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

Science.gov (United States)

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

2009-01-01

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

Measles Outbreak with Unique Virus Genotyping, Ontario, Canada, 2015.

Science.gov (United States)

Thomas, Shari; Hiebert, Joanne; Gubbay, Jonathan B; Gournis, Effie; Sharron, Jennifer; Severini, Alberto; Jiaravuthisan, Manisa; Shane, Amanda; Jaeger, Valerie; Crowcroft, Natasha S; Fediurek, Jill; Sander, Beate; Mazzulli, Tony; Schulz, Helene; Deeks, Shelley L

2017-07-01

The province of Ontario continues to experience measles virus transmissions despite the elimination of measles in Canada. We describe an unusual outbreak of measles in Ontario, Canada, in early 2015 that involved cases with a unique strain of virus and no known association among primary case-patients. A total of 18 cases of measles were reported from 4 public health units during the outbreak period (January 25-March 23, 2015); none of these cases occurred in persons who had recently traveled. Despite enhancements to case-patient interview methods and epidemiologic analyses, a source patient was not identified. However, the molecular epidemiologic analysis, which included extended sequencing, strongly suggested that all cases derived from a single importation of measles virus genotype D4. The use of timely genotype sequencing, rigorous epidemiologic investigation, and a better understanding of the gaps in surveillance are needed to maintain Ontario's measles elimination status.

Expression, crystallization and preliminary crystallographic study of mouse hepatitis virus (MHV) nucleocapsid protein C-terminal domain

International Nuclear Information System (INIS)

Tong, Xiaohang; Ma, Yanlin; Li, Xuemei

2010-01-01

The C-terminal domain of mouse hepatitis virus nucleocapsid protein has been overexpressed in E. coli, purified and crystallized. The crystal belonged to space group P422, with unit-cell parameters a = 66.6, c = 50.8 Å, and diffracted to 2.20 Å resolution. Mouse hepatitis virus (MHV) belongs to the group II coronaviruses. The virus produces nine genes encoding 11 proteins that could be recognized as structural proteins and nonstructural proteins and are crucial for viral RNA synthesis. The nucleocapsid (N) protein, one of the structural proteins, interacts with the 30.4 kb virus genomic RNA to form the helical nucleocapsid and associates with the membrane glycoprotein via its C-terminus to stabilize virion assembly. Here, the expression and crystallization of the MHV nucleocapsid protein C-terminal domain are reported. The crystals diffracted to 2.20 Å resolution and belonged to space group P422, with unit-cell parameters a = 66.6, c = 50.8 Å. Assuming the presence of two molecules in the asymmetric unit, the solvent content is 43.0% (V M = 2.16 Å 3 Da −1 )

Radioimmunoassay of measles virus antibodies in SSPE

International Nuclear Information System (INIS)

Jankowski, M.A.; Gut, W.; Kantoch, M.

1982-01-01

A sensitive radioimmunoassay (RIA) was introduced for detecting measles virus IgG and IgM antibodies. The hyperimmune response to the measles virus could be demonstrated more accurately by RIA than by haemagglutination inhibition (HI). The ratio between RIA and HI antibody titres was decidedly higher in sera and cerebrospinal fluids of patients with subacute sclerosing panencephalitis than in those of other groups tested. (author)

Improving molecular tools for global surveillance of measles virus.

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Bankamp, Bettina; Byrd-Leotis, Lauren A; Lopareva, Elena N; Woo, Gibson K S; Liu, Chunyu; Jee, Youngmee; Ahmed, Hinda; Lim, Wilina W; Ramamurty, Nalini; Mulders, Mick N; Featherstone, David; Bellini, William J; Rota, Paul A

2013-09-01

The genetic characterization of wild-type measles viruses plays an important role in the description of viral transmission pathways and the verification of measles elimination. The 450 nucleotides that encode the carboxyl-terminus of the nucleoprotein (N-450) are routinely sequenced for genotype analysis. The objectives of this study were to develop improved primers and controls for RT-PCR reactions used for genotyping of measles samples and to develop a method to provide a convenient, safe, and inexpensive means to distribute measles RNA for RT-PCR assays and practice panels. A newly designed, genetically defined synthetic RNA and RNA isolated from cells infected with currently circulating genotypes were used to compare the sensitivity of primer pairs in RT-PCR and nested PCR. FTA® cards loaded with lysates of measles infected cells were tested for their ability to preserve viral RNA and destroy virus infectivity. A new primer pair, MeV216/MeV214, was able to amplify N-450 from viruses representing 10 currently circulating genotypes and a genotype A vaccine strain and demonstrated 100-fold increased sensitivity compared to the previously used primer set. A nested PCR assay further increased the sensitivity of detection from patient samples. A synthetic positive control RNA was developed that produced PCR products that are distinguishable by size from PCR products amplified from clinical samples. FTA® cards completely inactivated measles virus and stabilized RNA for at least six months. These improved molecular tools will advance molecular characterization of circulating measles viruses globally and provide enhanced quality control measures. Published by Elsevier B.V.

Spread of Measles Virus in Europe

Centers for Disease Control (CDC) Podcasts

2011-10-06

Dr. Paul Rota, team lead for the Measles Laboratory, Division of Viral Diseases, at CDC, talks about a measles virus survey in Europe, 2008-2011.  Created: 10/6/2011 by National Center for Emerging and Zoonotic Infectious Diseases (NCEZID) and National Center for Immunization and Respiratory Diseases (NCIRD).   Date Released: 10/6/2011.

Distinct Contributions of Autophagy Receptors in Measles Virus Replication.

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Petkova, Denitsa S; Verlhac, Pauline; Rozières, Aurore; Baguet, Joël; Claviere, Mathieu; Kretz-Remy, Carole; Mahieux, Renaud; Viret, Christophe; Faure, Mathias

2017-05-22

Autophagy is a potent cell autonomous defense mechanism that engages the lysosomal pathway to fight intracellular pathogens. Several autophagy receptors can recognize invading pathogens in order to target them towards autophagy for their degradation after the fusion of pathogen-containing autophagosomes with lysosomes. However, numerous intracellular pathogens can avoid or exploit autophagy, among which is measles virus (MeV). This virus induces a complete autophagy flux, which is required to improve viral replication. We therefore asked how measles virus interferes with autophagy receptors during the course of infection. We report that in addition to NDP52/CALCOCO₂ and OPTINEURIN/OPTN, another autophagy receptor, namely T6BP/TAXIBP1, also regulates the maturation of autophagosomes by promoting their fusion with lysosomes, independently of any infection. Surprisingly, only two of these receptors, NDP52 and T6BP, impacted measles virus replication, although independently, and possibly through physical interaction with MeV proteins. Thus, our results suggest that a restricted set of autophagosomes is selectively exploited by measles virus to replicate in the course of infection.

Will Synergizing Vaccination with Therapeutics Boost Measles Virus Eradication?

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Plemper, Richard K; Hammond, Anthea L

2014-01-01

Introduction Measles virus is a major human pathogen responsible for approximately 150,000 measles deaths annually. The disease is vaccine preventable and eradication of the virus is considered feasible in principle. However, a herd immunity exceeding 95% is required to prevent sporadic viral outbreaks in a population. Declining disease prevalence combined with public anxieties about vaccination safety has increased vaccine refusal especially in the European region, which has resulted in measles resurgence in some areas. Areas covered Here, we discuss whether synergizing effective measles therapeutics with vaccination could contribute to solving an endgame conundrum of measles elimination by accelerating the eradication effort. Based on an anticipated use for protection of high-risk contacts of confirmed measles cases through post-exposure prophylaxis, we identify key elements of the desirable drug profile, review current disease management strategies and the state of experimental inhibitor candidates, evaluate the risk associated with viral escape from inhibition, and consider the potential of measles therapeutics for the management of persistent viral infection of the CNS. Assuming a post-measles world with waning measles immunity, we contemplate the possible impact of therapeutics on controlling the threat imposed by closely related zoonotic pathogens of the same genus as measles virus. Expert opinion Efficacious therapeutics given for post-exposure prophylaxis of high-risk social contacts of confirmed index cases may aid measles eradication by closing herd immunity gaps due to vaccine refusal or failure in populations with overall good vaccination coverage. The envisioned primarily prophylactic application of measles therapeutics to a predominantly pediatric and/or adolescent patient population dictates the drug profile; the article must be safe and efficacious, orally available, shelf-stable at ambient temperature, and amenable to cost-effective manufacture

Nucleocapsid-like structures of Ebola virus reconstructed using electron tomography

International Nuclear Information System (INIS)

Noda, T.; Aoyama, K.; Sagara, H.; Kida, H.; Kawaoka, Y.

2005-01-01

Electron tomography (ET) is a new technique for high resolution, three-dimensional (3D) reconstruction of pleiomocphic mac. n)molecular complexes, such as virus components. By employing this technique, we resolved the 3D structure of Ebola virus nucleocapsid-like (NC-like) structures in the cytoplasm of cells expressing NP, VP24, and VP35: the minimum components required to form these NC-like structures. Reconstruction of these tubular NC-like structures of Ebola virus showed them to be composed of left-handed helices spaced at short intervals, which is structurally consistent with other non-segmented negative-strand RNA viruses

Measles virus genotypes circulating in India, 2011-2015.

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Vaidya, Sunil R; Chowdhury, Deepika T

2017-05-01

The Government of India is accepted to participate in the measles elimination and rubella control goal 2020, hence genetic characterization of measles viruses (MeV) becomes essential. At National Reference Laboratory (National Institute of Virology, Pune), the throat swabs/urine specimens (n = 380) or PCR products (n = 219) obtained from the suspected measles cases were referred for the molecular testing and subsequently, MeV nucleoprotein (N) gene sequencing/genotyping. In addition, 2,449 suspected measles cases, mainly from the Maharashtra state were referred for the laboratory diagnosis. A detailed study was performed on N gene sequences obtained during last two decades. Indian MeV sequences obtained during 2011-2015 were compared with 1996-2010 sequences and genetic divergence was studied. Circulation of measles genotypes B3 (n = 3), D4 (n = 49), and D8 (n = 351) strains were observed in 19 States and three Union Territories of India. In addition, 64 measles viruses were isolated from 253 throat swab or urine specimens obtained from the suspected measles cases. During 2011-2015, 67.9% (1,663/2,449) suspected measles cases were laboratory confirmed. Molecular studies showed circulation of measles genotype B3 in India along with prominently circulating genotypes D4 and D8 except D7 strains. The genetic diversion within Indian B3, D4, and D8 genotypes was 0.3%, 1.1%, and 2.1%, respectively. The genetic divergence of Indian B3, D4, and D8 measles strains with the WHO reference sequences was 2.5%, 2.6%, and 1.8%, respectively. It is crucial data for national immunization program. More measles/rubella genotyping studies are necessary to track transmission and to support measles elimination and rubella control. J. Med. Virol. 89:753-758, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Complete genome sequences of six measles virus strains

NARCIS (Netherlands)

Phan, M.V.T. (My V.T.); C.M.E. Schapendonk (Claudia); B.B. Oude Munnink (Bas B.); M.P.G. Koopmans D.V.M. (Marion); R.L. de Swart (Rik); Cotten, M. (Matthew)

2018-01-01

textabstractGenetic characterization of wild-type measles virus (MV) strains is a critical component of measles surveillance and molecular epidemiology. We have obtained complete genome sequences of six MV strains belonging to different genotypes, using random-primed next generation sequencing.

In vitro assembly of Ebola virus nucleocapsid-like complex expressed in E. coli

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Ruchao Peng

2016-09-01

Full Text Available Abstract Ebola virus (EBOV harbors an RNA genome encapsidated by nucleoprotein (NP along with other viral proteins to form a nucleocapsid complex. Previous Cryo-eletron tomography and biochemical studies have shown the helical structure of EBOV nucleocapsid at nanometer resolution and the first 450 amino-acid of NP (NPΔ451–739 alone is capable of forming a helical nucleocapsid-like complex (NLC. However, the structural basis for NP-NP interaction and the dynamic procedure of the nucleocapsid assembly is yet poorly understood. In this work, we, by using an E. coli expression system, captured a series of images of NPΔ451–739 conformers at different stages of NLC assembly by negative-stain electron microscopy, which allowed us to picture the dynamic procedure of EBOV nucleocapsid assembly. Along with further biochemical studies, we showed the assembly of NLC is salt-sensitive, and also established an indispensible role of RNA in this process. We propose the diverse modes of NLC elongation might be the key determinants shaping the plasticity of EBOV virions. Our findings provide a new model for characterizing the self-oligomerization of viral nucleoproteins and studying the dynamic assembly process of viral nucleocapsid in vitro.

Immunogenicity of UV-inactivated measles virus

International Nuclear Information System (INIS)

Zahorska, R.; Mazur, N.; Korbecki, M.

1978-01-01

By means of the antigen extinction limit test it was shown that a triple dose vaccination of guinea pigs with UV-inactivated measles virus gave better results, than a single dose vaccination which was proved by the very low immunogenicity index. For both vaccination schemes (single and triple) the immune response was only sligthly influenced by a change of dose from 10 5 to 10 6 HadU 50 /ml or by the addition of aluminum adjuvant. In the antigen extinction limit test the antibody levels were determined by two methods (HIT and NT) the results of which were statistically equivalent. The UV-inactivated measles virus was also found to induce hemolysis-inhibiting antibodies. (orig.) [de

Generation of Recombinant Schmallenberg Virus Nucleocapsid Protein in Yeast and Development of Virus-Specific Monoclonal Antibodies

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Justas Lazutka

2014-01-01

Full Text Available Schmallenberg virus (SBV, discovered in continental Europe in late 2011, causes mild clinical signs in adult ruminants, including diarrhoea and reduced milk yield. However, fetal infection can lead to severe malformation in newborn offspring. To develop improved reagents for SBV serology, a high-level yeast expression system was employed to produce recombinant SBV nucleocapsid (N protein. Recombinant SBV N protein was investigated as an antigen in SBV-specific IgG enzyme immunoassay and used for generation of monoclonal antibodies (MAbs. Yeast-expressed SBV N protein was reactive with anti-SBV IgG-positive cow serum specimens collected from different farms of Lithuania. After immunization of mice with recombinant SBV N protein, four MAbs were generated. The MAbs raised against recombinant SBV N protein reacted with native viral nucleocapsids in SBV-infected BHK cells by immunofluorescence assay. The reactivity of recombinant N protein with SBV-positive cow serum specimens and the ability of the MAbs to recognize virus-infected cells confirm the antigenic similarity between yeast-expressed SBV N protein and native viral nucleocapsids. Our study demonstrates that yeast expression system is suitable for high-level production of recombinant SBV N protein and provides the first evidence on the presence of SBV-specific antibodies in cow serum specimens collected in Lithuania.

Identification of different lineages of measles virus strains circulating in Uttar Pradesh, North India

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Shakya Akhalesh

2012-10-01

Full Text Available Abstract Background Genetic analysis of measles viruses associated with recent cases and outbreaks has proven to bridge information gaps in routine outbreak investigations and has made a substantial contribution to measles control efforts by helping to identify the transmission pathways of the virus. Materials and methods The present study describes the genetic characterization of wild type measles viruses from Uttar Pradesh, India isolated between January 2008 and January 2011. In the study, 526 suspected measles cases from 15 outbreaks were investigated. Blood samples were collected from suspected measles outbreaks and tested for the presence of measles specific IgM; throat swab and urine samples were collected for virus isolation and RT-PCR. Genotyping of circulating measles viruses in Uttar Pradesh was performed by sequencing a 450-bp region encompassing the nucleoprotein hypervariable region and phylogenetic analysis. Results and conclusion Based on serological results, all the outbreaks were confirmed as measles. Thirty eight strains were obtained. Genetic analysis of circulating measles strains (n = 38 in Uttar Pradesh from 235 cases of laboratory-confirmed cases from 526 suspected measles cases between 2008 and 2011 showed that all viruses responsible for outbreaks were within clade D and all were genotype D8. Analysis of this region showed that it is highly divergent (up to 3.4% divergence in the nucleotide sequence and 4.1% divergence in the amino acid sequence between most distant strains. Considerable genetic heterogeneity was observed in the MV genotype D8 viruses in North India and underscores the need for continued surveillance and in particular increases in vaccination levels to decrease morbidity and mortality attributable to measles.

Antibody study in canine distemper virus nucleocapsid protein gene-immunized mice.

Science.gov (United States)

Yuan, B; Li, X Y; Zhu, T; Yuan, L; Hu, J P; Chen, J; Gao, W; Ren, W Z

2015-04-10

The gene for the nucleocapsid (N) protein of canine distemper virus was cloned into the pMD-18T vector, and positive recombinant plasmids were obtained by enzyme digestion and sequencing. After digestion by both EcoRI and KpnI, the plasmid was directionally cloned into the eukaryotic expression vector pcDNA; the positive clone pcDNA-N was screened by electrophoresis and then transfected into COS-7 cells. Immunofluorescence analysis results showed that the canine distemper virus N protein was expressed in the cytoplasm of transfected COS-7 cells. After emulsification in Freund's adjuvant, the recombinant plasmid pcDNA-N was injected into the abdominal cavity of 8-week-old BABL/c mice, with the pcDNA original vector used as a negative control. Mice were immunized 3 times every 2 weeks. The blood of immunized mice was drawn 2 weeks after completing the immunizations to measure titer levels. The antibody titer in the pcDNA-N test was 10(1.62 ± 0.164), while in the control group this value was 10(0.52 ± 0.56), indicating that specific humoral immunity was induced in canine distemper virus nucleocapsid protein-immunized mice.

Radioimmunoassay of measles virus hemagglutinin protein G

International Nuclear Information System (INIS)

Lund, G.A.; Salmi, A.A.

1982-01-01

Guinea pig and rabbit antisera from animals immunized with purified measles virus hemagglutinin (G) protein were used to establish a solid-phase four-layer radioimmunoassay for quantitative measurement of the G protein. The sensitivity of the assay was 2 ng of purified G protein, and 200 μg of protein from uninfected Vero cells neither decreased the sensitivity nor reacted non-specifically in the assay. Radioimmunoassay standard dose-response curves were established and unknown values interpolated from these using the logit program of a desktop computer. Using this procedure, a measles virus growth curve in infected Vero cells was determined by measurement of G protein production. Under these same conditions, hemagglutination was not sensitive enough to detect early hemagglutinin production. Viral antigens in canine distemper virus, Newcastle disease virus, parainfluenza viruses 1-4, simian virus 5, and respiratory syncytial virus-infected cell lysates did not cross-react in the radioimmunoassay. A small degree of cross-reactivity was detected with mumps viral antigens, both with Vero cell-derived (wild-type strain) and egg-derived (Enders strain) purified virus preparations and with a cell lysate antigen prepared from wild-type mumps virus-infected Vero cells. (Auth.)

Radioimmunoassay of measles virus hemagglutinin protein G

Energy Technology Data Exchange (ETDEWEB)

Lund, G A; Salmi, A A [Turku Univ. (Finland)

1982-08-01

Guinea pig and rabbit antisera from animals immunized with purified measles virus hemagglutinin (G) protein were used to establish a solid-phase four-layer radioimmunoassay for quantitative measurement of the G protein. The sensitivity of the assay was 2 ng of purified G protein, and 200 ..mu..g of protein from uninfected Vero cells neither decreased the sensitivity nor reacted non-specifically in the assay. Radioimmunoassay standard dose-response curves were established and unknown values interpolated from these using the logit program of a desktop computer. Using this procedure, a measles virus growth curve in infected Vero cells was determined by measurement of G protein production. Under these same conditions, hemagglutination was not sensitive enough to detect early hemagglutinin production. Viral antigens in canine distemper virus, Newcastle disease virus, parainfluenza viruses 1-4, simian virus 5, and respiratory syncytial virus-infected cell lysates did not cross-react in the radioimmunoassay. A small degree of cross-reactivity was detected with mumps viral antigens, both with Vero cell-derived (wild-type strain) and egg-derived (Enders strain) purified virus preparations and with a cell lysate antigen prepared from wild-type mumps virus-infected Vero cells.

Vaccine platform recombinant measles virus.

Science.gov (United States)

Mühlebach, Michael D

2017-10-01

The classic development of vaccines is lengthy, tedious, and may not necessarily be successful as demonstrated by the case of HIV. This is especially a problem for emerging pathogens that are newly introduced into the human population and carry the inherent risk of pandemic spread in a naïve population. For such situations, a considerable number of different platform technologies are under development. These are also under development for pathogens, where directly derived vaccines are regarded as too complicated or even dangerous due to the induction of inefficient or unwanted immune responses causing considerable side-effects as for dengue virus. Among platform technologies are plasmid-based DNA vaccines, RNA replicons, single-round infectious vector particles, or replicating vaccine-based vectors encoding (a) critical antigen(s) of the target pathogens. Among the latter, recombinant measles viruses derived from vaccine strains have been tested. Measles vaccines are among the most effective and safest life-attenuated vaccines known. Therefore, the development of Schwarz-, Moraten-, or AIK-C-strain derived recombinant vaccines against a wide range of mostly viral, but also bacterial pathogens was quite straightforward. These vaccines generally induce powerful humoral and cellular immune responses in appropriate animal models, i.e., transgenic mice or non-human primates. Also in the recent first clinical phase I trial, the results have been quite encouraging. The trial indicated the expected safety and efficacy also in human patients, interestingly independent from the level of prevalent anti-measles immunity before the trial. Thereby, recombinant measles vaccines expressing additional antigens are a promising platform for future vaccines.

