases; however, there are 26 known BTV serotypes showing little cross protection. The BTV serotype is mainly determined by genome

  19. Breaking resistance of pancreatic cancer cells to an attenuated vesicular stomatitis virus through a novel activity of IKK inhibitor TPCA-1.

    Science.gov (United States)

    Cataldi, Marcela; Shah, Nirav R; Felt, Sébastien A; Grdzelishvili, Valery Z

    2015-11-01

    Vesicular stomatitis virus (VSV) is an effective oncolytic virus against most human pancreatic ductal adenocarcinoma (PDAC) cell lines. However, some PDAC cell lines are highly resistant to oncolytic VSV-ΔM51 infection. To better understand the mechanism of resistance, we tested a panel of 16 small molecule inhibitors of different cellular signaling pathways, and identified TPCA-1 (IKK-β inhibitor) and ruxolitinib (JAK1/2 inhibitor), as strong enhancers of VSV-ΔM51 replication and virus-mediated oncolysis in all VSV-resistant PDAC cell lines. Both TPCA-1 and ruxolitinib similarly inhibited STAT1 and STAT2 phosphorylation and decreased expression of antiviral genes MxA and OAS. Moreover, an in situ kinase assay provided biochemical evidence that TPCA-1 directly inhibits JAK1 kinase activity. Together, our data demonstrate that TPCA-1 is a unique dual inhibitor of IKK-β and JAK1 kinase, and provide a new evidence that upregulated type I interferon signaling plays a major role in resistance of pancreatic cancer cells to oncolytic viruses. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Two single mutations in the fusion protein of Newcastle disease virus confer hemagglutinin-neuraminidase independent fusion promotion and attenuate the pathogenicity in chickens

    Science.gov (United States)

    The fusion (F) protein of Newcastle disease virus (NDV) plays an important role in viral infection and pathogenicity through mediating membrane fusion between the virion and host cells in the presence of the hemagglutinin-neuraminidase (HN). Previously, we obtained a velogenic NDV genotype VII muta...

  1. Highly Pathogenic New World Arenavirus Infection Activates the Pattern Recognition Receptor Protein Kinase R without Attenuating Virus Replication in Human Cells.

    Science.gov (United States)

    Huang, Cheng; Kolokoltsova, Olga A; Mateer, Elizabeth J; Koma, Takaaki; Paessler, Slobodan

    2017-10-15

    The arenavirus family consists of several highly pathogenic viruses, including the Old World (OW) arenavirus Lassa fever virus (LASV) and the New World (NW) Junin virus (JUNV) and Machupo virus (MACV). Host response to infection by these pathogenic arenaviruses is distinct in many aspects. JUNV and MACV infections readily induce an interferon (IFN) response in human cells, while LASV infection usually triggers an undetectable or weak IFN response. JUNV induces an IFN response through RIG-I, suggesting that the host non-self RNA sensor readily detects JUNV viral RNAs (vRNAs) during infection and activates IFN response. Double-stranded-RNA (dsRNA)-activated protein kinase R (PKR) is another host non-self RNA sensor classically known for its vRNA recognition activity. Here we report that infection with NW arenaviruses JUNV and MACV, but not OW LASV, activated PKR, concomitant with elevated phosphorylation of the translation initiation factor α subunit of eukaryotic initiation factor 2 (eIF2α). Host protein synthesis was substantially suppressed in MACV- and JUNV-infected cells but was only marginally reduced in LASV-infected cells. Despite the antiviral activity known for PKR against many other viruses, the replication of JUNV and MACV was not impaired but was slightly augmented in wild-type (wt) cells compared to that in PKR-deficient cells, suggesting that PKR or PKR activation did not negatively affect JUNV and MACV infection. Additionally, we found an enhanced IFN response in JUNV- or MACV-infected PKR-deficient cells, which was inversely correlated with virus replication.IMPORTANCE The detection of viral RNA by host non-self RNA sensors, including RIG-I and MDA5, is critical to the initiation of the innate immune response to RNA virus infection. Among pathogenic arenaviruses, the OW LASV usually does not elicit an interferon response. However, the NW arenaviruses JUNV and MACV readily trigger an IFN response in a RIG-I-dependent manner. Here, we demonstrate for

  2. Activation of A1-adenosine receptors promotes leukocyte recruitment to the lung and attenuates acute lung injury in mice infected with influenza A/WSN/33 (H1N1) virus.

    Science.gov (United States)

    Aeffner, Famke; Woods, Parker S; Davis, Ian C

    2014-09-01

    We have shown that bronchoalveolar epithelial A1-adenosine receptors (A1-AdoR) are activated in influenza A virus-infected mice. Alveolar macrophages and neutrophils also express A1-AdoRs, and we hypothesized that activation of A1-AdoRs on these cells will promote macrophage and neutrophil chemotaxis and activation and thereby play a role in the pathogenesis of influenza virus-induced acute lung injury. Wild-type (WT) C57BL/6 mice, congenic A1-AdoR knockout (A1-KO) mice, and mice that had undergone reciprocal bone marrow transfer were inoculated intranasally with 10,000 PFU/mouse influenza A/WSN/33 (H1N1) virus. Alternatively, WT mice underwent daily treatment with the A1-AdoR antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) from 1 day prior to inoculation. Infection increased bronchoalveolar lining fluid (BALF) adenosine comparably in WT and A1-KO mice. Infection of WT mice resulted in reduced carotid arterial O2 saturation (hypoxemia), lung pathology, pulmonary edema, reduced lung compliance, increased basal airway resistance, and hyperresponsiveness to methacholine. These effects were absent or significantly attenuated in A1-KO mice. Levels of BALF leukocytes, gamma interferon (IFN-γ), and interleukin 10 (IL-10) were significantly reduced in infected A1-KO mice, but levels of KC, IP-10, and MCP-1 were increased. Reciprocal bone marrow transfer resulted in WT-like lung injury severity, but BALF leukocyte levels increased only in WT and A1-KO mice with WT bone barrow. Hypoxemia, pulmonary edema, and levels of BALF alveolar macrophages, neutrophils, IFN-γ, and IL-10 were reduced in DPCPX-treated WT mice. Levels of viral replication did not differ between mouse strains or treatment groups. These findings indicate that adenosine activation of leukocyte A1-AdoRs plays a significant role in their recruitment to the infected lung and contributes to influenza pathogenesis. A1-AdoR inhibitor therapy may therefore be beneficial in patients with influenza virus

  3. Phylogeny of geminivirus coat protein sequences and digital PCR aid in identifying Spissistilus festinus (Say) as a vector of Grapevine red blotch-associated virus

    Science.gov (United States)

    Grapevine red blotch-associated virus (GRBaV) is a newly identified virus of grapevines, and a putative member of a new genus within the family Geminiviridae. This virus is associated with red blotch disease that was first reported in California in 2008. It affects the profitability of vineyards by ...

  4. 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...

  5. Principles for studying in vivo attenuation of virus mutants: defining the role of the cytomegalovirus gH/gL/gO complex as a paradigm.

    Science.gov (United States)

    Podlech, Jürgen; Reddehase, Matthias J; Adler, Barbara; Lemmermann, Niels A W

    2015-06-01

    Initial virus entry into cells of host organs and subsequent spread of viral progeny between tissue cells are events fundamental to viral pathogenesis. Glycoprotein complexes inserted in the virion envelope are critically involved in the cell entry process. Here we review and discuss recent work that has shed light on the in vivo role of the trimeric glycoprotein complex gH/gL/gO of murine cytomegalovirus (mCMV) as a model to propose the role of the corresponding complex of human CMV, for which experimental studies in vivo are not feasible due to the host species specificity of CMVs and evident ethical constraints. A novel approach combining gO transcomplementation of a genetically gO-deficient virus and a mathematical log-linear regression analysis of the viral multiplication kinetics in host tissues revealed a critical role of mCMV gH/gL/gO only in first target cell entry of virions arriving with the circulation, whereas intra-tissue spread proceeded unaffected also in the absence of gH/gL/gO. These findings predict that targeting gO for an antiviral intervention may be of prophylactic value in preventing the seeding of virus to organs, but will likely fail to interfere with an established primary organ infection or with recurrent infection after virus reactivation from latency within tissue cells. The demonstration in the murine model of alternative gH/gL complexes gH/gL/gO and gH/gL/MCK-2, substituting one another in a redundant fashion for securing viral spread in tissues, has the medically interesting bearing that targeting the gH/gL core complex directly may be a promising approach to preventing primary, established, and recurrent CMV infections.

  6. Infection of nonhost species dendritic cells in vitro with an attenuated myxoma virus induces gene expression that predicts its efficacy as a vaccine vector.

    Science.gov (United States)

    Top, S; Foulon, E; Pignolet, B; Deplanche, M; Caubet, C; Tasca, C; Bertagnoli, S; Meyer, G; Foucras, G

    2011-12-01

    Recombinant myxoma virus (MYXV) can be produced without a loss of infectivity, and its highly specific host range makes it an ideal vaccine vector candidate, although careful examination of its interaction with the immune system is necessary. Similar to rabbit bone marrow-derived dendritic cells (BM-DCs), ovine dendritic cells can be infected by SG33, a MYXV vaccine strain, and support recombinant antigen expression. The frequency of infected cells in the nonhost was lower and the virus cycle was abortive in these cell types. Among BM-DC subpopulations, Langerhans cell-like DCs were preferentially infected at low multiplicities of infection. Interestingly, ovine BM-DCs remained susceptible to MYXV after maturation, although apoptosis occurred shortly after infection as a function of the virus titer. When gene expression was assessed in infected BM-DC cultures, type I interferon (IFN)-related and inflammatory genes were strongly upregulated. DC gene expression profiles were compared with the profiles produced by other poxviruses in interaction with DCs, but very few commonalities were found, although genes that were previously shown to predict vaccine efficacy were present. Collectively, these data support the idea that MYXV permits efficient priming of adaptive immune responses and should be considered a promising vaccine vector along with other poxviruses.

  7. Infection of Nonhost Species Dendritic Cells In Vitro with an Attenuated Myxoma Virus Induces Gene Expression That Predicts Its Efficacy as a Vaccine Vector ▿ †

    Science.gov (United States)

    Top, S.; Foulon, E.; Pignolet, B.; Deplanche, M.; Caubet, C.; Tasca, C.; Bertagnoli, S.; Meyer, G.; Foucras, G.

    2011-01-01

    Recombinant myxoma virus (MYXV) can be produced without a loss of infectivity, and its highly specific host range makes it an ideal vaccine vector candidate, although careful examination of its interaction with the immune system is necessary. Similar to rabbit bone marrow-derived dendritic cells (BM-DCs), ovine dendritic cells can be infected by SG33, a MYXV vaccine strain, and support recombinant antigen expression. The frequency of infected cells in the nonhost was lower and the virus cycle was abortive in these cell types. Among BM-DC subpopulations, Langerhans cell-like DCs were preferentially infected at low multiplicities of infection. Interestingly, ovine BM-DCs remained susceptible to MYXV after maturation, although apoptosis occurred shortly after infection as a function of the virus titer. When gene expression was assessed in infected BM-DC cultures, type I interferon (IFN)-related and inflammatory genes were strongly upregulated. DC gene expression profiles were compared with the profiles produced by other poxviruses in interaction with DCs, but very few commonalities were found, although genes that were previously shown to predict vaccine efficacy were present. Collectively, these data support the idea that MYXV permits efficient priming of adaptive immune responses and should be considered a promising vaccine vector along with other poxviruses. PMID:21835800

  8. Modifications of the Helper Component-Protease of Zucchini yellow mosaic virus for Generation of Attenuated Mutants for Cross Protection Against Severe Infection.

    Science.gov (United States)

    Lin, Shih-Shun; Wu, Hui-Wen; Jan, Fuh-Jyh; Hou, Roger F; Yeh, Shyi-Dong

    2007-03-01

    ABSTRACT A nonpathogenic mild strain is essential for control of plant viruses by cross protection. Three amino acid changes, Arg(180)-->Ile(180) (GA mutation), Phe(205)-->Leu(205) (GB mutation), and Glu(396)-->Asn(396) (GC mutation), of the conserved motifs of the helper component-protease (HC-Pro) of a severe strain TW-TN3 of Zucchini yellow mosaic virus (ZYMV), a member of the genus Potyvirus, were generated from an infectious cDNA clone that carried a green fluorescent protein reporter. The infectivity of individual mutants containing single, double, or triple mutations was assayed on local and systemic hosts. On Chenopodium quinoa plants, the GB mutant induced necrotic lesions; the GA, GC, and GBC mutants induced chlorotic spots; and the GAB and GAC mutants induced local infection only visualized by fluorescence microscopy. On squash plants, the GA, GB, GC, and GBC mutants caused milder mosaic; the GAC mutant induced slight leaf mottling followed by recovering; and the GAB mutant did not induce conspicuous symptoms. Also, the GAC mutant, but not the GAB mutant, conferred complete cross protection against the parental virus carrying a mite allergen as a reporter. When tested on transgene-silenced transgenic squash, the ability of posttranscriptional gene silencing suppression of the mutated HC-Pro of GAC was not significantly affected. We concluded that the mutations of the HC-Pro of ZYMV reduce the degrees of pathogenicity on squash and also abolish the ability for eliciting the hypersensitive reaction on C. quinoa, and that the mutant GAC is a useful mild strain for cross protection.

  9. 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.

  10. HIV/AIDS Vaccine Candidates Based on Replication-Competent Recombinant Poxvirus NYVAC-C-KC Expressing Trimeric gp140 and Gag-Derived Virus-Like Particles or Lacking the Viral Molecule B19 That Inhibits Type I Interferon Activate Relevant HIV-1-Specific B and T Cell Immune Functions in Nonhuman Primates

    Science.gov (United States)

    García-Arriaza, Juan; Perdiguero, Beatriz; Heeney, Jonathan L.; Seaman, Michael S.; Montefiori, David C.; Yates, Nicole L.; Tomaras, Georgia D.; Ferrari, Guido; Foulds, Kathryn E.; Roederer, Mario; Self, Steven G.; Borate, Bhavesh; Gottardo, Raphael; Phogat, Sanjay; Tartaglia, Jim; Barnett, Susan W.; Burke, Brian; Cristillo, Anthony D.; Weiss, Deborah E.; Lee, Carter; Kibler, Karen V.; Jacobs, Bertram L.; Wagner, Ralf; Ding, Song; Pantaleo, Giuseppe

    2017-01-01

    ABSTRACT The nonreplicating attenuated poxvirus vector NYVAC expressing clade C(CN54) HIV-1 Env(gp120) and Gag-Pol-Nef antigens (NYVAC-C) showed limited immunogenicity in phase I clinical trials. To enhance the capacity of the NYVAC vector to trigger broad humoral responses and a more balanced activation of CD4+ and CD8+ T cells, here we compared the HIV-1-specific immunogenicity elicited in nonhuman primates immunized with two replicating NYVAC vectors that have been modified by the insertion of the K1L and C7L vaccinia virus host range genes and express the clade C(ZM96) trimeric HIV-1 gp140 protein or a Gag(ZM96)-Pol-Nef(CN54) polyprotein as Gag-derived virus-like particles (termed NYVAC-C-KC). Additionally, one NYVAC-C-KC vector was generated by deleting the viral gene B19R, an inhibitor of the type I interferon response (NYVAC-C-KC-ΔB19R). An immunization protocol mimicking that of the RV144 phase III clinical trial was used. Two groups of macaques received two doses of the corresponding NYVAC-C-KC vectors (weeks 0 and 4) and booster doses with NYVAC-C-KC vectors plus the clade C HIV-1 gp120 protein (weeks 12 and 24). The two replicating NYVAC-C-KC vectors induced enhanced and similar HIV-1-specific CD4+ and CD8+ T cell responses, similar levels of binding IgG antibodies, low levels of IgA antibodies, and high levels of antibody-dependent cellular cytotoxicity responses and HIV-1-neutralizing antibodies. Small differences within the NYVAC-C-KC-ΔB19R group were seen in the magnitude of CD4+ and CD8+ T cells, the induction of some cytokines, and the neutralization of some HIV-1 isolates. Thus, replication-competent NYVAC-C-KC vectors acquired relevant immunological properties as vaccine candidates against HIV/AIDS, and the viral B19 molecule exerts some control of immune functions. IMPORTANCE It is of special importance to find a safe and effective HIV/AIDS vaccine that can induce strong and broad T cell and humoral immune responses correlating with HIV-1

  11. HIV/AIDS Vaccine Candidates Based on Replication-Competent Recombinant Poxvirus NYVAC-C-KC Expressing Trimeric gp140 and Gag-Derived Virus-Like Particles or Lacking the Viral Molecule B19 That Inhibits Type I Interferon Activate Relevant HIV-1-Specific B and T Cell Immune Functions in Nonhuman Primates.

    Science.gov (United States)

    García-Arriaza, Juan; Perdiguero, Beatriz; Heeney, Jonathan L; Seaman, Michael S; Montefiori, David C; Yates, Nicole L; Tomaras, Georgia D; Ferrari, Guido; Foulds, Kathryn E; Roederer, Mario; Self, Steven G; Borate, Bhavesh; Gottardo, Raphael; Phogat, Sanjay; Tartaglia, Jim; Barnett, Susan W; Burke, Brian; Cristillo, Anthony D; Weiss, Deborah E; Lee, Carter; Kibler, Karen V; Jacobs, Bertram L; Wagner, Ralf; Ding, Song; Pantaleo, Giuseppe; Esteban, Mariano

    2017-05-01

    The nonreplicating attenuated poxvirus vector NYVAC expressing clade C(CN54) HIV-1 Env(gp120) and Gag-Pol-Nef antigens (NYVAC-C) showed limited immunogenicity in phase I clinical trials. To enhance the capacity of the NYVAC vector to trigger broad humoral responses and a more balanced activation of CD4+ and CD8+ T cells, here we compared the HIV-1-specific immunogenicity elicited in nonhuman primates immunized with two replicating NYVAC vectors that have been modified by the insertion of the K1L and C7L vaccinia virus host range genes and express the clade C(ZM96) trimeric HIV-1 gp140 protein or a Gag(ZM96)-Pol-Nef(CN54) polyprotein as Gag-derived virus-like particles (termed NYVAC-C-KC). Additionally, one NYVAC-C-KC vector was generated by deleting the viral gene B19R, an inhibitor of the type I interferon response (NYVAC-C-KC-ΔB19R). An immunization protocol mimicking that of the RV144 phase III clinical trial was used. Two groups of macaques received two doses of the corresponding NYVAC-C-KC vectors (weeks 0 and 4) and booster doses with NYVAC-C-KC vectors plus the clade C HIV-1 gp120 protein (weeks 12 and 24). The two replicating NYVAC-C-KC vectors induced enhanced and similar HIV-1-specific CD4+ and CD8+ T cell responses, similar levels of binding IgG antibodies, low levels of IgA antibodies, and high levels of antibody-dependent cellular cytotoxicity responses and HIV-1-neutralizing antibodies. Small differences within the NYVAC-C-KC-ΔB19R group were seen in the magnitude of CD4+ and CD8+ T cells, the induction of some cytokines, and the neutralization of some HIV-1 isolates. Thus, replication-competent NYVAC-C-KC vectors acquired relevant immunological properties as vaccine candidates against HIV/AIDS, and the viral B19 molecule exerts some control of immune functions.IMPORTANCE It is of special importance to find a safe and effective HIV/AIDS vaccine that can induce strong and broad T cell and humoral immune responses correlating with HIV-1 protection

  12. Radioiodide imaging and radiovirotherapy of multiple myeloma using VSV(Delta51)-NIS, an attenuated vesicular stomatitis virus encoding the sodium iodide symporter gene.

    Science.gov (United States)

    Goel, Apollina; Carlson, Stephanie K; Classic, Kelly L; Greiner, Suzanne; Naik, Shruthi; Power, Anthony T; Bell, John C; Russell, Stephen J

    2007-10-01

    Multiple myeloma is a radiosensitive malignancy that is currently incurable. Here, we generated a novel recombinant vesicular stomatitis virus [VSV(Delta51)-NIS] that has a deletion of methionine 51 in the matrix protein and expresses the human sodium iodide symporter (NIS) gene. VSV(Delta51)-NIS showed specific oncolytic activity against myeloma cell lines and primary myeloma cells and was able to replicate to high titers in myeloma cells in vitro. Iodide uptake assays showed accumulation of radioactive iodide in VSV(Delta51)-NIS-infected myeloma cells that was specific to the function of the NIS transgene. In bg/nd/xid mice with established subcutaneous myeloma tumors, administration of VSV(Delta51)-NIS resulted in high intratumoral virus replication and tumor regression. VSV-associated neurotoxicity was not observed. Intratumoral spread of the infection was monitored noninvasively by serial gamma camera imaging of (123)I-iodide biodistribution. Dosimetry calculations based on these images pointed to the feasibility of combination radiovirotherapy with VSV(Delta51)-NIS plus (131)I. Immunocompetent mice with syngeneic 5TGM1 myeloma tumors (either subcutaneous or orthotopic) showed significant enhancements of tumor regression and survival when VSV(Delta51)-NIS was combined with (131)I. These results show that VSV(Delta51)-NIS is a safe oncolytic agent with significant therapeutic potential in multiple myeloma.

  13. Glycyrrhizin inhibits porcine epidemic diarrhea virus infection and attenuates the proinflammatory responses by inhibition of high mobility group box-1 protein.

    Science.gov (United States)

    Huan, Chang-Chao; Wang, Hua-Xia; Sheng, Xiang-Xiang; Wang, Rui; Wang, Xin; Mao, Xiang

    2017-06-01

    Porcine epidemic diarrhea (PED), caused by porcine epidemic diarrhea virus (PEDV) infection, leads to significant economic losses in the swine industry worldwide. In our studies, we found that glycyrrhizin, the major component of licorice root extracts, could moderately inhibit PEDV infection in Vero cells, when analyzed by western blot, qRT-PCR and a plaque formation assay. We also revealed that glycyrrhizin inhibited the entry and replication of PEDV. In addition, we demonstrated that glycyrrhizin decreased the mRNA levels of proinflammatory cytokines. Since glycyrrhizin is a competitive inhibitor of high mobility group box-1 (HMGB1), we confirmed that TLR4 and RAGE (£ associated with PEDV pathogenesis during the infection in Vero cells. In summary, our studies provide a molecular basis for developing novel therapeutic methods to control PEDV infection, based on glycyrrhizin and its derivatives.

  14. Myxoma virus attenuates expression of activating transcription factor 4 (ATF4) which has implications for the treatment of proteasome inhibitor-resistant multiple myeloma.

    Science.gov (United States)

    Dunlap, Katherine M; Bartee, Mee Y; Bartee, Eric

    2015-01-01

    The recent development of chemotherapeutic proteasome inhibitors, such as bortezomib, has improved the outcomes of patients suffering from the plasma cell malignancy multiple myeloma. Unfortunately, many patients treated with these drugs still suffer relapsing disease due to treatment-induced upregulation of the antiapoptotic protein Mcl1. We have recently demonstrated that an oncolytic poxvirus, known as myxoma, can rapidly eliminate primary myeloma cells by inducing cellular apoptosis. The efficacy of myxoma treatment on proteasome inhibitor-relapsed or -refractory myeloma, however, remains unknown. We now demonstrate that myxoma-based elimination of myeloma is not affected by cellular resistance to proteasome inhibitors. Additionally, myxoma virus infection specifically prevents expression of Mcl1 following induction of the unfolded protein response, by blocking translation of the unfolded protein response activating transcription factor (ATF)4. These results suggest that myxoma-based oncolytic therapy represents an attractive option for myeloma patients whose disease is refractory to chemotherapeutic proteasome inhibitors due to upregulation of Mcl1.

  15. Implication of respiratory syncytial virus (RSV) F transgene sequence heterogeneity observed in Phase 1 evaluation of MEDI-534, a live attenuated parainfluenza type 3 vectored RSV vaccine.

    Science.gov (United States)

    Yang, Chin-Fen; Wang, C Kathy; Malkin, Elissa; Schickli, Jeanne H; Shambaugh, Cindy; Zuo, Fengrong; Galinski, Mark S; Dubovsky, Filip; Tang, Roderick S

    2013-06-10

    MEDI-534 is the first live vectored RSV vaccine candidate to be evaluated in seronegative children. It consists of the bovine parainfluenza virus type 3 (PIV3) genome with substituted human PIV3 F and HN glycoproteins engineered to express RSV F protein. A Phase 1 study of 49 healthy RSV and PIV3 seronegative children 6 to <24 months of age demonstrated an acceptable safety profile at the following doses: 10(4), 10(5) and 10(6)TCID50. After 3 doses of MEDI-534 at 10(6)TCID50, administered at 0, 2 and 4 month intervals, 100% of subjects seroresponded to PIV3, whereas only 50% seroresponded to RSV. To investigate the discordance in seroresponse rates, the RSV F transgene and its flanking non-coding nucleotides were sequenced from shed virus recovered from the nasal washes of 24 MEDI-534-vaccinated children. Eleven out of 24 samples contained no nucleotide changes in the analyzed region. The other 13 samples contained mixtures of variant subpopulations. Fifty-five percent exhibited changes in the transcription termination poly A gene sequences of the upstream bPIV3N gene while 21% had variant subpopulations in the RSV F open reading frame that resulted in pre-mature stop codons. Both types of changes are expected to reduce RSV F expression. Evaluation of the administered vaccine by dual immunofluorescence staining showed ~2.5% variants with low or no RSV F expression while single nucleotide primer extension detected ~1% variation at nucleotide 2045 that resulted in a pre-mature translational termination at codon 85. An association between shedding of variants and lower RSV F serological response was observed but it was not possible to establish a definitive clinical significance due to the small number of subjects in this study. Copyright © 2013 Elsevier Ltd. All rights reserved.

  16. Herpes simplex virus 2 (HSV-2 infected cell proteins are among the most dominant antigens of a live-attenuated HSV-2 vaccine.

    Directory of Open Access Journals (Sweden)

    Joshua J Geltz

    Full Text Available Virion glycoproteins such as glycoprotein D (gD are believed to be the dominant antigens of herpes simplex virus 2 (HSV-2. We have observed that mice immunized with a live HSV-2 ICP0- mutant virus, HSV-2 0ΔNLS, are 10 to 100 times better protected against genital herpes than mice immunized with a HSV-2 gD subunit vaccine (PLoS ONE 6:e17748. In light of these results, we sought to determine which viral proteins were the dominant antibody-generators (antigens of the live HSV-2 0ΔNLS vaccine. Western blot analyses indicated the live HSV-2 0ΔNLS vaccine elicited an IgG antibody response against 9 or more viral proteins. Many antibodies were directed against infected-cell proteins of >100 kDa in size, and only 10 ± 5% of antibodies were directed against gD. Immunoprecipitation (IP of total HSV-2 antigen with 0ΔNLS antiserum pulled down 19 viral proteins. Mass spectrometry suggested 44% of immunoprecipitated viral peptides were derived from two HSV-2 infected cells proteins, RR-1 and ICP8, whereas only 14% of immunoprecipitated peptides were derived from HSV-2's thirteen glycoproteins. Collectively, the results suggest the immune response to the live HSV-2 0ΔNLS vaccine includes antibodies specific for infected cell proteins, capsid proteins, tegument proteins, and glycoproteins. This increased breadth of antibody-generating proteins may contribute to the live HSV-2 vaccine's capacity to elicit superior protection against genital herpes relative to a gD subunit vaccine.

  17. Enhancement of Th1-biased protective immunity against avian influenza H9N2 virus via oral co-administration of attenuated Salmonella enterica serovar Typhimurium expressing chicken interferon-α and interleukin-18 along with an inactivated vaccine

    Directory of Open Access Journals (Sweden)

    Rahman Md

    2012-07-01

    Full Text Available Abstract Background Control of currently circulating re-assorted low-pathogenicity avian influenza (LPAI H9N2 is a major concern for both animal and human health. Thus, an improved LPAI H9N2 vaccination strategy is needed to induce complete immunity in chickens against LPAI H9N2 virus strains. Cytokines play a crucial role in mounting both the type and extent of an immune response generated following infection with a pathogen or after vaccination. To improve the efficacy of inactivated LPAI H9N2 vaccine, attenuated Salmonella enterica serovar Typhimurium was used for oral co-administration of chicken interferon-α (chIFN-α and chicken interleukin-18 (chIL-18 as natural immunomodulators. Results Oral co-administration of S. enterica serovar Typhimurium expressing chIFN-α and chIL-18, prior to vaccination with inactivated AI H9N2 vaccine, modulated the immune response of chickens against the vaccine antigen through enhanced humoral and Th1-biased cell-mediated immunity, compared to chickens that received single administration of S. enterica serovar Typhimurium expressing either chIFN-α or chIL-18. To further test the protective efficacy of this improved vaccination regimen, immunized chickens were intra-tracheally challenged with a high dose of LPAI H9N2 virus. Combined administration of S. enterica serovar Typhimurium expressing chIFN-α and chIL-18 showed markedly enhanced protection compared to single administration of the construct, as determined by mortality, clinical severity, and feed and water intake. This enhancement of protective immunity was further confirmed by reduced rectal shedding and replication of AIV H9N2 in different tissues of challenged chickens. Conclusions Our results indicate the value of combined administration of chIFN-α and chIL-18 using a Salmonella vaccine strain to generate an effective immunization strategy in chickens against LPAI H9N2.

  18. Blue Tongue Virus

    African Journals Online (AJOL)

    Anupama

    African Journal of Environmental Science and Technology Vol. 7(3), pp. 68-80, March ..... However, the disadvantages of attenuated BTV vaccines (Schultz ..... Sciences vol. 13, Nature Publishing Group, pp. 533–547. Mertens PPC, Diprose J (2004). The bluetongue virus core: a nano- scale transcription machine. Virus Res.

  19. Robust and Balanced Immune Responses to All 4 Dengue Virus Serotypes Following Administration of a Single Dose of a Live Attenuated Tetravalent Dengue Vaccine to Healthy, Flavivirus-Naive Adults

    Science.gov (United States)

    Kirkpatrick, Beth D.; Durbin, Anna P.; Pierce, Kristen K.; Carmolli, Marya P.; Tibery, Cecilia M.; Grier, Palmtama L.; Hynes, Noreen; Diehl, Sean A.; Elwood, Dan; Jarvis, Adrienne P.; Sabundayo, Beulah P.; Lyon, Caroline E.; Larsson, Catherine J.; Jo, Matthew; Lovchik, Janece M.; Luke, Catherine J.; Walsh, Mary C.; Fraser, Ellen A.; Subbarao, Kanta; Whitehead, Steven S.

    2015-01-01

    Background. The 4 serotypes of dengue virus, DENV-1–4, are the leading cause of arboviral disease globally. The ideal dengue vaccine would provide protection against all serotypes after a single dose. Methods. Two randomized, placebo-controlled trials were performed with 168 flavivirus-naive adults to demonstrate the safety and immunogenicity of a live attenuated tetravalent dengue vaccine (TV003), compared with those of a second tetravalent vaccine with an enhanced DENV-2 component (TV005), and to evaluate the benefit of a booster dose at 6 months. Safety data, viremia, and neutralizing antibody titers were evaluated. Results. A single dose of TV005 elicited a tetravalent response in 90% of vaccinees by 3 months after vaccination and a trivalent response in 98%. Compared with TV003, the higher-dose DENV-2 component increased the observed frequency of immunogenicity to DENV-2 in the TV005 trial. Both the first and second doses were well tolerated. Neither vaccine viremia, rash, nor a significant antibody boost were observed following a second dose. Conclusions. A single subcutaneous dose of TV005 dengue vaccine is safe and induces a tetravalent antibody response at an unprecedented frequency among vaccinees. A second dose has limited benefit and appears to be unnecessary. Studies to confirm these findings and assess vaccine efficacy will now move to populations in regions where DENV transmission is endemic. Clinical Trials Registration. NCT01072786 and NCT01436422. PMID:25801652

  20. Vaccination of Volunteers with Low-Dose, Live-Attenuated, Dengue Viruses Leads to Serotype-specific Immunologic and Virologic Profiles

    Science.gov (United States)

    Lindow, Janet C.; Durbin, Anna P.; Whitehead, Stephen S.; Pierce, Kristen K.; Carmolli, Marya P.; Kirkpatrick, Beth D.

    2013-01-01

    There are currently no vaccines or therapeutics to prevent dengue disease which ranges in severity from asymptomatic infections to life-threatening illness. The National Institute of Allergy and Infectious Diseases (NIAID) Division of Intramural Research has developed live, attenuated vaccines to each of the four dengue serotypes (DENV-1 – DENV-4). Two doses (10 PFU and 1000 PFU) of three monovalent vaccines were tested in human clinical trials to compare safety and immunogenicity profiles. DEN4Δ30 had been tested previously at multiple doses. The three dengue vaccine candidates tested (DEN1Δ30, DEN2/4Δ30, and DEN3Δ30/31) were very infectious, each with a Human Infectious Dose 50% ≤ 10 PFU. Further, infectivity rates ranged from 90 −100% regardless of dose, excepting DEN2/4Δ30 which dropped from 100% at the 1000 PFU dose to 60% at the 10 PFU dose. Mean geometric peak antibody titers did not differ significantly between doses for DEN1Δ30 (92 ± 19 vs. 214 ± 97, p = 0.08); however, significant differences were observed between the 10 PFU and 1000 PFU doses for DEN2/4Δ30, 19 ± 9 vs. 102 ± 25 (p = 0.001), and DEN3Δ30/31, 119 ± 135 vs. 50 ± 50 (p=0.046). No differences in the incidences of rash, neutropenia, or viremia were observed between doses for any vaccines, though the mean peak titer of viremia for DEN1Δ30 was higher at the 1000 PFU dose (0.5 ± 0 vs. 1.1 ± 0.1, p = 0.007). These data demonstrate that atarget dose of 1000 PFU for inclusion of each dengue serotype into a tetravalent vaccine is likely to be safe and generate a balanced immune response for all serotypes. PMID:23735680

  1. Serial changes in liver stiffness and controlled attenuation parameter following direct-acting antiviral therapy against hepatitis C virus genotype 1b.

    Science.gov (United States)

    Ogasawara, Nobuhiko; Kobayashi, Masahiro; Akuta, Norio; Kominami, Yoko; Fujiyama, Shunichiro; Kawamura, Yusuke; Sezaki, Hitomi; Hosaka, Tetsuya; Suzuki, Fumitaka; Saitoh, Satoshi; Suzuki, Yoshiyuki; Arase, Yasuji; Ikeda, Kenji; Kobayashi, Mariko; Kumada, Hiromitsu

    2018-02-01

    Little information is available on the impact of direct-acting antiviral (DAA) therapy on changes in liver fibrosis and steatosis. Liver stiffness (LS) and controlled attenuation parameter (CAP) values were evaluated using transient elastography. The study subjects were 214 elderly patients infected with HCV genotype 1b who received 24-week daclatasvir and asunaprevir dual therapy. All patients of this retrospective study had no hepatocellular carcinoma before and during DAA therapy. LS and CAP were assessed before treatment (baseline), at end of treatment (EOT), and at 24, 48, 72 weeks (W) after EOT. The rate of sustained viral response (SVR) by daclatasvir and asunaprevir therapy was 91%. LS values for the entire group correlated with Fib-4 index at baseline (r = 0.565, P < 0.001). LS in both chronic hepatitis group (Fib-4 index <3.25) and cirrhosis group (Fib-4 index ≥3.25) decreased significantly at each time point compared with baseline (P < 0.001). Especially, a larger decrease in LS from baseline to EOT was seen in the cirrhosis group than chronic hepatitis group (P < 0.001). LS was also significantly lower in the SVR group at EOT, 24W, 48W, 72W compared with baseline (P < 0.001). Even in the non-SVR group, LS tended to be lower at EOT (P = 0.039), 24W (P = 0.009), 48W (P = 0.475), 72W (P = 0.033) compared with baseline. CAP increased significantly following the treatment from baseline to 48W post-EOT (P = 0.018). Our results showed significant improvement in LS in response to daclatasvir and asunaprevir dual therapy. In the other hand, there was a tendency that CAP increased from baseline. © 2017 Wiley Periodicals, Inc.

  2. 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

    (mean 5,243), B21 (5,570), and B131 (5,333) at 8 d postinfection, How-ever, a virus-neutralizing antibody test did not reflect this result. Nevertheless, the MHC haplotype-associated protective immunity was further supported by the bursa of Fabricius (bursa) recovery from the disease, as measured...... by histological scorings of the bursa. Chickens carrying the BW1 haplotype had a significantly lower bursa lesion score (1.7) than the haplotypes B19 (mean 3.8), B21 (3.6), and B131 (4.3) 8 d postinfection. Furthermore, multiple line effects were found in other variables when comparing Day 6 with Day 8. Body...... weight, relative weights of the bursa and the spleen, percentage and relative number of MHC II molecules on MHC II-positive lymphocytes, percentage and relative number of CD4 molecules on CD4-positive lymphocytes, and the specific antibody response all differed significantly among lines. Line 1, with Red...

  3. Adeno-associated virus-mediated expression of myostatin propeptide improves the growth of skeletal muscle and attenuates hyperglycemia in db/db mice.

    Science.gov (United States)

    Jiang, J G; Shen, G F; Li, J; Qiao, C; Xiao, B; Yan, H; Wang, D W; Xiao, X

    2017-03-01

    Inhibition of myostatin, a negative growth modulator for muscle, can functionally enhance muscle mass and improve glucose and fat metabolism in myostatin propeptide (MPRO) transgenic mice. This study was to investigate whether myostatin inhibition by adeno-associated virus (AAV)-mediated gene delivery of MPRO could improve muscle mass and achieve therapeutic effects on glucose regulation and lipid metabolism in the db/db mice and the mechanisms involved in that process. Eight-week-old male db/db mice were administered saline, AAV-GFP and AAV-MPRO/Fc vectors and monitored random blood glucose levels and body weight for 36 weeks. Body weight gain was not different during follow-up among the groups, but AAV-MPRO/Fc vectors resulted high level of MPRO in the blood companied by an increase in skeletal muscle mass and muscle hypertrophy. In addition, AAV-MPRO/Fc-treated db/db mice showed significantly lower blood glucose and insulin levels and significantly increased glucose tolerance and insulin sensitivity compared with the control groups (Pmuscle, although no difference was observed in fat pad weights and serum TG and FFA levels. Finally, AAV-MPRO/Fc-treated mice had enhanced insulin signaling in the skeletal muscle. These data suggest that AAV-mediated MPRO therapy may provide an important clue for potential clinical applications to prevent type II diabetes, and these studies confirm that MPRO is a therapeutic target for type II diabetes.

  4. Myxoma virus attenuates expression of activating transcription factor 4 (ATF4 which has implications for the treatment of proteasome inhibitor–resistant multiple myeloma

    Directory of Open Access Journals (Sweden)

    Dunlap KM

    2015-01-01

    Full Text Available Katherine M Dunlap, Mee Y Bartee, Eric Bartee Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC, USA Abstract: The recent development of chemotherapeutic proteasome inhibitors, such as bortezomib, has improved the outcomes of patients suffering from the plasma cell malignancy multiple myeloma. Unfortunately, many patients treated with these drugs still suffer relapsing disease due to treatment-induced upregulation of the antiapoptotic protein Mcl1. We have recently demonstrated that an oncolytic poxvirus, known as myxoma, can rapidly eliminate primary myeloma cells by inducing cellular apoptosis. The efficacy of myxoma treatment on proteasome inhibitor–relapsed or –refractory myeloma, however, remains unknown. We now demonstrate that myxoma-based elimination of myeloma is not affected by cellular resistance to proteasome inhibitors. Additionally, myxoma virus infection specifically prevents expression of Mcl1 following induction of the unfolded protein response, by blocking translation of the unfolded protein response activating transcription factor (ATF4. These results suggest that myxoma-based oncolytic therapy represents an attractive option for myeloma patients whose disease is refractory to chemotherapeutic proteasome inhibitors due to upregulation of Mcl1. Keywords: drug resistance, oncolytic

  5. AIDS-related cancer in the era of highly active antiretroviral therapy (HAART): a model of the interplay of the immune system, virus, and cancer. "On the offensive--the Trojan Horse is being destroyed"--Part A: Kaposi's sarcoma.

    Science.gov (United States)

    Cheung, Tony W

    2004-01-01

    The introduction of highly active antiretroviral therapy (HAART), aimed at controlling human immunodeficiency virus (HIV), has been associated with a dramatic decrease in the incidence of acquired immunodeficiency syndrome-Kaposi's sarcoma (AIDS-KS) and the clinical manifestations of KS appear to be less aggressive. The pathogenesis of AIDS-related KS is related to a system of cytokines (e.g., interleukin-6) driven by autocrine and paracrine loops. More recently, human herpesvirus 8 (HHV-8), was discovered to be the putative etiological agent of this disease. This virus encodes several unique open reading frames that are homologs of human cellular proteins involved in cellular regulations, cell proliferation, apoptosis, and immune regulation. The treatment of this disease depends on whether it is "limited" disease or "extensive" disease. For "limited" disease, local therapy or non-bone marrow suppressive agents should be used. For "extensive" disease, new chemotherapeutic agents, such as liposomal anthracycline, which are active and have little adverse reactions, are indicated. The control of HIV infection continues to be essential. Knowledge of the pathogenesis of the disease has led to the development of novel treatment strategies, aimed at the inflammatory or angiogenesis cytokines necessary for growth or at HHV-8 as the target of therapy.

  6. KNOWLEDGE ATTITUDE AND PRACTICE STUDY OF HUMAN IMMUNO DEFICIENCY VIRUS AND AQUIRED IMMUNO DEFICIENCY SYNDROME (HIV/AIDS AMONG RURAL POPULATION OF TAMIL NADU (INDIA

    Directory of Open Access Journals (Sweden)

    Sanjay Kumar Gupta

    2013-01-01

    Full Text Available Research question: What is the knowledge, attitude and practice towards HIV/AIDS in a general population? Objectives: (1 To assess the knowledge about mode of transmission, treatment and prevention of HIV/AIDS. (2 To study the socio demographic pattern, myths and misconceptions. Study design: Community based cross sectional study. Setting: Chunampett Village, Tamilnadu. Duration: March to May 2007. Participants: 845 both males and females above the age of 18 years interviewed at home. Results: Population surveyed was 845, comprising of 482 (57.04% males and 363 (42.96% females. Most of them were Hindus (96.10%. Main occupation was agriculture (39.41% among males and house wives (33.73% among females. 40.35% respondents belonged to low socioeconomic status. Illiteracy rate was high especially among females (43%.Source of information about HIV/AIDS was mass media in about 85% of the population. Majority of individuals (58.5% were not aware that the disease was contagious. An overwhelming majority (98.59% were aware about the mode of transmission of HIV/AIDS through sexual route. However about 20% had myths regarding transmission of disease. 65% knew that HIV/AIDS is preventable, yet only 4% used condoms. A vast majority (60-65% were not aware that treatment and PEP were available free of cost in government hospitals. A majority of about 54.22% were of the opinion that the diagnosis of HIV/AIDS should not be kept confidential. Conclusion: The awareness about HIV / AIDS is high among the study population but the implementation of preventive measures is low. The knowledge about availability of prophylactic and therapeutic measures against HIV / AIDS in Govt. hospitals is also low.

  7. Foreign aid

    DEFF Research Database (Denmark)

    Tarp, Finn

    2008-01-01

    Foreign aid has evolved significantly since the Second World War in response to a dramatically changing global political and economic context. This article (a) reviews this process and associated trends in the volume and distribution of foreign aid; (b) reviews the goals, principles and instituti......Foreign aid has evolved significantly since the Second World War in response to a dramatically changing global political and economic context. This article (a) reviews this process and associated trends in the volume and distribution of foreign aid; (b) reviews the goals, principles...... and institutions of the aid system; and (c) discusses whether aid has been effective. While much of the original optimism about the impact of foreign aid needed modification, there is solid evidence that aid has indeed helped further growth and poverty reduction...

  8. 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.

  9. Women and AIDS.

    Science.gov (United States)

    Edemikpong, N B

    1990-01-01

    While the origin of the AIDS virus remains controversial, it is indisputable that AIDS is spreading worldwide. By June 1987, the World Health Organization estimated that 50 million Africans were infected with HIV and that the disease was epidemic in many parts of the continent. However, African governments chose to deny the threat of the disease. The AIDS crisis has diverted resources from other vital areas of disease prevention, health promotion, and research. Whereas AIDS is spread in developed nations by sexual promiscuity, by drug addicts sharing unclean hypodermic needles, and by homosexual behavior, in Africa cultural factors contribute to the transmission of AIDS. Female genital mutilation leads to extensive laceration of the female genitals upon initiation of sexual intercourse and/or to substitution of anal sex during the weeks and months before vaginal penetration can be achieved. In addition, the reuse of the same knives during the mutilation can spread HIV infection. Other factors that contribute to the spread of HIV in Africa include the patriarchal practice of polygamy, the subordinate position of women that makes them unable to insist on protection during intercourse, and a failure to screen blood used in transfusions. With all of these risk factors at play, women at the grassroots level must be equipped with the health education that is the only available tool to fight AIDS. Women's organizations can provide information and education to people at risk of acquiring HIV, counsel infected persons, ensure the safety of the blood supply, and work to overcome harmful traditional practices.

  10. Aids : A Rampant Intruder

    Directory of Open Access Journals (Sweden)

    Suresh Chandra

    2004-12-01

    Full Text Available The HIV/AIDS epidemic represents the most serious public health problem in India. There is no denial of the enormity of the problem. The prevalence of infection in all parts of the world highlights the spread from urban to rural areas and from high risk to general population. It is esti­mated that as on end of year 2004, 39.4 million people were infected with the virus. Migration of labour, low lit­eracy levels leading to low awareness, gender disparities, prevalence of sexually transmitted diseases and reproduc­tive tract infections are some of the factors attributed to the spread of HIV/AIDS.4.9 million ( 4.3 million - 6.4 million people have aquired HIV infection only in one year of span - 2004. The global AIDS epidemic killed 3.1 million ( 2,8 million- 3.5 million people in the past year.

  11. Modulation of systemic and mucosal immunity against an inactivated vaccine of Newcastle disease virus by oral co-administration of live attenuated Salmonella enterica serovar Typhimurium expressing chicken interleukin-18 and interferon-α.

    Science.gov (United States)

    Rahman, Md Masudur; Uyangaa, Erdenebelig; Han, Young Woo; Hur, Jin; Park, Sang-Youel; Lee, John Hwa; Kim, Koanhoi; Eo, Seong Kug

    2015-04-01

    Newcastle disease (ND) is a highly contagious disease of chickens causing significant economic losses worldwide. Due to limitations in the efficacy against currently circulating ND viruses, existing vaccination strategies require improvements, and incorporating immunomodulatory cytokines with existing vaccines might be a novel approach. Here, we investigated the systemic and mucosal immunomodulatory properties of oral co-administration of chicken interleukin-18 (chIL-18) and chicken interferon-α (chIFN-α) using attenuated Salmonella enterica serovar Typhimurium on an inactivated ND vaccine. Our results demonstrate that oral administration of S. enterica serovar Typhimurium expressing chIL-18 or chIFN-α provided enhanced systemic and mucosal immune responses, as determined by serum hemagglutination inhibition antibody and NDV Ag-specific IgG as well as NDV Ag-specific IgA in lung and duodenal lavages of chickens immunized with inactivated ND vaccine via the intramuscular or intranasal route. Notably, combined oral administration of S. enterica serovar Typhimurium expressing chIL-18 and chIFN-α significantly enhanced systemic and mucosal immunity in ND-vaccinated chickens, compared to single administration of S. enterica serovar Typhimurium expressing chIL-18 or chIFN-α. In addition, oral co-administration of S. enterica serovar Typhimurium expressing chIL-18 and chIFN-α provided enhanced NDV Ag-specific proliferation of peripheral blood mononuclear cells and Th1-biased cell-mediated immunity, compared to single administration of either construct. Therefore, our results provide valuable insight into the modulation of systemic and mucosal immunity by incorporation of immunomodulatory chIL-18 and chIFN-α using Salmonella vaccines into existing ND vaccines.

  12. AIDS: the hidden enemy.

    Science.gov (United States)

    Tinker, J; Sabatier, R

    1987-01-01

    This article discusses the acquired immunodeficiency syndrome (AIDS) epidemic an its effect on developing countries, with emphasis on Africa. The AIDS death toll will be high in the US: 180,000 by 1991, but it will be in the millions in developing countries. In Africa, AIDS is mainly transmitted heterosexually, is as prevalent among women as among men, and is taking a serious toll among professional classes and young wage earners. The social costs of funerals has increased, and company clinics and sick pay funds have been overwhelmed. In Uganda, the epidemic adds to the state of psychological shock people have sufferred because of the civil war. Medical professionals have been hard-pressed to acquire equipment for testing blood for the virus, although there have been efforts to protect blood supplies through exhaustive testing. Endemic tuberculosis becomes an even more serious problem in developing countries, since AIDS lowers resistance to it. AIDS also effects many developing country children, usually through infected mothers, who can transmit AIDS through breast milk or during pregnancy of birth. This poses a dilemma for promoters of breastfeeding. It is also feared that innoculation of immunosuppressed children may be dangerous. The global picture suggests that Africa is hardest hit: seropositivity prevalence ranges from 0.7% of Congo blood donors to 33% of male donors in Lusaka Zambia. Brazil's cases are mainly homosexual, and in Asia the prevalence is mostly low, although there is a great potential danger in countries where prostitution and heroin addiction are prevalent. The only effective weapon against AIDS is education and blood testing to prevent spread. Despite good education programs in some countries, e.g. Rwanda, there is still widespread ignorance of how AIDS is spread.