Sub-nucleocapsid nanoparticles: a nasal vaccine against respiratory syncytial virus.

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Xavier Roux

Full Text Available BACKGROUND: Bronchiolitis caused by the respiratory syncytial virus (RSV in infants less than two years old is a growing public health concern worldwide, and there is currently no safe and effective vaccine. A major component of RSV nucleocapsid, the nucleoprotein (N, has been so far poorly explored as a potential vaccine antigen, even though it is a target of protective anti-viral T cell responses and is remarkably conserved between human RSV A and B serotypes. We recently reported a method to produce recombinant N assembling in homogenous rings composed of 10-11 N subunits enclosing a bacterial RNA. These nanoparticles were named sub-nucleocapsid ring structure (N SRS. METHODOLOGY AND PRINCIPAL FINDINGS: The vaccine potential of N SRS was evaluated in a well-characterized and widely acknowledged mouse model of RSV infection. BALB/c adult mice were immunized intranasally with N SRS adjuvanted with the detoxified E. coli enterotoxin LT(R192G. Upon RSV challenge, vaccinated mice were largely protected against virus replication in the lungs, with a mild inflammatory lymphocytic and neutrophilic reaction in their airways. Mucosal immunization with N SRS elicited strong local and systemic immunity characterized by high titers of IgG1, IgG2a and IgA anti-N antibodies, antigen-specific CD8(+ T cells and IFN-gamma-producing CD4(+ T cells. CONCLUSIONS/SIGNIFICANCE: This is the first report of using nanoparticles formed by the recombinant nucleocapsid protein as an efficient and safe intra-nasal vaccine against RSV.

A population screening test for antibody to measles virus

International Nuclear Information System (INIS)

Friedman, M.G.

1981-01-01

In areas where sporadic cases of measles continue to occur in spite of vaccination programs, the availability of a simple screening test for determination of seropositivity to measles virus is desirable. A sensitive radioimmunoassay (RIA) screening test (ST) for the detection of IgG antibody to measles virus, based on a solid phase RIA, is described. The assays were performed on polyvinyl microtiter plates for which the RIAST requires only 5 μl of serum per subject. Antigen consisted of a sonicated extract of measles virus-infected Vero cells. Rabbit antihuman IgG specific for the Fc-segment of human IgG, labelled with 125 I, was used to detect human IgG bound to viral antigen. The basic RIA method was characterized by carrying out full titrations of sera of 53 healthy adults, 10 children, and 13 patients with measles-associated illness. These sera were also tested by the hemagglutination inhibition (HI) technique; most of the measles sera were also tested by complement fixation (CF). RIAST results (expressed as binding ratios) obtained for 52 healthy adults are compared with their RIA serum titers. Of the 200 sera of patients of various ages tested by the RIAST, 63 borderline sera were also tested by HI. The RIAST, which does not require serum treatment other than inactivation, proved to be more sensitive as an indicator of seropositivity than HI. Implications of the results and practical applications of the screening test are discussed. (author)

Performance Evaluation of the VIDAS® Measles IgG Assay and Its Diagnostic Value for Measuring IgG Antibody Avidity in Measles Virus Infection

Science.gov (United States)

Dina, Julia; Creveuil, Christian; Gouarin, Stephanie; Viron, Florent; Hebert, Amelie; Freymuth, Francois; Vabret, Astrid

2016-01-01

The objective of this study is primarily to compare the performance of the VIDAS® Measles immunoglobulin (Ig)G assay to that of two other serological assays using an immunoassay technique, Enzygnost® Anti-measles Virus/IgG (Siemens) and Measles IgG CAPTURE EIA® (Microimmune). The sensitivity and the agreement of the VIDAS® Measles IgG assay compared to the Enzygnost® Anti-measles Virus/IgG assay and the Measles IgG CAPTURE EIA® assay are 100%, 97.2% and 99.0%, 98.4%, respectively. The very low number of negative sera for IgG antibodies does not allow calculation of specificity. As a secondary objective, we have evaluated the ability of the VIDAS® Measles IgG assay to measure anti-measles virus IgG antibody avidity with the help of the VIDAS® CMV IgG Avidity reagent, using 76 sera from subjects with measles and 238 other sera. Different groups of populations were analyzed. In the primary infection measles group, the mean IgG avidity index was 0.16 (range of 0.07 to 0.93) compared to 0.79 (range of 0.25 to 1) in the serum group positive for IgG antibodies and negative for IgM. These data allow to define a weak anti-measles virus IgG antibody avidity as an avidity index (AI) 0.6. The VIDAS® Measles IgG assay has a performance equivalent to that of other available products. Its use, individual and quick, is well adapted to testing for anti-measles immunity in exposed subjects. PMID:27556477

High titer oncolytic measles virus production process by integration of dielectric spectroscopy as online monitoring system.

Science.gov (United States)

Grein, Tanja A; Loewe, Daniel; Dieken, Hauke; Salzig, Denise; Weidner, Tobias; Czermak, Peter

2018-05-01

Oncolytic viruses offer new hope to millions of patients with incurable cancer. One promising class of oncolytic viruses is Measles virus, but its broad administration to cancer patients is currently hampered by the inability to produce the large amounts of virus needed for treatment (10 10 -10 12 virus particles per dose). Measles virus is unstable, leading to very low virus titers during production. The time of infection and time of harvest are therefore critical parameters in a Measles virus production process, and their optimization requires an accurate online monitoring system. We integrated a probe based on dielectric spectroscopy (DS) into a stirred tank reactor to characterize the Measles virus production process in adherent growing Vero cells. We found that DS could be used to monitor cell adhesion on the microcarrier and that the optimal virus harvest time correlated with the global maximum permittivity signal. In 16 independent bioreactor runs, the maximum Measles virus titer was achieved approximately 40 hr after the permittivity maximum. Compared to an uncontrolled Measles virus production process, the integration of DS increased the maximum virus concentration by more than three orders of magnitude. This was sufficient to achieve an active Measles virus concentration of > 10 10 TCID 50 ml -1 . © 2017 Wiley Periodicals, Inc.

Measles Epidemics Among Children in Vietnam: Genomic Characterization of Virus Responsible for Measles Outbreak in Ho Chi Minh City, 2014

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Van H. Pham

2014-12-01

Conclusions: Measles viruses responsible for outbreaks in Southern Vietnam belonged to a genotype D8 variant group which had unique amino acid sequences in the N gene. Our report provides important genomic information about the virus for measles elimination in Southeast Asia.

MEASLES VIRUS IMMUNITY LEVEL STUDY IN PARTICULAR POPULATION GROUPS OF THE REPUBLIC OF GUINEA WITHIN THE FRAMEWORK OF GLOBAL MEASLES ELIMINATION PROGRAM. REPORT 2

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A. Yu. Popova

2017-01-01

Full Text Available A goal for measles elimination globally by 2010–2020 was recognized as one of the priorities in the WHO program “Health for All in the 21st Century” (1998. However measles outbreaks occurred in 2010–2016 in countries with high level of measles vaccine coverage including USA and some European countries.Large measles outbreaks were also registered on the African continent and particular in the Republic of Guinea as a result of the decline of measles vaccine coverage due to the Ebola virus epidemic in the Republic of Guinea in 2014–2015. WHO recommends carrying out the routine measles vaccination as well as the supplemental immunization activities after the stop of the Ebola virus transmission. Effectiveness of the activities is definitely connected with the detection of the epidemically significant for the supplemental immunization age groups. The aim of the study was to evaluate the measles immunity level in different age groups of population in the Republic of Guinea. Materials and methods. Twenty five blood serum samples of healthy adult Guineans aged 28–66 and 121 blood serum samples of adolescences and adults admitted to hospital in the town of Kindia (Republic of Guinea for indoor treatment were tested by ELISA. The specific measles virus antibodies were detected using the following commercial ELISA test-systems produced by Euroimmun Medizinische Labordiagnostika AG Company (Germany: IgM-antibodies — by “Anti-Measles Virus ELISA (IgM”, IgG-antibodi es — by “Anti-Measles Virus ELISA (IgG”, IgG-avidity measles virus antibodies — by “Avidity: Anti-Measles Virus ELISA (IgG”. A part of sera was studied by “Vector-Best IgM-measles” and “Vector-Best IgG-measles” ELISA test-systems (Russia. Results and discussion. The comparative quantitative study of the measles immunity level (i.e. IgG-antibodies titers of the healthy adult Guineans in 2015 and 2016 revealed the lack of IgGantibodies in serum

Population immunity to measles virus and the effect of HIV-1 infection after a mass measles vaccination campaign in Lusaka, Zambia: a cross-sectional survey.

Science.gov (United States)

Lowther, Sara A; Curriero, Frank C; Kalish, Brian T; Shields, Timothy M; Monze, Mwaka; Moss, William J

2009-03-21

Measles control efforts are hindered by challenges in sustaining high vaccination coverage, waning immunity in HIV-1-infected children, and clustering of susceptible individuals. Our aim was to assess population immunity to measles virus after a mass vaccination campaign in a region with high HIV prevalence. 3 years after a measles supplemental immunisation activity (SIA), we undertook a cross-sectional survey in Lusaka, Zambia. Households were randomly selected from a satellite image. Children aged 9 months to 5 years from selected households were eligible for enrolment. A questionnaire was administered to the children's caregivers to obtain information about measles vaccination history and history of measles. Oral fluid samples were obtained from children and tested for antibodies to measles virus and HIV-1 by EIA. 1015 children from 668 residences provided adequate specimens. 853 (84%) children had a history of measles vaccination according to either caregiver report or immunisation card. 679 children (67%) had antibodies to measles virus, and 64 (6%) children had antibodies to HIV-1. Children with antibodies to HIV-1 were as likely to have no history of measles vaccination as those without antibodies to HIV-1 (odds ratio [OR] 1.17, 95% CI 0.57-2.41). Children without measles antibodies were more likely to have never received measles vaccine than those with antibodies (adjusted OR 2.50, 1.69-3.71). In vaccinated children, 33 (61%) of 54 children with antibodies to HIV-1 also had antibodies to measles virus, compared with 568 (71%) of 796 children without antibodies to HIV-1 (p=0.1). 3 years after an SIA, population immunity to measles was insufficient to interrupt measles virus transmission. The use of oral fluid and satellite images for sampling are potential methods to assess population immunity and the timing of SIAs.

Liquid-phase and solid-phase radioimmunoassay with herpes simplex virus type 1 nucleocapsids

International Nuclear Information System (INIS)

Bystricka, M.; Rajcani, J.; Libikova, H.; Sabo, A.; Foeldes, O.; Sadlon, J.

1985-01-01

Liquid-phase radioimmunoassay and solid-phase radioimmunoassay are described using 125 I-labelled or immobilized nucleocapsids (NC) of herpes simplex virus (HSV) type1. These techniques appeared sensitive and specific for quantitation of HSV-NC antigens and corresponding antibodies. (author)

Host DNA synthesis-suppressing factor in culture fluid of tissue cultures infected with measles virus

International Nuclear Information System (INIS)

Minagawa, T.; Nakaya, C.; Iida, H.

1974-01-01

Host DNA synthesis is suppressed by the culture fluid of cell cultures infected with measles virus. This activity in the culture fluid is initiated somewhat later than the growth of infectious virus. Ninety percent of host DNA synthesis in HeLa cells is inhibited by culture fluid of 3-day-old cell cultures of Vero or HeLa cells infected with measles virus. This suppressing activity is not a property of the virion, but is due to nonvirion-associated componentnent which shows none of the activities of measles virus such as hemagglutination, hemolysis, or cell fusion nor does it have the antigenicity of measles virus as tested by complement-fixation or hemagglutination-inhibiting antibody blocking tests. Neutralization of the activity of this component is not attained with the pooled sera of convalescent measles patients. This component has molecular weights of about 45,000, 20,000, and 3,000 and appears to be a heat-stable protein. The production of host DNA suppressing factor (DSF) is blocked by cycloheximide. Neither uv-inactivated nor antiserum-neutralized measles virus produce DSF. Furthermore, such activity of nonvirion-associated component is not detected in the culture fluid of cultures infected with other RNA viruses such as poliovirus, vesicular stomatitis virus, or Sindbis virus. (auth)

Molecular epidemiology of measles virus in Italy during 2008

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Fabio Magurano

2013-03-01

Full Text Available INTRODUCTION. In view of the goal of measles elimination, it is of great importance to assess the circulation of wild-type measles virus (MV. Genetic analysis is indispensable to understand the epidemiology of measles. A large measles outbreak occurred in Italy in 2008, with over 4000 cases reported to the enhanced measles surveillance system introduced in 2007, 37% of which were laboratory confirmed. METHODS. Urine and saliva samples were collected during 2008. A phylogenetic analysis of measles sequences was performed in order to understand the epidemiological situation of wild-type (MV circulation in that period. RESULT AND DISCUSSION. Data showed predominant circulation of the genotype D4. Genotypes A, D8, D9 and H1 were also detected in a small number of samples, probably representing imported cases.

The Measles Virus Receptor SLAMF1 Can Mediate Particle Endocytosis.

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Gonçalves-Carneiro, Daniel; McKeating, Jane A; Bailey, Dalan

2017-04-01

The signaling lymphocyte activation molecule F1 (SLAMF1) is both a microbial sensor and entry receptor for measles virus (MeV). Herein, we describe a new role for SLAMF1 to mediate MeV endocytosis that is in contrast with the alternative, and generally accepted, model that MeV genome enters cells only after fusion at the cell surface. We demonstrated that MeV engagement of SLAMF1 induces dramatic but transient morphological changes, most prominently in the formation of membrane blebs, which were shown to colocalize with incoming viral particles, and rearrangement of the actin cytoskeleton in infected cells. MeV infection was dependent on these dynamic cytoskeletal changes as well as fluid uptake through a macropinocytosis-like pathway as chemical inhibition of these processes inhibited entry. Moreover, we identified a role for the RhoA-ROCK-myosin II signaling axis in this MeV internalization process, highlighting a novel role for this recently characterized pathway in virus entry. Our study shows that MeV can hijack a microbial sensor normally involved in bacterial phagocytosis to drive endocytosis using a complex pathway that shares features with canonical viral macropinocytosis, phagocytosis, and mechanotransduction. This uptake pathway is specific to SLAMF1-positive cells and occurs within 60 min of viral attachment. Measles virus remains a significant cause of mortality in human populations, and this research sheds new light on the very first steps of infection of this important pathogen. IMPORTANCE Measles is a significant disease in humans and is estimated to have killed over 200 million people since records began. According to current World Health Organization statistics, it still kills over 100,000 people a year, mostly children in the developing world. The causative agent, measles virus, is a small enveloped RNA virus that infects a broad range of cells during infection. In particular, immune cells are infected via interactions between glycoproteins found

Seroepidemiology and phylogenetic characterisation of measles virus in Ireland, 2004-2013.

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O' Riordan, Bernadette; Carr, Michael J; Connell, Jeff; Dunford, Linda; Hall, William W; Hassan, Jaythoon

2014-08-01

Ireland is classified as an area of high measles incidence. A World Health Organisation-European Region strategic plan exists for measles elimination by 2015. To retrospectively investigate measles outbreaks using all patient samples (sera and oral fluid) received for measles laboratory diagnosis and characterise the genetic diversity of circulating measles genotypes in Ireland. 704 cases of acute measles infection as determined by the presence of measles specific IgM in sera and oral fluids were confirmed at the National Virus Reference Laboratory. Measles positive samples (n=116) were examined by genotyping, sequence analysis and phylogenetic characterisation. Three measles outbreaks occurred over the study period: 2004, 2009/2010 and 2011. Measles IgM positivity ranged from 22-29% in outbreak years to 5-10% in the intervening years. Age profile analysis revealed that whereas individuals >10 years accounted for only 8% of cases in the 2004 outbreak, this increased to 33% and 29% in the 2009/2010 and 2011 outbreaks, respectively. The transmission and also importation events. Clade D viruses were exclusively found circulating in Ireland, with autochthonous transmission of diverse genotype D4 strains associated with large outbreaks across Europe. More recently, genotype D8 was identified and these were associated with importation events. This study provides a comprehensive genetic analysis of circulating measles genotypes in Ireland and discriminated between indigenous and imported viral strains. Notably, an increase in laboratory-confirmed measles cases in the greater than 10 years of age group was seen over the study period. This information is valuable to inform vaccination strategies with a focus on those populations who remain susceptible to measles infection. Copyright © 2014 Elsevier B.V. All rights reserved.

Measles to the Rescue: A Review of Oncolytic Measles Virus

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Sarah Aref

2016-10-01

Full Text Available Oncolytic virotherapeutic agents are likely to become serious contenders in cancer treatment. The vaccine strain of measles virus is an agent with an impressive range of oncolytic activity in pre-clinical trials with increasing evidence of safety and efficacy in early clinical trials. This paramyxovirus vaccine has a proven safety record and is amenable to careful genetic modification in the laboratory. Overexpression of the measles virus (MV receptor CD46 in many tumour cells may direct the virus to preferentially enter transformed cells and there is increasing awareness of the importance of nectin-4 and signaling lymphocytic activation molecule (SLAM in oncolysis. Successful attempts to retarget MV by inserting genes for tumour-specific ligands to antigens such as carcinoembryonic antigen (CEA, CD20, CD38, and by engineering the virus to express synthetic microRNA targeting sequences, and “blinding” the virus to the natural viral receptors are exciting measures to increase viral specificity and enhance the oncolytic effect. Sodium iodine symporter (NIS can also be expressed by MV, which enables in vivo tracking of MV infection. Radiovirotherapy using MV-NIS, chemo-virotherapy to convert prodrugs to their toxic metabolites, and immune-virotherapy including incorporating antibodies against immune checkpoint inhibitors can also increase the oncolytic potential. Anti-viral host immune responses are a recognized barrier to the success of MV, and approaches such as transporting MV to the tumour sites by carrier cells, are showing promise. MV Clinical trials are producing encouraging preliminary results in ovarian cancer, myeloma and cutaneous non-Hodgkin lymphoma, and the outcome of currently open trials in glioblastoma multiforme, mesothelioma and squamous cell carcinoma are eagerly anticipated.

External Quality Assessment for the Detection of Measles Virus by Reverse Transcription-PCR Using Armored RNA.

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Dong Zhang

Full Text Available In recent years, nucleic acid tests for detection of measles virus RNA have been widely applied in laboratories belonging to the measles surveillance system of China. An external quality assessment program was established by the National Center for Clinical Laboratories to evaluate the performance of nucleic acid tests for measles virus. The external quality assessment panel, which consisted of 10 specimens, was prepared using armored RNAs, complex of noninfectious MS2 bacteriophage coat proteins encapsulated RNA of measles virus, as measles virus surrogate controls. Conserved sequences amplified from a circulating measles virus strain or from a vaccine strain were encapsulated into these armored RNAs. Forty-one participating laboratories from 15 provinces, municipalities, or autonomous regions that currently conduct molecular detection of measles virus enrolled in the external quality assessment program, including 40 measles surveillance system laboratories and one diagnostic reagent manufacturer. Forty laboratories used commercial reverse transcription-quantitative PCR kits, with only one laboratory applying a conventional PCR method developed in-house. The results indicated that most of the participants (38/41, 92.7% were able to accurately detect the panel with 100% sensitivity and 100% specificity. Although a wide range of commercially available kits for nucleic acid extraction and reverse transcription polymerase chain reaction were used by the participants, only two false-negative results and one false-positive result were generated; these were generated by three separate laboratories. Both false-negative results were obtained with tests performed on specimens with the lowest concentration (1.2 × 104 genomic equivalents/mL. In addition, all 18 participants from Beijing achieved 100% sensitivity and 100% specificity. Overall, we conclude that the majority of the laboratories evaluated have reliable diagnostic capacities for the detection

Identification of measles virus genotype B3 associated with outbreaks in Islamabad, Pakistan, 2013-2015.

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Zaidi, Syed Sohail Zahoor; Hameed, Abdul; Suleman Rana, Muhammad; Alam, Muhammad Masroor; Umair, Massab; Aamir, Uzma Bashir; Hussain, Maqbool; Sharif, Salmaan; Shaukat, Shahzad; Angez, Mehar; Khurshid, Adnan

2017-11-09

Measles virus infection remains a significant cause of childhood mortality and morbidity despite continued global efforts and the availability of a safe and effective vaccine. Molecular analysis of indigenous measles viruses could provide critical information on outbreak linkages and transmission pathways that can aid the implementation of appropriate control programs in Pakistan. Blood samples and throat swabs were collected from subjects suspected with measles in Islamabad, Pakistan from 2013 to 2015. Serum samples were tested for the presence of measles immunoglobulin M (IgM) antibodies using enzyme-linked immunosorbent assay (ELISA) while throat swabs were used for the isolation (Vero/SLAM cell line) and subsequent characterization and phylogenetic analysis of measles strains. Of 373 blood samples, 66% tested positive for measles IgM. Male subjects were more often infected (58%) than female (42%) with the highest frequency of positive cases (63%) in the 0-5-years age group. Among the positive cases, only 13% had received one or two doses of the measles vaccine, while 87% were unvaccinated. Of 80 throat swabs, 29 (36%) showed a measles virus-specific cytopathic effect (CPE) and were characterized as genotype B3 through partial sequencing of the nucleoprotein (N) gene. Phylogenetic analysis revealed the Pakistani B3 strains to be closely related to strains from neighboring countries (Iran and Afghanistan) as well as with B3 viruses from the USA, Germany, and the UK. The study results showed that despite the availability of an effective vaccine, the burden of measles infections is very high in Pakistan due to poor routine immunization coverage even in major cities, including the capital city of Islamabad. It is imperative that national health authorities take urgent strategic steps to improve routine immunization and implement adequate molecular identification methods to tackle future measles outbreaks. Copyright © 2017 The Authors. Published by Elsevier Ltd

Mass Spectrometry Analysis Coupled with de novo Sequencing Reveals Amino Acid Substitutions in Nucleocapsid Protein from Influenza A Virus

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Zijian Li

2014-02-01

Full Text Available Amino acid substitutions in influenza A virus are the main reasons for both antigenic shift and virulence change, which result from non-synonymous mutations in the viral genome. Nucleocapsid protein (NP, one of the major structural proteins of influenza virus, is responsible for regulation of viral RNA synthesis and replication. In this report we used LC-MS/MS to analyze tryptic digestion of nucleocapsid protein of influenza virus (A/Puerto Rico/8/1934 H1N1, which was isolated and purified by SDS poly-acrylamide gel electrophoresis. Thus, LC-MS/MS analyses, coupled with manual de novo sequencing, allowed the determination of three substituted amino acid residues R452K, T423A and N430T in two tryptic peptides. The obtained results provided experimental evidence that amino acid substitutions resulted from non-synonymous gene mutations could be directly characterized by mass spectrometry in proteins of RNA viruses such as influenza A virus.

Measles vaccination of nonhuman primates provides partial protection against infection with canine distemper virus.

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

2014-04-01

Measles virus (MV) is being considered for global eradication, which would likely reduce compliance with MV vaccination. As a result, children will grow up without MV-specific immunity, creating a potential niche for closely related animal morbilliviruses such as canine distemper virus (CDV). Natural CDV infection causing clinical signs has never been reported in humans, but recent outbreaks in captive macaques have shown that CDV can cause disease in primates. We studied the virulence and tropism of recombinant CDV expressing enhanced green fluorescent protein in naive and measles-vaccinated cynomolgus macaques. In naive animals CDV caused viremia and fever and predominantly infected CD150(+) lymphocytes and dendritic cells. Virus was reisolated from the upper and lower respiratory tracts, but infection of epithelial or neuronal cells was not detectable at the time points examined, and the infections were self-limiting. This demonstrates that CDV readily infects nonhuman primates but suggests that additional mutations are necessary to achieve full virulence in nonnatural hosts. Partial protection against CDV was observed in measles-vaccinated macaques, as demonstrated by accelerated control of virus replication and limited shedding from the upper respiratory tract. While neither CDV infection nor MV vaccination induced detectable cross-reactive neutralizing antibodies, MV-specific neutralizing antibody levels of MV-vaccinated macaques were boosted by CDV challenge infection, suggesting that cross-reactive VN epitopes exist. Rapid increases in white blood cell counts in MV-vaccinated macaques following CDV challenge suggested that cross-reactive cellular immune responses were also present. This study demonstrates that zoonotic morbillivirus infections can be controlled by measles vaccination. Throughout history viral zoonoses have had a substantial impact on human health. Given the drive toward global eradication of measles, it is essential to understand the

Treatment of medulloblastoma with oncolytic measles viruses expressing the angiogenesis inhibitors endostatin and angiostatin

International Nuclear Information System (INIS)

Hutzen, Brian; Bid, Hemant Kumar; Houghton, Peter J; Pierson, Christopher R; Powell, Kimerly; Bratasz, Anna; Raffel, Corey; Studebaker, Adam W

2014-01-01

Medulloblastoma is the most common type of pediatric brain tumor. Although numerous factors influence patient survival rates, more than 30% of all cases will ultimately be refractory to conventional therapies. Current standards of care are also associated with significant morbidities, giving impetus for the development of new treatments. We have previously shown that oncolytic measles virotherapy is effective against medulloblastoma, leading to significant prolongation of survival and even cures in mouse xenograft models of localized and metastatic disease. Because medulloblastomas are known to be highly vascularized tumors, we reasoned that the addition of angiogenesis inhibitors could further enhance the efficacy of oncolytic measles virotherapy. Toward this end, we have engineered an oncolytic measles virus that express a fusion protein of endostatin and angiostatin, two endogenous and potent inhibitors of angiogenesis. Oncolytic measles viruses encoding human and mouse variants of a secretable endostatin/angiostatin fusion protein were designed and rescued according to established protocols. These viruses, known as MV-hE:A and MV-mE:A respectively, were then evaluated for their anti-angiogenic potential and efficacy against medulloblastoma cell lines and orthotopic mouse models of localized disease. Medulloblastoma cells infected by MV-E:A readily secrete endostatin and angiostatin prior to lysis. The inclusion of the endostatin/angiostatin gene did not negatively impact the measles virus’ cytotoxicity against medulloblastoma cells or alter its growth kinetics. Conditioned media obtained from these infected cells was capable of inhibiting multiple angiogenic factors in vitro, significantly reducing endothelial cell tube formation, viability and migration compared to conditioned media derived from cells infected by a control measles virus. Mice that were given a single intratumoral injection of MV-E:A likewise showed reduced numbers of tumor-associated blood

Single endemic genotype of measles virus continuously circulating in China for at least 16 years.

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Yan Zhang

Full Text Available The incidence of measles in China from 1991 to 2008 was reviewed, and the nucleotide sequences from 1507 measles viruses (MeV isolated during 1993 to 2008 were phylogenetically analyzed. The results showed that measles epidemics peaked approximately every 3 to 5 years with the range of measles cases detected between 56,850 and 140,048 per year. The Chinese MeV strains represented three genotypes; 1501 H1, 1 H2 and 5 A. Genotype H1 was the predominant genotype throughout China continuously circulating for at least 16 years. Genotype H1 sequences could be divided into two distinct clusters, H1a and H1b. A 4.2% average nucleotide divergence was found between the H1a and H1b clusters, and the nucleotide sequence and predicted amino acid homologies of H1a viruses were 92.3%-100% and 84.7%-100%, H1b were 97.1%-100% and 95.3%-100%, respectively. Viruses from both clusters were distributed throughout China with no apparent geographic restriction and multiple co-circulating lineages were present in many provinces. Cluster H1a and H1b viruses were co-circulating during 1993 to 2005, while no H1b viruses were detected after 2005 and the transmission of that cluster has presumably been interrupted. Analysis of the nucleotide and predicted amino acid changes in the N proteins of H1a and H1b viruses showed no evidence of selective pressure. This study investigated the genotype and cluster distribution of MeV in China over a 16-year period to establish a genetic baseline before MeV elimination in Western Pacific Region (WPR. Continuous and extensive MeV surveillance and the ability to quickly identify imported cases of measles will become more critical as measles elimination goals are achieved in China in the near future. This is the first report that a single endemic genotype of measles virus has been found to be continuously circulating in one country for at least 16 years.

The glycoprotein of measles virus

International Nuclear Information System (INIS)

Anttonen, O.; Jokinen, M.; Salmi, A.; Vainionpaeae, R.; Gahmberg, C.G.

1980-01-01

Measles virus was propagated in VERO cells and purified from the culture supernatants by two successive tartrate-density-gradient centrifugations. Surface carbohydrates were labelled both in vitro and in vivo with 3 H after treatment with galactose oxidase/NaB 3 H 4 or with [ 3 H]glucosamine. The major labelled glycoprotein in measles virions had a mol.wt. of 79000. After labelling with periodate/NaB 3 H 4 , which would result in specific labelling of sialic acid residues, the 79000-mol.wt. glycoprotein was very weakly labelled. This suggested that there is no or a very low amount of sialic acid in the virions. Further analysis of the glycoprotein showed that galactose is the terminal carbohydrate unit in the oligosaccharide, and the molecular weight of the glycopeptide obtained after Pronase digestion is about 3000. The oligosaccharide is attached to the polypeptide through an alkali-stable bond, indicating a N-glycosidic asparagine linkage. (author)

Measles Virus Neutralizing Antibodies in Intravenous Immunoglobulins: Is an Increase by Revaccination of Plasma Donors Possible?

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Modrof, Jens; Tille, Björn; Farcet, Maria R; McVey, John; Schreiner, Jessica A; Borders, Charles M; Gudino, Maria; Fitzgerald, Peter; Simon, Toby L; Kreil, Thomas R

2017-11-15

We report a screen of plasma donors confirming that widespread use of childhood measles vaccination since 1963 resulted in a decrease in average measles virus antibody titers among plasma donors, which is reflected in intravenous immunoglobulins (IVIGs). The measles virus antibody titer, however, is a potency requirement for IVIGs, as defined in a Food and Drug Administration regulation. To mitigate the decline in measles virus antibody titers in IVIGs and to ensure consistent product release, revaccination of plasma donors was investigated as a means to boost titers. However, revaccination-induced titer increases were only about 2-fold and short-lived. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Rapid Titration of Measles and Other Viruses: Optimization with Determination of Replication Cycle Length

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Grigorov, Boyan; Rabilloud, Jessica; Lawrence, Philip; Gerlier, Denis

2011-01-01

Background Measles virus (MV) is a member of the Paramyxoviridae family and an important human pathogen causing strong immunosuppression in affected individuals and a considerable number of deaths worldwide. Currently, measles is a re-emerging disease in developed countries. MV is usually quantified in infectious units as determined by limiting dilution and counting of plaque forming unit either directly (PFU method) or indirectly from random distribution in microwells (TCID50 method). Both methods are time-consuming (up to several days), cumbersome and, in the case of the PFU assay, possibly operator dependent. Methods/Findings A rapid, optimized, accurate, and reliable technique for titration of measles virus was developed based on the detection of virus infected cells by flow cytometry, single round of infection and titer calculation according to the Poisson's law. The kinetics follow up of the number of infected cells after infection with serial dilutions of a virus allowed estimation of the duration of the replication cycle, and consequently, the optimal infection time. The assay was set up to quantify measles virus, vesicular stomatitis virus (VSV), and human immunodeficiency virus type 1 (HIV-1) using antibody labeling of viral glycoprotein, virus encoded fluorescent reporter protein and an inducible fluorescent-reporter cell line, respectively. Conclusion Overall, performing the assay takes only 24–30 hours for MV strains, 12 hours for VSV, and 52 hours for HIV-1. The step-by-step procedure we have set up can be, in principle, applicable to accurately quantify any virus including lentiviral vectors, provided that a virus encoded gene product can be detected by flow cytometry. PMID:21915289

JST Thesaurus Headwords and Synonyms: measles virus [MeCab user dictionary for science technology term[Archive

Lifescience Database Archive (English)

Full Text Available MeCab user dictionary for science technology term measles virus 名詞 一般 * * * * 麻疹ウイル...ス マシンウイルス マシンウイルス Thesaurus2015 200906067469554060 C LS07 UNKNOWN_2 measles virus

The molecular basis of the antigenic cross-reactivity between measles and cowpea mosaic viruses

International Nuclear Information System (INIS)

Olszewska, Wieslawa; Steward, Michael W.

2003-01-01

Two nonrelated viruses, cowpea mosaic virus (wtCPMV) and measles virus (MV), were found to induce cross-reactive antibodies. The nature of this cross-reactivity was studied and results are presented here demonstrating that antiserum raised against wtCPMV reacted with peptide from the fusion (F) protein of MV. Furthermore, the F protein of MV was shown to share an identical conformational B cell epitope with the small subunit of CPMV coat protein. Passive transfer of anti-wtCPMV antibodies into BALB/c mice conferred partial protection against measles virus induced encephalitis. The results are discussed in the context of cross-protection

Measles Virus Fusion Protein: Structure, Function and Inhibition

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Philippe Plattet

2016-04-01

Full Text Available Measles virus (MeV, a highly contagious member of the Paramyxoviridae family, causes measles in humans. The Paramyxoviridae family of negative single-stranded enveloped viruses includes several important human and animal pathogens, with MeV causing approximately 120,000 deaths annually. MeV and canine distemper virus (CDV-mediated diseases can be prevented by vaccination. However, sub-optimal vaccine delivery continues to foster MeV outbreaks. Post-exposure prophylaxis with antivirals has been proposed as a novel strategy to complement vaccination programs by filling herd immunity gaps. Recent research has shown that membrane fusion induced by the morbillivirus glycoproteins is the first critical step for viral entry and infection, and determines cell pathology and disease outcome. Our molecular understanding of morbillivirus-associated membrane fusion has greatly progressed towards the feasibility to control this process by treating the fusion glycoprotein with inhibitory molecules. Current approaches to develop anti-membrane fusion drugs and our knowledge on drug resistance mechanisms strongly suggest that combined therapies will be a prerequisite. Thus, discovery of additional anti-fusion and/or anti-attachment protein small-molecule compounds may eventually translate into realistic therapeutic options.

Single Endemic Genotype of Measles Virus Continuously Circulating in China for at Least 16 Years

Science.gov (United States)

Wang, Huiling; Zhu, Zhen; Ji, Yixin; Liu, Chunyu; Zhang, Xiaojie; Sun, Liwei; Zhou, Jianhui; Lu, Peishan; Hu, Ying; Feng, Daxing; Zhang, Zhenying; Wang, Changyin; Fang, Xueqiang; Zheng, Huanying; Liu, Leng; Sun, Xiaodong; Tang, Wei; Wang, Yan; Liu, Yan; Gao, Hui; Tian, Hong; Ma, Jiangtao; Gu, Suyi; Wang, Shuang; Feng, Yan; Bo, Fang; Liu, Jianfeng; Si, Yuan; Zhou, Shujie; Ma, Yuyan; Wu, Shengwei; Zhou, Shunde; Li, Fangcai; Ding, Zhengrong; Yang, Zhaohui; Rota, Paul A.; Featherstone, David; Jee, Youngmee; Bellini, William J.; Xu, Wenbo

2012-01-01

The incidence of measles in China from 1991 to 2008 was reviewed, and the nucleotide sequences from 1507 measles viruses (MeV) isolated during 1993 to 2008 were phylogenetically analyzed. The results showed that measles epidemics peaked approximately every 3 to 5 years with the range of measles cases detected between 56,850 and 140,048 per year. The Chinese MeV strains represented three genotypes; 1501 H1, 1 H2 and 5 A. Genotype H1 was the predominant genotype throughout China continuously circulating for at least 16 years. Genotype H1 sequences could be divided into two distinct clusters, H1a and H1b. A 4.2% average nucleotide divergence was found between the H1a and H1b clusters, and the nucleotide sequence and predicted amino acid homologies of H1a viruses were 92.3%–100% and 84.7%–100%, H1b were 97.1%–100% and 95.3%–100%, respectively. Viruses from both clusters were distributed throughout China with no apparent geographic restriction and multiple co-circulating lineages were present in many provinces. Cluster H1a and H1b viruses were co-circulating during 1993 to 2005, while no H1b viruses were detected after 2005 and the transmission of that cluster has presumably been interrupted. Analysis of the nucleotide and predicted amino acid changes in the N proteins of H1a and H1b viruses showed no evidence of selective pressure. This study investigated the genotype and cluster distribution of MeV in China over a 16-year period to establish a genetic baseline before MeV elimination in Western Pacific Region (WPR). Continuous and extensive MeV surveillance and the ability to quickly identify imported cases of measles will become more critical as measles elimination goals are achieved in China in the near future. This is the first report that a single endemic genotype of measles virus has been found to be continuously circulating in one country for at least 16 years. PMID:22532829

Measles

Science.gov (United States)

Measles is an infectious disease caused by a virus. It spreads easily from person to person. It ... down Tiny white spots inside the mouth Sometimes measles can lead to serious problems. There is no ...

Immunogenicity of peptides of measles virus origin and influence of adjuvants.

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Halassy, Beata; Mateljak, Sanja; Bouche, Fabienne B; Pütz, Mike M; Muller, Claude P; Frkanec, Ruza; Habjanec, Lidija; Tomasić, Jelka

2006-01-12

Epitope-based peptide antigens have been under development for protection against measles virus. The immunogenicity of five peptides composed of the same B cell epitope (BCE) (H236-250 of the measles virus hemagglutinin), and different T cell epitopes of measles virus fusion protein (F421-435, F256-270, F288-302) and nucleoprotein (NP335-345) was studied in mice (subcutaneous immunisation). The adjuvant effects of peptidoglycan monomer (PGM), Montanide ISA 720 and 206 were also investigated. Results showed basic differences in peptide immunogenicity that were consistent with already described structural differences. PGM elevated peptide-specific IgG when applied together with four of five tested peptides. A strong synergistic effect was observed after co-immunisation of mice with a mixture containing all five chimeric peptides in small and equal amounts. Results revealed for the first time that immunisation with several peptides having the common BCE generated significantly higher levels of both anti-peptide and anti-BCE IgG in comparison to those obtained after immunisation with a single peptide in much higher quantity. Further improvement of immune response was obtained after incorporation of such a peptide mixture into oil-based adjuvants.

The Ondersteport Canine distemper virus strain and measles ...

African Journals Online (AJOL)

Three groups of dogs aged three months each were used in an experiment to assess efficacy of imported Canine distemper vaccine (Ondersteport strain) and measles vaccine in protecting Nigerian dogs against local isolates of Canine distemper virus. Each group consisted of four randomly selected puppies. One group ...

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

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

2001-06-01

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

Ebola virus VP24 interacts with NP to facilitate nucleocapsid assembly and genome packaging.

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Banadyga, Logan; Hoenen, Thomas; Ambroggio, Xavier; Dunham, Eric; Groseth, Allison; Ebihara, Hideki

2017-08-09

Ebola virus causes devastating hemorrhagic fever outbreaks for which no approved therapeutic exists. The viral nucleocapsid, which is minimally composed of the proteins NP, VP35, and VP24, represents an attractive target for drug development; however, the molecular determinants that govern the interactions and functions of these three proteins are still unknown. Through a series of mutational analyses, in combination with biochemical and bioinformatics approaches, we identified a region on VP24 that was critical for its interaction with NP. Importantly, we demonstrated that the interaction between VP24 and NP was required for both nucleocapsid assembly and genome packaging. Not only does this study underscore the critical role that these proteins play in the viral replication cycle, but it also identifies a key interaction interface on VP24 that may serve as a novel target for antiviral therapeutic intervention.

Occurrence of measles in a country with elimination status: Amplifying measles infection in hospitalized children due to imported virus.

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Eom, HyeEun; Park, YoungJoon; Kim, JooWhee; Yang, Jeong-Sun; Kang, HaeJi; Kim, Kisoon; Chun, Byung Chul; Park, Ok; Hong, Jeong Ik

2018-01-01

The Republic of Korea declared measles elimination in 2006. However, a measles outbreak occurred in 2013. This study aimed to identify the epidemiological characteristics of the sources of infection and the pattern of measles transmission in 2013 in South Korea. We utilized surveillance data, epidemiological data, immunization registry data, and genetic information. We describe the epidemiological characteristics of all measles case patients (sex, age distribution, vaccination status, sources of infection) as well as details of the outbreak (the pattern of transmission, duration, mean age of patients, and generation time). In 2013, a total of 107 measles cases were notified. Most patients were infants (43.0%) and unvaccinated individuals (60.7%). We identified 4 imported and 103 import-related cases. A total of 105 cases were related to four outbreaks that occurred in Gyeongnam, northern Gyeonggi, southern Gyeonggi, and Seoul. The predominant circulating genotype was B3 type, which was identified in the Gyeongnam, northern Gyeonggi, and southern Gyeonggi outbreaks. The B3 type had not been in circulation in South Korea in the previous 3 years; virologic evidence suggests that these outbreaks were import-related. Most measles cases in South Korea have been associated with imported measles virus. Although Korea has maintained a high level of herd immunity, clustering of susceptible people can cause such measles outbreaks.

Implementation of a National Measles Elimination Program in Iran: Phylogenetic Analysis of Measles Virus Strains Isolated during 2010–2012 Outbreaks

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Salimi, Vahid; Abbasi, Simin; Zahraei, Seyed Mohsen; Fatemi-Nasab, Ghazal; Adjaminezhad-Fard, Fatemeh; Shadab, Azadeh; Ghavami, Nastaran; Zareh-Khoshchehre, Raziyeh; Soltanshahi, Rambod; Bont, Louis; Mokhtari-Azad, Talat

2014-01-01

Measles virus (MV) causes small and large outbreaks in Iran. Molecular assays allow identifying and the sources of measles imported from neighboring countries. We carried out a phylogenetic analysis of measles virus circulating in Iran over the period 2010–2012. Specimens from suspected cases of measles were collected from different regions of Iran. Virus isolation was performed on urine and throat swabs. Partial nucleoprotein gene segments of MV were amplified by RT-PCR. PCR products of 173 samples were sequenced and analyzed. The median age of confirmed cases was 2 years. Among all confirmed cases, 32% had unknown vaccination status, 20% had been vaccinated, and 48% had not been vaccinated. Genotypes B3 and D8 (for the first time), H1 and D4 were detected mainly in unvaccinated toddlers and young children. Genotype B3 became predominant in 2012 and was closely related to African strains. H1 strains were also found in small and large outbreaks during 2012 but were not identical to Iranian H1-2009 strains. A majority of the Iranian D4 strains during 2010–2012 outbreaks were linked to the D4 strain identified in the Pakistan in 2007. We identified a single case in 2010 belonging to D8 genotype with 99.7% identity to Indian isolates. Although the vaccination program is currently good enough to prevent nationwide epidemics and successfully decreased measles incidence in Iran, the fraction of protected individuals in the population was not high enough to prevent continuous introduction of cases from abroad. Due to increasing number of susceptible individuals in some areas, sustained transmission of the newly introduced viral genotype remains possible. PMID:24736720

Annexin A2 Mediates the Localization of Measles Virus Matrix Protein at the Plasma Membrane.