  13. Imparting Temperature Sensitivity and Attenuation in Ferrets to A/Puerto Rico/8/34 Influenza Virus by Transferring the Genetic Signature for Temperature Sensitivity from Cold-Adapted A/Ann Arbor/6/60

    OpenAIRE

    Jin, Hong; Zhou, Helen; Lu, Bin; Kemble, George

    2004-01-01

    The four temperature-sensitive (ts) loci identified in the PB1 and PB2 gene segments of cold-adapted A/Ann Arbor/6/60 influenza virus, the master donor virus for influenza A virus (MDV-A) FluMist vaccines, were introduced into a divergent A/Puerto Rico/8/34 influenza virus strain. Recombinant A/Puerto Rico/8/34 virus with these four introduced ts loci exhibited both ts and att phenotypes similar to those of MDV-A, which could be used as a donor virus for manufacturing large quantities of inac...

  14. Treatment of facial lipoatrophy with polymethylmethacrylate among patients with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS): impact on the quality of life.

    Science.gov (United States)

    Quintas, Rodrigo C S; de França, Emmanuel R; de Petribú, Kátia C L; Ximenes, Ricardo A A; Quintas, Lóren F F M; Cavalcanti, Ernando L F; Kitamura, Marco A P; Magalhães, Kássia A A; Paiva, Késsia C F; Filho, Demócrito B Miranda

    2014-04-01

    The lipodystrophy syndrome is characterized by selective loss of subcutaneous fat on the face and extremities (lipoatrophy) and/or accumulation of fat around the neck, abdomen, and thorax (lipohypertrophy). The aim of this study has been to assess the impact of polymethylmethacrylate facial treatment on quality of life, self-perceived facial image, and the severity of depressive symptoms in patients living with HIV/AIDS. A non-randomized before and after interventional study was developed. Fifty-one patients underwent facial filling. The self-perceived quality of life, facial image, and degree of depressive symptoms were measured by the Short-Form 36 and HIV/AIDS--Targeted quality of life questionnaires, by a visual analogue scale and by the Beck depression inventory, respectively, before and three months after treatment. Six of the eight domains of Short-Form 36 and eight of the nine dimensions of the HIV/AIDS--Targeted quality of life questionnaires, together with the visual analogue scale and by the Beck depression inventory scores, revealed a statistically significant improvement. The only adverse effects registered were edema and ecchymosis. The treatment of facial lipoatrophy improved the self-perceived quality of life and facial image as well as any depressive symptoms among patients with HIV/AIDS. © 2014 The International Society of Dermatology.

  15. [Consensus statement of the National AIDS Plan Secretariat, Spanish Society of Emergency Medicine and AIDS Study Group of the Spanish Society of Infectious Diseases and Clinical Microbiology on Emergency and Human Immunodeficiency Virus Infection].

    Science.gov (United States)

    2013-01-01

    Supporting non-HIV specialist professionals in the treatment of patients with urgent diseases resulting from HIV infection. These recommendations have been agreed by an expert panel from the National AIDS Plan Secretariat, the Spanish Society of Emergency Medicine, and the AIDS Study Group. A review has been made of the safety and efficacy results of clinical trials and cohort studies published in biomedical journals (PubMed and Embase) or presented at conferences. The strength of each recommendation (A, B, C) and the level of supporting evidence (I, II, III) are based on a modification of the criteria of the Infectious Diseases Society of America. The data to be collected from the emergency medical history in order to recognize the patient at risk of HIV infection were specified. It stressed the basic knowledge of ART principles and its importance in terms of decline in morbidity and mortality of HIV+ patients and referring to the HIV specialist for follow-up, where appropriate, including drug interactions. Management of different emergency situations that may occur in patients with HIV infection is also mentioned. The non-HIV specialist professional, will find the necessary tools to approach HIV patients with an emergency disease. Copyright © 2012 Elsevier España, S.L. All rights reserved.

  16. Educating Brazilian workers about AIDS.

    Science.gov (United States)

    1991-12-01

    This article contains a the script for a slide-tape presentation entitled Working Against AIDS, a presentation developed by the Brazil Family Planning Association (BEMFAM) which is designed to debunk common misconceptions about the disease. This audio-visual, which targets Brazilian workers, can be used during talks, seminars, and meetings. A discussion of the issues involved usually follows the presentation of Working Against AIDS. The presentation contains 30 illustrated slides (these are included in the article). The presentation begins by explaining that much of the information concerning AIDS is prejudicial and misleading. The next few slides point out some of the common misconceptions about AIDS, such as claims denying the existence of the disease, or suggestions that only homosexuals and prostitutes are at risk. The presentation then goes on to explain the ways in which the virus can and cannot be transmitted. Then it discusses how the virus destroys the body's natural defenses and explains the ensuing symptoms. Slides 14 and 15 point out that no cure yet exists for AIDS, making prevention essential. Slides 16-23 explain what actions are considered to be high risk and which ones do not entail risk. Noting that AIDS can be prevented, slide 24 says that the disease should not present an obstacle to spontaneous manifestations of human relations. The next slide explains that condoms should always be used when having sex with someone who could be infected with AIDS. Finally slides 26-30 demonstrate the proper way to use and dispose of a condom.

  17. Pressure surge attenuator

    Science.gov (United States)

    Christie, Alan M.; Snyder, Kurt I.

    1985-01-01

    A pressure surge attenuation system for pipes having a fluted region opposite crushable metal foam. As adapted for nuclear reactor vessels and heads, crushable metal foam is disposed to attenuate pressure surges.

  18. [Disclosing the virus, hiding the patients: follow-up tests (CD4 and VL) and the physician-patient relationship in the AIDS setting].

    Science.gov (United States)

    Guzmán, Julio L D; Iriart, Jorge Alberto Bernstein

    2009-05-01

    The aim of this study is to discuss the meanings associated with the CD4 lymphocyte count and HIV plasma viral load (VL) for patients living with AIDS and the attending physicians, seeking to analyze the impacts of the increasing use of these tests in the treatment setting. A qualitative study was performed in two HIV/AIDS referral centers with participant observation and semi-structured interviews with 27 patients living with AIDS and four physicians. Observation of the medical consultations showed that they are quick, objective, and centered on the CD4 and VL test results, thus reinforcing a hegemonic view of medical knowledge and a biomedical perspective that instrumentalizes their practice. For physicians and patients, the tests tend to reflect the 'truth' on the patient's disease, to the detriment of the patient history and clinical examination, impacting the therapeutic relationship and leading to the physician's lack of attention to the patients' subjectivity. More than ever, there is a need to reclaim good clinical practice and acknowledge the subject's role in medical practice as a healing art.

  19. A candidate HIV/AIDS vaccine (MVA-B lacking vaccinia virus gene C6L enhances memory HIV-1-specific T-cell responses.

    Directory of Open Access Journals (Sweden)

    Juan García-Arriaza

    Full Text Available The vaccinia virus (VACV C6 protein has sequence similarities with the poxvirus family Pox_A46, involved in regulation of host immune responses, but its role is unknown. Here, we have characterized the C6 protein and its effects in virus replication, innate immune sensing and immunogenicity in vivo. C6 is a 18.2 kDa protein, which is expressed early during virus infection and localizes to the cytoplasm of infected cells. Deletion of the C6L gene from the poxvirus vector MVA-B expressing HIV-1 Env, Gag, Pol and Nef antigens from clade B (MVA-B ΔC6L had no effect on virus growth kinetics; therefore C6 protein is not essential for virus replication. The innate immune signals elicited by MVA-B ΔC6L in human macrophages and monocyte-derived dendritic cells (moDCs are characterized by the up-regulation of the expression of IFN-β and IFN-α/β-inducible genes. In a DNA prime/MVA boost immunization protocol in mice, flow cytometry analysis revealed that MVA-B ΔC6L enhanced the magnitude and polyfunctionality of the HIV-1-specific CD4+ and CD8+ T-cell memory immune responses, with most of the HIV-1 responses mediated by the CD8+ T-cell compartment with an effector phenotype. Significantly, while MVA-B induced preferentially Env- and Gag-specific CD8+ T-cell responses, MVA-B ΔC6L induced more Gag-Pol-Nef-specific CD8+ T-cell responses. Furthermore, MVA-B ΔC6L enhanced the levels of antibodies against Env in comparison with MVA-B. These findings revealed that C6 can be considered as an immunomodulator and that deleting C6L gene in MVA-B confers an immunological benefit by enhancing IFN-β-dependent responses and increasing the magnitude and quality of the T-cell memory immune responses to HIV-1 antigens. Our observations are relevant for the improvement of MVA vectors as HIV-1 vaccines.

  20. HIV/AIDS: The Case of Initiation

    African Journals Online (AJOL)

    Abstract. The Human Immuno-Deficiency Virus (HIV) and Acquired Immune Defi- ciency Syndrome (AIDS) have become a major health problem in Zam- bia. Because of the threat HIV/AIDS poses to the nation, the government of Zambia embarked on a public health campaign aimed at combating the scourge. However, so ...

  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. ... get answers to any questions you have about HIV/AIDS. Your public health department and health care provider ...

  2. Brand Aid

    DEFF Research Database (Denmark)

    Richey, Lisa Ann; Ponte, Stefano

    A critical account of the rise of celebrity-driven “compassionate consumption” Cofounded by the rock star Bono in 2006, Product RED exemplifies a new trend in celebrity-driven international aid and development, one explicitly linked to commerce, not philanthropy. Brand Aid offers a deeply informed...

  3. Modern diets and diseases: NO-zinc balance. Under Th1, zinc and nitrogen monoxide (NO) collectively protect against viruses, AIDS, autoimmunity, diabetes, allergies, asthma, infectious diseases, atherosclerosis and cancer.

    Science.gov (United States)

    Sprietsma, J E

    1999-07-01

    Thanks to progress in zinc research, it is now possible to describe in more detail how zinc ions (Zn++) and nitrogen monoxide (NO), together with glutathione (GSH) and its oxidized form, GSSG, help to regulate immune responses to antigens. NO appears to be able to liberate Zn++ from metallothionein (MT), an intracellular storage molecule for metal ions such as zinc (Zn++) and copper (Cu++). Both Zn++ and Cu++ show a concentration-dependent inactivation of a protease essential for the proliferation of the AIDS virus HIV-1, while zinc can help prevent diabetes complications through its intracellular activation of the enzyme sorbitol dehydrogenase (SDH). A Zn++ deficiency can lead to a premature transition from efficient Th1-dependent cellular antiviral immune functions to Th2-dependent humoral immune functions. Deficiencies of Zn++, NO and/or GSH shift the Th1/Th2 balance towards Th2, as do deficiencies of any of the essential nutrients (ENs) - a group that includes methionine, cysteine, arginine, vitamins A, B, C and E, zinc and selenium (Se) - because these are necessary for the synthesis and maintenance of sufficient amounts of GSH, MT and NO. Via the Th1/Th2 balance, Zn++, NO, MT and GSH collectively determine the progress and outcome of many diseases. Disregulation of the Th1/Th2 balance is responsible for autoimmune disorders such as diabetes mellitus. Under Th2, levels of interleukin-4 (II-4), II-6, II-10, leukotriene B4 (LTB4) and prostaglandin E2 (PGE2) are raised, while levels of II-2, Zn++, NO and other substances are lowered. This makes things easier for viruses like HIV-1 which multiply in Th2 cells but rarely, if ever, in Th1 cells. AIDS viruses (HIVs) enter immune cells with the aid of the CD4 cell surface receptor in combination with a number of co-receptors which include CCR3, CCR5 and CXCR4. Remarkably, the cell surface receptor for LTB4 (BLTR) also seems to act as a co-receptor for CD4, which helps HIVs to infect immune cells. The Th2 cytokine II-4

  4. Molecular Characterization of Attenuated Junin Virus Variants.

    Science.gov (United States)

    1992-07-14

    y 0. Grau XXVII Reuni6n Anual de la Sociedad Argentina de Investigaci6n Bioquimica , Huer- ta Grande (C6rdoba) 21-24 October, 1991. This is...Argentina de Investigaci6n Bioquimica , Huer- ta Grande (C6rdoba) 21-24 October, 1991 This is basicaly the paper #1, presented in Spanish at the

  5. Genetically modified viruses: vaccines by design.

    Science.gov (United States)

    Stephenson, J R

    2001-03-01

    Vaccination has been one of the most successful and cost-effective health interventions ever employed. One disease (smallpox) has been eradicated, another (poliomyelitis) should disappear early in the new millennium and a third (measles) should follow shortly after. Conventional vaccines usually depend on one of three development processes, attenuation of virulent organisms (by passage in cell culture and/or experimental animals), killing of virulent organisms (by chemical inactivation) or the purification of immunogenic molecules (either proteins or carbohydrates) from whole organisms. These traditional processes, although serendipitous and poorly understood, have produced effective pharmaceutical products which give excellent protection against diseases such as smallpox, rabies, measles, yellow fever, tetanus and diphtheria. In spite of these successes however, the application of these protocols have failed to produce safe and efficacious vaccines against other infectious diseases which kill or maim tens of millions of people every year. The most important of these are malaria, AIDS, herpes, dengue fever and some forms of viral hepatitis. Consequently, fundamentally new technologies are required to tackle these important infections. One of the most promising has been the development of genetically modified viruses. This process normally involves taking a proven safe and efficacious vaccine virus, such as vaccinia or adenovirus, and modifying its genome to include genes coding for immunogenic proteins from other viruses such as HIV or measles. This review will describe the generation of such novel vaccine vectors and compare their advantages and shortcomings. In addition the literature describing their use as experimental vaccines will also be reviewed.

  6. Viruses - from pathogens to vaccine carriers.

    Science.gov (United States)

    Small, Juliana C; Ertl, Hildegund C J

    2011-10-01

    Vaccination is mankind's greatest public health success story. By now vaccines to many of the viruses that once caused fatal childhood diseases are routinely used throughout the world. Traditional methods of vaccine development through inactivation or attenuation of viruses have failed for some of the most deadly human pathogens, necessitating new approaches. Genetic modification of viruses not only allows for their attenuation but also for incorporation of sequences from other viruses, turning one pathogen into a vaccine carrier for another. Recombinant viruses have pros and cons as vaccine carriers, as discussed below using vectors based on adenovirus, herpesvirus, flavivirus, and rhabdovirus as examples.

  7. Caribbean AIDS explosion examined.

    Science.gov (United States)

    2000-03-13

    Homophobia, sex tourism, infidelity, and poverty are major factors causing a rapid explosion of AIDS and increasingly infecting women in the Caribbean. The region has the second largest incidence of AIDS in the world after Africa. The number of people with the HIV virus is likely greater than 500,000 and could be as high as 700,000, about twice the previously reported figures. Societal norms encourage homosexuals to have heterosexual relationships, and married men to have extramarital affairs, while poverty forces men and women to prostitution, often with tourists. In addition, a survey of 8100 school children in 4 English-speaking Caribbean islands revealed that 42% of the children had experienced sex before the age of 10 years; 62% had experienced it by age 12. This finding may reflect a high rate of child molestation in the region.

  8. Mycobacterial Infections in AIDS

    Directory of Open Access Journals (Sweden)

    A Ross Hill

    1991-01-01

    Full Text Available Tuberculosis (TB remains uniquely important among acquired immune deficiency syndrome (AIDS-associated opportunistic infections: it presents the greatest public health hazard worldwide, is the most readily curable, and is largely preventable with existing means. Given the expanding pool of human immunodeficiency virus (HIV seropositive persons, particularly in developing nations where Mycobacterium tuberculosis remains a leading health problem, one can expect a continued rise in TB cases during the 1990s. Global efforts to eliminate TB are now inextricably entwined with the effectiveness of measures to curtail the HIV epidemic. Mycobacterium avium complex infection, currently an intractable late complication of aids, may increase in clinical importance as success in managing other opportunistic infections and HIV disease itself improves. Understanding of the pathogenesis and management of mycobacterial diseases should increase rapidly given the renewed research spurred on by the advent of HIV.

  9. Paediatric AIDS in Nigeria.

    Science.gov (United States)

    1993-10-01

    The World Health Organization EPIMODEL computer program has projected that in 1993, there will be 41,023 cumulative cases of AIDS and 642,897 cumulative HIV infections among Nigerian adults. 1.2% of pregnant Nigerian women are reported to be HIV seropositive, 20-30% of whom can be expected to transmit HIV to their offspring. There are therefore many cases of pediatric HIV infection and AIDS in Nigeria. Infants and children can also be infected with HIV through the receipt of HIV-contaminated blood or blood products during transfusion, the use of unsterilized syringes and needles, and the use of contaminated instruments by traditional healers for circumcision, scarification, and tattoos. Vertical transmission, however, is the mode through which pediatric AIDS is most commonly spread. Preventive measures should therefore be directed toward promoting HIV risk reduction behaviors. Diagnosing AIDS and securing the laboratory confirmation of HIV infection are problematic in poor tropical countries like Nigeria. HIV-infected infants of unimpaired immunological status should be immunized with measles, injectable diphtheria/tetanus/pertussis, and inactivated polio virus vaccines. However, measles vaccine must not be given to an already immunocompromised patient. Likewise, BCG vaccination and oral live poliovaccine should not be given to HIV-infected children.

  10. THE PREVALENCE OF HUMAN IMMUNODEFIENCY VIRUS-1 (HIV-1 SUBTYPES AND TRANSMISSION METHOD AMONG HIV/AIDS INFECTION PATIENT IN TULUNGAGUNG, EAST JAVA INDONESIA

    Directory of Open Access Journals (Sweden)

    Achmad Ardianto

    2015-05-01

    Full Text Available The rapid epidemic growth of HIV is continuing in Indonesia. There are some factors which have influenced the spreading of this epidemic in Indonesia, such as the poor awareness to avoid unsafe free sex attitude and the sharing of needles and syringes among intravenous drug users (IDUs. The sexual transmission of HIV has also apparently increased in Tulungagung. Commercial sex workers play a significant role in the spread of HIV in Tulungagung. People in Tulungagung have worked at other countries as Indonesian migrants. This condition can cause the increase number of HIV-1 case and the possibility of genetic variation (subtype HIV-1 in Tulungagung. This research is aimed to analyze the subtype and to determine estimation of transmission mode on infected patient of HIV-1 and AIDS who came to Seruni clinic Dr. Iskak hospital in Tulungagung. 40 HIV?AIDSpatients were interviewed to determine the subtype and the transmission mode. The results showed that 14 of 40 plasma samples (35% were successfully to amplified and sequenced. OverallCRF01-AE wereidentified as predominant subtype among HIV/AIDS patients in Tulungagung. Based on individual information, 31 of 40 subjects (77% were heterosexual transmission.

  11. AIDS Therapies.

    Science.gov (United States)

    Yarchoan, Robert; And Others

    1988-01-01

    Reports on one drug which is already in clinical use and the possibility of designing others that interrupt specific phases of the life cycle of the virus. Uses a chart, pictures, and diagrams to accompany explanations. (RT)

  12. HIV / AIDS

    Science.gov (United States)

    ... in the United States and the international community. Globally, AIDS-related deaths have dropped by 45 percent ... Career Stage Postdocs' Guide to Gaining Independence Small Business Programs Compare NIAID’s Small Business Programs High-Priority ...

  13. Seroprevalence of hepatitis B virus and hepatitis C virus co-infection among people living with HIV/AIDS visiting antiretroviral therapy centres in Nepal: a first nationally representative study.

    Science.gov (United States)

    Ionita, G; Malviya, A; Rajbhandari, R; Schluter, W William; Sharma, G; Kakchapati, S; Rijal, S; Dixit, S

    2017-07-01

    To assess the prevalence of human immunodeficiency virus (HIV), hepatitis C virus (HCV), and hepatitis B virus (HBV) co-infections among people living with HIV (PLHIV) in Nepal. A sample of 677 PLHIV representing key affected populations (KAP) in Nepal, who were undergoing antiretroviral (ART) therapy in ART clinics around the country, were voluntarily enrolled in the study. Rapid kit-based testing followed by ELISA for validation was performed, focusing on HBV surface antigen (HBsAg) and antibodies against HCV (anti-HCV). A multivariate logistic regression model was used to identify factors associated with HBV and HCV co-infection. HCV and HBV co-infection among the 677 PLHIV was found to be 19% (95% confidence interval (CI) 16.6-22.7%) and 4.4% (95% CI 3.1-6.6%), respectively. The Eastern Region had the highest percentage of HCV infection (48%). The age group with the highest rates of co-infection was 30-39 years (58% and 70%, respectively, for HCV and HBV co-infection). After adjusting for confounding, males were more likely to have HBV co-infection than females (adjusted odds ratio (AOR) 4.61, 95% CI 1.42-14.98). Similarly, PLHIV who were male (AOR 5.7, 95% CI 2.06-15.98), had a secondary level of education (AOR 3.04, 95% CI 1.06-8.70), or who were drug users (AOR 28.7, 95% CI 14.9-55.22) were significantly more likely to have HCV co-infection. This first ever national assessment of HIV, HBV, and HCV co-infection performed among PLHIV in Nepal demonstrates that HCV and HBV infections are a health threat to this population and that interventions are required to mitigate the effects of co-infection and to prevent further morbidity and mortality. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  14. CRMP-2 peptide mediated decrease of high and low voltage-activated calcium channels, attenuation of nociceptor excitability, and anti-nociception in a model of AIDS therapy-induced painful peripheral neuropathy

    Directory of Open Access Journals (Sweden)

    Piekarz Andrew D

    2012-07-01

    Full Text Available Abstract Background The ubiquity of protein-protein interactions in biological signaling offers ample opportunities for therapeutic intervention. We previously identified a peptide, designated CBD3, that suppressed inflammatory and neuropathic behavioral hypersensitivity in rodents by inhibiting the ability of collapsin response mediator protein 2 (CRMP-2 to bind to N-type voltage-activated calcium channels (CaV2.2 [Brittain et al. Nature Medicine 17:822–829 (2011]. Results and discussion Here, we utilized SPOTScan analysis to identify an optimized variation of the CBD3 peptide (CBD3A6K that bound with greater affinity to Ca2+ channels. Molecular dynamics simulations demonstrated that the CBD3A6K peptide was more stable and less prone to the unfolding observed with the parent CBD3 peptide. This mutant peptide, conjugated to the cell penetrating motif of the HIV transduction domain protein TAT, exhibited greater anti-nociception in a rodent model of AIDS therapy-induced peripheral neuropathy when compared to the parent TAT-CBD3 peptide. Remarkably, intraperitoneal administration of TAT-CBD3A6K produced none of the minor side effects (i.e. tail kinking, body contortion observed with the parent peptide. Interestingly, excitability of dissociated small diameter sensory neurons isolated from rats was also reduced by TAT-CBD3A6K peptide suggesting that suppression of excitability may be due to inhibition of T- and R-type Ca2+ channels. TAT-CBD3A6K had no effect on depolarization-evoked calcitonin gene related peptide (CGRP release compared to vehicle control. Conclusions Collectively, these results establish TAT-CBD3A6K as a peptide therapeutic with greater efficacy in an AIDS therapy-induced model of peripheral neuropathy than its parent peptide, TAT-CBD3. Structural modifications of the CBD3 scaffold peptide may result in peptides with selectivity against a particular subset of voltage-gated calcium channels resulting in a multipharmacology of

  15. 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…

  16. AIDS: What Early Childhood Educators Need To Know.

    Science.gov (United States)

    Spar, Ruth

    Noting that Acquired Immune Deficiency Syndrome (AIDS) is expected to become the fifth leading cause of death for children ages 1 to 4, this paper provides relevant information on AIDS and the Human Immunodeficiency Virus (HIV) to help educators understand that they can work with children and adults who are HIV positive or who have AIDS. The…

  17. Home Economists in the Workplace: Formulating HIV/AIDS Policy.

    Science.gov (United States)

    Stanberry, Anne M.

    1991-01-01

    Reviews facts about human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS), HIV transmission, and prevention of HIV/AIDS; discusses risks for contracting HIV; reviews relevant legislation regarding the rights of employees, employers, and consumers; describes HIV/AIDS workplace policies and procedures; and presents implications…

  18. 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

  19. Response of a simian immunodeficiency virus (SIVmac251 to raltegravir: a basis for a new treatment for simian AIDS and an animal model for studying lentiviral persistence during antiretroviral therapy

    Directory of Open Access Journals (Sweden)

    Greenhouse Jack

    2010-03-01

    Full Text Available Abstract Background In this study we successfully created a new approach to ART in SIVmac251 infected nonhuman primates. This drug regimen is entirely based on drugs affecting the pre-integration stages of replication and consists of only two nucleotidic/nucleosidic reverse transcriptase inhibitors (Nt/NRTIs and raltegravir, a promising new drug belonging to the integrase strand transfer inhibitor (INSTI class. Results In acutely infected human lymphoid CD4+ T-cell lines MT-4 and CEMx174, SIVmac251 replication was efficiently inhibited by raltegravir, which showed an EC90 in the low nanomolar range. This result was confirmed in primary macaque PBMCs and enriched CD4+ T cell fractions. In vivo monotherapy with raltegravir for only ten days resulted in reproducible decreases in viral load in two different groups of animals. When emtricitabine (FTC and tenofovir (PMPA were added to treatment, undetectable viral load was reached in two weeks, and a parallel increase in CD4 counts was observed. In contrast, the levels of proviral DNA did not change significantly during the treatment period, thus showing persistence of this lentiviral reservoir during therapy. Conclusions In line with the high conservation of the three main amino acids Y143, Q148 and N155 (responsible for raltegravir binding and molecular docking simulations showing similar binding modes of raltegravir at the SIVmac251 and HIV-1 IN active sites, raltegravir is capable of inhibiting SIVmac251 replication both in tissue culture and in vivo. This finding may help to develop effective ART regimens for the simian AIDS model entirely based on drugs adopted for treatment in humans. This ART-treated AIDS nonhuman primate model could be employed to find possible strategies for virus eradication from the body.

  20. Cell culture attenuation eliminates rMd5deltaMeq-induced bursal and thymic atrophy and renders the mutant virus as an effective and safe vaccine against Marek's disease

    Science.gov (United States)

    Marek’s disease virus (MDV) encodes a basic leucine zipper oncoprotein, meq, which structurally resembles jun/fos family of transcriptional activators. It has been clearly demonstrated that deletion of meq results in loss of transformation and oncogenic capacity of MDV. The rMd5'meq virus provided s...

  1. 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.

  2. [Will AIDS overtake them?].

    Science.gov (United States)

    Boukhari, S

    UNICEF estimates that the streets are now the home of some 5 million African children aged 7-15 who are victims of rapid population growth and urbanization as well as the disintegration of traditional family structure. These children, deprived of a home and of all parental control, are potentially very vulnerable to the threat of AIDS. Prostitution, which is almost institutionalized in the most impoverished urban areas, represents for young girls the most immediate means of survival and occasionally even of helping their families. Male prostitution is highly tabu and marginal in sub-Saharan Africa, and is only slightly developed around the tourist hotels. Homeless children are somewhat protected against contamination through the blood by their lack of access to health care. Intravenous drugs are rare in Africa, and drug use is at most an indirect risk factor for AIDS to the extent that in increases the need for money and weakens the immune system. The frequency of sexually transmitted diseases, deplorable hygienic conditions, and poor general health of homeless children increase their risk of contracting the virus. Many homeless children do not even know of the existence of condoms and in any event condoms are usually inaccessible or too costly for them. Homeless children, like the general population, have false ideas about AIDS that discourage self-protective behaviors. In addition they are cut off from the activities of existing prevention programs. In a context of permanent daily insecurity, AIDS appears as just 1 more menace among others. According to an anthropologist working with the UNESCO program to help homeless children, the only way of making such children aware of the threat of AIDS in the large African cities will be to increase the number of prevention programs targeted at them. At the same time, the children need to be educated and taught an income-generating skill; in short, they need to be given a reason to believe in the future.

  3. [GeSIDA/National AIDS Plan: Consensus document on antiretroviral therapy in adults infected by the human immunodeficiency virus (Updated January 2014)].

    Science.gov (United States)

    2014-01-01

    This consensus document is an update of combined antiretroviral therapy (cART) guidelines for HIV-1 infected adult patients. To formulate these recommendations a panel composed of members of the Grupo de Estudio de Sida and the Plan Nacional sobre el Sida reviewed the efficacy and safety advances in clinical trials, cohort and pharmacokinetic studies published in medical journals (PubMed and Embase) or presented in medical scientific meetings. Recommendations strength and the evidence in which they are supported are based on modified criteria of the Infectious Diseases Society of America. In this update, antiretroviral therapy (ART) is recommended for all patients infected by type 1 human immunodeficiency virus (HIV-1). The strength and grade of the recommendation varies with the clinical circumstances: CDC stage B or C disease (A-I), asymptomatic patients (depending on the CD4+ T-lymphocyte count: 500 cells/μL, B-III), comorbid conditions (HIV nephropathy, chronic hepatitis caused by HBV or HCV, age >55years, high cardiovascular risk, neurocognitive disorders, and cancer, A-II), and prevention of transmission of HIV (mother-to-child or heterosexual, A-I; men who have sex with men, A-III). The objective of ART is to achieve an undetectable plasma viral load. Initial ART should always comprise a combination of 3 drugs, including 2 nucleoside reverse transcriptase inhibitors and a third drug from a different family (non-nucleoside reverse transcriptase inhibitor, protease inhibitor, or integrase inhibitor). Some of the possible initial regimens have been considered alternatives. This update presents the causes and criteria for switching ART in patients with undetectable plasma viral load and in cases of virological failure where rescue ART should comprise 2 or 3 drugs that are fully active against the virus. An update is also provided for the specific criteria for ART in special situations (acute infection, HIV-2 infection, and pregnancy) and with comorbid

  4. [National consensus document by GESIDA/National Aids Plan on antiretroviral treatment in adults infected by the human immunodeficiency virus (January 2011 update)].

    Science.gov (United States)

    2011-03-01

    The update of these adult antiretroviral treatment (cART) recommendations has been carried out by consensus of a panel consisting of members of the Grupo de Estudio de Sida (Gesida, AIDS Study Group) and the Plan Nacional sobre el Sida (PNS, Spanish AIDS Plan) who have reviewed the antiretroviral efficacy and safety advances in clinical trials, cohort and pharmacokinetic studies published in medical journals (PubMed and Embase), or presented in medical scientific meetings. Three levels of evidence were defined according to the data source: randomized studies (level A), cohort or case-control studies (level B), and expert opinion (level C). The decision to recommend, consider or not to recommend antiretroviral treatment (ART) was established by consensus in each situation. The current treatment of choice for HIV infection is the combination of three drugs. Combined ART is recommended in patients with symptomatic HIV infection, and guidelines on this treatment in patients with an opportunistic type C infection are included. In asymptomatic patients, initiation of ART is recommended on the basis of CD4 lymphocyte counts, plasma viral load and patient co-morbidities, as follows: a) therapy should be started in patients with CD4 counts treatment criteria, high cardiovascular risk, HIV nephropathy, viral load > 100,000 copies/ mL, proportion of CD4 cells 55 years, and in cases of discordant serological sexual couples in order to reduce transmission. cART should include 2 reverse transcriptase inhibitor nucleoside analogues (AN) and a non-analogue reverse transcriptase inhibitor (NN) or 2 AN and a ritonavir boosted protease inhibitor (PI/ r), but other combinations are possible. The panel has consensually selected and prioritized some drug combinations, some of them co-formulated. The objective of cART is to achieve an undetectable viral load. Adherence to therapy plays an essential role in maintaining antiviral response. Therapeutic options are limited after c

  5. Face singular do cuidado familiar à criança portadora do vírus HIV/AIDS Cara singular del Cuidado Familiar al niño Portador del Vírus VIH/ SIDA Singular view of family care for children with the HIV / AIDS virus

    Directory of Open Access Journals (Sweden)

    Giovana Calcagno Gomes

    2012-01-01

    Full Text Available OBJETIVO: Conhecer as vivências da família no cuidado à criança portadora do vírus HIV/AIDS. MÉTODOS: Foi realizado em um hospital universitário no primeiro semestre de 2010. Participaram sete familiares cuidadores. Os dados foram coletados por entrevistas semiestruturadas e analisados pela técnica de Análise Temática. RESULTADOS: Evidenciou-se o silenciamento do diagnóstico pelo familiar cuidador que passa a viver em função do cuidado à criança. Como dificuldades para cuidar, destacam-se as condições de saúde da mãe ou sua morte, as hospitalizações como comprometedoras da escolarização e reveladoras do diagnóstico e o medo em contar o diagnóstico à criança. CONCLUSÃO: Acredita-se que os profissionais da saúde/enfermagem necessitam empregar estratégias que possibilitem a essas famílias melhor enfrentamento do cotidiano, assessorando-as para o cuidado, fornecendo informações sobre o HIV/AIDS às pessoas de seu círculo social, diminuindo o estigma e a discriminação a que estão expostas essas crianças.OBJETIVO: Conocer las vivencias de la familia en el cuidado del niño portador del virus VIH/SIDA. MÉTODOS: Fue realizado en un hospital universitario en el primer semestre de 2010. Participaron siete familiares cuidadores. Los datos fueron recolectados por medio de entrevistas semiestructuradas y analizadas por la técnica de Análisis Temático. RESULTADOS: Se evidenció el silenciamiento del diagnóstico por parte del familiar cuidador quien pasa a vivir en función del cuidado al niño. Como dificultades para cuidar, se destacan las condiciones de salud de la madre o su muerte, las hospitalizaciones como comprometedoras de la escolarización y reveladoras del diagnóstico y el miedo para comunicar el diagnóstico al niño. CONCLUSIÓN: Se cree que los profesionales de la salud/enfermería necesitan emplear estrategias que posibiliten a esas familias un mejor enfrentamiento del cotidiano, asesorándolas para

  6. Newcastle Disease Virus Vectored Bivalent Vaccine against Virulent Infectious Bursal Disease and Newcastle Disease of Chickens

    Directory of Open Access Journals (Sweden)

    Sohini Dey

    2017-09-01

    Full Text Available Newcastle disease virus (NDV strain F is a lentogenic vaccine strain used for primary vaccination in day-old chickens against Newcastle disease (ND in India and Southeast Asian countries. Recombinant NDV-F virus and another recombinant NDV harboring the major capsid protein VP2 gene of a very virulent infectious bursal disease virus (IBDV; namely rNDV-F and rNDV-F/VP2, respectively, were generated using the NDV F strain. The rNDV-F/VP2 virus was slightly attenuated, as compared to the rNDV-F virus, as evidenced from the mean death time and intracerebral pathogenicity index analysis. This result indicates that rNDV-F/VP2 behaves as a lentogenic virus and it is stable even after 10 serial passages in embryonated chicken eggs. When chickens were vaccinated with the rNDV F/VP2, it induced both humoral and cell mediated immunity, and was able to confer complete protection against very virulent IBDV challenge and 80% protection against virulent NDV challenge. These results suggest that rNDV-F could be an effective and inherently safe vaccine vector. Here, we demonstrate that a bivalent NDV-IBDV vaccine candidate generated by reverse genetics method is safe, efficacious and cost-effective, which will greatly aid the poultry industry in developing countries.

  7. Types of Hearing Aids

    Science.gov (United States)

    ... Consumer Devices Consumer Products Hearing Aids Types of Hearing Aids Share Tweet Linkedin Pin it More sharing ... are some features for hearing aids? What are hearing aids? Hearing aids are sound-amplifying devices designed ...

  8. Computer simulations of the interaction of human immunodeficiency virus (HIV) aspartic protease with spherical gold nanoparticles: implications in acquired immunodeficiency syndrome (AIDS)

    Science.gov (United States)

    Whiteley, Chris G.; Lee, Duu-Jong

    2016-09-01

    The interaction of gold nanoparticles (AuNP) with human immune-deficiency virus aspartic protease (HIVPR) is modelled using a regime of molecular dynamics simulations. The simulations of the ‘docking’, first as a rigid-body complex, and eventually through flexible-fit analysis, creates 36 different complexes from four initial orientations of the nanoparticle strategically positioned around the surface of the enzyme. The structural deviations of the enzymes from the initial x-ray crystal structure during each docking simulation are assessed by comparative analysis of secondary structural elements, root mean square deviations, B-factors, interactive bonding energies, dihedral angles, radius of gyration (R g), circular dichroism (CD), volume occupied by C α , electrostatic potentials, solvation energies and hydrophobicities. Normalisation of the data narrows the selection from the initial 36 to one ‘final’ probable structure. It is concluded that, after computer simulations on each of the 36 initial complexes incorporating the 12 different biophysical techniques, the top five complexes are the same no matter which technique is explored. The significance of the present work is an expansion of an earlier study on the molecular dynamic simulation for the interaction of HIVPR with silver nanoparticles. This work is supported by experimental evidence since the initial ‘orientation’ of the AgNP with the enzyme is the same as the ‘final’ AuNP-HIVPR complex generated in the present study. The findings will provide insight into the forces of the binding of the HIVPR to AuNP. It is anticipated that the protocol developed in this study will act as a standard process for the interaction of any nanoparticle with any biomedical target.

  9. Enhanced antibody responses elicited by a CpG adjuvant do not improve the protective effect of an aldrithiol-2-inactivated simian immunodeficiency virus therapeutic AIDS vaccine.

    Science.gov (United States)

    Wang, Yichuan; Blozis, Shelley A; Lederman, Michael; Krieg, Arthur; Landay, Alan; Miller, Christopher J

    2009-04-01

    The potential benefit of using unmethylated CpG oligoribodeoxynucleotides (ODN) as an adjuvant in a therapeutic simian immunodeficiency virus (SIV) vaccine consisting of AT2-inactivated SIVmac239 was evaluated in SIV-infected rhesus macaques receiving antiretroviral therapy (ART). We hypothesized that using CpG ODN as an adjuvant in therapeutic vaccination would enhance SIV-specific immune responses and suppress SIV replication after ART was stopped. To test our hypothesis, we immunized chronically SIV-infected rhesus macaques receiving ART with one of the following therapeutic vaccines: (i) AT2-inactivated SIVmac239, (ii) CpG10103 plus AT2-inactivated SIVmac239, (iii) CpG10103, and (iv) saline. While immunization with CpG plus AT2-SIVmac239 significantly increased SIV-specific immunoglobulin G (IgG) antibody titers, the mean plasma viral RNA (vRNA) level in these animals after ART did not differ from those of saline-treated animals. The AT2-inactivated SIVmac239-immunized animal group had a significantly higher mean SIV-specific gamma interferon T-cell response after three immunizations and lower plasma vRNA levels for 6 weeks after ART was withdrawn compared to the saline-treated animal group. Compared to the saline control group, the animal group treated with CpG alone had a significantly higher mean SIV-specific lymphocyte proliferation index and a higher rate of plasma vRNA rebound after ART. These results demonstrate that while the use of CpG as an adjuvant enhances SIV-specific antibody responses, this does not improve the control of SIV replication after ART is stopped. The lack of benefit may be related to the high levels of SIV-specific lymphocyte proliferation in the CpG adjuvant group.

  10. Drug susceptibility to etravirine and darunavir among Human Immunodeficiency Virus Type 1-derived pseudoviruses in treatment-experienced patients with HIV/AIDS in South Korea.

    Science.gov (United States)

    Kwon, Oh-Kyung; Kim, Sung Soon; Rhee, Jee Eun; Kee, Mee-Kyung; Park, Mina; Oh, Hye-Ri; Choi, Ju-Yeon

    2015-04-09

    In South Korea, about 20 types of antiretroviral drugs are used in the treatment of patients with human immunodeficiency virus/acquired immune deficiency syndrome. Since 2010, raltegravir, etravirine, and darunavir have been spotlighted as new drugs for highly active antiretroviral therapy (HAART)-experienced adults with resistant HIV-1 in South Korea. In this study, we investigated potential susceptibility of pseudoviruses derived from treatment-experienced Korean patients to etravirine vs efavirenz and to darunavir vs amprenavir and indinavir using a modified single-round assay. Pseudoviruses derived from nine treatment-experienced patients infected with HIV-1 were investigated by comparison with the wild-type strain pNL4-3. The 50% inhibitory concentration (IC50) values were calculated and drug susceptibility was compared. The intensity of genotypic drug resistance was classified based on the 'SIR' interpretation of the Stanford data base. Drug susceptibility was generally higher for etravirine and darunavir compared with efavirenz, amprenavir, and indinavir in pseudoviruses derived from treatment-experienced patients. Pseudoviruses derived from patients KRB4025 and KRB8014, who exhibited long-term use of protease inhibitors, showed an outside of tested drug concentration, especially for amprenavir and indinavir. However, they exhibited a lower fold-change in resistance to darunavir. Etravirine and darunavir have been used in HAART since 2010 in South Korea. Therefore, these antiretroviral drugs together with other newly introduced antiretroviral drugs are interesting for the optimal treatment of patients with treatment failure. This study may help to find a more effective HAART in the case of HIV-1 infected patients that have difficulty being treated.

  11. [Analysis of costs and cost-effectiveness of preferred GESIDA/National AIDS Plan regimens for initial antiretroviral therapy in human immunodeficiency virus infected adult patients in 2013].

    Science.gov (United States)

    Blasco, Antonio Javier; Llibre, Josep M; Arribas, José Ramón; Boix, Vicente; Clotet, Bonaventura; Domingo, Pere; González-García, Juan; Knobel, Hernando; López, Juan Carlos; Lozano, Fernando; Miró, José M; Podzamczer, Daniel; Santamaría, Juan Miguel; Tuset, Montserrat; Zamora, Laura; Lázaro, Pablo; Gatell, Josep M

    2013-11-01

    The GESIDA and National AIDS Plan panel of experts have proposed "preferred regimens" of antiretroviral treatment (ART) as initial therapy in HIV infected patients for 2013. The objective of this study is to evaluate the costs and effectiveness of initiating treatment with these "preferred regimens". An economic assessment of costs and effectiveness (cost/effectiveness) was performed using decision tree analysis models. Effectiveness was defined as the probability of having viral load Cost of initiating treatment with an ART regime was defined as the costs of ART and its consequences (adverse effects, changes of ART regime and drug resistance analyses) during the first 48weeks. The perspective of the analysis is that of the National Health System was applied, only taking into account differential direct costs: ART (official prices), management of adverse effects, resistance studies, and determination of HLA B*5701. The setting is Spain and the costs are those of 2013. A sensitivity deterministic analysis was performed, constructing three scenarios for each regimen: baseline, most favourable, and most unfavourable cases. In the baseline case scenario, the cost of initiating treatment ranges from 6,747euros for TDF/FTC+NVP to 12,059euros for TDF/FTC+RAL. The effectiveness ranges between 0.66 for ABC/3TC+LPV/r and ABC/3TC+ATV/r, and 0.87 for TDF/FTC+RAL and ABC/3TC+RAL. Effectiveness, in terms of cost/effectiveness, varies between 8,396euros and 13,930euros per responder at 48weeks, for TDF/FTC/RPV and TDF/FTC+RAL, respectively. Taking ART at official prices, the most effective regimen was TDF/FTC/RPV, followed by the rest of non-nucleoside containing regimens. The sensitivity analysis confirms the robustness of these findings. Copyright © 2013 Elsevier España, S.L. All rights reserved.

  12. Brand Aid

    DEFF Research Database (Denmark)

    Richey, Lisa Ann; Ponte, Stefano

    2011-01-01

    activists, scholars and venture capitalists, discusses the pros and cons of changing the world by ‘voting with your dollars’. Lisa Ann Richey and Stefano Ponte (Professor at Roskilde University and Senior Researcher at DIIS respectively), authors of Brand Aid: Shopping Well to Save the World, highlight how...

  13. [Consensus Statement by GeSIDA/National AIDS Plan Secretariat on antiretroviral treatment in adults infected by the human immunodeficiency virus (Updated January 2013)].

    Science.gov (United States)

    2013-11-01

    This consensus document is an update of combined antiretroviral therapy (cART) guidelines for HIV-1 infected adult patients. To formulate these recommendations a panel composed of members of the GeSIDA/National AIDS Plan Secretariat (Grupo de Estudio de Sida and the Secretaría del Plan Nacional sobre el Sida) reviewed the efficacy and safety advances in clinical trials, cohort and pharmacokinetic studies published in medical journals (PubMed and Embase) or presented in medical scientific meetings. The strength of the recommendations and the evidence which support them are based on a modification of the criteria of Infectious Diseases Society of America. cART is recommended in patients with symptoms of HIV infection, in pregnant women, in serodiscordant couples with high risk of transmission, in hepatitisB co-infection requiring treatment, and in HIV nephropathy. cART is recommended in asymptomatic patients if CD4 is 500cells/μl cART should be considered in the case of chronic hepatitisC, cirrhosis, high cardiovascular risk, plasma viral load >100.000 copies/ml, proportion of CD4 cells 55years. The objective of cART is to achieve an undetectable viral load. The first cART should include 2 reverse transcriptase inhibitors (RTI) nucleoside analogs and a third drug (a non-analog RTI, a ritonavir boosted protease inhibitor, or an integrase inhibitor). The panel has consensually selected some drug combinations, for the first cART and specific criteria for cART in acute HIV infection, in tuberculosis and other HIV related opportunistic infections, for the women and in pregnancy, in hepatitisB or C co-infection, in HIV-2 infection, and in post-exposure prophylaxis. These new guidelines update previous recommendations related to first cART (when to begin and what drugs should be used), how to monitor, and what to do in case of viral failure or adverse drug reactions. cART specific criteria in comorbid patients and special situations are similarly updated. Copyright

  14. 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...

  15. Dental Practice, Human Immunodeficiency Virus Transmission and ...

    African Journals Online (AJOL)

    The acquired immune deficiency syndrome (AIDS) is a major cause of death in Africa today and it is estimated that 80% of the over 40 million people living with human immunodeficiency virus (HIV)/AIDS (PLWHA) world-wide are residing in sub-Saharan countries.[1] In Nigeria, AIDS was first reported in 1986 following the ...

  16. Human immunodeficiency virus, AIDS, and drug consumption in South America and the Caribbean: epidemiological evidence and initiatives to curb the epidemic El virus de la inmunodeficiencia humana, el sida y el consumo de drogas en América del Sur y el Caribe: pruebas epidemiológicas e iniciativas para frenar la epidemia

    Directory of Open Access Journals (Sweden)

    Mariana A Hacker

    2005-11-01

    Full Text Available OBJECTIVE: The paper reviews data on drug use in relation to the spread of human immuno-deficiency virus and AIDS in South America and the Caribbean. METHODS: 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. RESULTS: 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. CONCLUSION: 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.RESUMEN OBJETIVO: En el trabajo se revisan los datos acerca del consumo de drogas en relación con la propagación del virus de la inmunodeficiencia humana y el sida en Amé-rica del Sur y el Caribe. MÉTODOS: La información se obtuvo mediante una revisión exhaustiva de las principales bases de datos bibliográficas, así como de sitios en la web

  17. Satellite RNAs and Satellite Viruses.

    Science.gov (United States)

    Palukaitis, Peter

    2016-03-01

    Satellite RNAs and satellite viruses are extraviral components that can affect either the pathogenicity, the accumulation, or both of their associated viruses while themselves being dependent on the associated viruses as helper viruses for their infection. Most of these satellite RNAs are noncoding RNAs, and in many cases, have been shown to alter the interaction of their helper viruses with their hosts. In only a few cases have the functions of these satellite RNAs in such interactions been studied in detail. In particular, work on the satellite RNAs of Cucumber mosaic virus and Turnip crinkle virus have provided novel insights into RNAs functioning as noncoding RNAs. These effects are described and potential roles for satellite RNAs in the processes involved in symptom intensification or attenuation are discussed. In most cases, models describing these roles involve some aspect of RNA silencing or its suppression, either directly or indirectly involving the particular satellite RNA.

  18. PAN substitutions A37S, A37S/I61T and A37S/V63I attenuate the replication of H7N7 influenza A virus by impairing the polymerase and endonuclease activities.

    Science.gov (United States)

    Hu, Meng; Yuan, Shuofeng; Ye, Zi-Wei; Singh, Kailash; Li, Cun; Shuai, Huiping; Fai, Ng; Chow, Billy K C; Chu, Hin; Zheng, Bo-Jian

    2017-03-01

    Substitutions in the PA N-terminus (PAN) of influenza A viruses are associated with viral pathogenicity. During our previous study, which identified PAN-V63I and -A37S/I61T/V63I/V100A substitutions as virulence determinants, we observed a severe decrease in virus growth and transcription/replication capacity posed by PAN-A37S/V100A substitution. To further delineate the significance of substitutions at these positions, we generated mutant H7N7 viruses bearing the substitutions PAN-A37S, -A37S/I61T, -A37S/V63I, -V100A, -I61T/V100A and -V63I/V100A by reverse genetics. Our results showed that all mutant viruses except PAN-V100A showed a significantly reduced growth capability in infected cells. At the same time, the PAN-A37S, -A37S/I61T and -A37S/V63I mutant viruses displayed decreased viral transcription and replication by diminishing virus RNA synthesis activity. Biochemical assays indicated that the substitutions PAN-A37S, -A37S/I61T and -A37S/V63I suppressed the polymerase and endonuclease activities when compared with those of the wild-type. Together, our results demonstrated that the PAN-A37S, -A37S/I61T and -A37S/V63I substitutions contributed to a decreased pathogenicity of avian H7N7 influenza A virus.