Science.gov (United States)

Koga, Ritsuko; Kubota, Marie; Hashiguchi, Takao; Yanagi, Yusuke; Ohno, Shinji

2018-02-28

Annexins are a family of structurally related proteins that bind negatively charged membrane phospholipids in a Ca 2+ -dependent manner. Annexin A2 (AnxA2), a member of the family, has been implicated in a variety of cellular functions including the organization of membrane domains, vesicular trafficking and cell-cell adhesion. AnxA2 generally forms the heterotetrameric complex with a small Ca 2+ -binding protein S100A10. Measles virus (MV), a member of the family Paramyxoviridae , is an enveloped virus with a nonsegmented negative strand RNA genome. Knockdown of AnxA2 greatly reduced MV growth in cells, without affecting its entry and viral RNA production. In MV-infected, AnxA2-knockdown cells, the expression level of the matrix (M) protein, but not other viral proteins, was reduced compared with that in control cells, and the distribution of the M protein at the plasma membrane was decreased. The M protein lines the inner surface of the envelope and plays an important role in virus assembly by connecting the nucleocapsid to the envelope proteins. The M protein bound to AnxA2 independently of AnxA2's phosphorylation or its association with S100A10, and was co-localized with AnxA2 within cells. Truncation of the N-terminal 10 amino acid residues, but not the N-terminal 5 residues, compromised the ability of the M protein to interact with AnxA2 and localize at the plasma membrane. These results indicate that AnxA2 mediates the localization of the MV M protein at the plasma membrane by interacting with its N-terminal region (especially residues at positions 6-10), thereby aiding in MV assembly. IMPORTANCE Measles virus (MV) is an important human pathogen, still claiming ∼ 100,000 lives per year despite the presence of effective vaccines, and causes occasional outbreaks even in developed countries. Replication of viruses largely relies on the functions of host cells. Our study revealed that the reduction of the host protein annexin A2 compromises the replication of

Not all that rashes is measles:

International Nuclear Information System (INIS)

Ibrahim, S. A.; Mustafa, O. A.

1998-01-01

Measles is a major cause of infant mortality in third world countries, leading to approximately one million deaths each year. The WHO aims to globally eradicate measles virus at the beginning of the next century, which will need a major effort in particular in countries like Sudan. To achieve goal epidemiological studies I am needed to estimate the magnitude of the problem for which accurate diagnostic test are needed. We therefore conducted a study in El hag Yousif area (population 500 000) in Khartoum North where measles is prevalent despite vaccination effort by EPI. We studied the accuracy of the WHO criteria for clinical diagnosis in comparison with laboratory diagnosis during a one-year period. A total of 145 under five suspected measles cases were identified by active, case finding and examined. 111 cases fully complied with the WHO criteria for diagnosis of clinical measles. Out of 103 clinical measles cases, tested using prototype rapid measles test IgM Elisa and Pcr, 77(75%) were measles positive. A battery of virus test was run on 21 sera out of the 26(25%) measles negatives: Herpes virus-6, Epstein-Bar and Dengue viruses were detected in five, one and one case, respectively. It was concluded that one out of every four cases diagnosed by the clinical as measles rash is probably caused by other viruses. (Author)

Wild type measles virus attenuation independent of type I IFN

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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.

Antagonism of the Phosphatase PP1 by the Measles Virus V Protein Is Required for Innate Immune Escape of MDA5

NARCIS (Netherlands)

Davis, Meredith E.; Wang, May K.; Rennick, Linda J.; Full, Florian; Gableske, Sebastian; Mesman, Annelies W.; Gringhuis, Sonja I.; Geijtenbeek, Teunis B. H.; Duprex, W. Paul; Gack, Michaela U.

2014-01-01

The cytosolic sensor MDA5 is crucial for antiviral innate immune defense against various RNA viruses including measles virus; as such, many viruses have evolved strategies to antagonize the antiviral activity of MDA5. Here, we show that measles virus escapes MDA5 detection by targeting the

Naturally processed measles virus peptide eluted from class II HLA-DRB1*03 recognized by T lymphocytes from human blood

International Nuclear Information System (INIS)

Ovsyannikova, Inna G.; Johnson, Kenneth L.; Naylor, Stephen; Muddiman, David C.; Poland, Gregory A.

2003-01-01

This is the first report of the direct identification of a HLA-DRB1*03 measles-derived peptide from measles virus infected EBV-transformed B cells. We purified HLA-DR3-peptide complexes from EBV-B cells infected with measles virus (Edmonston strain) and sequenced the HLA-DR3-peptides by mass spectrometry. A class II peptide, derived from a measles phosphoprotein, ASDVETAEGGEIHELLRLQ (P1, residues 179-197), exhibited the capacity to stimulate peripheral blood mononuclear cells to proliferate. Our data provides direct evidence that the antigenic peptide of measles virus was processed by antigen-presenting cells, presented in the context of HLA class II molecules, and was recognized by peripheral blood T cells from healthy individuals previously immunized with measles vaccine. The approach described herein provides a useful methodology for the future identification of HLA-presented pathogen-derived epitopes using mass spectrometry. The study of cell-mediated immune responses to the measles-derived peptide in immune persons should provide significant insight into the design and development of new vaccines

Spread of Measles Virus D4-Hamburg, Europe, 2008–2011

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Mihneva, Zefira; Gold, Hermann; Baumgarte, Sigrid; Baillot, Armin; Helble, Rudolph; Roggendorf, Hedwig; Bosevska, Golubinka; Nedeljkovic, Jasminka; Makowka, Agata; Hutse, Veronik; Holzmann, Heidemarie; Aberle, Stefan W.; Cordey, Samuel; Necula, Gheorghe; Mentis, Andreas; Korukluoğlu, Gulay; Carr, Michael; Brown, Kevin E.; Hübschen, Judith M.; Muller, Claude P.; Mulders, Mick N.; Santibanez, Sabine

2011-01-01

A new strain of measles virus, D4-Hamburg, was imported from London to Hamburg in December 2008 and subsequently spread to Bulgaria, where an outbreak of >24,300 cases was observed. We analyzed spread of the virus to demonstrate the importance of addressing hard-to-reach communities within the World Health Organization European Region regarding access to medical care and vaccination campaigns. The D4-Hamburg strain appeared during 2009–2011 in Poland, Ireland, Northern Ireland, Austria, Greece, Romania, Turkey, Macedonia, Serbia, Switzerland, and Belgium and was repeatedly reimported to Germany. The strain was present in Europe for >27 months and led to >25,000 cases in 12 countries. Spread of the virus was prevalently but not exclusively associated with travel by persons in the Roma ethnic group; because this travel extends beyond the borders of any European country, measures to prevent the spread of measles should be implemented by the region as a whole. PMID:21801615

Solution structure of the C-terminal X domain of the measles virus phosphoprotein and interaction with the intrinsically disordered C-terminal domain of the nucleoprotein.

Science.gov (United States)

Gely, Stéphane; Lowry, David F; Bernard, Cédric; Jensen, Malene R; Blackledge, Martin; Costanzo, Stéphanie; Bourhis, Jean-Marie; Darbon, Hervé; Daughdrill, Gary; Longhi, Sonia

2010-01-01

In this report, the solution structure of the nucleocapsid-binding domain of the measles virus phosphoprotein (XD, aa 459-507) is described. A dynamic description of the interaction between XD and the disordered C-terminal domain of the nucleocapsid protein, (N(TAIL), aa 401-525), is also presented. XD is an all alpha protein consisting of a three-helix bundle with an up-down-up arrangement of the helices. The solution structure of XD is very similar to the crystal structures of both the free and bound form of XD. One exception is the presence of a highly dynamic loop encompassing XD residues 489-491, which is involved in the embedding of the alpha-helical XD-binding region of N(TAIL). Secondary chemical shift values for full-length N(TAIL) were used to define the precise boundaries of a transient helical segment that coincides with the XD-binding domain, thus shedding light on the pre-recognition state of N(TAIL). Titration experiments with unlabeled XD showed that the transient alpha-helical conformation of N(TAIL) is stabilized upon binding. Lineshape analysis of NMR resonances revealed that residues 483-506 of N(TAIL) are in intermediate exchange with XD, while the 475-482 and 507-525 regions are in fast exchange. The N(TAIL) resonance behavior in the titration experiments is consistent with a complex binding model with more than two states.

Charge neutralization as the major factor for the assembly of nucleocapsid-like particles from C-terminal truncated hepatitis C virus core protein

OpenAIRE

Theo Luiz Ferraz de Souza; Sheila Maria Barbosa de Lima; Vanessa L. de Azevedo Braga; David S. Peabody; Davis Fernandes Ferreira; M. Lucia Bianconi; Andre Marco de Oliveira Gomes; Jerson Lima Silva; Andréa Cheble de Oliveira

2016-01-01

Background Hepatitis C virus (HCV) core protein, in addition to its structural role to form the nucleocapsid assembly, plays a critical role in HCV pathogenesis by interfering in several cellular processes, including microRNA and mRNA homeostasis. The C-terminal truncated HCV core protein (C124) is intrinsically unstructured in solution and is able to interact with unspecific nucleic acids, in the micromolar range, and to assemble into nucleocapsid-like particles (NLPs) in vitro. The specific...

Vaccination against measles: a neverending story.

NARCIS (Netherlands)

K.J. Stittelaar (Koert); R.L. de Swart (Rik); A.D.M.E. Osterhaus (Albert)

2002-01-01

textabstractMeasles, a highly contagious viral disease, is a major childhood killer in developing countries, accounting for almost 1 million deaths every year globally. Measles virus normally does not cause a persistent infection, no animal reservoir for measles virus exists, no vector is involved

Rescue of Infectious Particles from Preassembled Alphavirus Nucleocapsid Cores▿†

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Snyder, Jonathan E.; Azizgolshani, Odisse; Wu, Bingbing; He, Yingpei; Lee, Aih Cheun; Jose, Joyce; Suter, Daniel M.; Knobler, Charles M.; Gelbart, William M.; Kuhn, Richard J.

2011-01-01

Alphaviruses are small, spherical, enveloped, positive-sense, single-stranded, RNA viruses responsible for considerable human and animal disease. Using microinjection of preassembled cores as a tool, a system has been established to study the assembly and budding process of Sindbis virus, the type member of the alphaviruses. We demonstrate the release of infectious virus-like particles from cells expressing Sindbis virus envelope glycoproteins following microinjection of Sindbis virus nucleocapsids purified from the cytoplasm of infected cells. Furthermore, it is shown that nucleocapsids assembled in vitro mimic those isolated in the cytoplasm of infected cells with respect to their ability to be incorporated into enveloped virions following microinjection. This system allows for the study of the alphavirus budding process independent of an authentic infection and provides a platform to study viral and host requirements for budding. PMID:21471237

Viral Oncolysis — Can Insights from Measles Be Transferred to Canine Distemper Virus?

Directory of Open Access Journals (Sweden)

Stefanie Lapp

2014-06-01

Full Text Available Neoplastic diseases represent one of the most common causes of death among humans and animals. Currently available and applied therapeutic options often remain insufficient and unsatisfactory, therefore new and innovative strategies and approaches are highly needed. Periodically, oncolytic viruses have been in the center of interest since the first anecdotal description of their potential usefulness as an anti-tumor treatment concept. Though first reports referred to an incidental measles virus infection causing tumor regression in a patient suffering from lymphoma several decades ago, no final treatment concept has been developed since then. However, numerous viruses, such as herpes-, adeno- and paramyxoviruses, have been investigated, characterized, and modified with the aim to generate a new anti-cancer treatment option. Among the different viruses, measles virus still represents a highly interesting candidate for such an approach. Numerous different tumors of humans including malignant lymphoma, lung and colorectal adenocarcinoma, mesothelioma, and ovarian cancer, have been studied in vitro and in vivo as potential targets. Moreover, several concepts using different virus preparations are now in clinical trials in humans and may proceed to a new treatment option. Surprisingly, only few studies have investigated viral oncolysis in veterinary medicine. The close relationship between measles virus (MV and canine distemper virus (CDV, both are morbilliviruses, and the fact that numerous tumors in dogs exhibit similarities to their human counterpart, indicates that both the virus and species dog represent a highly interesting translational model for future research in viral oncolysis. Several recent studies support such an assumption. It is therefore the aim of the present communication to outline the mechanisms of morbillivirus-mediated oncolysis and to stimulate further research in this potentially expanding field of viral oncolysis in a highly

Viral Oncolysis — Can Insights from Measles Be Transferred to Canine Distemper Virus?

Science.gov (United States)

Lapp, Stefanie; Pfankuche, Vanessa M.; Baumgärtner, Wolfgang; Puff, Christina

2014-01-01

Neoplastic diseases represent one of the most common causes of death among humans and animals. Currently available and applied therapeutic options often remain insufficient and unsatisfactory, therefore new and innovative strategies and approaches are highly needed. Periodically, oncolytic viruses have been in the center of interest since the first anecdotal description of their potential usefulness as an anti-tumor treatment concept. Though first reports referred to an incidental measles virus infection causing tumor regression in a patient suffering from lymphoma several decades ago, no final treatment concept has been developed since then. However, numerous viruses, such as herpes-, adeno- and paramyxoviruses, have been investigated, characterized, and modified with the aim to generate a new anti-cancer treatment option. Among the different viruses, measles virus still represents a highly interesting candidate for such an approach. Numerous different tumors of humans including malignant lymphoma, lung and colorectal adenocarcinoma, mesothelioma, and ovarian cancer, have been studied in vitro and in vivo as potential targets. Moreover, several concepts using different virus preparations are now in clinical trials in humans and may proceed to a new treatment option. Surprisingly, only few studies have investigated viral oncolysis in veterinary medicine. The close relationship between measles virus (MV) and canine distemper virus (CDV), both are morbilliviruses, and the fact that numerous tumors in dogs exhibit similarities to their human counterpart, indicates that both the virus and species dog represent a highly interesting translational model for future research in viral oncolysis. Several recent studies support such an assumption. It is therefore the aim of the present communication to outline the mechanisms of morbillivirus-mediated oncolysis and to stimulate further research in this potentially expanding field of viral oncolysis in a highly suitable

Epidemiology of two large measles virus outbreaks in Catalonia

Science.gov (United States)

Torner, Núria; Anton, Andres; Barrabeig, Irene; Lafuente, Sara; Parron, Ignasi; Arias, César; Camps, Neus; Costa, Josep; Martínez, Ana; Torra, Roser; Godoy, Pere; Minguell, Sofia; Ferrús, Glòria; Cabezas, Carmen; Domínguez, Ángela; Elimination Program Surveillance Network of Spain, the Measles

2013-01-01

Measles cases in the European Region have been increasing in the last decade; this illustrates the challenge of what we are now encountering in the form of pediatric preventable diseases. In Catalonia, autochthonous measles was declared eliminated in the year 2000 as the result of high measles-mumps-rubella vaccine (MMR) coverage for first and second dose (15 mo and 4 y) since the mid-1990s. From then on, sporadic imported cases and small outbreaks appeared, until in 2006–2007 a large measles outbreak affecting mostly unvaccinated toddlers hit the Barcelona Health Region. Consequently, in January 2008, first dose administration of MMR was lowered from 15 to 12 mo of age. A new honeymoon period went by until the end of 2010, when several importations of cases triggered new sustained transmission of different wild measles virus genotypes, but this time striking young adults. The aim of this study is to show the effect of a change in MMR vaccination schedule policy, and the difference in age incidence and hospitalization rates of affected individuals between both outbreaks. Epidemiologic data were obtained by case interviews and review of medical records. Samples for virological confirmation and genotyping of cases were collected as established in the Measles Elimination plan guidelines. Incidence rate (IR), rate ratio (RR) and their 95% CI and hospitalization rate (HR) by age group were determined. Statistic z was used for comparing proportions. Total number of confirmed cases was 305 in the 2010 outbreak and 381 in the 2006–2007 outbreak; mean age 20 y (SD 14.8 y; 3 mo to 51 y) vs. 15 mo (SD 13.1 y; 1 mo to 50 y). Highest proportion of cases was set in ≥ 25 y (47%) vs. 24.2% in 2006 (p < 0.001). Differences in IR for ≤ 15 mo (49/100,000 vs. 278.2/100,000; RR: 3,9; 95%CI 2,9–5.4) and in overall HR 29.8% vs. 15.7% were all statistically significant (p < 0.001). The change of the month of age for the administration of the first MMR dose proved successful to

Vaccination against acute respiratory virus infections and measles in man.

NARCIS (Netherlands)

A.D.M.E. Osterhaus (Albert); P. de Vries (Petra)

1992-01-01

textabstractSeveral viruses may cause more or less severe acute respiratory infections in man, some of which are followed by systemic infection. Only for influenza and measles are licensed vaccines available at present. The protection induced by influenza vaccines, which are based on inactivated

Structural and mechanistic studies of measles virus illuminate paramyxovirus entry.

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Richard K Plemper

2011-06-01

Full Text Available Measles virus (MeV, a member of the paramyxovirus family of enveloped RNA viruses and one of the most infectious viral pathogens identified, accounts for major pediatric morbidity and mortality worldwide although coordinated efforts to achieve global measles control are in place. Target cell entry is mediated by two viral envelope glycoproteins, the attachment (H and fusion (F proteins, which form a complex that achieves merger of the envelope with target cell membranes. Despite continually expanding knowledge of the entry strategies employed by enveloped viruses, our molecular insight into the organization of functional paramyxovirus fusion complexes and the mechanisms by which the receptor binding by the attachment protein triggers the required conformational rearrangements of the fusion protein remain incomplete. Recently reported crystal structures of the MeV attachment protein in complex with its cellular receptors CD46 or SLAM and newly developed functional assays have now illuminated some of the fundamental principles that govern cell entry by this archetype member of the paramyxovirus family. Here, we review these advances in our molecular understanding of MeV entry in the context of diverse entry strategies employed by other members of the paramyxovirus family.

Engineered measles virus Edmonston strain used as a novel oncolytic viral system against human hepatoblastoma

International Nuclear Information System (INIS)

Zhang, Shu-Cheng; Wang, Wei-Lin; Cai, Wei-Song; Jiang, Kai-Lei; Yuan, Zheng-Wei

2012-01-01

Hepatoblastoma (HB) is the most common primary, malignant pediatric liver tumor in children. The treatment results for affected children have markedly improved in recent decades. However, the prognosis for high-risk patients who have extrahepatic extensions, invasion of the large hepatic veins, distant metastases and very high alpha-fetoprotein (AFP) serum levels remains poor. There is an urgent need for the development of novel therapeutic approaches. An attenuated strain of measles virus, derived from the Edmonston vaccine lineage, was genetically engineered to produce carcinoembryonic antigen (CEA). We investigated the antitumor potential of this novel viral agent against human HB both in vitro and in vivo. Infection of the Hep2G and HUH6 HB cell lines, at multiplicities of infection (MOIs) ranging from 0.01 to 1, resulted in a significant cytopathic effect consisting of extensive syncytia formation and massive cell death at 72–96 h after infection. Both of the HB lines overexpressed the measles virus receptor CD46 and supported robust viral replication, which correlated with CEA production. The efficacy of this approach in vivo was examined in murine Hep2G xenograft models. Flow cytometry assays indicated an apoptotic mechanism of cell death. Intratumoral administration of MV-CEA resulted in statistically significant delay of tumor growth and prolongation of survival. The engineered measles virus Edmonston strain MV-CEA has potent therapeutic efficacy against HB cell lines and xenografts. Trackable measles virus derivatives merit further exploration in HB treatment

Porcine Epidemic Diarrhea Virus 3C-Like Protease-Mediated Nucleocapsid Processing: Possible Link to Viral Cell Culture Adaptability.

Science.gov (United States)

Jaru-Ampornpan, Peera; Jengarn, Juggragarn; Wanitchang, Asawin; Jongkaewwattana, Anan

2017-01-15

Porcine epidemic diarrhea virus (PEDV) causes severe diarrhea and high mortality rates in newborn piglets, leading to massive losses to the swine industry worldwide during recent epidemics. Intense research efforts are now focusing on defining viral characteristics that confer a growth advantage, pathogenicity, or cell adaptability in order to better understand the PEDV life cycle and identify suitable targets for antiviral or vaccine development. Here, we report a unique phenomenon of PEDV nucleocapsid (N) cleavage by the PEDV-encoded 3C-like protease (3Cpro) during infection. The identification of the 3Cpro cleavage site at the C terminus of N supported previous observations that PEDV 3Cpro showed a substrate requirement slightly different from that of severe acute respiratory syndrome coronavirus (SARS-CoV) 3Cpro and revealed a greater flexibility in its substrate recognition site. This cleavage motif is present in the majority of cell culture-adapted PEDV strains but is missing in emerging field isolates. Remarkably, reverse-genetics-derived cell culture-adapted PEDV AVCT12 harboring uncleavable N displayed growth retardation in Vero E6-APN cells compared to the wild-type virus. These observations altogether shed new light on the investigation and characterization of the PEDV nucleocapsid protein and its possible link to cell culture adaptation. Recurrent PEDV outbreaks have resulted in enormous economic losses to swine industries worldwide. To gain the upper hand in combating this disease, it is necessary to understand how this virus replicates and evades host immunity. Characterization of viral proteins provides important clues to mechanisms by which viruses survive and spread. Here, we characterized an intriguing phenomenon in which the nucleocapsids of some PEDV strains are proteolytically processed by the virally encoded main protease. Growth retardation in recombinant PEDV carrying uncleavable N suggests a replication advantage provided by the cleavage

Advances in the design and development of oncolytic measles viruses

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Hutzen B

2015-08-01

Full Text Available Brian Hutzen,1 Corey Raffel,2 Adam W Studebaker1 1Center for Childhood Cancer and Blood Diseases, The Research Institute at Nationwide Children’s Hospital, Columbus, OH, USA; 2Department of Neurological Surgery and Pediatrics, University of California, San Francisco, San Francisco, CA, USA Abstract: A successful oncolytic virus is one that selectively propagates and destroys cancerous tissue without causing excessive damage to the normal surrounding tissue. Oncolytic measles virus (MV is one such virus that exhibits this characteristic and thus has rapidly emerged as a potentially useful anticancer modality. Derivatives of the Edmonston MV vaccine strain possess a remarkable safety record in humans. Promising results in preclinical animal models and evidence of biological activity in early phase trials contribute to the enthusiasm. Genetic modifications have enabled MV to evolve from a vaccine agent to a potential anticancer therapy. Specifically, alterations of the MV genome have led to improved tumor selectivity and delivery, therapeutic potency, and immune system modulation. In this article, we will review the advancements that have been made in the design and development of MV that have led to its use as a cancer therapy. In addition, we will discuss the evidence supporting its use, as well as the challenges associated with MV as a potential cancer therapeutic. Keywords: virotherapy, measles virus, oncolytic therapy

Measles vaccination of nonhuman primates provides partial protection against infection with canine distemper virus

NARCIS (Netherlands)

R.D. de Vries (Rory); M. Ludlow (Martin); R.J. Verbugh (Joyce); G. van Amerongen (Geert); S. Yüksel (Selma); D.T. Nguyen (Tien); S. McQuaid (Stephen); A.D.M.E. Osterhaus (Albert); W.P. Duprex (Paul); R.L. de Swart (Rik)

2014-01-01

textabstractMeasles virus (MV) is being considered for global eradication, which would likely reduce compliance with MV vaccination. As a result, children will grow up without MV-specific immunity, creating a potential niche for closely related animal morbilliviruses such as canine distemper virus

Upon Infection the Cellular WD Repeat-containing Protein 5 (WDR5) Localizes to Cytoplasmic Inclusion Bodies and Enhances Measles Virus Replication.

Science.gov (United States)

Ma, Dzwokai; George, Cyril X; Nomburg, Jason; Pfaller, Christian K; Cattaneo, Roberto; Samuel, Charles E

2017-12-13

Replication of negative-strand RNA viruses occurs in association with discrete cytoplasmic foci called inclusion bodies. Whereas inclusion bodies represent a prominent subcellular structure induced by viral infection, our knowledge of the cellular protein components involved in inclusion body formation and function is limited. Using measles virus-infected HeLa cells, we found that the WD repeat-containing protein 5 (WDR5), a subunit of histone H3 lysine 4 methyltransferases, was selectively recruited to virus-induced inclusion bodies. Furthermore, WDR5 was found in complexes containing viral proteins associated with RNA replication. WDR5 was not detected with mitochondria, stress granules, or other known secretory or endocytic compartments of infected cells. WDR5 deficiency decreased both viral protein production and infectious virus yields. Interferon production was modestly increased in WDR5 deficient cells. Thus, our study identifies WDR5 as a novel viral inclusion body-associated cellular protein and suggests a role for WDR5 in promoting viral replication. IMPORTANCE Measles virus is a human pathogen that remains a global concern with more than 100,000 measles-related deaths annually despite the availability of an effective vaccine. As measles continues to cause significant morbidity and mortality, understanding the virus-host interactions at the molecular level that affect virus replication efficiency is important for development and optimization of treatment procedures. Measles virus is an RNA virus that encodes six genes and replicates in the cytoplasm of infected cells in discrete cytoplasmic replication bodies, though little is known of the biochemical nature of these structures. Here we show that the cellular protein WDR5 is enriched in the cytoplasmic viral replication factories and enhances virus growth. WDR5-containing protein complex includes viral proteins responsible for viral RNA replication. Thus, we have identified WDR5 as a host factor that

A model for the dynamic nuclear/nucleolar/cytoplasmic trafficking of the porcine reproductive and respiratory syndrome virus (PRRSV) nucleocapsid protein based on live cell imaging

International Nuclear Information System (INIS)

You, Jae-Hwan; Howell, Gareth; Pattnaik, Asit K.; Osorio, Fernando A.; Hiscox, Julian A.

2008-01-01

Porcine reproductive and respiratory syndrome virus (PRRSV), an arterivirus, in common with many other positive strand RNA viruses, encodes a nucleocapsid (N) protein which can localise not only to the cytoplasm but also to the nucleolus in virus-infected cells and cells over-expressing N protein. The dynamic trafficking of positive strand RNA virus nucleocapsid proteins and PRRSV N protein in particular between the cytoplasm and nucleolus is unknown. In this study live imaging of permissive and non-permissive cell lines, in conjunction with photo-bleaching (FRAP and FLIP), was used to investigate the trafficking of fluorescent labeled (EGFP) PRRSV-N protein. The data indicated that EGFP-PRRSV-N protein was not permanently sequestered to the nucleolus and had equivalent mobility to cellular nucleolar proteins. Further the nuclear import of N protein appeared to occur faster than nuclear export, which may account for the observed relative distribution of N protein between the cytoplasm and the nucleolus

Measles & rubella outbreaks in Maharashtra State, India

Science.gov (United States)

Vaidya, Sunil R.; Kamble, Madhukar B.; Chowdhury, Deepika T.; Kumbhar, Neelakshi S.

2016-01-01

Background & objectives: Under the outbreak-based measles surveillance in Maharashtra State the National Institute of Virology at Pune receives 3-5 serum samples from each outbreak and samples from the local hospitals in Pune for laboratory diagnosis. This report describes one year data on the measles and rubella serology, virus isolation and genotyping. Methods: Maharashtra State Health Agencies investigated 98 suspected outbreaks between January-December 2013 in the 20 districts. Altogether, 491 serum samples were received from 20 districts and 126 suspected cases from local hospitals. Samples were tested for the measles and rubella IgM antibodies by commercial enzyme immunoassay (EIA). To understand the diagnostic utility, a subset of serum samples (n=53) was tested by measles focus reduction neutralization test (FRNT). Further, 37 throat swabs and 32 urine specimens were tested by measles reverse transcription (RT)-PCR and positive products were sequenced. Virus isolation was performed in Vero hSLAM cells. Results: Of the 98 suspected measles outbreaks, 61 were confirmed as measles, 12 as rubella and 21 confirmed as the mixed outbreaks. Four outbreaks remained unconfirmed. Of the 126 cases from the local hospitals, 91 were confirmed for measles and three for rubella. Overall, 93.6 per cent (383/409) confirmed measles cases were in the age group of 0-15 yr. Measles virus was detected in 18 of 38 specimens obtained from the suspected cases. Sequencing of PCR products revealed circulation of D4 (n=9) and D8 (n=9) strains. Four measles viruses (three D4 & one D8) were isolated. Interpretation & conclusions: Altogether, 94 measles and rubella outbreaks were confirmed in 2013 in the State of Maharasthra indicating the necessity to increase measles vaccine coverage in the State. PMID:27121521

A chimeric measles virus with a lentiviral envelope replicates exclusively in CD4+/CCR5+ cells

International Nuclear Information System (INIS)

Mourez, Thomas; Mesel-Lemoine, Mariana; Combredet, Chantal; Najburg, Valerie; Cayet, Nadege; Tangy, Frederic

2011-01-01

We generated a replicating chimeric measles virus in which the hemagglutinin and fusion surface glycoproteins were replaced with the gp160 envelope glycoprotein of simian immunodeficiency virus (SIVmac239). Based on a previously cloned live-attenuated Schwarz vaccine strain of measles virus (MV), this chimera was rescued at high titers using reverse genetics in CD4+ target cells. Cytopathic effect consisted in the presence of large cell aggregates evolving to form syncytia, as observed during SIV infection. The morphology of the chimeric virus was identical to that of the parent MV particles. The presence of SIV gp160 as the only envelope protein on chimeric particles surface altered the cell tropism of the new virus from CD46+ to CD4+ cells. Used as an HIV candidate vaccine, this MV/SIVenv chimeric virus would mimic transient HIV-like infection, benefiting both from HIV-like tropism and the capacity of MV to replicate in dendritic cells, macrophages and lymphocytes.

The recombinant globular head domain of the measles virus hemagglutinin protein as a subunit vaccine against measles.

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Lobanova, Liubov M; Eng, Nelson F; Satkunarajah, Malathy; Mutwiri, George K; Rini, James M; Zakhartchouk, Alexander N

2012-04-26

Despite the availability of live attenuated measles virus (MV) vaccines, a large number of measles-associated deaths occur among infants in developing countries. The development of a measles subunit vaccine may circumvent the limitations associated with the current live attenuated vaccines and eventually contribute to global measles eradication. Therefore, the goal of this study was to test the feasibility of producing the recombinant globular head domain of the MV hemagglutinin (H) protein by stably transfected human cells and to examine the ability of this recombinant protein to elicit MV-specific immune responses. The recombinant protein was purified from the culture supernatant of stably transfected HEK293T cells secreting a tagged version of the protein. Two subcutaneous immunizations with the purified recombinant protein alone resulted in the production of MV-specific serum IgG and neutralizing antibodies in mice. Formulation of the protein with adjuvants (polyphosphazene or alum) further enhanced the humoral immune response and in addition resulted in the induction of cell-mediated immunity as measured by the production of MV H-specific interferon gamma (IFN-γ) and interleukin 5 (IL-5) by in vitro re-stimulated splenocytes. Furthermore, the inclusion of polyphosphazene into the vaccine formulation induced a mixed Th1/Th2-type immune response. In addition, the purified recombinant protein retained its immunogenicity even after storage at 37°C for 2 weeks. Copyright © 2012 Elsevier Ltd. All rights reserved.

Morbillivirus Experimental Animal Models: Measles Virus Pathogenesis Insights from Canine Distemper Virus.

Science.gov (United States)

da Fontoura Budaszewski, Renata; von Messling, Veronika

2016-10-11

Morbilliviruses share considerable structural and functional similarities. Even though disease severity varies among the respective host species, the underlying pathogenesis and the clinical signs are comparable. Thus, insights gained with one morbillivirus often apply to the other members of the genus. Since the Canine distemper virus (CDV) causes severe and often lethal disease in dogs and ferrets, it is an attractive model to characterize morbillivirus pathogenesis mechanisms and to evaluate the efficacy of new prophylactic and therapeutic approaches. This review compares the cellular tropism, pathogenesis, mechanisms of persistence and immunosuppression of the Measles virus (MeV) and CDV. It then summarizes the contributions made by studies on the CDV in dogs and ferrets to our understanding of MeV pathogenesis and to vaccine and drugs development.

Virions and intracellular nucleocapsids produced during mixed heterotypic influenza infection of MDCK cells

International Nuclear Information System (INIS)

Sklyanskaya, E.I.; Varich, N.L.; Amvrosieva, T.V.; Kaverin, N.V.

1985-01-01

Phenotypically mixed virus yields, obtained by coinfection of MDCK cells with influenza A/WSN/33 and B/Lee/40 viruses, contained both A/WSN/33 and B/Lee/40 NP proteins, as revealed by polyacrylamide gel electrophoresis of the purified 14 C-amino acids-labeled virus. Virions were lysed with 0.6 M KCl-Triton X-100 buffer, and nucleocapsids were immunoprecipitated with antibodies against NP protein of influenza A virus. Polyacrylamide gel electrophoresis of the immunoprecipitate revealed NP protein of A/WSN/33 but not of B/Lee/40 virus. However, in similar experiments with the lysates of doubly infected cells, the band of B/Lee/40 NP protein was revealed in the polyacrylamide gel electrophoresis patterns of the immunoprecipitates. In an attempt to analyze the RNA content of the immune complexes, the authors absorbed the lysates of doubly infected [ 3 H]uridine-labeled cells with protein A-containing Staphylococcus aureus covered with antibodies against the NP protein of influenza A virus. RNA extracted from the immune complexes contained genomic RNA segments of both A/WSN/33 and B/Lee/40 viruses. In control samples containing an artificial mixture of cell lysates separately infected with each virus, the analysis revealed homologous components (i.e., A/WSN/33 NP protein or RNA segments) in the immune complexes. The results suggest the presence of phenotypically mixed nucleocapsids in the cells doubly infected with influenza A and B viruses; in the course of the virion formation, the nucleocapsids lacking the heterologous NP protein are selected

Genetic Characterization of the Hemagglutinin Genes of Wild-Type Measles Virus Circulating in China, 1993–2009

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Zhu, Zhen; Liu, Chunyu; Mao, Naiying; Ji, Yixin; Wang, Huiling; Jiang, Xiaohong; Li, Chongshan; Tang, Wei; Feng, Daxing; Wang, Changyin; Zheng, Lei; Lei, Yue; Ling, Hua; Zhao, Chunfang; Ma, Yan; He, Jilan; Wang, Yan; Li, Ping; Guan, Ronghui; Zhou, Shujie; Zhou, Jianhui; Wang, Shuang; Zhang, Hong; Zheng, Huanying; Liu, Leng; Ma, Hemuti; Guan, Jing; Lu, Peishan; Feng, Yan; Zhang, Yanjun; Zhou, Shunde; Xiong, Ying; Ba, Zhuoma; Chen, Hui; Yang, Xiuhui; Bo, Fang; Ma, Yujie; Liang, Yong; Lei, Yake; Gu, Suyi; Liu, Wei; Chen, Meng; Featherstone, David; Jee, Youngmee; Bellini, William J.; Rota, Paul A.; Xu, Wenbo

2013-01-01

Background China experienced several large measles outbreaks in the past two decades, and a series of enhanced control measures were implemented to achieve the goal of measles elimination. Molecular epidemiologic surveillance of wild-type measles viruses (MeV) provides valuable information about the viral transmission patterns. Since 1993, virologic surveillnace has confirmed that a single endemic genotype H1 viruses have been predominantly circulating in China. A component of molecular surveillance is to monitor the genetic characteristics of the hemagglutinin (H) gene of MeV, the major target for virus neutralizing antibodies. Principal Findings Analysis of the sequences of the complete H gene from 56 representative wild-type MeV strains circulating in China during 1993–2009 showed that the H gene sequences were clustered into 2 groups, cluster 1 and cluster 2. Cluster1 strains were the most frequently detected cluster and had a widespread distribution in China after 2000. The predicted amino acid sequences of the H protein were relatively conserved at most of the functionally significant amino acid positions. However, most of the genotype H1 cluster1 viruses had an amino acid substitution (Ser240Asn), which removed a predicted N-linked glycosylation site. In addition, the substitution of Pro397Leu in the hemagglutinin noose epitope (HNE) was identified in 23 of 56 strains. The evolutionary rate of the H gene of the genotype H1 viruses was estimated to be approximately 0.76×10−3 substitutions per site per year, and the ratio of dN to dS (dN/dS) was measles in China. PMID:24073194

A putative non-hr origin of DNA replication in the HindIII-K fragment of Autographa californica multiple nucleocapsid nuclear polyhedrosis virus

NARCIS (Netherlands)

Kool, M.; Goldbach, R. W.; Vlak, J. M.

1994-01-01

In addition to the seven known homologous regions (hrs) of Autographa californica multiple nucleocapsid polyhedrosis virus (AcMNPV) the HindIII-K fragment was also found to carry a putative ori, although this fragment does not contain an hr. Deletion analysis showed that this ori contains several

Identification of Rift Valley Fever Virus Nucleocapsid Protein-RNA Binding Inhibitors Using a High-Throughput Screening Assay

OpenAIRE

Ellenbecker, Mary; Lanchy, Jean-Marc; Lodmell, J. Stephen

2012-01-01

Rift Valley fever virus (RVFV) is an emerging infectious pathogen that causes severe disease in humans and livestock and has the potential for global spread. Currently, there is no proven effective treatment for RVFV infection and there is no licensed vaccine. Inhibition of RNA binding to the essential viral nucleocapsid (N) protein represents a potential anti-viral therapeutic strategy because all of the functions performed by N during infection involve RNA binding. To target this interactio...

The pathogenesis of measles

NARCIS (Netherlands)

de Vries, Rory D.; Mesman, Annelies W.; Geijtenbeek, Teunis B. H.; Duprex, W. Paul; de Swart, Rik L.

2012-01-01

Measles is an important cause of childhood morbidity and mortality in developing countries. Measles virus (MV) is transmitted via the respiratory route and causes systemic disease. Over the last decade, identification of new cellular receptors and studies in animal models have challenged the

Construction of a recombinant viral vector containing part of the nucleocapsid protein gene of newcastle disease virus

Energy Technology Data Exchange (ETDEWEB)

Bader, D.E.

1995-09-01

This report describes the procedures used to clone a 673 base pair gene fragment of the major nucleocapsid protein gene of Newcastle disease virus into a viral vector molecule for the purpose of maintaining a stable, long-term, renewable source of this target sequence for gene probe studies. The gene fragment was prepared by reverse-transcription polymerase chain reaction of Newcastle disease virus RNA and was cloned into the viral DNA vector Ml3mp18 RF to produce a recombinant DNA molecule. The cloned fragment was shown to be present in the recombinant clones based on (i) clonal selection on indicator plates; (ii) restriction enzyme analysis; (iii) gene probe analysis and (iv) nested PCR amplification.

A novel, polymer-coated oncolytic measles virus overcomes immune suppression and induces robust antitumor activity

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Kaname Nosaki

2016-01-01

Full Text Available Although various therapies are available to treat cancers, including surgery, chemotherapy, and radiotherapy, cancer has been the leading cause of death in Japan for the last 30 years, and new therapeutic modalities are urgently needed. As a new modality, there has recently been great interest in oncolytic virotherapy, with measles virus being a candidate virus expected to show strong antitumor effects. The efficacy of virotherapy, however, was strongly limited by the host immune response in previous clinical trials. To enhance and prolong the antitumor activity of virotherapy, we combined the use of two newly developed tools: the genetically engineered measles virus (MV-NPL and the multilayer virus-coating method of layer-by-layer deposition of ionic polymers. We compared the oncolytic effects of this polymer-coated MV-NPL with the naked MV-NPL, both in vitro and in vivo. In the presence of anti-MV neutralizing antibodies, the polymer-coated virus showed more enhanced oncolytic activity than did the naked MV-NPL in vitro. We also examined antitumor activities in virus-treated mice. Complement-dependent cytotoxicity and antitumor activities were higher in mice treated with polymer-coated MV-NPL than in mice treated with the naked virus. This novel, polymer-coated MV-NPL is promising for clinical cancer therapy in the future.

Proof-of-principle that a decoy virus protects oncolytic measles virus against neutralizing antibodies

OpenAIRE

Xu C; Goß AV; Dorneburg C; Debatin KM; Wei J; Beltinger C

2018-01-01

Chun Xu,1,2,* Annika Verena Goß,1,* Carmen Dorneburg,1 Klaus-Michael Debatin,1 Jiwu Wei,2 Christian Beltinger1 1Department of Pediatrics and Adolescent Medicine, Section of Experimental Pediatric Oncology, University Medical Center Ulm, Ulm, Germany; 2Jiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University, China *These authors contributed equally to this work Background: Attenuated oncolytic measles virus (OMV) is a promising antitumor agent in early-phase cl...

Autographa californica multiple nucleopolyhedrovirus ac75 is required for egress of nucleocapsids from the nucleus and formation of de novo intranuclear membrane microvesicles.

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Ya-Jun Guo

Full Text Available In this study, Autographa californica multiple nucleopolyhedrovirus ac75 was functionally characterized. Ac75 has homologs in all sequenced genomes of alphabaculoviruses, betabaculoviruses, and gammabaculoviruses. It was determined to encode a protein that is associated with the nucleocapsid of budded virus and with both envelope and nucleocapsids of occlusion-derived virus. Sf9 cells transfected by an ac75-knockout bacmid resulted in the infection being restricted to single cells. No budded virus were detected although viral DNA replication and late gene expression were unaffected. Electron microscopy revealed that the virogenic stroma, nucleocapsids and occlusion bodies appeared normal in the cells transfected by an ac75-knockout bacmid. However, the nucleocapsids were unenveloped, the occlusion bodies did not contain any virions or nucleocapsids, and no nucleocapsids were found outside the nucleus or spanning the nuclear membrane. In addition, de novo intranuclear membrane microvesicles that are the precursor of occlusion-derived virus envelopes were absent in the nuclei of transfected cells. Confocal microscopy showed that AC75 protein appeared in the cytoplasm as early as 6 hours post infection. It localized to the ring zone at the periphery of the nucleus from 15 to 24 hours post infection and demonstrated light blocky cloud-like distribution in the center of the nucleus. AC75 was found to co-immunoprecipitate with BV and ODV associated envelope protein ODV-E25. The data from this study suggest that ac75 is essential for induction of the intranuclear membrane microvesicles, it appears to be required for the intranuclear envelopment of nucleocapsids, and is also essential for egress of nucleocapsids from the nuclei, in infected cells.