  19. Landing gear noise attenuation

    Science.gov (United States)

    Moe, Jeffrey W. (Inventor); Whitmire, Julia (Inventor); Kwan, Hwa-Wan (Inventor); Abeysinghe, Amal (Inventor)

    2011-01-01

    A landing gear noise attenuator mitigates noise generated by airframe deployable landing gear. The noise attenuator can have a first position when the landing gear is in its deployed or down position, and a second position when the landing gear is in its up or stowed position. The noise attenuator may be an inflatable fairing that does not compromise limited space constraints associated with landing gear retraction and stowage. A truck fairing mounted under a truck beam can have a compliant edge to allow for non-destructive impingement of a deflected fire during certain conditions.

  20. The history of AIDS exceptionalism

    Directory of Open Access Journals (Sweden)

    Smith Julia H

    2010-12-01

    Full Text Available Abstract In the history of public health, HIV/AIDS is unique; it has widespread and long-lasting demographic, social, economic and political impacts. The global response has been unprecedented. AIDS exceptionalism - the idea that the disease requires a response above and beyond "normal" health interventions - began as a Western response to the originally terrifying and lethal nature of the virus. More recently, AIDS exceptionalism came to refer to the disease-specific global response and the resources dedicated to addressing the epidemic. There has been a backlash against this exceptionalism, with critics claiming that HIV/AIDS receives a disproportionate amount of international aid and health funding. This paper situations this debate in historical perspective. By reviewing histories of the disease, policy developments and funding patterns, it charts how the meaning of AIDS exceptionalism has shifted over three decades. It argues that while the connotation of the term has changed, the epidemic has maintained its course, and therefore some of the justifications for exceptionalism remain.

  1. Ebola Virus and Marburg Virus

    Science.gov (United States)

    Ebola virus and Marburg virus Overview Ebola virus and Marburg virus are related viruses that cause hemorrhagic fevers — illnesses marked by severe bleeding (hemorrhage), organ failure and, in many ...

  2. Tactile Aids

    Directory of Open Access Journals (Sweden)

    Mohtaramossadat Homayuni

    1996-04-01

    Full Text Available Tactile aids, which translate sound waves into vibrations that can be felt by the skin, have been used for decades by people with severe/profound hearing loss to enhance speech/language development and improve speechreading.The development of tactile aids dates from the efforts of Goults and his co-workers in the 1920s; Although The power supply was too voluminous and it was difficult to carry specially by children, it was too huge and heavy to be carried outside the laboratories and its application was restricted to the experimental usage. Nowadays great advances have been performed in producing this instrument and its numerous models is available in markets around the world.

  3. Complete Genome Sequence of Capripoxvirus Strain KSGP 0240 from a Commercial Live Attenuated Vaccine.

    Science.gov (United States)

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

    2016-10-20

    Capripoxviruses cause economically important diseases in domestic ruminants in regions endemic for these viruses. We report here the complete genome sequence of the KSGP 0240 vaccine strain from the live attenuated vaccine Kenyavac (JOVAC). Copyright © 2016 Vandenbussche et al.

  4. Aujeszky's disease virus production in disposable bioreactor

    Indian Academy of Sciences (India)

    Madhu

    financial losses, the vaccination of pigs with attenuated live or inactivated vaccines is widely performed. A laboratory- attenuated ADV replicates well in BHK 21 cells (Puentes. Aujeszky's disease virus production in disposable bioreactor. I SLIVAC. 1, V GAURINA SRČEK. 1, K RADOŠEVIĆ. 1, I KMETIČ. 2 and Z KNIEWALD.

  5. Clampdown on AIDS information in E. Africa.

    Science.gov (United States)

    Hitchcock, B

    1986-01-01

    What is most alarming about Acquired Immune Deficiency Syndrome (AIDS) in East Africa is that it is taboo. The reason for the clamping down on publicity in Kenya is that the government sees AIDS as a killer of tourism, the country's 2nd largest revenue earner. The government of Kenya, like several other African governments, is reacting to the widespread belief in the West that AIDS originated in Africa and that it is rampant in Central and East Africa. These "facts" have yet to be proven conclusively by medical evidence. It is certain that a large percentage of the population of these regions have antibodies to the virus HTLV-III, which causes AIDS. From this, virologists deduce that the people concerned must have been exposed to the AIDS virus. The Western media has exaggerated the African AIDS connection and given the impression that African countries are gripped in raging AIDS epidemics. In response to the alarmist publicity, some African countries have clamped down in information about the disease. The result is that the Western press feels confirmed in its fears and the local population, depending on rumor and heresay, have been living in a state of absolute panic. Instead of allaying fears, the clampdown on news has fueled dangerous rumors at home and frightened away tourists. Whatever may be causing the disease and wherever it may have come from, there is no question at all that there are now confirmed cases of AIDS in East and Central Africa. Thus far, the number of confirmed cases if relatively small, but if governments continue to try and hide the facts from the public, there is a real danger of an epidemic developing. A ministerial statement admits to 7 confirmed AIDS cases in Kenya. There are discrepancies in the reports, however. Doctors interviewed by "New African" in Nairobi recently believe the situation is far more serious than the government admits. Doctors in Kenya make the point that the country is highly vulnerable to the spread of AIDS

  6. Successful vaccination strategies that protect aged mice from lethal challenge from influenza virus and heterologous severe acute respiratory syndrome coronavirus.

    Science.gov (United States)

    Sheahan, Timothy; Whitmore, Alan; Long, Kristin; Ferris, Martin; Rockx, Barry; Funkhouser, William; Donaldson, Eric; Gralinski, Lisa; Collier, Martha; Heise, Mark; Davis, Nancy; Johnston, Robert; Baric, Ralph S

    2011-01-01

    Newly emerging viruses often circulate as a heterogeneous swarm in wild animal reservoirs prior to their emergence in humans, and their antigenic identities are often unknown until an outbreak situation. The newly emerging severe acute respiratory syndrome coronavirus (SARS-CoV) and reemerging influenza virus cause disproportionate disease in the aged, who are also notoriously difficult to successfully vaccinate, likely due to immunosenescence. To protect against future emerging strains, vaccine platforms should induce broad cross-reactive immunity that is sufficient to protect from homologous and heterologous challenge in all ages. From initial studies, we hypothesized that attenuated Venezuelan equine encephalitis virus (VEE) replicon particle (VRP) vaccine glycoproteins mediated vaccine failure in the aged. We then compared the efficacies of vaccines bearing attenuated (VRP(3014)) or wild-type VEE glycoproteins (VRP(3000)) in young and aged mice within novel models of severe SARS-CoV pathogenesis. Aged animals receiving VRP(3000)-based vaccines were protected from SARS-CoV disease, while animals receiving the VRP(3014)-based vaccines were not. The superior protection for the aged observed with VRP(3000)-based vaccines was confirmed in a lethal influenza virus challenge model. While the VRP(3000) vaccine's immune responses in the aged were sufficient to protect against lethal homologous and heterologous challenge, our data suggest that innate defects within the VRP(3014) platform mediate vaccine failure. Exploration into the mechanism(s) of successful vaccination in the immunosenescent should aid in the development of successful vaccine strategies for other viral diseases disproportionately affecting the elderly, like West Nile virus, influenza virus, norovirus, or other emerging viruses of the future.

  7. Immunogenicity and safety of a live attenuated varicella vaccine in ...

    African Journals Online (AJOL)

    To investigate the safety of live attenuated varicella vaccine (aka strain) and the optimal virus titre/ dose required for immunogenicity in healthy South African children. ... Six subjects who were initially seropositive maintained or increased their titres post-vaccination; 3 of the 6 showed a booster response (a ;:;, 4-fold increase ...

  8. Immunogenicity and safety of a live attenuated varicella vaccine in ...

    African Journals Online (AJOL)

    Objectives. To investigate the safety of live attenuated varicella vaccine (aka strain) and the optimal virus titre/ dose required for immunogenicity in healthy South African children. Design. Double-blind randomised clinical study using two different lots of varicella vaccine, each at two different titres. Subjects were randomly ...

  9. 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 changes of the viral genome

    Science.gov (United States)

    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 Fev...

  10. Negotiating Aid

    DEFF Research Database (Denmark)

    Whitfield, Lindsay; Fraser, Alastair

    2011-01-01

    This article presents a new analytical approach to the study of aid negotiations. Building on existing approaches but trying to overcome their limitations, it argues that factors outside of individual negotiations (or the `game' in game-theoretic approaches) significantly affect the preferences o...... after agreements have been signed. It argues that Botswana, Ethiopia and Rwanda have been more successful than the other five cases in levering negotiating capital from the economic, political, ideological and institutional conditions under which negotiations occur.......This article presents a new analytical approach to the study of aid negotiations. Building on existing approaches but trying to overcome their limitations, it argues that factors outside of individual negotiations (or the `game' in game-theoretic approaches) significantly affect the preferences...... of actors, the negotiating strategies they fashion, and the success of those strategies. This approach was employed to examine and compare the experiences of eight countries: Botswana, Ethiopia, Ghana, Mali, Mozambique, Rwanda, Tanzania and Zambia. The article presents findings from these country studies...

  11. Neuropsychiatric manifestations of AIDS-spectrum disorders.

    Science.gov (United States)

    Perry, S; Jacobsen, P

    1986-02-01

    Psychiatric symptoms among patients with acquired immune deficiency syndrome (AIDS) may be functional reactions to contracting a fatal and stigmatizing disease or may be secondary to malignancies and opportunistic infections in the central nervous system (CNS). More recent evidence indicates that HTLV-III, the virus that causes AIDS, directly infects the CNS and may cause psychiatric symptoms before signs of immunodeficiency, cognitive impairment, or neurological abnormalities emerge. AIDS-related organic mental syndromes may mimic functional disorders such as chronic mild depression and acute psychosis. Both of these common presentations are illustrated with detailed case reports, and diagnostic and management guidelines are provided.

  12. [No remedy for AIDS?].

    Science.gov (United States)

    Ramirez, M M

    1993-01-01

    Vila Mimosa, a site of street prostitution in Rio de Janeiro since the 1930s, is the place of work for over 2000 prostitution who charge an average of $3-4 per client. Several years ago the Association of Prostitutes of Rio de Janeiro (APRJ) was founded by Eunice Coelho Reis. APRJ membership has increased steadily and its list of accomplishments is impressive. A state hospital performs free medical examinations of APRJ members, and the Brazilian family planning association BEMFAM provides 180,000 condoms each month. AIDS control projects have also been successful, and no APRJ members have contracted HIV infection. In the country with the 4th highest rate of infection, the rigid norm of condom use adopted by the prostitutes of Vila Mimosa has led to effective prevention of sexually transmitted diseases. The prostitutes report however that a large proportion of their clients resist condom use, sometimes violently. The proportion of seropositive individuals who are women has been rising steadily. Family Health International estimates that the proportion of new cases among women has risen from 25% in 1990 to 40% at present. AIDS prevention campaigns are attempting to persuade women to "negotiate" condom use during sex. But power relations between the sexes place women at a disadvantage. Men often make the sexual decisions. Socialization patterns of females in Latin America are oriented to maternity. Passive sexual behavior has become a primary obstacle to adoption of safer sex practices. The World Health Organization estimates that currently 9-11 million persons are latent carriers of the HIV virus. Prostitution originating in poverty and unemployment, the vulnerability of adolescents who begin their sexual lives with little knowledge of contraception or sexually transmitted diseases, and the lack of sex education that transcends the biological to consider interpersonal relations are all factors that hinder AIDS prevention.

  13. Pakistan combats hidden AIDS menace.

    Science.gov (United States)

    1996-05-20

    The conservative Islamic society in Pakistan associates human immunodeficiency virus (HIV) infections and acquired immunodeficiency syndrome (AIDS) with prostitution, homosexuality, and drug abuse, activities which are prohibited in Pakistan. There are 1000 reported cases of HIV, 55 with advanced AIDS (53 have died) in Pakistan. Birjees Mazhar Kazi, head of the National AIDS Program, believes that, based on the computer model of the World Health Organization (WHO), the number of HIV cases in Pakistan can be 50,000 to 80,000. Prime Minister Benazir Bhutto's government has allocated $2 million for AIDS prevention. Although some officials argue that Islamic strictures and traditional social pressures discourage sexual license, the poor public health and education standards in Pakistan make it vulnerable to AIDS. Drug abuse has risen in the last 20 years; there are an estimated 1.5 million heroin users among an estimated 3 million addicts. According to Health Ministry Director General Naik Muhammad Shaikh, the government has established 30 HIV/AIDS screening centers and is sponsoring a law that would require all blood banks to provide only safe blood and blood products for transfusion. Marvi states that the reuse and poor disposal of needles, a common practice in Pakistan, could be responsible for most of the transmission there of AIDS and hepatitis C. Health experts acknowledge the obstacles placed in the way of AIDS awareness campaigns by sex taboos and religious sensitivities; condoms cannot be mentioned or displayed in shops, or used in electronic or print media campaigns. They can be mentioned in a recorded message on a 24-hr AIDS hotline. Community-based and nongovernmental organizations are being used to reach segments of society who cannot use the hotline. Eunuchs (hijras), who are much in demand as "female" entertainers at weddings, are particularly resistant to safe sex messages, according to Abid Atiq, head of the information and education section of the

  14. Development of live attenuated influenza vaccines against pandemic influenza strains.

    Science.gov (United States)

    Coelingh, Kathleen L; Luke, Catherine J; Jin, Hong; Talaat, Kawsar R

    2014-07-01

    Avian and animal influenza viruses can sporadically transmit to humans, causing outbreaks of varying severity. In some cases, further human-to-human virus transmission does not occur, and the outbreak in humans is limited. In other cases, sustained human-to-human transmission occurs, resulting in worldwide influenza pandemics. Preparation for future pandemics is an important global public health goal. A key objective of preparedness is to gain an understanding of how to design, test, and manufacture effective vaccines that could be stockpiled for use in a pandemic. This review summarizes results of an ongoing collaboration to produce, characterize, and clinically test a library of live attenuated influenza vaccine strains (based on Ann Arbor attenuated Type A strain) containing protective antigens from influenza viruses considered to be of high pandemic potential.

  15. Can we get AIDS from mosquito bites?

    Science.gov (United States)

    Iqbal, M M

    1999-08-01

    Human immunodeficiency virus, or HIV, is a human retrovirus that infects lymphocytes and other cells bearing the CD4 surface marker. The virus is transmitted primarily by sexual and parental routes. There are two ways blood feeding arthropods can spread disease, mechanically, by simple transfer of virus between hosts by contaminated mouth parts, or, biologically, which would require virus replication in arthropod tissues (especially salivary glands). There are some important factors which have proven that AIDS is not transmitted by mosquito bite. These factors are: (1) AIDS virus can not replicate inside the mosquito, bed bug, flea, or other blood sucking insect and the lack of replication of HIV in arthropod cells due to lack of T4 antigen on cell surface, and (2) it is unlikely that HIV is transmitted by insects, given the low infectivity of HIV and the short survival of the virus in the mosquito. HIV appears to be much less easily transmitted probably due to lower titers of virus in body fluids. So, on the basis of experimental evidence and probability estimates, it has been concluded that the likelihood of mechanical or biological transmission of HIV by insects is virtually nonexistent.

  16. Radiofrequency attenuator and method

    Science.gov (United States)

    Warner, Benjamin P [Los Alamos, NM; McCleskey, T Mark [Los Alamos, NM; Burrell, Anthony K [Los Alamos, NM; Agrawal, Anoop [Tucson, AZ; Hall, Simon B [Palmerston North, NZ

    2009-01-20

    Radiofrequency attenuator and method. The attenuator includes a pair of transparent windows. A chamber between the windows is filled with molten salt. Preferred molten salts include quarternary ammonium cations and fluorine-containing anions such as tetrafluoroborate (BF.sub.4.sup.-), hexafluorophosphate (PF.sub.6.sup.-), hexafluoroarsenate (AsF.sub.6.sup.-), trifluoromethylsulfonate (CF.sub.3SO.sub.3.sup.-), bis(trifluoromethylsulfonyl)imide ((CF.sub.3SO.sub.2).sub.2N.sup.-), bis(perfluoroethylsulfonyl)imide ((CF.sub.3CF.sub.2SO.sub.2).sub.2N.sup.-) and tris(trifluoromethylsulfonyl)methide ((CF.sub.3SO.sub.2).sub.3C.sup.-). Radicals or radical cations may be added to or electrochemically generated in the molten salt to enhance the RF attenuation.

  17. 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.

  18. Modulation of systemic and mucosal immunity against an inactivated vaccine of Newcastle disease virus by oral co-administration of live attenuated Salmonella enterica serovar Typhimurium expressing chicken interleukin-18 and interferon-?

    OpenAIRE

    Rahman, Md. Masudur; UYANGAA, Erdenebelig; Han, Young Woo; Hur, Jin; Park, Sang-Youel; Lee, John Hwa; Kim, Koanhoi; EO, Seong Kug

    2014-01-01

    Newcastle disease (ND) is a highly contagious disease of chickens causing significant economic losses worldwide. Due to limitations in the efficacy against currently circulating ND viruses, existing vaccination strategies require improvements, and incorporating immunomodulatory cytokines with existing vaccines might be a novel approach. Here, we investigated the systemic and mucosal immunomodulatory properties of oral co-administration of chicken interleukin-18 (chIL-18) and chicken interfero...

  19. The nucleocapsid proteins of mouse hepatitis virus and severe acute respiratory syndrome coronavirus share the same IFN-β antagonizing mechanism: attenuation of PACT-mediated RIG-I/ MDA5 activation.

    Science.gov (United States)

    Ding, Zhen; Fang, Liurong; Yuan, Shuangling; Zhao, Ling; Wang, Xunlei; Long, Siwen; Wang, Mohan; Wang, Dang; Foda, Mohamed Frahat; Xiao, Shaobo

    2017-07-25

    Coronaviruses (CoVs) are a huge threat to both humans and animals and have evolved elaborate mechanisms to antagonize interferons (IFNs). Nucleocapsid (N) protein is the most abundant viral protein in CoV-infected cells, and has been identified as an innate immunity antagonist in several CoVs, including mouse hepatitis virus (MHV) and severe acute respiratory syndrome (SARS)-CoV. However, the underlying molecular mechanism(s) remain unclear. In this study, we found that MHV N protein inhibited Sendai virus and poly(I:C)-induced IFN-β production by targeting a molecule upstream of retinoic acid-induced gene I (RIG-I) and melanoma differentiation gene 5 (MDA5). Further studies showed that both MHV and SARS-CoV N proteins directly interacted with protein activator of protein kinase R (PACT), a cellular dsRNA-binding protein that can bind to RIG-I and MDA5 to activate IFN production. The N-PACT interaction sequestered the association of PACT and RIG-I/MDA5, which in turn inhibited IFN-β production. However, the N proteins from porcine epidemic diarrhea virus (PEDV) and porcine reproductive and respiratory syndrome virus (PRRSV), which are also classified in the order Nidovirales, did not interact and counteract with PACT. Taken together, our present study confirms that both MHV and SARS-CoV N proteins can perturb the function of cellular PACT to circumvent the innate antiviral response. However, this strategy does not appear to be used by all CoVs N proteins.

  20. VSV infection is sensed by Drosophila, attenuates nutrient signaling, and thereby activates antiviral autophagy.

    Science.gov (United States)

    Cherry, Sara

    2009-10-01

    Innate immune mechanisms are the first line of defense against pathogens including viruses. This work identifies autophagy, an innate intracellular degradative pathway, as antiviral against Vesicular Stomatitis Virus (VSV) in Drosophila. VSV is sensed by cells via the surface glycoprotein leading to the attenuation of the nutrient signaling pathway thereby activating an antiviral autophagic program.

  1. Construction of a doxycycline-dependent simian immunodeficiency virus reveals a nontranscriptional function of tat in viral replication

    NARCIS (Netherlands)

    Das, Atze T.; Klaver, Bep; Harwig, Alex; Vink, Monique; Ooms, Marcel; Centlivre, Mireille; Berkhout, Ben

    2007-01-01

    In the quest for an effective vaccine against human immunodeficiency virus (HIV), live attenuated virus vaccines have proven to be very effective in the experimental model system of simian immunodeficiency virus (SIV) in macaques. However, live attenuated HIV vaccines are considered unsafe for use

  2. Viruses, dendritic cells and the lung

    Directory of Open Access Journals (Sweden)

    Graham Barney S

    2001-06-01

    Full Text Available Abstract The interaction between viruses and dendritic cells (DCs is varied and complex. DCs are key elements in the development of a host response to pathogens such as viruses, but viruses have developed survival tactics to either evade or diminish the immune system that functions to kill and eliminate these micro-organisms. In the present review we summarize current concepts regarding the function of DCs in the immune system, our understanding of how viruses alter DC function to attenuate both the virus-specific and global immune response, and how we may be able to exploit DC function to prevent or treat viral infections.

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

    Science.gov (United States)

    1991-02-28

    pathophysiology measured during follow-up. I. Compare neuropsychiatric and psychosocial findings in HIV-infected military personnel with non-infected military...venipuncture, and possible rare side effects of PTU therapy - hypothyroidism , skin rash, myalgias, arthralgias, hepatitis, edema. *23 RV47 A Randomized

  4. Mechanisms of Cytotoxicity of the Aids Virus

    Science.gov (United States)

    1994-08-01

    of significant inverse correlaticns ware detemined between results of transcript detection and inmunological parameters ard clinical parameters. Fig 57... inmunological parameters. Statistical significance (at the level of p<O.05) was achieved in the oorrelation of gag transcripts with (C)4 cell count, CDC...34, STEVEN P. ADAMSII, AND JEFFREY I. GORDONt§ Departments of * Pediatrics . tMedicine. IMolecular Microbiology, and §Molecular Biology and Pharmacology

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

    Science.gov (United States)

    1993-07-15

    Dermatology Microflora"(comploted) Smith RV22 Retrospective Review Gtter RV44 HIV/ Syphilis Johnson RV44 Propylthiouracil 1aCivito XV40 Chatges-Blood...follows: 1) To identify all HIV positive or HIV exposed pregnant women as early in gestation as possible and obtain blood samples in each trimester...of HZV Infection on the Clinical manifestations and Response to Treatment of Syphilis ’- This protocol had the purpose of defining the risk factors

  6. Illusions of Immortality: The Confrontation of Adolescence and AIDS.

    Science.gov (United States)

    New York State Dept. of Health, Albany.

    Acquired Immune Deficiency Syndrome (AIDS) is a potent and a present danger for teenagers, casting a dark shadow over their lives now and in the future. A small, but significant, number of teenagers will develop Human Immune Virus (HIV)-related illness before they turn 20; a far greater number will become infected with the virus during…

  7. 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...

  8. Ritual Impurities: Perspectives of Women Living with HIV and AIDS ...

    African Journals Online (AJOL)

    This paper seeks to explore the women's perspectives on HIV (Human Immunodeficiency Virus) and AIDS (Acquired Immunodeficiency Syndrome). Thus, a qualitative exploratory-descriptive study was conducted among women living with HIV (WLWHIV) and AIDS in Mankweng and the surrounding villages of Limpopo ...

  9. Assessing AIDS Awareness among Students of a Regional Public Institution.

    Science.gov (United States)

    Brown, Wayne E.; Franklin, Harvey L.

    Acquired Immune Deficiency Syndrome (AIDS) could be a leading cause of death in American youth before the end of this century. Awareness is the starting point in preventing the spread of the AIDS epidemic. Infection from Human Immunodeficiency Virus (HIV) is absolutely preventable if people are aware of the potential for becoming infected and act…

  10. Bloodborne transmission of Hiv/Aids in Africa: Challenges and ...

    African Journals Online (AJOL)

    The causative agent of Acquired Immune Deficiency Syndrome (AIDS), is the human immuno-deficiency virus(HIV). Two types of HIV( types 1 and 2), have been linked with AIDS. HIV-2, has been described mainly in West Africa. HIV can be transmitted both in cellular and plasma components of blood. Bloodborne ...

  11. Natural attenuation of herbicides

    DEFF Research Database (Denmark)

    Tuxen, Nina; Højberg, Anker Lajer; Broholm, Mette Martina

    2002-01-01

    A field injection experiment in a sandy, aerobic aquifer showed that two phenoxy acids MCPP (mecoprop) and dichlorprop were degraded within I in downgradient of the injection wells after an apparent lag period. The plume development and microbial measurements indicated that microbial growth....... The observations may be important for application of natural attenuation as a remedy in field scale systems....

  12. Controlling Multicycle Replication of Live-Attenuated HIV-1 Using an Unnatural Genetic Switch.

    Science.gov (United States)

    Yuan, Zhe; Wang, Nanxi; Kang, Guobin; Niu, Wei; Li, Qingsheng; Guo, Jiantao

    2017-04-21

    A safe and effective human immunodeficiency virus type 1 (HIV-1) vaccine is urgently needed, but remains elusive. While HIV-1 live-attenuated vaccine can provide potent protection as demonstrated in rhesus macaque-simian immunodeficiency virus model, the potential pathogenic consequences associated with the uncontrolled virus replication preclude such vaccine from clinical applications. We investigated a novel approach to address this problem by controlling live-attenuated HIV-1 replication through an unnatural genetic switch that was based on the amber suppression strategy. Here we report the construction of all-in-one live-attenuated HIV-1 mutants that contain genomic copy of the amber suppression system. This genetic modification resulted in viruses that were capable of multicycle replication in vitro and could be switched on and off using an unnatural amino acid as the cue. This stand-alone, replication-controllable attenuated HIV-1 virus represents an important step toward the generation of a safe and efficacious live-attenuated HIV-1 vaccine. The strategy reported in this work can be adopted for the development of other live-attenuated vaccines.

  13. Freeze-drying of live virus vaccines: A review.

    Science.gov (United States)

    Hansen, L J J; Daoussi, R; Vervaet, C; Remon, J-P; De Beer, T R M

    2015-10-13

    Freeze-drying is the preferred method for stabilizing live, attenuated virus vaccines. After decades of research on several aspects of the process like the stabilization and destabilization mechanisms of the live, attenuated viruses during freeze-drying, the optimal formulation components and process settings are still matter of research. The molecular complexity of live, attenuated viruses, the multiple destabilization pathways and the lack of analytical techniques allowing the measurement of physicochemical changes in the antigen's structure during and after freeze-drying mean that they form a particular lyophilization challenge. The purpose of this review is to overview the available information on the development of the freeze-drying process of live, attenuated virus vaccines, herewith focusing on the freezing and drying stresses the viruses can undergo during processing as well as on the mechanisms and strategies (formulation and process) that are used to stabilize them during freeze-drying. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. Microbiota fúngica conjuntival: estudo comparativo entre pacientes com AIDS, pacientes infectados pelo HIV e pacientes HIV-negativos antes da era do HAART Fungal microbiota: comparative study between patients with acquired immunodeficiency syndrome, patients infected with human immunodeficiency virus and immunocompetent individuals before the HAART era

    Directory of Open Access Journals (Sweden)

    Procópio Miguel dos Santos

    1999-12-01

    Full Text Available Foi pesquisada a presença de fungos na conjuntiva ocular de 23 pacientes com AIDS, 24 pacientes infectados pelo HIV, ambos de controle ambulatorial e 48 indivíduos HIV negativos, durante um ano, nos meses de fevereiro, abril, julho e outubro. O fungo mais isolado foi Penicillium sp, seguido de Aspergillus sp, Candida sp e Rhodotorula sp. Embora sem diferença significante, em todas as coletas foi verificado um crescimento maior de fungos na conjuntiva dos portadores de AIDS, seguido pelo grupo infectado pelo HIV e em menor número nos indivíduos HIV-negativos.Samples from the ocular conjunctiva of 23 patients with AIDS, 24 patients infected with human immunodeficiency virus (HIV and 48 immunocompetent individuals were taken during the months of February, April, July and October. During the year an increase in fungi of the conjunctiva of the AIDS patients, followed by patients infected with HIV and a smaller percentage in healtly people was observed. The most frequently isolated fungus was Penicillium sp followed by Aspergillus sp, Candida sp and Rhodotorula sp.

  15. Differential Survival for Men and Women with HIV/AIDS-Related Neurologic Diagnoses

    OpenAIRE

    Martha L Carvour; Jerald P Harms; Lynch, Charles F.; Randall R Mayer; Meier, Jeffery L.; Dawei Liu; Torner, James C.

    2015-01-01

    Objectives Neurologic complications of human immunodeficiency virus (HIV) infection and acquired immune deficiency syndrome (AIDS) frequently lead to disability or death in affected patients. The aim of this study was to determine whether survival patterns differ between men and women with HIV/AIDS-related neurologic disease (neuro-AIDS). Methods Retrospective cohort data from a statewide surveillance database for HIV/AIDS were used to characterize survival following an HIV/AIDS-related neuro...

  16. 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

  17. AIDS: The Impact on the Criminal Justice System Management of Aids in Corrections.

    Science.gov (United States)

    1991-01-01

    Island, the former home of a now- abandoned leprosy sanatorium, be used as the site.’ The 1986 1 2 political campaign waged by Lyndon LaRouche in...because of their AIDS status; of public and private employees to job equity ; of children to 4 attend school; and of all people with AIDS to obtain...Prediction of course and end of a disease, and outlook based on these factors. Retrovirus: A genus of viruses which contains the enzyme reverse

  18. Animal Bites: First Aid

    Science.gov (United States)

    First aid Animal bites: First aid Animal bites: First aid By Mayo Clinic Staff These guidelines can help you care for a minor animal bite, such ... 26, 2017 Original article: http://www.mayoclinic.org/first-aid/first-aid-animal-bites/basics/ART-20056591 . Mayo ...

  19. HIV/AIDS - resources

    Science.gov (United States)

    Resources - HIV/AIDS ... information on AIDS : AIDS.gov -- www.aids.gov AIDS Info -- aidsinfo.nih.gov The Henry J. Kaiser Family Foundation -- www.kff.org/hivaids US Centers for Disease Control and Prevention -- www.cdc.gov/hiv

  20. Urgent challenges in implementing live attenuated influenza vaccine.

    Science.gov (United States)

    Singanayagam, Anika; Zambon, Maria; Lalvani, Ajit; Barclay, Wendy

    2017-08-02

    Conflicting reports have emerged about the effectiveness of the live attenuated influenza vaccine. The live attenuated influenza vaccine appears to protect particularly poorly against currently circulating H1N1 viruses that are derived from the 2009 pandemic H1N1 viruses. During the 2015-16 influenza season, when pandemic H1N1 was the predominant virus, studies from the USA reported a complete lack of effectiveness of the live vaccine in children. This finding led to a crucial decision in the USA to recommend that the live vaccine not be used in 2016-17 and to switch to the inactivated influenza vaccine. Other countries, including the UK, Canada, and Finland, however, have continued to recommend the use of the live vaccine. This policy divergence and uncertainty has far reaching implications for the entire global community, given the importance of the production capabilities of the live attenuated influenza vaccine for pandemic preparedness. In this Personal View, we discuss possible explanations for the observed reduced effectiveness of the live attenuated influenza vaccine and highlight the underpinning scientific questions. Further research to understand the reasons for these observations is essential to enable informed public health policy and commercial decisions about vaccine production and development in coming years. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Mitogen-activated Protein Kinase Kinase 2 (MEK2), a Novel E2-interacting Protein, Promotes the Growth of Classical Swine Fever Virus via Attenuation of the JAK-STAT Signaling Pathway.

    Science.gov (United States)

    Wang, Jinghan; Chen, Shucheng; Liao, Yajin; Zhang, Enyu; Feng, Shuo; Yu, Shaoxiong; Li, Lian-Feng; He, Wen-Rui; Li, Yongfeng; Luo, Yuzi; Sun, Yuan; Zhou, Mo; Wang, Xiao; Munir, Muhammad; Li, Su; Qiu, Hua-Ji

    2016-09-07

    Mitogen-activated protein kinase kinase/extracellular regulated kinase (MEK1/2/ERK1/2) cascade is involved in the replication of several members of the Flaviviridae family including hepatitis C virus and dengue virus. The effects of the cascade on the replication of classical swine fever virus (CSFV), a fatal pestivirus of pigs, remain unknown. In this study, MEK2 was identified as a novel binding partner of the E2 protein of CSFV using yeast two-hybrid screening. The E2-MEK2 interaction was confirmed by glutathione S-transferase pulldown, coimmunoprecipitation, and laser confocal microscopy assays. The C-termini of E2 [amino acids (aa) 890-1053] and MEK2 (aa 266-400) were mapped to be crucial for the interaction. Overexpression of MEK2 significantly promoted the replication of CSFV, whereas knockdown of MEK2 by lentivirus-mediated small hairpin RNAs dramatically inhibited CSFV replication. In addition, CSFV infection induced a biphasic activation of ERK1/2, the downstream signaling molecules of MEK2. Furthermore, the replication of CSFV was markedly inhibited in PK-15 cells treated with U0126, a specific inhibitor for MEK1/2/ERK1/2, whereas MEK2 did not affect CSFV replication after blocking the interferon-induced Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling pathway by ruxolitinib, a JAK-STAT-specific inhibitor. Taken together, our results indicate that MEK2 positively regulates the replication of CSFV through inhibiting the JAK-STAT signaling pathway. Mitogen-activated protein kinase kinase 2 (MEK2) is a kinase that operates immediately upstream of extracellular regulated kinase 1/2 (ERK1/2) and links to Raf and ERK via phosphorylation. Currently, little is known about the role of MEK2 in the replication of classical swine fever virus (CSFV), a devastating porcine pestivirus. Here, we investigate the roles of MEK2 and the MEK2/ERK1/2 cascade in the growth of CSFV for the first time. We show that MEK2 positively regulates CSFV

  2. Mitogen-Activated Protein Kinase Kinase 2, a Novel E2-Interacting Protein, Promotes the Growth of Classical Swine Fever Virus via Attenuation of the JAK-STAT Signaling Pathway

    Science.gov (United States)

    Wang, Jinghan; Chen, Shucheng; Liao, Yajin; Zhang, Enyu; Feng, Shuo; Yu, Shaoxiong; Li, Lian-Feng; He, Wen-Rui; Li, Yongfeng; Luo, Yuzi; Sun, Yuan; Zhou, Mo; Wang, Xiao; Munir, Muhammad

    2016-01-01

    ABSTRACT The mitogen-activated protein kinase kinase/extracellular regulated kinase (MEK1/2/ERK1/2) cascade is involved in the replication of several members of the Flaviviridae family, including hepatitis C virus and dengue virus. The effects of the cascade on the replication of classical swine fever virus (CSFV), a fatal pestivirus of pigs, remain unknown. In this study, MEK2 was identified as a novel binding partner of the E2 protein of CSFV using yeast two-hybrid screening. The E2-MEK2 interaction was confirmed by glutathione S-transferase pulldown, coimmunoprecipitation, and laser confocal microscopy assays. The C termini of E2 (amino acids [aa] 890 to 1053) and MEK2 (aa 266 to 400) were mapped to be crucial for the interaction. Overexpression of MEK2 significantly promoted the replication of CSFV, whereas knockdown of MEK2 by lentivirus-mediated small hairpin RNAs dramatically inhibited CSFV replication. In addition, CSFV infection induced a biphasic activation of ERK1/2, the downstream signaling molecules of MEK2. Furthermore, the replication of CSFV was markedly inhibited in PK-15 cells treated with U0126, a specific inhibitor for MEK1/2/ERK1/2, whereas MEK2 did not affect CSFV replication after blocking the interferon-induced Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling pathway by ruxolitinib, a JAK-STAT-specific inhibitor. Taken together, our results indicate that MEK2 positively regulates the replication of CSFV through inhibiting the JAK-STAT signaling pathway. IMPORTANCE Mitogen-activated protein kinase kinase 2 (MEK2) is a kinase that operates immediately upstream of extracellular regulated kinase 1/2 (ERK1/2) and links to Raf and ERK via phosphorylation. Currently, little is known about the role of MEK2 in the replication of classical swine fever virus (CSFV), a devastating porcine pestivirus. Here, we investigated the roles of MEK2 and the MEK2/ERK1/2 cascade in the growth of CSFV for the first time. We show

  3. Macroeconomic Issues in Foreign Aid

    DEFF Research Database (Denmark)

    Hjertholm, Peter; Laursen, Jytte; White, Howard

    foreign aid, macroeconomics of aid, gap models, aid fungibility, fiscal response models, foreign debt,......foreign aid, macroeconomics of aid, gap models, aid fungibility, fiscal response models, foreign debt,...

  4. 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.

  5. Virus driven evolution: a probable explanation for "Similia Similibus Curantur" philosophy.

    Science.gov (United States)

    Carlucci, M J; Damonte, E B; Scolaro, L A

    2011-07-01

    Despite the advances in biomedical knowledge, there remain many challenging and significant unsolved problems among which are included viral pathogenesis and antiviral therapy, as main topics in human health. On this respect, for instance, our knowledge about human immunodeficiency virus and AIDS is still insufficient to deal with problems of immense significance, such as the possible "natural cure" for a chronic infection or the induction of protective immunity against this agent. At the same time, new viral diseases of humans and animals continue to emerge or re-emerge, due to changes in host susceptibility and/or in virus virulence as well as to re-introduction of a virus that had disappeared from a defined population. These changes, at least in part, may appear as a consequence of antiviral therapies and lead to the selection of viral mutants. Moreover, taking into account that viruses have been studied as causative agents of conspicuous diseases a broad spectrum of uncertainty is still present when unapparent persistent infections are considered. Based on Hippocrates (460-357 b.C.E) natural philosophy, "Natura Morborum Medicatrix" which represents the natural healing force, i.e.: "Nature cures diseases"; and "Similia Similibus Curantur" which means "like cure like", we propose the use of natural compounds with chemical structures similar to cellular membrane components. On this approach, sulfated polysaccharides obtained from marine algae may act as a driving force for the emergence of attenuated viruses, enabling this way a practical approach for preventive therapies for herpes simplex virus infection. At the same time, viruses would be creative tools and their contribution by adding new genetic identity to their host are set points of genesis in the growth of the tree of life. Copyright © 2011 Elsevier B.V. All rights reserved.

  6. Home Health Aides

    Science.gov (United States)

    ... State & Area Data Explore resources for employment and wages by state and area for home health aides and personal care aides. Similar Occupations Compare the job duties, education, job growth, and pay of home health aides ...

  7. Heart attack first aid

    Science.gov (United States)

    First aid - heart attack; First aid - cardiopulmonary arrest; First aid - cardiac arrest ... A heart attack occurs when the blood flow that carries oxygen to the heart is blocked. The heart muscle ...

  8. Puncture Wounds: First Aid

    Science.gov (United States)

    ... I, et al., eds. Skin problems. In: American Medical Association Handbook of First Aid and Emergency Care. New York, N.Y.: Random House; 2009. Jan. 12, 2018 Original article: http://www.mayoclinic.org/first-aid/first-aid- ...

  9. HIV/AIDS Coinfection

    Science.gov (United States)

    ... Delta Coinfection Hepatitis C Coinfection HIV/AIDS Coinfection HIV/AIDS Coinfection Approximately 10% of the HIV-infected population ... Disease Control and Prevention website to learn about HIV/AIDS and Viral Hepatitis guidelines and resources. Home About ...

  10. 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

  11. Papal policy, poverty, and AIDS.

    Science.gov (United States)

    Morley, D

    1990-06-30

    Papal "pronouncements" have been a major cause of the Philippines' increasing poverty, and of its failure to promote the only method proved to limit the spread of the acquired immunodeficiency syndrome (AIDS). Kenya has a growth rate of 3-4% and will double its population in 17 years. The UK has an average family size of 1.8 children. This is due to contraceptive usage. The poor lack knowledge and funds to ignore the rulings of the Catholic Church. Families will have 7 or more children without access to modern contraceptives. The Philippine elite are 90% Catholic, and disregard church policy and use contraceptives. Therefore, they have small families. Abortion is widely used in Latin America. It is the leading cause of death of women aged 15-39. The Philippines is industrializing rapidly; businessmen, however, do not see a future in producing condoms here. Widespread availability of condoms would limit the spread of AIDS. Mainly surveys show that in 1989 only 5 to 10/1000 prostitutes were positive for human immunodeficiency virus (HIV). Other Asian countries have shown large increases in HIV infection occurrence in 2-3 years. Pope John Paul has been telling young people in Burkina Faso that they "must face the plagues of modern times." He did not identify these plaques. However, Monsignore Carlo Cafara, dean of John Paul II's Institute for Marriage and Family Studies at the Vatican, told a recent conference that when 1 partner of a married couple is positive for AIDS, it is preferable to risk catching the AIDS virus than to use condoms. St. Paul would have approved the use of modern contraceptive methods.

  12. Fluid dynamic bowtie attenuators

    Science.gov (United States)

    Szczykutowicz, Timothy P.; Hermus, James

    2015-03-01

    Fluence field modulated CT allows for improvements in image quality and dose reduction. To date, only 1-D modulators have been proposed, the extension to 2-D modulation is difficult with solid-metal attenuation-based modulators. This work proposes to use liquids and gas to attenuate the x-ray beam which can be arrayed allowing for 2-D fluence modulation. The thickness of liquid and the pressure for a given path length of gas were determined that provided the same attenuation as 30 cm of soft tissue at 80, 100, 120, and 140 kV. Gaseous Xenon and liquid Iodine, Zinc Chloride, and Cerium Chloride were studied. Additionally, we performed some proof-of-concept experiments in which (1) a single cell of liquid was connected to a reservoir which allowed the liquid thickness to be modulated and (2) a 96 cell array was constructed in which the liquid thickness in each cell was adjusted manually. Liquid thickness varied as a function of kV and chemical composition, with Zinc Chloride allowing for the smallest thickness; 1.8, 2.25, 3, and 3.6 cm compensated for 30 cm of soft tissue at 80, 100, 120, and 140 kV respectively. The 96 cell Iodine attenuator allowed for a reduction in both dynamic range to the detector and scatter to primary ratio. Successful modulation of a single cell was performed at 0, 90, and 130 degrees using a simple piston/actuator. The thickness of liquids and the Xenon gas pressure seem logistically implementable within the constraints of CBCT and diagnostic CT systems.

  13. Thailand: AIDS crisis looms.

    Science.gov (United States)

    Smith, D G

    1990-03-31

    Although Thailand's Ministry of Public Health has recorded slightly under 15,000 cases of human immunodeficiency virus (HIV) infection to date, an independent team of health and medical experts has estimated that 200,000-300,000 Thais are infected. Moreover, the team has predicted that 1.6 million people--2.5% of the population--will be infected by 1995 in the absence of an aggressive, immediate prevention campaign. When AIDS 1st emerged in Thailand in the mid-1980s, it was largely restricted to homosexual prostitutes who came into contact with foreign men in gay bars. Soon, however, HIV infections was spreading rapidly among intravenous drug abusers and the infection rate among this group is currently estimated to be 45%. Another heavily affected group has been poorly paid prostitutes who work in Thailand's brothels; rates of 44-70% infectivity have been recorded among these women. Most recently, HIV infection has shown signs of entering the general population. Of the recorded cases of HIV infection in Chiang Mai, 59% involve prostitutes, 17% are workers, 6% are civil servants, 7% are students, and 2% are housewives. The sex ratio of HIV-infected persons has changed from 17 males per 1 female in 1986 to 5 males for every 1 female in 1989. Since the change in government in 1988, Thailand has stepped up AIDS education and information dissemination activities and condom use has increased by as much as 70%. Given the gravity of the situation, however, assistance from the World Bank and United Nations agencies in addition to the World Health Organization are needed.

  14. Breaking Barriers to an AIDS Model with Macaque-Tropic HIV-1 Derivatives

    OpenAIRE

    Kimata, Jason T; Hongmei Ruan; Rajesh Thippeshappa

    2012-01-01

    The development of an animal model of human immunodeficiency virus type 1 (HIV-1)/AIDS that is suitable for preclinical testing of antiretroviral therapy, vaccines, curative strategies, and studies of pathogenesis has been hampered by the human-specific tropism of HIV-1. Although simian immunodeficiency virus (SIV) or HIV-1/SIV chimeric viruses (SHIVs)-rhesus macaque models are excellent surrogates for AIDS research, the genetic differences between SIV or SHIV and HIV-1 limit their utility as...

  15. HIV/AIDS and family support systems: A situation analysis of people ...

    African Journals Online (AJOL)

    HIV/AIDS and family support systems: A situation analysis of people living with HIV/AIDS in Lagos State. ... Findings revealed that as HIV/AIDS strikes at parents, grand parents are assuming responsibility for bringing up the children of the infected persons and the orphans of those killed by the virus. It was striking that some ...

  16. Teachers' Perception of Inclusion of NIV/AIDS in the School ...

    African Journals Online (AJOL)

    This study investigated teachers' perception of inclusion of HIV/AIDS into Health Education curriculum as a panacea for the spread of AIDS pandemic among secondary school students in Enugu State. Acquired Immune Deficiency syndrome (AIDS), a disease caused by human immune Deficiency Virus presently has no ...

  17. Genome-wide association study implicates PARD3B-based AIDS restriction

    NARCIS (Netherlands)

    Troyer, Jennifer L.; Nelson, George W.; Lautenberger, James A.; Chinn, Leslie; McIntosh, Carl; Johnson, Randall C.; Sezgin, Efe; Kessing, Bailey; Malasky, Michael; Hendrickson, Sher L.; Li, Guan; Pontius, Joan; Tang, Minzhong; An, Ping; Winkler, Cheryl A.; Limou, Sophie; Le Clerc, Sigrid; Delaneau, Olivier; Zagury, Jean-François; Schuitemaker, Hanneke; van Manen, Daniëlle; Bream, Jay H.; Gomperts, Edward D.; Buchbinder, Susan; Goedert, James J.; Kirk, Gregory D.; O'Brien, Stephen J.

    2011-01-01

    Host genetic variation influences human immunodeficiency virus (HIV) infection and progression to AIDS. Here we used clinically well-characterized subjects from 5 pretreatment HIV/AIDS cohorts for a genome-wide association study to identify gene associations with rate of AIDS progression. European

  18. Factors that affect awareness about the spread of HIV/AIDS in rural ...

    African Journals Online (AJOL)

    identify factors that strongly affected awareness about HIV/AIDS. Results showed that awareness about HIV/AIDS was strongly affected by willingness to change sexual behaviour, regular use of condoms, sexually transmitted diseases, number of sexual partners and knowledge of transmission of the HIV/AIDS virus.

  19. Japanese encephalitis virus vaccine candidates generated by chimerization with dengue virus type 4.

    Science.gov (United States)

    Gromowski, Gregory D; Firestone, Cai-Yen; Hanson, Christopher T; Whitehead, Stephen S

    2014-05-23

    Japanese encephalitis virus (JEV) is a leading cause of viral encephalitis worldwide and vaccination is one of the most effective ways to prevent disease. A suitable live-attenuated JEV vaccine could be formulated with a live-attenuated tetravalent dengue vaccine for the control of these viruses in endemic areas. Toward this goal, we generated chimeric virus vaccine candidates by replacing the precursor membrane (prM) and envelope (E) protein structural genes of recombinant dengue virus type 4 (rDEN4) or attenuated vaccine candidate rDEN4Δ30 with those of wild-type JEV strain India/78. Mutations were engineered in E, NS3 and NS4B protein genes to improve replication in Vero cells. The chimeric viruses were attenuated in mice and some elicited modest but protective levels of immunity after a single dose. One particular chimeric virus, bearing E protein mutation Q264H, replicated to higher titer in tissue culture and was significantly more immunogenic in mice. The results are compared with live-attenuated JEV vaccine strain SA14-14-2. Published by Elsevier Ltd.

  20. Management of viral infections in AIDS patients.

    Science.gov (United States)

    Drucker, J L; King, D H

    1987-01-01

    Viral infections, predominantly those of the herpes virus family, account for up to 16% of all clinically significant infections in AIDS patients. Acyclovir has provided successful treatment in AIDS patients suffering from severe herpes simplex and herpes zoster virus infections. Preliminary results are presented on newly developed acyclovir analogues. Desciclovir, an oral prodrug of acyclovir which is metabolized to acyclovir in vivo, allows treatment of virus infections per os, where high serum levels are needed, e.g. in Epstein-Barr virus infections. BW B759U, another analogue of acyclovir, has been used for the treatment of life-threatening or sight-threatening cytomegalovirus infections in AIDS patients. More than 80% of the patients treated for retinitis experienced stabilization or clinical improvement. Antiviral efficacy was demonstrated in 73% of the patients. Azidothymidine, a nucleoside analogue of thymidine, has been developed specifically to treat the HIV infection. Its antiviral activity is based on inhibition of reverse transcriptase. Phase I studies have demonstrated that azidothymidine is well tolerated. Its ability to cross the blood brain barrier makes it an attractive candidate for treatment of HIV. Trials to determine efficacy are in progress.

  1. Preliminary guidelines for the evaluation and management of dyslipidemia in adults infected with human immunodeficiency virus and receiving antiretroviral therapy: Recommendations of the Adult AIDS Clinical Trial Group Cardiovascular Disease Focus Group

    NARCIS (Netherlands)

    Dubé, M. P.; Sprecher, D.; Henry, W. K.; Aberg, J. A.; Torriani, F. J.; Hodis, H. N.; Schouten, J. [=Judith; Levin, J.; Myers, G.; Zackin, R.; Nevin, T.; Currier, J. S.

    2000-01-01

    Dyslipidemia is a prevalent condition that affects patients infected with human immunodeficiency virus (HIV) who are receiving antiretroviral therapy, These preliminary recommendations summarize the current understanding in this area and propose guidelines for management. Existing guidelines for the

  2. ECHO virus

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/001340.htm ECHO virus To use the sharing features on this page, please enable JavaScript. Enteric cytopathic human orphan (ECHO) viruses are a group of viruses that can lead ...