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

International Nuclear Information System (INIS)

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

2009-01-01

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

Molecular characterization of wild-type measles viruses in Tamil Nadu, India, during 2005-2006: relationship of genotype D8 strains from Tamil Nadu to global strains.

Science.gov (United States)

Duraisamy, Raja; Rota, Paul A; Palani, Gunasekaran; Elango, Varalakshmi; Sambasivam, Mohana; Lowe, Luis; Lopareva, Elena; Ramamurty, Nalini

2012-02-01

Molecular characterization of measles viruses is a valuable tool for measuring the effectiveness of measles control and elimination programmes. WHO recommends that virological surveillance be conducted during all phases of measles control to document circulation of indigenous strains and trace future importation. This report describes the genetic characterization of wild type measles viruses from Tamil Nadu, India isolated between January 2005 and January 2006. In the study, 304 suspected measles cases (292 from 56 outbreaks and 12 sporadic cases) were investigated. Blood samples were collected from suspected measles outbreaks and 11 suspected sporadic cases and tested for the presence of measles and rubella specific IgM. Based on serological results, 53 outbreaks were confirmed as measles, 2 as a combination of measles and rubella, and 1 negative for both. Eight sporadic cases were confirmed as measles and one as rubella. Throat swab and urine samples were collected for virus isolation and 28 isolates were obtained. Sequencing and analysis showed that 3 isolates belonged to genotype D4 and 25 to genotype D8. Comparison of the genotype D8 sequences from Tamil Nadu with previously reported genotype D8 sequences from India and abroad showed six distinct clusters with Tamil Nadu strains forming two clusters. This study has established baseline molecular data and is the first report that describes genetic diversity of circulating measles strains in Tamil Nadu, a state in India. D8 has multiple lineages and this has been linked with importation of measles into the USA and UK. Copyright © 2011 Wiley Periodicals, Inc.

Coronavirus nucleocapsid proteins assemble constitutively in high molecular oligomers

NARCIS (Netherlands)

Cong, Yingying; Kriegenburg, Franziska; de Haan, Cornelis A. M.; Reggiori, Fulvio

2017-01-01

Coronaviruses (CoV) are enveloped viruses and rely on their nucleocapsid N protein to incorporate the positive-stranded genomic RNA into the virions. CoV N proteins form oligomers but the mechanism and relevance underlying their multimerization remain to be fully understood. Using in vitro pull-down

DNA vaccine encoding nucleocapsid and surface proteins of wild type canine distemper virus protects its natural host against distemper.

Science.gov (United States)

Cherpillod, P; Tipold, A; Griot-Wenk, M; Cardozo, C; Schmid, I; Fatzer, R; Schobesberger, M; Zurbriggen, R; Bruckner, L; Roch, F; Vandevelde, M; Wittek, R; Zurbriggen, A

2000-07-01

Canine distemper virus (CDV), a member of the genus Morbillivirus induces a highly infectious, frequently lethal disease in dogs and other carnivores. Current vaccines against canine distemper consisting of attenuated viruses have been in use for many years and have greatly reduced the incidence of distemper in the dog population. However, certain strains may not guarantee adequate protection and others can induce post vaccinal encephalitis. We tested a DNA vaccine for its ability to protect dogs, the natural host of CDV, against distemper. We constructed plasmids containing the nucleocapsid, the fusion, and the attachment protein genes of a virulent canine distemper virus strain. Mice inoculated with these plasmids developed humoral and cellular immune responses against CDV antigens. Dogs immunized with the expression plasmids developed virus-neutralizing antibodies. Significantly, vaccinated dogs were protected against challenge with virulent CDV, whereas unvaccinated animals succumbed to distemper.

In vitro measles virus infection of human lymphocyte subsets demonstrates high susceptibility and permissiveness of both naive and memory B cells

NARCIS (Netherlands)

B.M. Laksono (Brigitta); C. Grosserichter-Wagener (Christina); R.D. de Vries (Rory); Langeveld, S.A.G. (Simone A.G.); M.D. Brem (Maarten); J.J.M. van Dongen (Jacques); Katsikis, P.D. (Peter D.); M.P.G. Koopmans D.V.M. (Marion); M.C. van Zelm (Menno); R.L. de Swart (Rik)

2018-01-01

textabstractMeasles is characterized by a transient immune suppression, leading to an increased risk of opportunistic infections. Measles virus (MV) infection of immune cells is mediated by the cellular receptor CD150, expressed by subsets of lymphocytes, dendritic cells, macrophages, and

Nectin-4 Interactions Govern Measles Virus Virulence in a New Model of Pathogenesis, the Squirrel Monkey (Saimiri sciureus).

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Delpeut, Sébastien; Sawatsky, Bevan; Wong, Xiao-Xiang; Frenzke, Marie; Cattaneo, Roberto; von Messling, Veronika

2017-06-01

In addition to humans, only certain nonhuman primates are naturally susceptible to measles virus (MeV) infection. Disease severity is species dependent, ranging from mild to moderate for macaques to severe and even lethal for certain New World monkey species. To investigate if squirrel monkeys ( Saimiri sciureus ), which are reported to develop a course of disease similar to humans, may be better suited than macaques for the identification of virulence determinants or the evaluation of therapeutics, we infected them with a green fluorescent protein-expressing MeV. Compared to cynomolgus macaques ( Macaca fascicularis ) infected with the same virus, the squirrel monkeys developed more-severe immunosuppression, higher viral load, and a broader range of clinical signs typical for measles. In contrast, infection with an MeV unable to interact with the epithelial receptor nectin-4, while causing immunosuppression, resulted in only a mild and transient rash and a short-lived elevation of the body temperature. Similar titers of the wild-type and nectin-4-blind MeV were detected in peripheral blood mononuclear cells and lymph node homogenates, but only the wild-type virus was found in tracheal lavage fluids and urine. Thus, our study demonstrates the importance of MeV interactions with nectin-4 for clinical disease in the new and better-performing S. sciureus model of measles pathogenesis. IMPORTANCE The characterization of mechanisms underlying measles virus clinical disease has been hampered by the lack of an animal model that reproduces the course of disease seen in human patients. Here, we report that infection of squirrel monkeys ( Saimiri sciureus ) fulfills these requirements. Comparative infection with wild-type and epithelial cell receptor-blind viruses demonstrated the importance of epithelial cell infection for clinical disease, highlighting the spread to epithelia as an attractive target for therapeutic strategies. Copyright © 2017 American Society for

Structure of a Venezuelan equine encephalitis virus assembly intermediate isolated from infected cells

International Nuclear Information System (INIS)

Lamb, Kristen; Lokesh, G.L.; Sherman, Michael; Watowich, Stanley

2010-01-01

Venezuelan equine encephalitis virus (VEEV) is a prototypical enveloped ssRNA virus of the family Togaviridae. To better understand alphavirus assembly, we analyzed newly formed nucleocapsid particles (termed pre-viral nucleocapsids) isolated from infected cells. These particles were intermediates along the virus assembly pathway, and ultimately bind membrane-associated viral glycoproteins to bud as mature infectious virus. Purified pre-viral nucleocapsids were spherical with a unimodal diameter distribution. The structure of one class of pre-viral nucleocapsids was determined with single particle reconstruction of cryo-electron microscopy images. These studies showed that pre-viral nucleocapsids assembled into an icosahedral structure with a capsid stoichiometry similar to the mature nucleocapsid. However, the individual capsomers were organized significantly differently within the pre-viral and mature nucleocapsids. The pre-viral nucleocapsid structure implies that nucleocapsids are highly plastic and undergo glycoprotein and/or lipid-driven rearrangements during virus self-assembly. This mechanism of self-assembly may be general for other enveloped viruses.

Global eradication of measles: Are we poised?

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Raghavendra D Kulkarni

2017-01-01

Full Text Available Measles, a highly infectious viral disease is the next target for eradication following poliovirus. Decades of experience with highly effective vaccination has invigorated us to take on this virus. The task is not only Titanic but is laced with intricate issues. Recently, an outbreak of fever with rash occurred on a tertiary care teaching hospital campus and was confirmed serologically as measles outbreak by IgMELISA. Therefore, we searched the literature related to outbreaks, transmission of the measles virus, age groups involved, vaccination strategies, vaccination failure and epidemiological features of the disease and reviewed the possible reasons for such outbreaks and problems in the global eradication of the virus.

Nucleocapsid Protein from Fig Mosaic Virus Forms Cytoplasmic Agglomerates That Are Hauled by Endoplasmic Reticulum Streaming

Science.gov (United States)

Ishikawa, Kazuya; Miura, Chihiro; Maejima, Kensaku; Komatsu, Ken; Hashimoto, Masayoshi; Tomomitsu, Tatsuya; Fukuoka, Misato; Yusa, Akira; Yamaji, Yasuyuki

2014-01-01

ABSTRACT Although many studies have demonstrated intracellular movement of viral proteins or viral replication complexes, little is known about the mechanisms of their motility. In this study, we analyzed the localization and motility of the nucleocapsid protein (NP) of Fig mosaic virus (FMV), a negative-strand RNA virus belonging to the recently established genus Emaravirus. Electron microscopy of FMV-infected cells using immunogold labeling showed that NPs formed cytoplasmic agglomerates that were predominantly enveloped by the endoplasmic reticulum (ER) membrane, while nonenveloped NP agglomerates also localized along the ER. Likewise, transiently expressed NPs formed agglomerates, designated NP bodies (NBs), in close proximity to the ER, as was the case in FMV-infected cells. Subcellular fractionation and electron microscopic analyses of NP-expressing cells revealed that NBs localized in the cytoplasm. Furthermore, we found that NBs moved rapidly with the streaming of the ER in an actomyosin-dependent manner. Brefeldin A treatment at a high concentration to disturb the ER network configuration induced aberrant accumulation of NBs in the perinuclear region, indicating that the ER network configuration is related to NB localization. Dominant negative inhibition of the class XI myosins, XI-1, XI-2, and XI-K, affected both ER streaming and NB movement in a similar pattern. Taken together, these results showed that NBs localize in the cytoplasm but in close proximity to the ER membrane to form enveloped particles and that this causes passive movements of cytoplasmic NBs by ER streaming. IMPORTANCE Intracellular trafficking is a primary and essential step for the cell-to-cell movement of viruses. To date, many studies have demonstrated the rapid intracellular movement of viral factors but have failed to provide evidence for the mechanism or biological significance of this motility. Here, we observed that agglomerates of nucleocapsid protein (NP) moved rapidly

A transgenic mouse model for measles virus infection of the brain

Science.gov (United States)

Rall, Glenn F.; Manchester, Marianne; Daniels, Lia R.; Callahan, Eric M.; Belman, Alec R.; Oldstone, Michael B. A.

1997-01-01

In addition to the rash, fever, and upper respiratory tract congestion that are the hallmarks of acute measles virus (MV) infection, invasion of the central nervous system (CNS) can occur, establishing a persistent infection primarily in neurons. The recent identification of the human membrane glycoprotein, CD46, as the MV receptor allowed for the establishment of transgenic mice in which the CD46 gene was transcriptionally regulated by a neuron-specific promoter. Expression of the measles receptor rendered primary CD46-positive neurons permissive to infection with MV–Edmonston. Notably, viral transmission within these cultures occurred in the absence of extracellular virus, presumably via neuronal processes. No infection was seen in nontransgenic mice inoculated intracerebrally with MV–Edmonston. In contrast, scattered neurons were infected following inoculation of transgenic adults, and an impressive widespread neuronal infection was established in transgenic neonates. The neonatal infection resulted in severe CNS disease by 3–4 weeks after infection. Illness was characterized initially by awkward gait and a lack of mobility, and in later stages seizures leading to death. These results show that expression of the MV receptor on specific murine cells (neurons) in vivo is absolutely essential to confer both susceptibility to infection and neurologic disease by this human virus. The disparity in clinical findings between neonatal and adult transgenic mice indicates that differences exist between the developing and mature CNS with respect to MV infection and pathogenesis. PMID:9114047

Measles virus-specified polypeptides in infected cells

International Nuclear Information System (INIS)

Vainionpaepae, R.

1979-01-01

The synthesis of wild-type measles virus-specified polypeptides in Vero cells in pulse-chase experiments, in cells with synchronized protein synthesis by high salt concentration, and in the presence of proteolytic enzyme inhibitors was analyzed by polyacrylamide slab-gel electrophoresis. Six major (L, G, 2, NP, 5 and M) structural polypeptides were identified in infected cells. The results of pulse-chase experiments suggested that most of the structural polypeptides were synthesized at their final length. Polypeptide M was found to be sensitive to trypsin. In TLCK-treated cells its molecular weight was about 1000-2000 daltons higher than in untreated cells. A minor virus-specific polypeptide with a molecular weight of about 23,000 was found as a very faint and diffuse band. In addition, three nonstructural polypeptides with molecular weights of 65,000, 38,000 and 18,000 were also detected. The experiments with proteolytic enzyme inhibitors and with synchronized protein synthesis suggested that the polypeptide with a molecular weight of 65,000 might be a precursor of the structural polypeptide 5. (author)

Improving molecular tools for global surveillance of measles virus⋆

Science.gov (United States)

Bankamp, Bettina; Byrd-Leotis, Lauren A.; Lopareva, Elena N.; Woo, Gibson K.S.; Liu, Chunyu; Jee, Youngmee; Ahmed, Hinda; Lim, Wilina W.; Ramamurty, Nalini; Mulders, Mick N.; Featherstone, David; Bellini, William J.; Rota, Paul A.

2017-01-01

Background The genetic characterization of wild-type measles viruses plays an important role in the description of viral transmission pathways and the verification of measles elimination. The 450 nucleotides that encode the carboxyl-terminus of the nucleoprotein (N-450) are routinely sequenced for genotype analysis. Objectives The objectives of this study were to develop improved primers and controls for RT-PCR reactions used for genotyping of measles samples and to develop a method to provide a convenient, safe, and inexpensive means to distribute measles RNA for RT-PCR assays and practice panels. Study design A newly designed, genetically defined synthetic RNA and RNA isolated from cells infected with currently circulating genotypes were used to compare the sensitivity of primer pairs in RT-PCR and nested PCR. FTA® cards loaded with lysates of measles infected cells were tested for their ability to preserve viral RNA and destroy virus infectivity. Results A new primer pair, MeV216/MeV214, was able to amplify N-450 from viruses representing 10 currently circulating genotypes and a genotype A vaccine strain and demonstrated 100-fold increased sensitivity compared to the previously used primer set. A nested PCR assay further increased the sensitivity of detection from patient samples. A synthetic positive control RNA was developed that produced PCR products that are distinguishable by size from PCR products amplified from clinical samples. FTA® cards completely inactivated measles virus and stabilized RNA for at least six months. Conclusions These improved molecular tools will advance molecular characterization of circulating measles viruses globally and provide enhanced quality control measures. PMID:23806666

Measles re-emergence in Northern Italy: Pathways of measles virus genotype D8, 2013-2014.

Science.gov (United States)

Amendola, Antonella; Bianchi, Silvia; Lai, Alessia; Canuti, Marta; Piralla, Antonio; Baggieri, Melissa; Ranghiero, Alberto; Piatti, Alessandra; Tanzi, Elisabetta; Zehender, Gianguglielmo; Magurano, Fabio; Baldanti, Fausto

2017-03-01

Molecular surveillance and advanced phylogenetic methods are important tools to track the pathways of Measles virus (MV) genotypes, provide evidence for the interruption of endemic transmission and verify the elimination of the disease. The aims of this study were to describe the genetic profile of MV genotype D8 (D8-MV) strains circulating in Northern Italy (Lombardy Region) during the 2013-2014 period and to analyze the transmission chains and estimate the introduction time points using a phylogenetic approach. Forty-four strains of D8-MV identified from 12 outbreaks and 28 cases reported as sporadic were analyzed. Molecular analysis was performed by sequencing the highly variable 450nt region of the N gene of MV genome (N-450), as recommended by the WHO. Phylogenetic analyses and tree time-scaled reconstruction were performed with BEAST software. We could trace back the transmission pathways that resulted in three chains of transmission, two introductions with limited spread (two familiar outbreaks), and two single introductions (true sporadic cases). The D8-Taunton transmission chain, which was involved in 7 outbreaks and 13 sporadic cases, was endemic during the studied period. Furthermore, two novel local variants emerged independently in March 2014 and caused two transmission chains linked to at least 3 outbreaks. Overall, viral diversity was high and strains belonging to 5 different variants were identified. The results of this study clearly demonstrate that multiple lineages of D8-MV co-circulated in Northern Italy. Measles can be considered a re-emerging disease in Italy and additional efforts are necessary to achieve measles elimination goal. Copyright © 2016 Elsevier B.V. All rights reserved.

Measles virus C protein suppresses gamma-activated factor formation and virus-induced cell growth arrest

International Nuclear Information System (INIS)

Yokota, Shin-ichi; Okabayashi, Tamaki; Fujii, Nobuhiro

2011-01-01

Measles virus (MeV) produces two accessory proteins, V and C, from the P gene. These accessory proteins have been reported to contribute to efficient virus proliferation through the modulation of host cell events. Our previous paper described that Vero cell-adapted strains of MeV led host cells to growth arrest through the upregulation of interferon regulatory factor 1 (IRF-1), and wild strains did not. In the present study, we found that C protein expression levels varied among MeV strains in infected SiHa cells. C protein levels were inversely correlated with IRF-1 expression levels and with cell growth arrest. Forced expression of C protein released cells from growth arrest. C-deficient recombinant virus efficiently upregulated IRF-1 and caused growth arrest more efficiently than the wild-type virus. C protein preferentially bound to phosphorylated STAT1 and suppressed STAT1 dimer formation. We conclude that MeV C protein suppresses IFN-γ signaling pathway via inhibition of phosphorylated STAT1 dimerization.

SLAM- and nectin-4-independent noncytolytic spread of canine distemper virus in astrocytes.

Science.gov (United States)

Alves, Lisa; Khosravi, Mojtaba; Avila, Mislay; Ader-Ebert, Nadine; Bringolf, Fanny; Zurbriggen, Andreas; Vandevelde, Marc; Plattet, Philippe

2015-05-01

Measles and canine distemper viruses (MeV and CDV, respectively) first replicate in lymphatic and epithelial tissues by using SLAM and nectin-4 as entry receptors, respectively. The viruses may also invade the brain to establish persistent infections, triggering fatal complications, such as subacute sclerosis pan-encephalitis (SSPE) in MeV infection or chronic, multiple sclerosis-like, multifocal demyelinating lesions in the case of CDV infection. In both diseases, persistence is mediated by viral nucleocapsids that do not require packaging into particles for infectivity but are directly transmitted from cell to cell (neurons in SSPE or astrocytes in distemper encephalitis), presumably by relying on restricted microfusion events. Indeed, although morphological evidence of fusion remained undetectable, viral fusion machineries and, thus, a putative cellular receptor, were shown to contribute to persistent infections. Here, we first showed that nectin-4-dependent cell-cell fusion in Vero cells, triggered by a demyelinating CDV strain, remained extremely limited, thereby supporting a potential role of nectin-4 in mediating persistent infections in astrocytes. However, nectin-4 could not be detected in either primary cultured astrocytes or the white matter of tissue sections. In addition, a bioengineered "nectin-4-blind" recombinant CDV retained full cell-to-cell transmission efficacy in primary astrocytes. Combined with our previous report demonstrating the absence of SLAM expression in astrocytes, these findings are suggestive for the existence of a hitherto unrecognized third CDV receptor expressed by glial cells that contributes to the induction of noncytolytic cell-to-cell viral transmission in astrocytes. While persistent measles virus (MeV) infection induces SSPE in humans, persistent canine distemper virus (CDV) infection causes chronic progressive or relapsing demyelination in carnivores. Common to both central nervous system (CNS) infections is that

Cap-dependent translational control of oncolytic measles virus infection in malignant mesothelioma.

Science.gov (United States)

Jacobson, Blake A; Sadiq, Ahad A; Tang, Shaogeng; Jay-Dixon, Joe; Patel, Manish R; Drees, Jeremy; Sorenson, Brent S; Russell, Stephen J; Kratzke, Robert A

2017-09-08

Malignant mesothelioma has a poor prognosis for which there remains an urgent need for successful treatment approaches. Infection with the Edmonston vaccine strain (MV-Edm) derivative of measles virus results in lysis of cancer cells and has been tested in clinical trials for numerous tumor types including mesothelioma. Many factors play a role in MV-Edm tumor cell selectivity and cytopathic activity while also sparing non-cancerous cells. The MV-Edm receptor CD46 (cluster of differentiation 46) was demonstrated to be significantly higher in mesothelioma cells than in control cells. In contrast, mesothelioma cells are not reliant upon the alternative MV-Edm receptor nectin-4 for entry. MV-Edm treatment of mesothelioma reduced cell viability and also invoked apoptotic cell death. Forced expression of eIF4E or translation stimulation following IGF-I (insulin-like growth factor 1) exposure strengthened the potency of measles virus oncolytic activity. It was also shown that repression of cap-dependent translation by treatment with agents [4EASO, 4EGI-1] that suppress host cell translation or by forcing cells to produce an activated repressor protein diminishes the strength of oncolytic viral efficacy.

Crystallization and preliminary crystallographic analysis of the measles virus hemagglutinin in complex with the CD46 receptor

International Nuclear Information System (INIS)

Santiago, César; Gutiérrez-Rodríguez, Angel; Tucker, Paul A.; Stehle, Thilo; Casasnovas, José M.

2009-01-01

A complex of the measles virus hemagglutinin and the CD46 receptor representing the initial step of the cell infection has been crystallized. The measles virus (MV) hemagglutinin (MV-H) mediates the attachment of MV particles to cell-surface receptors for entry into host cells. MV uses two receptors for attachment to host cells: the complement-control protein CD46 and the signalling lymphocyte activation molecule (SLAM). The MV-H glycoprotein from an Edmonston MV variant and the MV-binding fragment of the CD46 receptor were overproduced in mammalian cells and used to crystallize an MV-H–CD46 complex. Well diffracting crystals containing two complexes in the asymmetric unit were obtained and the structure of the complex was solved by the molecular-replacement method

Measles virus antibody responses in children randomly assigned to receive standard-titer edmonston-zagreb measles vaccine at 4.5 and 9 months of age, 9 months of age, or 9 and 18 months of age

DEFF Research Database (Denmark)

Martins, Cesario; Garly, May-Lill; Bale, Carlitos

2014-01-01

The World Health Organization recommends administration of measles vaccine (MV) at age 9 months in low-income countries. We tested the measles virus antibody response at 4.5, 9, 18, and 24 months of age for children randomly assigned to receive standard-titer Edmonston-Zagreb MV at 4.5 and 9 months...

Hantaan Virus Nucleocapsid Protein Binds to Importin alpha Proteins and Inhibits Tumor Necrosis Factor Alpha-Induced Activation of Nuclear Factor Kappa B

Science.gov (United States)

2008-11-19

Microbiology . All Rights Reserved. Hantaan Virus Nucleocapsid Protein Binds to Importin Proteins and Inhibits Tumor Necrosis Factor Alpha-Induced...Division, U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland 21702,1 and Department of Microbiology , Mount Sinai...34–36. 32. Prescott , J., C. Ye, G. Sen, and B. Hjelle. 2005. Induction of innate immune response genes by Sin Nombre hantavirus does not require

Autographa californica multiple nucleopolyhedrovirus ac53 plays a role in nucleocapsid assembly

International Nuclear Information System (INIS)

Liu Chao; Li Zhaofei; Wu Wenbi; Li Lingling; Yuan Meijin; Pan Lijing; Yang Kai; Pang Yi

2008-01-01

Autographa californica multiple nucleopolyhedrovirus (AcMNPV) orf53 (ac53) is a highly conserved gene existing in all sequenced Lepidoptera and Hymenoptera baculoviruses, but its function remains unknown. To investigate its role in the baculovirus life cycle, an ac53 deletion virus (vAc ac53KO-PH-GFP ) was generated through homologous recombination in Escherichia coli. Fluorescence and light microscopy and titration analysis revealed that vAc ac53KO-PH-GFP could not produce infectious budded virus in infected Sf9 cells. Real-time PCR demonstrated that the ac53 deletion did not affect the levels of viral DNA replication. Electron microscopy showed that many lucent tubular shells devoid of the nucleoprotein core are present in the virogenic stroma and ring zone, indicating that the ac53 knockout affected nucleocapsid assembly. With a recombinant virus expressing an Ac53-GFP fusion protein, we observed that Ac53 was distributed within the cytoplasm and nucleus at 24 h post-infection, but afterwards accumulated predominantly near the nucleus-cytoplasm boundary. These data demonstrate that ac53 is involved in nucleocapsid assembly and is an essential gene for virus production

Modified measles versus rubella versus atypical measles: One and same thing

Directory of Open Access Journals (Sweden)

Surender Nikhil Gupta

2015-01-01

Full Text Available Introduction: In outbreak settings, more than one virus may be infecting the given population. In twin or triple outbreak of measles, German measles (rubella, and varicella in highly immunized hilly areas, maximal number of the case patients in all the hilly villages belonged to the older age group. It suggested an obvious shift to the higher age group, warranting second dose opportunity in such case scenario. The clinical presentations of viral diseases are too similar to differentiate. The aim is to clearly categorize the case patients of modified measles, rubella, and atypical measles in outbreak settings. Results: Four outbreaks are listed. In the first one, sixty case patients were identified from 1026 people in 5 villages. Of these, 41 were diagnosed by clinically, 8 were laboratory confirmed as measles and 11 were epidemiologically linked German measles case patients. Seventy percent of the cases were vaccinated for measles. In second case, we identified 29/35 measles and 6/35 were confirmed as epidemiologically linked unvaccinated chickenpox case patients. In third one, we identified 116 cases in eight villages (112/116 clinically and 04/116 laboratory confirmed. Majority of cases were immunized against measles, but only minor cases for rubella. In fourth case, we identified 505 case patients from mixed outbreaks of varicella, measles and rubella (30/505 clinically, 467/505 epidemiologically linked and 8/505 laboratory confirmed case patients from a study population of 3280. In all the four outbreaks, prima facie, the clinical presentations of both rubella and modified measles were difficult to differentiate. Discussion: On the basis of outbreak investigation and analytical inference, it has been observed that the symtomatology of modified measles and laboratory confirmed rubella case patients/epidemiologically linked cases are so similar placed that many a time, it becomes much difficult to line list the cases in one section of modified

Cloning and characterization of DNA complementary to the canine distemper virus mRNA encoding matrix, phosphoprotein, and nucleocapsid protein

International Nuclear Information System (INIS)

Rozenblatt, S.; Eizenberg, O.; Englund, G.; Bellini, W.J.

1985-01-01

Double-stranded cDNA synthesized from total polyadenylate-containing mRNA, extracted from monkey kidney cells infected with canine distemper virus (CDV), has been cloned into the PstI site of Escherichia coli plasmid pBR322. Clones containing canine distemper virus DNA were identified by hybridization to a canine distemper virus-specific, 32 P-labeled cDNA. Four specific clones containing different classes of sequences have been identified. The cloned plasmids contain inserts of 800 (clone 44-80), 960 (clone 74-16), 1700 (clone 364), and 950 (clone 40-9) base pairs. The sizes of the mRNA species complementary to these inserts are 1500, 1850, 1850 and 2500 nucleotides, respectively, as determined by the Northern technique. Three of the cloned DNA fragments were further identified as the reverse transcripts of the mRNA coding for the matrix, phosphoprotein, and nucleocapsid protein of CDV

Cloning and characterization of DNA complementary to the canine distemper virus mRNA encoding matrix, phosphoprotein, and nucleocapsid protein

Energy Technology Data Exchange (ETDEWEB)

Rozenblatt, S.; Eizenberg, O.; Englund, G.; Bellini, W.J.

1985-02-01

Double-stranded cDNA synthesized from total polyadenylate-containing mRNA, extracted from monkey kidney cells infected with canine distemper virus (CDV), has been cloned into the PstI site of Escherichia coli plasmid pBR322. Clones containing canine distemper virus DNA were identified by hybridization to a canine distemper virus-specific, /sup 32/P-labeled cDNA. Four specific clones containing different classes of sequences have been identified. The cloned plasmids contain inserts of 800 (clone 44-80), 960 (clone 74-16), 1700 (clone 364), and 950 (clone 40-9) base pairs. The sizes of the mRNA species complementary to these inserts are 1500, 1850, 1850 and 2500 nucleotides, respectively, as determined by the Northern technique. Three of the cloned DNA fragments were further identified as the reverse transcripts of the mRNA coding for the matrix, phosphoprotein, and nucleocapsid protein of CDV.

Measles, immune suppression and vaccination: direct and indirect nonspecific vaccine benefits.

Science.gov (United States)

Mina, Michael J

2017-06-01

The measles virus is among the most transmissible viruses known to infect humans. Prior to measles vaccination programs, measles infected over 95% of all children and was responsible for over 4 million deaths each year. Measles vaccination programs have been among the greatest public health achievements reducing, eliminating endemic measles in the whole of the Americas and across much of the globe. Where measles vaccines are introduced, unexpectedly large reductions in all-cause childhood mortality have been observed. These gains appear to derive in part from direct heterologous benefits of measles vaccines that enhance innate and adaptive immune responses. Additionally, by preventing measles infections, vaccination prevents measles-associated short- and long-term immunomodulating effects. Before vaccination, these invisible hallmarks of measles infections increased vulnerability to non-measles infections in nearly all children for weeks, months, or years following acute infections. By depleting measles incidence, vaccination has had important indirect benefits to reduce non-measles mortality. Delineating the relative importance of these two modes of survival benefits following measles vaccine introduction is of critical public health importance. While both support continued unwavering global commitments to measles vaccination programs until measles eradication is complete, direct heterologous benefits of measles vaccination further support continued commitment to measles vaccination programs indefinitely. We discuss what is known about direct and indirect nonspecific measles vaccine benefits, and their implications for continued measles vaccination programs. © 2017 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

Bovine leukemia virus nucleocapsid protein is an efficient nucleic acid chaperone

International Nuclear Information System (INIS)

Qualley, Dominic F.; Sokolove, Victoria L.; Ross, James L.

2015-01-01

Nucleocapsid proteins (NCs) direct the rearrangement of nucleic acids to form the most thermodynamically stable structure, and facilitate many steps throughout the life cycle of retroviruses. NCs bind strongly to nucleic acids (NAs) and promote NA aggregation by virtue of their cationic nature; they also destabilize the NA duplex via highly structured zinc-binding motifs. Thus, they are considered to be NA chaperones. While most retroviral NCs are structurally similar, differences are observed both within and between retroviral genera. In this work, we compare the NA binding and chaperone activity of bovine leukemia virus (BLV) NC to that of two other retroviral NCs: human immunodeficiency virus type 1 (HIV-1) NC, which is structurally similar to BLV NC but from a different retrovirus genus, and human T-cell leukemia virus type 1 (HTLV-1) NC, which possesses several key structural differences from BLV NC but is from the same genus. Our data show that BLV and HIV-1 NCs bind to NAs with stronger affinity in relation to HTLV-1 NC, and that they also accelerate the annealing of complementary stem-loop structures to a greater extent. Analysis of kinetic parameters derived from the annealing data suggests that while all three NCs stimulate annealing by a two-step mechanism as previously reported, the relative contributions of each step to the overall annealing equilibrium are conserved between BLV and HIV-1 NCs but are different for HTLV-1 NC. It is concluded that while BLV and HTLV-1 belong to the same genus of retroviruses, processes that rely on NC may not be directly comparable. - Highlights: • BLV NC binds strongly to DNA and RNA. • BLV NC promotes mini-TAR annealing as well as HIV-1 NC. • Annealing kinetics suggest a low degree of similarity between BLV NC and HTLV-1 NC

Bovine leukemia virus nucleocapsid protein is an efficient nucleic acid chaperone

Energy Technology Data Exchange (ETDEWEB)

Qualley, Dominic F., E-mail: dqualley@berry.edu; Sokolove, Victoria L.; Ross, James L.

2015-03-13

Nucleocapsid proteins (NCs) direct the rearrangement of nucleic acids to form the most thermodynamically stable structure, and facilitate many steps throughout the life cycle of retroviruses. NCs bind strongly to nucleic acids (NAs) and promote NA aggregation by virtue of their cationic nature; they also destabilize the NA duplex via highly structured zinc-binding motifs. Thus, they are considered to be NA chaperones. While most retroviral NCs are structurally similar, differences are observed both within and between retroviral genera. In this work, we compare the NA binding and chaperone activity of bovine leukemia virus (BLV) NC to that of two other retroviral NCs: human immunodeficiency virus type 1 (HIV-1) NC, which is structurally similar to BLV NC but from a different retrovirus genus, and human T-cell leukemia virus type 1 (HTLV-1) NC, which possesses several key structural differences from BLV NC but is from the same genus. Our data show that BLV and HIV-1 NCs bind to NAs with stronger affinity in relation to HTLV-1 NC, and that they also accelerate the annealing of complementary stem-loop structures to a greater extent. Analysis of kinetic parameters derived from the annealing data suggests that while all three NCs stimulate annealing by a two-step mechanism as previously reported, the relative contributions of each step to the overall annealing equilibrium are conserved between BLV and HIV-1 NCs but are different for HTLV-1 NC. It is concluded that while BLV and HTLV-1 belong to the same genus of retroviruses, processes that rely on NC may not be directly comparable. - Highlights: • BLV NC binds strongly to DNA and RNA. • BLV NC promotes mini-TAR annealing as well as HIV-1 NC. • Annealing kinetics suggest a low degree of similarity between BLV NC and HTLV-1 NC.

Measles Cases during Ebola Outbreak, West Africa, 2013-2106.

Science.gov (United States)

Colavita, Francesca; Biava, Mirella; Castilletti, Concetta; Quartu, Serena; Vairo, Francesco; Caglioti, Claudia; Agrati, Chiara; Lalle, Eleonora; Bordi, Licia; Lanini, Simone; Guanti, Michela Delli; Miccio, Rossella; Ippolito, Giuseppe; Capobianchi, Maria R; Di Caro, Antonino

2017-06-01

The recent Ebola outbreak in West Africa caused breakdowns in public health systems, which might have caused outbreaks of vaccine-preventable diseases. We tested 80 patients admitted to an Ebola treatment center in Freetown, Sierra Leone, for measles. These patients were negative for Ebola virus. Measles virus IgM was detected in 13 (16%) of the patients.

A chimeric measles virus with canine distemper envelope protects ferrets from lethal distemper challenge.

Science.gov (United States)

Rouxel, Ronan Nicolas; Svitek, Nicholas; von Messling, Veronika

2009-08-06

CDV infects a broad range of carnivores, and over the past decades it has caused outbreaks in a variety of wild carnivore populations. Since the currently available live-attenuated vaccine is not sufficiently safe in these highly susceptible species, we produced a chimeric virus combining the replication complex of the measles Moraten vaccine strain with the envelope of a recent CDV wild type isolate. The resulting virus did not cause disease or immunosuppression in ferrets and conferred protection from challenge with a lethal wild type strain, demonstrating its potential value for wildlife conservation efforts.

Transport of Ebolavirus Nucleocapsids Is Dependent on Actin Polymerization: Live-Cell Imaging Analysis of Ebolavirus-Infected Cells.

Science.gov (United States)

Schudt, Gordian; Dolnik, Olga; Kolesnikova, Larissa; Biedenkopf, Nadine; Herwig, Astrid; Becker, Stephan

2015-10-01

Transport of ebolavirus (EBOV) nucleocapsids from perinuclear viral inclusions, where they are formed, to the site of budding at the plasma membrane represents an obligatory step of virus assembly. Until now, no live-cell studies on EBOV nucleocapsid transport have been performed, and participation of host cellular factors in this process, as well as the trajectories and speed of nucleocapsid transport, remain unknown. Live-cell imaging of EBOV-infected cells treated with different inhibitors of cellular cytoskeleton was used for the identification of cellular proteins involved in the nucleocapsid transport. EBOV nucleocapsids were visualized by expression of green fluorescent protein (GFP)-labeled nucleocapsid viral protein 30 (VP30) in EBOV-infected cells. Incorporation of the fusion protein VP30-GFP into EBOV nucleocapsids was confirmed by Western blot and indirect immunofluorescence analyses. Importantly, VP30-GFP fluorescence was readily detectable in the densely packed nucleocapsids inside perinuclear viral inclusions and in the dispersed rod-like nucleocapsids located outside of viral inclusions. Live-cell imaging of EBOV-infected cells revealed exit of single nucleocapsids from the viral inclusions and their intricate transport within the cytoplasm before budding at the plasma membrane. Nucleocapsid transport was arrested upon depolymerization of actin filaments (F-actin) and inhibition of the actin-nucleating Arp2/3 complex, and it was not altered upon depolymerization of microtubules or inhibition of N-WASP. Actin comet tails were often detected at the rear end of nucleocapsids. Marginally located nucleocapsids entered filopodia, moved inside, and budded from the tip of these thin cellular protrusions. Live-cell imaging of EBOV-infected cells revealed actin-dependent long-distance transport of EBOV nucleocapsids before budding at the cell surface. These findings provide useful insights into EBOV assembly and have potential application in the development

Validation of a commercially available indirect ELISA using a nucleocapside recombinant protein for detection of Schmallenberg virus antibodies.

Directory of Open Access Journals (Sweden)

Emmanuel Bréard

Full Text Available A newly developed Enzym Like Immuno Sorbant Assay (ELISA based on the recombinant nucleocapsid protein (N of Schmallenberg virus (SBV was evaluated and validated for the detection of SBV-specific IgG antibodies in ruminant sera by three European Reference Laboratories. Validation data sets derived from sheep, goat and bovine sera collected in France and Germany (n = 1515 in 2011 and 2012 were categorized according to the results of a virus neutralization test (VNT or an indirect immuno-fluorescence assay (IFA. The specificity was evaluated with 1364 sera from sheep, goat and bovine collected in France and Belgium before 2009. Overall agreement between VNT and ELISA was 98.9% and 98.3% between VNT and IFA, indicating a very good concordance between the different techniques. Although cross-reactions with other Orthobunyavirus from the Simbu serogroup viruses might occur, it is a highly sensitive, specific and robust ELISA-test validated to detect anti-SBV antibodies. This test can be applied for SBV sero-diagnostics and disease-surveillance studies in ruminant species in Europe.

Detection of measles IgM antibodies in children at Kaduna ...

African Journals Online (AJOL)

Measles virus IgM antibodies virus was assayed for in 270 sera from children aged 5 months to 8 years attending Yusuf Dantsoho Memorial Hospital, Kaduna, Northern Nigeria, using ELISA. Out of the 270 sera, 192(71.1%) tested positive to measles IgM and 78(28.9%) negative. The sample distribution was 137 from males, ...

Phylogenetic and epidemiological analysis of measles outbreaks in Denmark, 2013 to 2014

DEFF Research Database (Denmark)

Rasmussen, Lasse Dam; Fonager, Jannik; Knudsen, Lisbet Krause

2015-01-01

Despite the introduction of safe, effective vaccines decades ago and joint global public health efforts to eliminate measles, this vaccine-preventable disease continues to pose threats to children's health worldwide. During 2013 and 2014, measles virus was introduced into Denmark through several...... an outbreak. The majority of the cases were unvaccinated (n = 27) or recipients of one dose of measles-mumps-rubella (MMR) vaccine (n = 7). In addition, two fully vaccinated adult cases were reported in 2014. We demonstrate the transmission of measles virus in a population in which the two-dose MMR...... vaccination coverage rate was 80% and how even vaccinated individuals may be at risk of contracting measles once transmission has been established....

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

OpenAIRE

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

2003-01-01

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

Immune status of health care workers to measles virus: evaluation of protective titers in four measles IgG EIAs

NARCIS (Netherlands)

Dorigo-Zetsma, J.W.; Hall, M.A.; Vreeswijk, J.; Vries, J.J. de; Vossen, A.C.; Hulscher, H.I. Ten; Kerkhof, J.; Smits, G.P.; Ruijs, W.L.M.; Koopmans, M.P.; Binnendijk, R.S. van

2015-01-01

BACKGROUND: Following the recognition of a measles case in a hospital in The Netherlands, health care workers (HCW) from the premises were screened by a commercial enzyme immunoassay (EIA) for measles IgG to identify persons at risk for measles. At least 10% of the HCW were tested measles

Epitope Dampening Monotypic Measles Virus Hemagglutinin Glycoprotein Results in Resistance to Cocktail of Monoclonal Antibodies

Science.gov (United States)

Lech, Patrycja J.; Tobin, Gregory J.; Bushnell, Ruth; Gutschenritter, Emily; Pham, Linh D.; Nace, Rebecca; Verhoeyen, Els; Cosset, François-Loïc; Muller, Claude P.; Russell, Stephen J.; Nara, Peter L.

2013-01-01

The measles virus (MV) is serologically monotypic. Life-long immunity is conferred by a single attack of measles or following vaccination with the MV vaccine. This is contrary to viruses such as influenza, which readily develop resistance to the immune system and recur. A better understanding of factors that restrain MV to one serotype may allow us to predict if MV will remain monotypic in the future and influence the design of novel MV vaccines and therapeutics. MV hemagglutinin (H) glycoprotein, binds to cellular receptors and subsequently triggers the fusion (F) glycoprotein to fuse the virus into the cell. H is also the major target for neutralizing antibodies. To explore if MV remains monotypic due to a lack of plasticity of the H glycoprotein, we used the technology of Immune Dampening to generate viruses with rationally designed N-linked glycosylation sites and mutations in different epitopes and screened for viruses that escaped monoclonal antibodies (mAbs). We then combined rationally designed mutations with naturally selected mutations to generate a virus resistant to a cocktail of neutralizing mAbs targeting four different epitopes simultaneously. Two epitopes were protected by engineered N-linked glycosylations and two epitopes acquired escape mutations via two consecutive rounds of artificial selection in the presence of mAbs. Three of these epitopes were targeted by mAbs known to interfere with receptor binding. Results demonstrate that, within the epitopes analyzed, H can tolerate mutations in different residues and additional N-linked glycosylations to escape mAbs. Understanding the degree of change that H can tolerate is important as we follow its evolution in a host whose immunity is vaccine induced by genotype A strains instead of multiple genetically distinct wild-type MVs. PMID:23300970

[Measles in Germany: An Epidemiological Analysis and First Measures for Containment].