  3. Human Immunodeficiency Virus Infection Occupational Post ...

    African Journals Online (AJOL)

    opsig

    potentially infected body fluids so that they can present themselves rapidly for risk assessment and commencement of ART if necessary in the event of an occupational exposure to HIV. INTRODUCTION. Human Immunodeficiency Virus (HIV) is the virus that causes Acquired Immune Deficiency Syndrome. (AIDS). It can be ...

  4. Ethnopharmacology of human immunodeficiency virus in South ...

    African Journals Online (AJOL)

    Infection with the human immunodeficiency virus (HIV), the etiologic agent of acquired immune deficiency syndrome (AIDS), continues to pose an unprecedented public health problem of enormous proportions worldwide. Current treatment options for HIV/AIDS have not been satisfactory and the quest for effective curative or ...

  5. Types of Foreign Aid

    DEFF Research Database (Denmark)

    Bjørnskov, Christian

    Foreign aid is given for many purposes and different intentions, yet most studies treat aid flows as a unitary concept. This paper uses factor analysis to separate aid flows into different types. The main types can be interpreted as aid for economic purposes, social purposes, and reconstruction...

  6. 21 CFR 866.3240 - Equine encephalomyelitis virus serological reagents.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Equine encephalomyelitis virus serological... § 866.3240 Equine encephalomyelitis virus serological reagents. (a) Identification. Equine... tests to identify antobodies to equine encephalomyelitis virus in serum. The identification aids in the...

  7. genetics of resistance to groundnut rosette virus disease abstract ...

    African Journals Online (AJOL)

    ACSS

    2014-02-03

    Feb 3, 2014 ... Groundnut rosette virus disease is caused by synergyistic interaction of three viral agents, namely, groundnut rosette virus (GRV), its satelitte RNA (Sat RNA) and groundnut rosette assistor virus (GRAV). GRAV plays an important role in aiding aphid transmission, alongside the other two viral components.

  8. Divergent immune responses and disease outcomes in piglets immunized with inactivated and attenuated H3N2 swine influenza vaccines in the presence of maternally-derived antibodies

    Science.gov (United States)

    Vaccine-associated enhanced respiratory disease (VAERD) can occur in pigs immunized with whole-inactivated influenza virus (WIV) vaccine and subsequently infected with an antigenically divergent virus of the same HA subtype. Live-attenuated influenza virus (LAIV) vaccines administered intranasally h...

  9. 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.

  10. The Master Hearing Aid

    Science.gov (United States)

    Curran, James R.

    2013-01-01

    As early as the 1930s the term Master Hearing Aid (MHA) described a device used in the fitting of hearing aids. In their original form, the MHA was a desktop system that allowed for simulated or actual adjustment of hearing aid components that resulted in a changed hearing aid response. Over the years the MHA saw many embodiments and contributed to a number of rationales for the fitting of hearing aids. During these same years, the MHA was viewed by many as an inappropriate means of demonstrating hearing aids; the audio quality of the desktop systems was often superior to the hearing aids themselves. These opinions and the evolution of the MHA have molded the modern perception of hearing aids and the techniques used in the fitting of hearing aids. This article reports on a history of the MHA and its influence on the fitting of hearing aids. PMID:23686682

  11. Psychosocial issues in pediatric human immunodeficiency virus.

    Science.gov (United States)

    Adler, R K

    2000-01-01

    This article discusses the psychosocial issues associated with pediatric human immunodeficiency virus and acquired immunodeficiency syndrome (HIV/AIDS). Using a psychosocial model instead of the usual medical or rehabilitation model will challenge speech-language pathologists to incorporate an understanding of the psychosocial stresses that affect a child's progression through HIV/AIDS and ensure that they receive adequate consideration in a total treatment model. A case study illustrates the relationship between communication disorders and HIV/AIDS.

  12. Sounding the alarm. AIDS update no. 403.

    Science.gov (United States)

    1994-08-17

    When the first international AIDS conference in Asia opened in Yokohama last week, the world's experts had bleak news. They said 10 million Asians could be carrying the AIDS virus by the end of the century--25%-30% of the global total. Some 250,000 people in the region are suffering from full-blown AIDS, with another 2 million infected by the virus. In Thailand, the sex industry is a key factor, said Prayura Kunasol, an official of the country's Ministry of Public Health. Three-quarters of all Thai cases--8580 AIDS victims and 600,000 infected patients--are linked to sexual activity. Widespread ignorance also fuels the epidemic, especially in China and India, according to participants in a Manila meeting organized by the Asian Development Bank in early August. Though 91% of city folks in China had heard of AIDS, only about a quarter could tell correctly how it was transmitted and a mere 5% knew the symptoms. In India, eight out of ten men say they're aware of the disease. But six of ten housewives had never heard of it. While heterosexual sex is the leading means of transmission, intravenous drug use, transfusions of tainted blood and unsterilized medical equipment also pose problems. In Yokohama, Japanese Prime Minister Murayama Tomiichi told some 11,000 delegates and observers from 120 countries that Tokyo was ready to step up efforts to combat "a global problem confronting all humanity." full text

  13. 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...... 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...

  14. The AIDS Pandemic in Uganda : Social Capital and the Role of NGOs in Alleviating the Impact of HIV/AIDS

    OpenAIRE

    Muriisa, Roberts Kabeba

    2007-01-01

    AIDS has a devastating impact on individuals and society. It is defined as Acquired Immune Deficiency Syndrome and it is a condition caused by the Human Immunodeficiency Virus (HIV). This condition occurs when people who have lived with HIV for a long time lose their immunity and become susceptible to various opportunistic infections. AIDS often results in death. At present, there is neither a vaccine against HIV nor a cure for AIDS. Apart from the numerous deaths it causes, HIV/AIDS has othe...

  15. The Attenuated Live Yellow Fever Virus 17D Infects the Thymus and Induces Thymic Transcriptional Modifications of Immunomodulatory Genes in C57BL/6 and BALB/C Mice

    Directory of Open Access Journals (Sweden)

    Breno Luiz Melo-Lima

    2015-01-01

    Full Text Available Thymus is involved in induction of self-tolerance in T lymphocytes, particularly due to Aire activity. In peripheral tissues, Treg cells and immunomodulatory molecules, like the major histocompatibility complex (MHC class Ib molecules, are essential for maintenance of autotolerance during immune responses. Viral infections can trigger autoimmunity and modify thymic function, and YFV17D immunization has been associated with the onset of autoimmunity, being contraindicated in patients with thymic disorders. Aiming to study the influence of YFV17D immunization on the transcriptional profiles of immunomodulatory genes in thymus, we evaluated the gene expression of AIRE, FOXP3, H2-Q7 (Qa-2/HLA-G, H2-T23 (Qa-1/HLA-E, H2-Q10, and H2-K1 following immunization with 10,000 LD50 of YFV17D in C57BL/6 and BALB/c mice. The YFV17D virus replicated in thymus and induced the expression of H2-Q7 (Qa-2/HLA-G and H2-T23 (Qa-1/HLA-E transcripts and repressed the expression of AIRE and FOXP3. Transcriptional expression varied according to tissue and mouse strain analyzed. Expression of H2-T23 (Qa-1/HLA-E and FOXP3 was induced in thymus and liver of C57BL/6 mice, which exhibited defective control of viral load, suggesting a higher susceptibility to YFV17D infection. Since the immunization with YFV17D modulated thymus gene expression in genetically predisposed individuals, the vaccine may be related to the onset of autoimmunity disorders.

  16. TREM-1 deficiency can attenuate disease severity without affecting pathogen clearance.

    Directory of Open Access Journals (Sweden)

    Benjamin Weber

    2014-01-01

    Full Text Available Triggering receptor expressed on myeloid cells-1 (TREM-1 is a potent amplifier of pro-inflammatory innate immune reactions. While TREM-1-amplified responses likely aid an improved detection and elimination of pathogens, excessive production of cytokines and oxygen radicals can also severely harm the host. Studies addressing the pathogenic role of TREM-1 during endotoxin-induced shock or microbial sepsis have so far mostly relied on the administration of TREM-1 fusion proteins or peptides representing part of the extracellular domain of TREM-1. However, binding of these agents to the yet unidentified TREM-1 ligand could also impact signaling through alternative receptors. More importantly, controversial results have been obtained regarding the requirement of TREM-1 for microbial control. To unambiguously investigate the role of TREM-1 in homeostasis and disease, we have generated mice deficient in Trem1. Trem1(-/- mice are viable, fertile and show no altered hematopoietic compartment. In CD4(+ T cell- and dextran sodium sulfate-induced models of colitis, Trem1(-/- mice displayed significantly attenuated disease that was associated with reduced inflammatory infiltrates and diminished expression of pro-inflammatory cytokines. Trem1(-/- mice also exhibited reduced neutrophilic infiltration and decreased lesion size upon infection with Leishmania major. Furthermore, reduced morbidity was observed for influenza virus-infected Trem1(-/- mice. Importantly, while immune-associated pathologies were significantly reduced, Trem1(-/- mice were equally capable of controlling infections with L. major, influenza virus, but also Legionella pneumophila as Trem1(+/+ controls. Our results not only demonstrate an unanticipated pathogenic impact of TREM-1 during a viral and parasitic infection, but also indicate that therapeutic blocking of TREM-1 in distinct inflammatory disorders holds considerable promise by blunting excessive inflammation while preserving the

  17. 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

  18. The Economics of HIV/AIDS in Low-Income Countries: The Case for Prevention

    OpenAIRE

    David Canning

    2006-01-01

    There are two approaches to reducing the burden of sickness and death associated with the human immunodeficiency virus (HIV), which leads to acquired immunodeficiency syndrome (AIDS): treatment and prevention. Despite large international aid flows for HIV/AIDS, the needs for prevention and treatment in low- and middle-income countries outstrip the resources available. Thus, it becomes necessary to set priorities. With limited resources, should the focus of efforts to combat HIV/AIDS be on pre...

  19. Magnesium levels in AIDS-associated tuberculosis or cryptococcosis patients, and relationship with treatment response

    OpenAIRE

    Ronceros, Gerardo; Instituto de Investigaciones Clínicas, Facultad de Medicina, Universidad Nacional Mayor de San Marcos. Lima, Perú. Laboratorio Clínico, Hospital Dos de Mayo. Lima, Perú. médico cirujano.; Huaroto, Luz; Instituto de Investigaciones Clínicas, Facultad de Medicina, UNMSM; Alvarado Ortíz, Carlos; Instituto de Investigaciones Clínicas, Facultad de Medicina, UNMSM

    2013-01-01

    OBJECTIVE: To demostrate that human immunodeficiency virus (HIV) patients in acquired immunodeficiency syndrome (AIDS) phase associated with tuberculosis (TB) or cryptococcosis have hypomagnesemia-related inadequate treatment response. DESIGN: Prospective and longitudinal study. MATERIALS AND METHODS: We studied 300 subjects, divided in six groups of 50 patients each: positive HIV patients, TB patients, AIDS patients with TB, AIDS patients with cryptococcosis, no-AIDS patients with acute infe...

  20. 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.

  1. Determinación del perfil hormonal en hombres infectados con el virus del síndrome de la inmunodeficiencia adquirida (SIDA Determination of the hormonal profile in AIDS-infected men

    Directory of Open Access Journals (Sweden)

    Víctor M. Cabrera Oliva

    2002-12-01

    Full Text Available Se realizó un estudio descriptivo transversal del perfil hormonal en hombres infectados con el virus de la inmunodeficiencia adquirida. Se incluyeron 34 sujetos divididos en 2 grupos: El grupo I, compuesto por 14 hombres sanos, VIH-negativos, con edad de 25,4 ± 2,3 años, índice de masa corporal (IMC de 24,0 ± 1,8 kg/m2 y recuento de linfocitos CD4+ de 689 ± 208 ´ 106 cél/L. El II, compuesto por 20 hombres infectados con VIH de reciente diagnóstico y que no estaban sometidos a ningún tratamiento antirretroviral, con edad de 26,9 ± 6,3 años, IMC de 22,1±2,81 kg/m2 y recuento de células CD4+ de 104 ± 112 ´ 106 cél/L. Se determinaron las concentraciones plasmáticas de FSH, LH, prolactina, cortisol, testosterona, T3, T4 y TSH. Se establecieron las correlaciones entre las concentraciones de testosterona y prolactina y los recuentos de células CD4+ y entre las concentraciones de FSH y LH contra las concentraciones de testosterona. Las concentraciones de T3, T4, TSH, cortisol y prolactina no mostraron diferencias estadísticamente significativas cuando se compararon con las determinaciones en las muestras plasmáticas de los sujetos sanos. Se hallaron concentraciones de FSH y de LH superiores (p £ 0,05 para el grupo de hombres infectados con VIH, mientras que las de testosterona estuvieron significativamente disminuidas (p £ 0,05. Para el grupo de pacientes infectados por VIH, la correlación entre las concentraciones de testosterona y los recuentos de células CD4+ fue de y = 0,104 en una función de pendiente negativa, mientras que para el grupo de sujetos sanos el valor fue de p = 0,145, pero con una función de pendiente positiva. Las correlaciones entre las concentraciones de prolactina contra las de testosterona y los recuentos de células CD4+, fueron muy similares. Se comprobó que el hipogonadismo en los pacientes afectados por VIH está relacionado con un aumento significativo en las concentraciones de FSH y LH, mientras

  2. Women and AIDS: sociopolitical issues.

    Science.gov (United States)

    Smeltzer, S C

    1992-01-01

    HIV infection and AIDS in women will continue without adequate diagnosis and treatment as long as women are not treated as full partners in society. Until issues related to women and their place in society are considered within the sociopolitical context, women who are at risk for HIV infection, those infected with the HIV virus, and those with AIDS will continue to receive inadequate attention. The National Center for Nursing's National Action Agenda, Nursing and the HIV Epidemic, provides some direction for addressing these issues and those that relate to practice, education, research, and health policy. It is incumbent on nurse researchers to conduct research related to the critical issues associated with HIV infection and AIDS in women, disseminate the findings of that research, and use those findings to inform and move health policy in this area forward. It is equally important to understand the issues that affect women--ethnic considerations, sexual practices, IV drug use--within the context or present political climate of our society. That climate allowed an NIH study that could identify risky sexual behaviors of adolescent and adult subjects who consent to participate in such a study to be called to a halt--not because of concerns about the study design or the scientific rigor of the study, but because of an elected official's fear that asking such questions will encourage these behaviors and his personal belief that such issues should not be discussed in polite society. These issues must be brought forward, acknowledged, and discussed if they are to be dealt with effectively. Otherwise, the relentless course of AIDS will continue.(ABSTRACT TRUNCATED AT 250 WORDS)

  3. First aid kit

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/001958.htm First aid kit To use the sharing features on this ... ahead, you can create a well-stocked home first aid kit. Keep all of your supplies in one ...

  4. Head injury - first aid

    Science.gov (United States)

    ... medlineplus.gov/ency/article/000028.htm Head injury - first aid To use the sharing features on this page, ... a concussion can range from mild to severe. First Aid Learning to recognize a serious head injury and ...

  5. First Aid: Influenza (Flu)

    Science.gov (United States)

    ... Flu Vaccine? Eating Disorders Arrhythmias First Aid: The Flu KidsHealth > For Parents > First Aid: The Flu Print ... tiredness What to Do If Your Child Has Flu Symptoms: Call your doctor. Encourage rest. Keep your ...

  6. Aids for visual impairment.

    OpenAIRE

    Dudley, N. J.

    1990-01-01

    This article provides only a flavour of the type and range of aids available to the visually impaired person. Many other aids for leisure, learning, and daily living are illustrated in the RNIB equipment and games catalogue.

  7. HIV/AIDS Basics

    Science.gov (United States)

    ... Partner Spotlight Awareness Days Get Tested Find an HIV testing site near you. Enter ZIP code or ... AIDS Get Email Updates on AAA Anonymous Feedback HIV/AIDS Media Infographics Syndicated Content Podcasts Slide Sets ...

  8. 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.

  9. Deletion of the vaccinia virus gene A46R, encoding for an inhibitor of TLR signalling, is an effective approach to enhance the immunogenicity in mice of the HIV/AIDS vaccine candidate NYVAC-C.

    Directory of Open Access Journals (Sweden)

    Beatriz Perdiguero

    Full Text Available Viruses have developed strategies to counteract signalling through Toll-like receptors (TLRs that are involved in the detection of viruses and induction of proinflammatory cytokines and IFNs. Vaccinia virus (VACV encodes A46 protein which disrupts TLR signalling by interfering with TLR: adaptor interactions. Since the innate immune response to viruses is critical to induce protective immunity, we studied whether deletion of A46R gene in a NYVAC vector expressing HIV-1 Env, Gag, Pol and Nef antigens (NYVAC-C improves immune responses against HIV-1 antigens. This question was examined in human macrophages and in mice infected with a single A46R deletion mutant of the vaccine candidate NYVAC-C (NYVAC-C-ΔA46R. The viral gene A46R is not required for virus replication in primary chicken embryo fibroblast (CEF cells and its deletion in NYVAC-C markedly increases TNF, IL-6 and IL-8 secretion by human macrophages. Analysis of the immune responses elicited in BALB/c mice after DNA prime/NYVAC boost immunization shows that deletion of A46R improves the magnitude of the HIV-1-specific CD4 and CD8 T cell immune responses during adaptive and memory phases, maintains the functional profile observed with the parental NYVAC-C and enhances anti-gp120 humoral response during the memory phase. These findings establish the immunological role of VACV A46R on innate immune responses of macrophages in vitro and antigen-specific T and B cell immune responses in vivo and suggest that deletion of viral inhibitors of TLR signalling is a useful approach for the improvement of poxvirus-based vaccine candidates.

  10. Aid and growth regressions

    DEFF Research Database (Denmark)

    Hansen, Henrik; Tarp, Finn

    2001-01-01

    . There are, however, decreasing returns to aid, and the estimated effectiveness of aid is highly sensitive to the choice of estimator and the set of control variables. When investment and human capital are controlled for, no positive effect of aid is found. Yet, aid continues to impact on growth via...... investment. We conclude by stressing the need for more theoretical work before this kind of cross-country regressions are used for policy purposes....

  11. First Aid: Croup

    Science.gov (United States)

    ... to the Gynecologist? Blood Test: Thyroid Peroxidase Antibodies First Aid: Croup KidsHealth > For Parents > First Aid: Croup Print A A A Croup is a ... For Kids For Parents MORE ON THIS TOPIC First Aid: Coughing X-Ray Exam: Neck Why Is Hand ...

  12. First Aid: Burns

    Science.gov (United States)

    ... to the Gynecologist? Blood Test: Thyroid Peroxidase Antibodies First Aid: Burns KidsHealth > For Parents > First Aid: Burns Print A A A Scald burns from ... THIS TOPIC Kitchen: Household Safety Checklist Fireworks Safety First Aid: Sunburn Firesetting Fire Safety Burns Household Safety: Preventing ...

  13. First Aid: Rashes

    Science.gov (United States)

    ... to the Gynecologist? Blood Test: Thyroid Peroxidase Antibodies First Aid: Rashes KidsHealth > For Parents > First Aid: Rashes Print A A A Rashes can be ... For Kids For Parents MORE ON THIS TOPIC First Aid: Skin Infections Poison Ivy Erythema Multiforme Hives (Urticaria) ...

  14. Stroke: First Aid

    Science.gov (United States)

    First aid Stroke: First aid Stroke: First aid By Mayo Clinic Staff A stroke occurs when there's bleeding into your brain or when blood flow to your ... cells start dying. Seek immediate medical assistance. A stroke is a true emergency. The sooner treatment is ...

  15. Hearing-aid tester

    Science.gov (United States)

    Kessinger, R.; Polhemus, J. T.; Waring, J. G.

    1977-01-01

    Hearing aids are automatically checked by circuit that applies half-second test signal every thirty minutes. If hearing-aid output is distorted, too small, or if battery is too low, a warning lamp is activated. Test circuit is incorporated directly into hearing-aid package.

  16. Dislocation: First Aid

    Science.gov (United States)

    First aid Dislocation: First aid Dislocation: First aid By Mayo Clinic Staff A dislocation is an injury in which the ends of your bones are forced from ... a collision during contact or high-speed sports. Dislocation usually involves the body's larger joints. In adults, ...

  17. Determinants of State Aid

    NARCIS (Netherlands)

    Buiren, K.; Brouwer, E.

    2010-01-01

    From economic theory we derive a set of hypotheses on the determination of state aid. Econometric analysis on EU state aid panel data is carried out to test whether the determinants we expect on the basis of theory, correspond to the occurrence of state aid in practice in the EU. We find that

  18. 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.

  19. Aid and development

    DEFF Research Database (Denmark)

    Tarp, Finn

    2006-01-01

    evolved since World War II in response to a dramatically changing global political and economic context. I review the aid process and associated trends in the volume and distribution of aid and categorize some of the key goals, principles and institutions of the aid system. The evidence on whether aid has...... been effective in furthering economic growth and development is discussed in some detail. I add perspective and identify some critical unresolved issues. I finally turn to the current development debate and discuss some key concerns, I believe should be kept in mind in formulating any agenda for aid...

  20. Prophylaxis Against Mycobacterium avium Complex Infection in AIDS

    OpenAIRE

    Cameron, DW

    1994-01-01

    Disseminated Mycobacterium avium complex (MAC) infection in AIDS is increasing in frequency, although it remains under-recognized due to unlocalized clinical manifestations and subtle initial presentation, if not the need for specialized laboratory diagnostic methods. Ultimately, MAC accounts for much of the “wasting syndrome” in the natural history of human immunodeficiency virus disease. Multidrug treatment of MAC in AIDS is problematic. That MAC is preventable has been demonstrated, and ho...

  1. Structural and Functional Studies on the Fusion and Attachment Envelope Glycoproteins of Nipah Virus and Hendra Virus

    Science.gov (United States)

    2003-01-01

    Embo J, 1990. 9(6): p. 2017-22. 37. Pelet, T., J. Curran, and D. Kolakofsky, The P gene of bovine parainfluenza virus 3 expresses all three reading... parainfluenza viruses (hPIV) 1-4, respiratory syncytial virus (RSV), and simian virus 5 (SV5) (reviewed in (33)). The genomes of paramyxoviruses, as a...virus (NDV) (58), human parainfluenza virus (hPIV) (59), and most recently with MeV (60), but these observations have often been with the aid of

  2. 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…

  3. AIDS-related cancer in the era of highly active antiretroviral therapy (HAART): a model of the interplay of the immune system, virus, and cancer. "On the offensive--the Trojan Horse is being destroyed"--Part B: Malignant lymphoma.

    Science.gov (United States)

    Cheung, Tony W

    2004-01-01

    The impact of highly active antiretroviral therapy (HAART) on the incidence of non-Hodgkin's lymphoma was less obvious initially, although primary central nervous system lymphoma (PCNSL) has dropped precipitously since the introduction of HAART. The pathogenesis of acquired immunodeficiency syndrome-related lymphoma is multifactorial. Epstein-Barr virus plays a significant role in these diseases, especially Burkitt lymphoma and PCNSL. Data regarding the effect of HAART on the natural history and treatment outcomes of these malignancies are emerging. The possibility of direct and indirect roles of human immunodeficiency virus in the carcinogenesis suggests that antiretroviral therapy may be an important component of the treatment for these malignancies. The simultaneous administration of HAART and chemotherapy does not appear to significantly alter the toxicity profile, although the information with respect to the interaction of HAART and chemotherapy is limited. The use of biological agents, for example, monoclonal antibody against CD-20, is being explored to improve the clinical outcome of this disease.

  4. Hearing Aid Assembly

    Science.gov (United States)

    Grugel, Richard N. (Inventor)

    2002-01-01

    Progress in hearing aids has come a long way. Yet despite such progress hearing aids are not the perfect answer to many hearing problems. Some adult ears cannot accommodate tightly fitting hearing aids. Mouth movements such as chewing, talking, and athletic or other active endeavors also lead to loosely fitting ear molds. It is well accepted that loosely fitting hearing aids are the cause of feedback noise. Since feedback noise is the most common complaint of hearing aid wearers it has been the subject of various patents. Herein a hearing aid assembly is provided eliminating feedback noise. The assembly includes the combination of a hearing aid with a headset developed to constrict feedback noise.

  5. The ubiquitin proteasome system plays a role in venezuelan equine encephalitis virus infection.

    Directory of Open Access Journals (Sweden)

    Moushimi Amaya

    Full Text Available Many viruses have been implicated in utilizing or modulating the Ubiquitin Proteasome System (UPS to enhance viral multiplication and/or to sustain a persistent infection. The mosquito-borne Venezuelan equine encephalitis virus (VEEV belongs to the Togaviridae family and is an important biodefense pathogen and select agent. There are currently no approved vaccines or therapies for VEEV infections; therefore, it is imperative to identify novel targets for therapeutic development. We hypothesized that a functional UPS is required for efficient VEEV multiplication. We have shown that at non-toxic concentrations Bortezomib, a FDA-approved inhibitor of the proteasome, proved to be a potent inhibitor of VEEV multiplication in the human astrocytoma cell line U87MG. Bortezomib inhibited the virulent Trinidad donkey (TrD strain and the attenuated TC-83 strain of VEEV. Additional studies with virulent strains of Eastern equine encephalitis virus (EEEV and Western equine encephalitis virus (WEEV demonstrated that Bortezomib is a broad spectrum inhibitor of the New World alphaviruses. Time-of-addition assays showed that Bortezomib was an effective inhibitor of viral multiplication even when the drug was introduced many hours post exposure to the virus. Mass spectrometry analyses indicated that the VEEV capsid protein is ubiquitinated in infected cells, which was validated by confocal microscopy and immunoprecipitation assays. Subsequent studies revealed that capsid is ubiquitinated on K48 during early stages of infection which was affected by Bortezomib treatment. This study will aid future investigations in identifying host proteins as potential broad spectrum therapeutic targets for treating alphavirus infections.

  6. Identification of the Mechanisms Causing Reversion to Virulence in an Attenuated SARS-CoV for the Design of a Genetically Stable Vaccine.

    Science.gov (United States)

    Jimenez-Guardeño, Jose M; Regla-Nava, Jose A; Nieto-Torres, Jose L; DeDiego, Marta L; Castaño-Rodriguez, Carlos; Fernandez-Delgado, Raul; Perlman, Stanley; Enjuanes, Luis

    2015-10-01

    A SARS-CoV lacking the full-length E gene (SARS-CoV-∆E) was attenuated and an effective vaccine. Here, we show that this mutant virus regained fitness after serial passages in cell culture or in vivo, resulting in the partial duplication of the membrane gene or in the insertion of a new sequence in gene 8a, respectively. The chimeric proteins generated in cell culture increased virus fitness in vitro but remained attenuated in mice. In contrast, during SARS-CoV-∆E passage in mice, the virus incorporated a mutated variant of 8a protein, resulting in reversion to a virulent phenotype. When the full-length E protein was deleted or its PDZ-binding motif (PBM) was mutated, the revertant viruses either incorporated a novel chimeric protein with a PBM or restored the sequence of the PBM on the E protein, respectively. Similarly, after passage in mice, SARS-CoV-∆E protein 8a mutated, to now encode a PBM, and also regained virulence. These data indicated that the virus requires a PBM on a transmembrane protein to compensate for removal of this motif from the E protein. To increase the genetic stability of the vaccine candidate, we introduced small attenuating deletions in E gene that did not affect the endogenous PBM, preventing the incorporation of novel chimeric proteins in the virus genome. In addition, to increase vaccine biosafety, we introduced additional attenuating mutations into the nsp1 protein. Deletions in the carboxy-terminal region of nsp1 protein led to higher host interferon responses and virus attenuation. Recombinant viruses including attenuating mutations in E and nsp1 genes maintained their attenuation after passage in vitro and in vivo. Further, these viruses fully protected mice against challenge with the lethal parental virus, and are therefore safe and stable vaccine candidates for protection against SARS-CoV.

  7. Identification of the Mechanisms Causing Reversion to Virulence in an Attenuated SARS-CoV for the Design of a Genetically Stable Vaccine

    Science.gov (United States)

    Nieto-Torres, Jose L.; DeDiego, Marta L.; Castaño-Rodriguez, Carlos; Fernandez-Delgado, Raul; Perlman, Stanley; Enjuanes, Luis

    2015-01-01

    A SARS-CoV lacking the full-length E gene (SARS-CoV-∆E) was attenuated and an effective vaccine. Here, we show that this mutant virus regained fitness after serial passages in cell culture or in vivo, resulting in the partial duplication of the membrane gene or in the insertion of a new sequence in gene 8a, respectively. The chimeric proteins generated in cell culture increased virus fitness in vitro but remained attenuated in mice. In contrast, during SARS-CoV-∆E passage in mice, the virus incorporated a mutated variant of 8a protein, resulting in reversion to a virulent phenotype. When the full-length E protein was deleted or its PDZ-binding motif (PBM) was mutated, the revertant viruses either incorporated a novel chimeric protein with a PBM or restored the sequence of the PBM on the E protein, respectively. Similarly, after passage in mice, SARS-CoV-∆E protein 8a mutated, to now encode a PBM, and also regained virulence. These data indicated that the virus requires a PBM on a transmembrane protein to compensate for removal of this motif from the E protein. To increase the genetic stability of the vaccine candidate, we introduced small attenuating deletions in E gene that did not affect the endogenous PBM, preventing the incorporation of novel chimeric proteins in the virus genome. In addition, to increase vaccine biosafety, we introduced additional attenuating mutations into the nsp1 protein. Deletions in the carboxy-terminal region of nsp1 protein led to higher host interferon responses and virus attenuation. Recombinant viruses including attenuating mutations in E and nsp1 genes maintained their attenuation after passage in vitro and in vivo. Further, these viruses fully protected mice against challenge with the lethal parental virus, and are therefore safe and stable vaccine candidates for protection against SARS-CoV. PMID:26513244

  8. Women and HIV/AIDS

    Science.gov (United States)

    ... AIDS from other websites National Women and Girls HIV/AIDS Awareness Day Blog topics HIV and AIDS Breaking Down ... t Miss a Beat National Women and Girls HIV/AIDS Awareness Day National Women's Health Week Supporting Nursing Moms ...

  9. Regional brain structural dysmorphology in human immunodeficiency virus infection: effects of acquired immune deficiency syndrome, alcoholism, and age.

    Science.gov (United States)

    Pfefferbaum, Adolf; Rosenbloom, Margaret J; Sassoon, Stephanie A; Kemper, Carol A; Deresinski, Stanley; Rohlfing, Torsten; Sullivan, Edith V

    2012-09-01

    Human immunodeficiency virus (HIV) infection and alcoholism each carries liability for disruption of brain structure and function integrity. Despite considerable prevalence of HIV-alcoholism comorbidity, few studies examined the potentially heightened burden of disease comorbidity. Participants were 342 men and women: 110 alcoholics, 59 with HIV infection, 65 with HIV infection and alcoholism, and 108 healthy control subjects. This design enabled examination of independent and combined effects of HIV infection and alcoholism along with other factors (acquired immune deficiency syndrome [AIDS]-defining events, hepatitis C infection, age) on regional brain volumes derived from T1-weighted magnetic resonance images. Brain volumes, expressed as Z scores corrected for intracranial volume and age, were measured in 20 tissue and 5 ventricular and sulcal regions. The most profound and consistent volume deficits occurred with alcohol use disorders, notable in the cortical mantle, insular and anterior cingulate cortices, thalamus, corpus callosum, and frontal sulci. The HIV-only group had smaller thalamic and larger frontal sulcal volumes than control subjects. HIV disease-related factors associated with greater volume abnormalities included CD4 cell count nadir, clinical staging, history of AIDS-defining events, infection age, and current age. Longer sobriety and less lifetime alcohol consumption were predictive of attenuated brain volume abnormalities in both alcohol groups. Having HIV infection with alcoholism and AIDS had an especially poor outcome on brain structures. That longer periods of sobriety and less lifetime alcohol consumption were predictive of attenuated brain volume abnormalities encourages the inclusion of alcohol recovery efforts in HIV/AIDS therapeutic settings. Copyright © 2012 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  10. The development of AIDS or AIDS-related conditions in a cohort of HIV antibody-positive homosexual men during a 3-year follow-up period

    DEFF Research Database (Denmark)

    Pedersen, C; Kolby, P; Sindrup, J

    1989-01-01

    One hundred and thirty-three homosexual men seropositive for the antibody against human immunodeficiency virus (HIV) were enrolled in a prospective study in 1984-85. The 3-year cumulative incidences of the acquired immunodeficiency syndrome (AIDS) and AIDS-related conditions, by life-table analyses...

  11. 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…

  12. 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

  13. SEISMIC ATTENUATION FOR RESERVOIR CHARACTERIZATION

    Energy Technology Data Exchange (ETDEWEB)

    Joel Walls; M.T. Taner; Gary Mavko; Jack Dvorkin

    2002-04-01

    Wave-induced variations of pore pressure in a partially-saturated reservoir result in oscillatory liquid flow. The viscous losses during this flow are responsible for wave attenuation. The same viscous effects determine the changes in the dynamic bulk modulus of the system versus frequency. These changes are necessarily linked to attenuation via the causality condition. We analytically quantify the frequency dependence of the bulk modulus of a partially saturated rock by assuming that saturation is patchy and then link these changes to the inverse quality factor. As a result, the P-wave attenuation is quantitatively linked to saturation and thus can serve as a saturation indicator.

  14. Chikungunya virus

    Science.gov (United States)

    Chikungunya virus infection; Chikungunya ... Where Chikungunya is Found Before 2013, the virus was found in Africa, Asia, Europe, and the Indian and Pacific oceans. In late 2013, outbreaks occurred for the first time in the ...

  15. Zika Virus

    Science.gov (United States)

    ... through blood transfusions. There have been outbreaks of Zika virus in the United States, Africa, Southeast Asia, the ... not travel to areas where there is a Zika virus outbreak. If you do decide to travel, first ...

  16. Chikungunya Virus

    Science.gov (United States)

    ... Gaines, PhD, MPH, MA, CHES Differentiating Chikungunya From Dengue: A Clinical Challenge For Travelers CDC Travelers' Health Chikungunya Virus Home Prevention Transmission Symptoms & Treatment Geographic Distribution Chikungunya virus in the United States ...

  17. Zika Virus

    Science.gov (United States)

    ... Funding CDC Activities For Healthcare Providers Clinical Evaluation & Disease Sexual Transmission HIV Infection & Zika Virus Testing for Zika Test Specimens – At Time of Birth Diagnostic Tests Understanding Zika Virus Test Results ...

  18. Proteção fetal contra o vírus da diarréia viral bovina (BVDV em vacas prenhes previamente imunizadas com uma vacina experimental atenuada Fetal protection against bovine viral diarrhea virus (BVDV in pregnant cows previously immunized with an experimental attenuated vaccine

    Directory of Open Access Journals (Sweden)

    Sandra Arenhart

    2008-10-01

    ôde ser examinado para a presença de vírus. Outra vaca vacinada pariu um bezerro positivo para o vírus (5,2%. Em resumo, a vacina experimental induziu títulos adequados de anticorpos na maioria dos animais; e a resposta imunológica induzida pela vacinação foi capaz de conferir proteção fetal e prevenir as perdas reprodutivas frente ao desafio com um pool de amostras heterólogas de BVDV. Assim, essa vacina experimental pode representar uma boa alternativa para a redução das perdas reprodutivas associadas com a infecção pelo BVDV.This paper reports the antibody response and fetal protection in pregnant cows conferred by an experimental vaccine containing two attenuated strains of bovine viral diarrhea virus (BVDV-1 and BVDV-2. Cows (n=19 were vaccinated twice, with a 34 days-interval, with the experimental vaccine and together with non-vaccinated controls (n=18, were mated and challenged between days 60 and 90 of gestation by intranasal inoculation of four heterologous BVDV-1 and BVDV-2 isolates. The antibody response was evaluated by serum-neutralization tests performed at different intervals after vaccination (days 34, 78 and 138 post-vaccination [pv]. Fetal protection was monitored by ultrassonographic and clinical examination of the dams and fetuses during the rest of gestation; and through virological and serological examination of pre-colostral blood obtained from aborted and/or recently born fetuses/calves. At the day of challenge (day 138 pv, all vaccinated cows had neutralizing antibodies in high titers against BVDV-1 (1,280->10,240, and with one exception (titer 20, presented moderate to high titers to BVDV-2 (80-1,280. At the end of the monitoring, only three out of 18 control cows (16.6% delivered healthy, virus-free calves. Fifteen non-vaccinated cows (83.3% presented signs of fetal infection and/or had reproductive losses. Seven of these cows (38.8% delivered virus-positive calves; five were healthy and survived (27.7%; two were premature or weak

  19. Molecular characterisation of virulence graded field isolates of myxoma virus

    OpenAIRE

    Parra Francisco; Alonso Jose; Baragaño Aroa; Nicieza Ines; Dalton Kevin P

    2010-01-01

    Abstract Background Myxoma virus (MV) has been endemic in Europe since shortly after its deliberate release in France in 1952. While the emergence of more resistant hosts and more transmissible and attenuated virus is well documented, there have been relatively few studies focused on the sequence changes incurred by the virus as it has adapted to its new host. In order to identify regions of variability within the MV genome to be used for phylogenetic studies and to try to investigate causes ...

  20. Stability, biophysical properties and effect of ultracentrifugation and diafiltration on measles virus and mumps virus.

    Science.gov (United States)

    Sviben, Dora; Forčić, Dubravko; Kurtović, Tihana; Halassy, Beata; Brgles, Marija

    2016-06-01

    Measles virus and mumps virus (MeV and MuV) are enveloped RNA viruses used for production of live attenuated vaccines for prophylaxis of measles and mumps disease, respectively. For biotechnological production of and basic research on these viruses, the preparation of highly purified and infectious viruses is a prerequisite, and to meet that aim, knowledge of their stability and biophysical properties is crucial. Our goal was to carry out a detailed investigation of the stability of MeV and MuV under various pH, temperature, shear stress, filtration and storage conditions, as well as to evaluate two commonly used purification techniques, ultracentrifugation and diafiltration, with regard to their efficiency and effect on virus properties. Virus titers were estimated by CCID50 assay, particle size and concentration were measured by Nanoparticle tracking analysis (NTA) measurements, and the host cell protein content was determined by ELISA. The results demonstrated the stability of MuV and MeV at pH 9. Storage without stabilizer did not result in structural changes, but the reduction in infectivity after 24 hours was significant at +37 °C. Vortexing of the viruses resulted in significant particle degradation, leading to lower virus titers, whereas pipetting had much less impact on virus viability. Diafiltration resulted in higher recovery of both total and infectious virus particles than ultracentrifugation. These results provide important data for research on all upstream and downstream processes on these two viruses regarding biotechnological production and basic research.

  1. Registered nurses improving screening rates for non AIDS related comorbidities in people living with HIV

    National Research Council Canada - National Science Library

    Biggs, Karen; Power, Melissa

    2015-01-01

    Objective: To establish whether a nurse-led screening and brief intervention project could improve screening rates for non-AIDS comorbidities in people living with Human Immunodeficiency Virus (HIV). Design...

  2. 32. EMPIRICAL EVIDENCE OF THE SPREAD OF HIV/AIDS ' IN A ...

    African Journals Online (AJOL)

    1999-03-01

    Chirimuuta & Chirimuuta ... Although the virus causing AIDS is surely American by Adoption, not by birth (emphasis mine), the most likely ... visited on the Sodom and Gomorra of sinners such as the homosexual communities of San ...

  3. The Prevalence of HIV/AIDS Epidemic in Anambra State, Nigeria ...

    African Journals Online (AJOL)

    /AID prevalence in Anambra State, Nigeria. Since the discovery of Human Immune Deficiency Virus (HIV) over three decades ago, it has plundered the global populations with impunity, resulting in the death of millions of people.

  4. 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.

  5. Integrated Microfluidic Variable Optical Attenuator

    Science.gov (United States)

    2005-11-28

    indices , the optical output power is gradually attenuated. We obtain a maximum attenuation of 28 dB when the fluid refractive index changes from 1.557 to...Electron. 23, pp. 1348-1354 (2005). 14. J. M. Ruano, V. Benoit, J. S. Aitchison , and J. M. Cooper, “Flame hydrolysis deposition of glass on silicon for...different refractive indices flowing in a microfluidic channel as the cladding for a segment of straight optical waveguide. Recently, the integration of

  6. 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

  7. 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.

  8. Cardiovascular implications from untreated human immunodeficiency virus infection

    DEFF Research Database (Denmark)

    Baker, Jason V; Lundgren, Jens D

    2011-01-01

    Atherosclerotic cardiovascular disease (CVD) has become an important cause of morbidity and mortality among individuals with human immunodeficiency virus (HIV) infection with access to antiretroviral medications, as the risk for AIDS has fallen and life expectancy improved. Traditional CVD risk...

  9. Radiographic imaging of aids

    CERN Document Server

    Mahmoud, M B

    2002-01-01

    The acquired immunodeficiency syndrome (AIDS) has impacted the civilized world like no other disease. This research aimed to discuss some of the main aids-related complications and their detection by radiology tests, specifically central nervous system and musculoskeletal system disorders. The objectives are: to show specific characteristics of various diseases of HIV patient, to analyze the effect of pathology in patients by radiology, to enhance the knowledge of technologists in aids imaging and to improve communication skills between patient and radiology technologists.

  10. AIDS in South Africa.

    Science.gov (United States)

    Ijsselmuiden, C; Evian, C; Matjilla, J; Steinberg, M; Schneider, H

    1993-01-01

    The National AIDS Convention in South Africa (NACOSA) in October 1992 was the first real attempt to address HIV/AIDS. In Soweto, government, the African National Congress, nongovernmental organizations, and organized industry and labor representatives worked for 2 days to develop a national plan of action, but it did not result in a united effort to fight AIDS. The highest HIV infection rates in South Africa are among the KwaZulu in Natal, yet the Inkatha Freedom Party did not attend NACOSA. This episode exemplifies the key obstacles for South Africa to prevent and control AIDS. Inequality of access to health care may explain why health workers did not diagnose the first AIDS case in blacks until 1985. Migrant labor, Bantu education, and uprooted communities affect the epidemiology of HIV infection. Further, political and social polarization between blacks and whites contributes to a mindset that AIDS is limited to the other race which only diminishes the personal and collective sense of susceptibility and the volition and aptitude to act. The Department of National Health and Population Development's voluntary register of anonymously reported cases of AIDS specifies 1517 cumulative AIDS cases (October 1992), but this number is low. Seroprevalence studies show between 400,000-450,000 HIV positive cases. Public hospitals cannot give AIDS patients AZT and DDI. Few communities provided community-based care. Not all hospitals honor confidentiality and patients' need for autonomy. Even though HIV testing is not mandatory, it is required sometimes, e.g., HIV testing of immigrants. AIDS Training, Information and Counselling Centers are in urban areas, but not in poor areas where the need is most acute. The government just recently developed in AIDS education package for schools, but too many people consider it improper, so it is not being used. The poor quality education provided blacks would make it useless anyhow. Lifting of the academic boycott will allow South African

  11. JPRS Report, Epidemiology, Aids

    Science.gov (United States)

    1991-06-06

    Related Deaths [Havana Radio Progreso Network, 24 May 91] ...... 21 HONDURAS Alarming Increase in AIDS [Tegucigalpa LA TRIBUNA, 15 Mar 91...Update of AIDS Cases, AIDS-Related Deaths bisexuals, 7 percent. In terms of death among all cases, FL2405194491 Havana Radio Progreso Network 29 percent...involving a controlled follow up. most affected are San Pedro Sula (79 percent increase), This program includes radio and television messages El Progreso (86

  12. Evaluation of the Protective Efficacy of Recombinant Vesicular Stomatitis Virus Vectors Against Marburg Hemorrhagic Fever in Nonhuman Primate Models

    Science.gov (United States)

    2007-01-19

    VSV (Simon, Cardomone et al. 1990), borna disease virus (Formella, Jehle et al. 2000), and Sinbis virus (Karpf, Lenches et al. 1997). The...C., et al. (2000). "Sequence variability of Borna disease virus : resistance to superinfection may contribute to high genome stability in...Marburg virus disease ". S Afr Med J 66(2):50-4 Roberts, A., L. Buonocore, et al. (1999). "Attenuated vesicular stomatitis viruses as vaccine vectors." J

  13. Aid and Development

    DEFF Research Database (Denmark)

    Tarp, Finn

    evolved since World War II in response to a dramatically changing global political and economic context. I review the aid process and associated trends in the volume and distribution of aid and categorize some of the key goals, principles and institutions of the aid system. The evidence on whether aid has...... been effective in furthering economic growth and development is discussed in some detail. I add perspective and identify some critical unresolved issues. I finally turn to the current development debate and discuss some key concerns, which I believe should be kept in mind in formulating any agenda...

  14. Music and hearing aids.

    Science.gov (United States)

    Madsen, Sara M K; Moore, Brian C J

    2014-10-31

    The signal processing and fitting methods used for hearing aids have mainly been designed to optimize the intelligibility of speech. Little attention has been paid to the effectiveness of hearing aids for listening to music. Perhaps as a consequence, many hearing-aid users complain that they are not satisfied with their hearing aids when listening to music. This issue inspired the Internet-based survey presented here. The survey was designed to identify the nature and prevalence of problems associated with listening to live and reproduced music with hearing aids. Responses from 523 hearing-aid users to 21 multiple-choice questions are presented and analyzed, and the relationships between responses to questions regarding music and questions concerned with information about the respondents, their hearing aids, and their hearing loss are described. Large proportions of the respondents reported that they found their hearing aids to be helpful for listening to both live and reproduced music, although less so for the former. The survey also identified problems such as distortion, acoustic feedback, insufficient or excessive gain, unbalanced frequency response, and reduced tone quality. The results indicate that the enjoyment of listening to music with hearing aids could be improved by an increase of the input and output dynamic range, extension of the low-frequency response, and improvement of feedback cancellation and automatic gain control systems. © The Author(s) 2014.

  15. Aid, growth, and development

    DEFF Research Database (Denmark)

    Arndt, Channing; Jones, Edward Samuel; Tarp, Finn

    2010-01-01

    The micro-macro paradox has been revived. Despite broadly positive evaluations at the micro- and meso-levels, recent literature doubts the ability of foreign aid to foster economic growth and development. This paper assesses the aid-growth literature and, taking inspiration from the program...... evaluation literature, we re-examine key hypotheses. In our findings, aid has a positive and statistically significant causal effect on growth over the long run, with confidence intervals conforming to levels suggested by growth theory. Aid remains a key tool for enhancing the development prospects of poor...

  16. Music and Hearing Aids

    Science.gov (United States)

    Moore, Brian C. J.

    2014-01-01

    The signal processing and fitting methods used for hearing aids have mainly been designed to optimize the intelligibility of speech. Little attention has been paid to the effectiveness of hearing aids for listening to music. Perhaps as a consequence, many hearing-aid users complain that they are not satisfied with their hearing aids when listening to music. This issue inspired the Internet-based survey presented here. The survey was designed to identify the nature and prevalence of problems associated with listening to live and reproduced music with hearing aids. Responses from 523 hearing-aid users to 21 multiple-choice questions are presented and analyzed, and the relationships between responses to questions regarding music and questions concerned with information about the respondents, their hearing aids, and their hearing loss are described. Large proportions of the respondents reported that they found their hearing aids to be helpful for listening to both live and reproduced music, although less so for the former. The survey also identified problems such as distortion, acoustic feedback, insufficient or excessive gain, unbalanced frequency response, and reduced tone quality. The results indicate that the enjoyment of listening to music with hearing aids could be improved by an increase of the input and output dynamic range, extension of the low-frequency response, and improvement of feedback cancellation and automatic gain control systems. PMID:25361601

  17. Isospora belli associated recurrent diarrhea in a child with AIDS

    OpenAIRE

    Nateghi Rostami, M.; Nikmanesh, B.; Haghi-Ashtiani, M. T.; Monajemzadeh, M; M Douraghi; Ghalavand, Z.; Kashi, L

    2013-01-01

    Persistent diarrhea is a major manifestation of Acquired Immunodeficiency Syndrome (AIDS) which might be more complicated in Human Immunodeficiency Virus (HIV) infected children especially those from developing countries. There are numerous reports showing the emergence of intestinal opportunistic coccidian parasites, mostly Cryptosporidium parvum and Isospora belli in HIV-infected individuals. The prevalence of isosporiasis is probably underestimated in developing countries because routinely...

  18. HIV/AIDS knowledge, sexual behaviour and condom use among ...

    African Journals Online (AJOL)

    identified virus (84.3%), bacteria (3.5%) and excessive drinking of alcohol (8.7%) as some of the causes of HIV/AIDS. Some ways of contacting it included penetrative sex (96.2%), sharing shaver blade (57.1%) and maternal transmission (48.7%). Cases of misconception abound. Respondents who indicated they sometimes ...

  19. Psychiatric Disorders Among People Living With HIV/AIDS Attending ...

    African Journals Online (AJOL)

    Human Immunodeficiency Virus (HIV) infection has been associated with development of psychiatric disorders in people living with HIV/AIDS (PLWHA). These disorders could occur at any stage of the disease. The presence of these psychiatric disorders may affect the adherence to the use of anti-retroviral medications as ...

  20. Understanding HIV and AIDS: Preparing Students for Practice.