Science.gov (United States)

Matysiak-Klose, Dorothea; Wicker, Sabine

2017-11-01

Measles are one of the most contagious diseases of mankind. Measles incidence has declined worldwide since the introduction of vaccinations. Due to low numbers of measles cases in countries with high vaccination rates the population is not aware of possible complications of measles any more. Measles elimination is an important goal set by all regions of the World Health Organization. However, it remains a challenge for Germany and other European countries. Because of a high proportion of susceptibles in specific population and age groups outbreaks take place in Germany every year after importation of the virus. More than 50 % of measles cases are 20 years and older. However, the highest incidences have been seen in two-year-olds since several years. In addition to epidemiological findings such as case numbers and risk groups, genotyping permits e. g. an assessment of the endemic circulation of viruses. Suspicion of a measles case should result in immediate and consistent measures. © Georg Thieme Verlag KG Stuttgart · New York.

Rash after measles vaccination: laboratory analysis of cases reported in São Paulo, Brazil

Directory of Open Access Journals (Sweden)

Oliveira Maria I

2002-01-01

Full Text Available OBJECTIVE: The clinical differential diagnosis of rash due to viral infections is often difficult, and misdiagnosis is not rare, especially after the introduction of measles and rubella vaccination. A study to determine the etiological diagnosis of exanthema was carried out in a group of children after measles vaccination. METHODS: Sera collected from children with rash who received measles vaccine were reported in 1999. They were analyzed for IgM antibodies against measles virus, rubella virus, human parvovirus B19 (HPV B19 using ELISA commercial techniques, and human herpes virus 6 (HHV 6 using immunofluorescence commercial technique. Viremia for each of those viruses was tested using a polimerase chain reaction (PCR. RESULTS: A total of 17 cases of children with exanthema after measles immunization were reported in 1999. The children, aged 9 to 12 months (median 10 months, had a blood sample taken for laboratory analysis. The time between vaccination and the first rash signs varied from 1 to 60 days. The serological results of those 17 children suspected of measles or rubella infection showed the following etiological diagnosis: 17.6% (3 in 17 HPV B19 infection; 76.5% (13 in 17 HHV 6 infection; 5.9% (1 in 17 rash due to measles vaccine. CONCLUSIONS: The study data indicate that infection due to HPV B19 or HHV 6 can be misdiagnosed as exanthema due to measles vaccination. Therefore, it is important to better characterize the etiology of rash in order to avoid attributing it incorrectly to measles vaccine.

Rash after measles vaccination: laboratory analysis of cases reported in São Paulo, Brazil

Directory of Open Access Journals (Sweden)

Maria I Oliveira

2002-04-01

Full Text Available OBJECTIVE: The clinical differential diagnosis of rash due to viral infections is often difficult, and misdiagnosis is not rare, especially after the introduction of measles and rubella vaccination. A study to determine the etiological diagnosis of exanthema was carried out in a group of children after measles vaccination. METHODS: Sera collected from children with rash who received measles vaccine were reported in 1999. They were analyzed for IgM antibodies against measles virus, rubella virus, human parvovirus B19 (HPV B19 using ELISA commercial techniques, and human herpes virus 6 (HHV 6 using immunofluorescence commercial technique. Viremia for each of those viruses was tested using a polimerase chain reaction (PCR. RESULTS: A total of 17 cases of children with exanthema after measles immunization were reported in 1999. The children, aged 9 to 12 months (median 10 months, had a blood sample taken for laboratory analysis. The time between vaccination and the first rash signs varied from 1 to 60 days. The serological results of those 17 children suspected of measles or rubella infection showed the following etiological diagnosis: 17.6% (3 in 17 HPV B19 infection; 76.5% (13 in 17 HHV 6 infection; 5.9% (1 in 17 rash due to measles vaccine. CONCLUSIONS: The study data indicate that infection due to HPV B19 or HHV 6 can be misdiagnosed as exanthema due to measles vaccination. Therefore, it is important to better characterize the etiology of rash in order to avoid attributing it incorrectly to measles vaccine.

Parental influenza virion nucleocapsids are efficiently transported into the nuclei of murine cells expressing the nuclear interferon-induced Mx protein.

Science.gov (United States)

Broni, B; Julkunen, I; Condra, J H; Davies, M E; Berry, M J; Krug, R M

1990-12-01

The interferon-induced murine Mx1 protein, which is localized in the nucleus, most likely specifically blocks influenza virus replication by inhibiting nuclear viral mRNA synthesis, including the mRNA synthesis catalyzed by inoculum (parental) virion nucleocapsids (R. M. Krug, M. Shaw, B. Broni, G. Shapiro, and O. Haller, J. Virol. 56:201-206, 1985). We tested two possible mechanisms for this inhibition. First, we determined whether the transport of parental nucleocapsids into the nucleus was inhibited in murine cells expressing the nuclear Mx1 protein. To detect the Mx1 protein, we prepared rabbit antibodies against the Mx1 protein with a CheY-Mx fusion protein expressed in bacteria. The fate of parental nucleocapsids was monitored by immunofluorescence with an appropriate dilution of monoclonal antibody to the nucleocapsid protein. The protein synthesis inhibitor anisomycin was added to the cells 30 min prior to infection, so that the only nucleocapsids protein molecules in the cells were those associated with nucleocapsids of the parental virus. These nucleocapsids were efficiently transported into the nuclei of murine cells expressing the Mx1 protein, indicating that this protein most likely acts after the parental nucleocapsids enter the nucleus. The second possibility was that the murine Mx1 protein might act in the nucleus to inhibit viral mRNA synthesis indirectly via new cap-binding activities that sequestered cellular capped RNAs away from the viral RNA transcriptase. We show that the same array of nuclear cap-binding proteins was present in Mx-positive and Mx-negative cells treated with interferon. Interestingly, a large amount of a 43-kDa cap-binding activity appeared after interferon treatment of both Mx-positive and Mx-negative cells. Hence, the appearance of new cap-binding activities was unlikely to account for the Mx-specific inhibition of viral mRNA synthesis. These results are most consistent with the possibility that the Mx1 protein acts

Molecular detection of measles virus from children during a sporadic ...

African Journals Online (AJOL)

Background: According to the World Health Organization (WHO), African region accounts for 36% of deaths caused by measles worldwide. Nigeria has, over the years, recorded the highest average annual measles incidence per 100,000 populations in Africa. Measles epidemics have consistently been reported in northern ...

Unique Measles Virus in Canada

Centers for Disease Control (CDC) Podcasts

2017-08-24

Dr. Shelley Deeks, chief of communicable diseases at Public Health Ontario, discusses a measles outbreak in Canada.  Created: 8/24/2017 by National Center for Emerging and Zoonotic Infectious Diseases (NCEZID).   Date Released: 8/24/2017.

Sequence analysis of measles virus strains collected during the pre- and early-vaccination era in Denmark reveals a considerable diversity of ancient strains

DEFF Research Database (Denmark)

Christensen, Laurids Siig; Schöller, S.; Schierup, M. H.

2002-01-01

A total of 199 serum samples from patients with measles collected in Denmark, Greenland and the Faroe Islands from 1964 to 1983 were analysed by PCR. Measles virus (MV) RNA could be detected in 38 (19%) of the samples and a total of 18 strains were subjected to partial sequence analysis of the he......A total of 199 serum samples from patients with measles collected in Denmark, Greenland and the Faroe Islands from 1964 to 1983 were analysed by PCR. Measles virus (MV) RNA could be detected in 38 (19%) of the samples and a total of 18 strains were subjected to partial sequence analysis...... of the hemagglutinin gene. The strains exhibited a considerable genomic diversity, which is at odds with the assumption that one genome type prevailed among globally circulating MV strains prior to the advent of live-attenuated vaccines. Our data indicate that the similarity of the various vaccine strains...... is attributed to their having originated from the same primary isolate. Consequently, it is implied that a small number of clinical manifestations of MV worldwide from which strains similar to the vaccine strain were identified were vaccine related rather than being caused by members of a persistently...

Measles in Sudan: Diagnosis, Epidemiology and Humoral Immune Response

NARCIS (Netherlands)

H.S. El Mubarak

2004-01-01

textabstractDespite the availability of safe and effective live attenuated vaccines, measles remains endemic in many developing countries. Little is known about the pathogenesis of measles virus (MV) infections in the areas of itsendemicity, largely due to the limited infrastructure and political

Measles in HIV-infected children in southern Africa | Sheikh | South ...

African Journals Online (AJOL)

. Given the high human immunodeficiency virus (HIV) prevalence in the region, the particular features of measles in HIV-infected individuals are of interest to clinicians, especially as regards children, as are measles immunisation strategies for ...

[Differences in oligomerization of nucleocapsid protein of epidemic human influenza A(H1N1), A(H1N2) and B viruses].

Science.gov (United States)

Prokudina, E N; Semenova, N P; Chumakov, V M; Burtseva, E I; Slepushkin, A N

2003-01-01

A comparative analysis of involving the nucleocapsid protein (NP) into shaping-up of SDS-resistant oligomers was carried out presently in circulating epidemic strains of human influenza, viruses A and B. The study results of viral isolates obtained from clinical samples and recent standard strains revealed that the involvement of NP in the SDS-resistant oligomers, which are different in various subtypes of influenza A viruses. According to this sign, the human viruses A(9H3N2) are close to the avian ones, in which, as proved by us previously, virtually the entire NP transforms itself into the oligomers resistant to SDS. About 10-20% of NP are involved in shaping-up the virus influenza A(H1N1) of SDS-resistant oligomers. No SDS-resistant NP-oligomers were detected in influenza of type B. It is suggested that the prevalence of human viruses A(H3N2) in NP-oligomers are the peculiarities of NP structure and of the presence of the PB1 protein from avian influenza virus.

The Unstructured Paramyxovirus Nucleocapsid Protein Tail Domain Modulates Viral Pathogenesis through Regulation of Transcriptase Activity.

Science.gov (United States)

Thakkar, Vidhi D; Cox, Robert M; Sawatsky, Bevan; da Fontoura Budaszewski, Renata; Sourimant, Julien; Wabbel, Katrin; Makhsous, Negar; Greninger, Alexander L; von Messling, Veronika; Plemper, Richard K

2018-04-15

The paramyxovirus replication machinery comprises the viral large (L) protein and phosphoprotein (P-protein) in addition to the nucleocapsid (N) protein, which encapsidates the single-stranded RNA genome. Common to paramyxovirus N proteins is a C-terminal tail (Ntail). The mechanistic role and relevance for virus replication of the structurally disordered central Ntail section are unknown. Focusing initially on members of the Morbillivirus genus, a series of measles virus (MeV) and canine distemper virus (CDV) N proteins were generated with internal deletions in the unstructured tail section. N proteins with large tail truncations remained bioactive in mono- and polycistronic minireplicon assays and supported efficient replication of recombinant viruses. Bioactivity of Ntail mutants extended to N proteins derived from highly pathogenic Nipah virus. To probe an effect of Ntail truncations on viral pathogenesis, recombinant CDVs were analyzed in a lethal CDV/ferret model of morbillivirus disease. The recombinant viruses displayed different stages of attenuation ranging from ameliorated clinical symptoms to complete survival of infected animals, depending on the molecular nature of the Ntail truncation. Reinfection of surviving animals with pathogenic CDV revealed robust protection against a lethal challenge. The highly attenuated virus was genetically stable after ex vivo passaging and recovery from infected animals. Mechanistically, gradual viral attenuation coincided with stepwise altered viral transcriptase activity in infected cells. These results identify the central Ntail section as a determinant for viral pathogenesis and establish a novel platform to engineer gradual virus attenuation for next-generation paramyxovirus vaccine design. IMPORTANCE Investigating the role of the paramyxovirus N protein tail domain (Ntail) in virus replication, we demonstrated in this study that the structurally disordered central Ntail region is a determinant for viral

Genotyping of circulating measles strains in Italy in 2010

Directory of Open Access Journals (Sweden)

Melissa Baggieri

2014-12-01

Full Text Available INTRODUCTION: The European Regional Office of the World Health Organization developed a strategic approach to stop the indigenous transmission of measles in its 53 Member States by 2015. In Italy, laboratory surveillance activity is implemented by the National Reference Laboratory for Measles and Rubella at the Italian National Institute of Health (Istituto Superiore di Sanità, Rome. The role of the National Reference Laboratory is to strengthen surveillance systems through rigorous case investigation and laboratory confirmation of suspected sporadic cases and outbreaks. Genetic characterization of wild-type measles virus is an essential component of the laboratory-based surveillance. This study describes the molecular characterization of measles virus strains isolated during 2010. METHODS: Dried blood spots, urine and oral fluid samples were collected from patients with a suspected measles infection. Serological tests were performed on capillary blood, and viral detection was performed on urine and oral fluid samples through molecular assay. Positive samples were sequenced and phylogenetically analysed. RESULTS AND DISCUSSION: The phylogenetic analysis showed a co-circulation of genotypes D4 and D8, and sporadic cases associated to genotypes D9 and B3. Then, molecular epidemiology of measles cases permitted to establish that D4 and D8 were the endemic genotypes in Italy during 2010.

CD147/EMMPRIN acts as a functional entry receptor for measles virus on epithelial cells.

Science.gov (United States)

Watanabe, Akira; Yoneda, Misako; Ikeda, Fusako; Terao-Muto, Yuri; Sato, Hiroki; Kai, Chieko

2010-05-01

Measles is a highly contagious human disease caused by measles virus (MeV) and remains the leading cause of death in children, particularly in developing countries. Wild-type MeV preferentially infects lymphocytes by using signaling lymphocytic activation molecule (SLAM), whose expression is restricted to hematopoietic cells, as a receptor. MeV also infects other epithelial and neuronal cells that do not express SLAM and causes pneumonia and diarrhea and, sometimes, serious symptoms such as measles encephalitis and subacute sclerosing panencephalitis. The discrepancy between the tissue tropism of MeV and the distribution of SLAM-positive cells suggests that there are unknown receptors other than SLAM for MeV. Here we identified CD147/EMMPRIN (extracellular matrix metalloproteinase inducer), a transmembrane glycoprotein, which acts as a receptor for MeV on epithelial cells. Furthermore, we found the incorporation of cyclophilin B (CypB), a cellular ligand for CD147, in MeV virions, and showed that inhibition of CypB incorporation significantly attenuated SLAM-independent infection on epithelial cells, while it had no effect on SLAM-dependent infection. To date, MeV infection was considered to be triggered by binding of its hemagglutinin (H) protein and cellular receptors. Our present study, however, indicates that MeV infection also occurs via CD147 and virion-associated CypB, independently of MeV H. Since CD147 is expressed in a variety of cells, including epithelial and neuronal cells, this molecule possibly functions as an entry receptor for MeV in SLAM-negative cells. This is the first report among members of the Mononegavirales that CD147 is used as a virus entry receptor via incorporated CypB in the virions.

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

International Nuclear Information System (INIS)

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

2006-01-01

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

[EIA-IgG antibody measles prevention level estimated from measles neutralizing, particle agglutination and hemagglutination-inhibition antibody titer].

Science.gov (United States)

Takayama, Naohide; Saika, Shizuko; Ichinohe, Sadato

2009-09-01

Measles hemagglutination inhibition (HI) antibody titer, widely used in clinical practice to simply and easily determine the measles immunity level has, in recent years, been increasingly replaced by measles IgG-antibody titer determined by enzyme-immunoassay (EIA). HI antibody titer appears to reflect this protective level, because HI measures the antibody against H protein required for the measles virus to adhere to host cells. EIA-IgG antibody titer does not correlate with the protective level, similar to particle agglutination (PA) titer, because EIA measures different antibodies, including those unrelated to measles protection. After determining HI, PA, neutralizing test (NT) results, and EIA-IgG antibody titer for individual specimens, we compared EIA-IgG antibody titer obtained using an EIA-Kit (Denka Seiken) to HI, PA, and NT titer with the following results: (1) Subjects with EIA-IgG titer of > or = 12.0 may be protected against measles: (2) Subjects with EIA-IgG titer of 4.0 to 8.0 appear to be protected insufficiently requiring a booster dose against measles: (3) Subjects with EIA-IgG titer of 8.0 to 12.0 may benefit from booster vaccination.

Identification of Rift Valley fever virus nucleocapsid protein-RNA binding inhibitors using a high-throughput screening assay.

Science.gov (United States)

Ellenbecker, Mary; Lanchy, Jean-Marc; Lodmell, J Stephen

2012-09-01

Rift Valley fever virus (RVFV) is an emerging infectious pathogen that causes severe disease in humans and livestock and has the potential for global spread. Currently, there is no proven effective treatment for RVFV infection, and there is no licensed vaccine. Inhibition of RNA binding to the essential viral nucleocapsid (N) protein represents a potential antiviral therapeutic strategy because all of the functions performed by N during infection involve RNA binding. To target this interaction, we developed a fluorescence polarization-based high-throughput drug-screening assay and tested 26 424 chemical compounds for their ability to disrupt an N-RNA complex. From libraries of Food and Drug Administration-approved drugs, druglike molecules, and natural product extracts, we identified several lead compounds that are promising candidates for medicinal chemistry.

Measles virus antibody responses in children randomly assigned to receive standard-titer edmonston-zagreb measles vaccine at 4.5 and 9 months of age, 9 months of age, or 9 and 18 months of age.

Science.gov (United States)

Martins, Cesario; Garly, May-Lill; Bale, Carlitos; Rodrigues, Amabelia; Njie-Jobe, Jainaba; Benn, Christine S; Whittle, Hilton; Aaby, Peter

2014-09-01

The World Health Organization recommends administration of measles vaccine (MV) at age 9 months in low-income countries. We tested the measles virus antibody response at 4.5, 9, 18, and 24 months of age for children randomly assigned to receive standard-titer Edmonston-Zagreb MV at 4.5 and 9 months, at 9 months, or at 9 and 18 months of age. At 4.5 months of age, 75% had nonprotective measles virus antibody levels. Following receipt of MV at 4.5 months of age, 77% (316/408) had protective antibody levels at 9 months of age; after a second dose at 9 months of age, 97% (326/337) had protective levels at 24 months of age. In addition, the response at both 9 and 24 months of age was inversely correlated with the antibody level at receipt of the first dose of MV, and the second dose of MV, received at 9 months of age, provided a significant boost in antibody level to children who had low antibody levels. In the group of 318 children who received MV at 9 months of age, with or without a second dose at 18 months of age, 99% (314) had protective levels at 24 months of age. The geometric mean titer at 24 months of age was significantly lower in the group that received MV at 4.5 and 9 months of age than in the group that received MV at 9 months of age (P = .0001). In conclusion, an early 2-dose MV schedule was associated with protective measles virus antibody levels at 24 months of age in nearly all children. Clinical Trials Registration. NCT00168558. © 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.

The measles virus N(TAIL)-XD complex: an illustrative example of fuzziness.

Science.gov (United States)

Longhi, Sonia

2012-01-01

In this chapter, I focus on the biochemical and structural characterization of the complex between the intrinsically disordered C-terminal domain of the measles virus nucleoprotein (N(TAIL)) and the C-terminal X domain (XD) of the viral phosphoprotein (P). I summarize the main experimental data available so far pointing out the prevalently disordered nature of N(TAIL) even after complex formation and the role of the flexible C-terminal appendage in the binding reaction. I finally discuss the possible functional role of these residual disordered regions within the complex in terms of their ability to capture other regulatory, binding partners.

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

Science.gov (United States)

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

2004-01-26

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

Biosynthesis of measles virus hemagglutinin in persistently infected cells

International Nuclear Information System (INIS)

Bellini, W.J.; Silver, G.D.; McFarlin, D.E.

1983-01-01

The synthesis of the hemagglutinin (HA) glycoprotein of measles virus was investigated in a persistently infected cell line using a monoclonal anti-HA. The synthesis of the HA protein was shown to be associated with the rough endoplasmic reticulum. The unglycosylated (HA 0 ) apoprotein is synthesized as a 65.000 dalton peptide and is inserted into the rough endoplasmic reticulum as a transmembrane protein with approximately 2 to 3000 daltons of the peptide exposed to the cytoplasmic membrane surface. Primary glycosylation of the HA protein was found to occur through the lipid-linked carrier, dolichol-phosphate, as determined by inhibition of glycosylation by tunicamycin. Glycosylation, however, was not a prerequisite for membrane insertion. Endo-β-N-acetyl-Glucosaminidase H digestion of the fully glycosylated HA protein indicated that both simple and complex oligosaccharides are present on the surface glycoprotein. (Author)

Nucleocapsid-Independent Specific Viral RNA Packaging via Viral Envelope Protein and Viral RNA Signal

OpenAIRE

Narayanan, Krishna; Chen, Chun-Jen; Maeda, Junko; Makino, Shinji

2003-01-01

For any of the enveloped RNA viruses studied to date, recognition of a specific RNA packaging signal by the virus's nucleocapsid (N) protein is the first step described in the process of viral RNA packaging. In the murine coronavirus a selective interaction between the viral transmembrane envelope protein M and the viral ribonucleoprotein complex, composed of N protein and viral RNA containing a short cis-acting RNA element, the packaging signal, determines the selective RNA packaging into vi...

Parental influenza virion nucleocapsids are efficiently transported into the nuclei of murine cells expressing the nuclear interferon-induced Mx protein.

OpenAIRE

Broni, B; Julkunen, I; Condra, J H; Davies, M E; Berry, M J; Krug, R M

1990-01-01

The interferon-induced murine Mx1 protein, which is localized in the nucleus, most likely specifically blocks influenza virus replication by inhibiting nuclear viral mRNA synthesis, including the mRNA synthesis catalyzed by inoculum (parental) virion nucleocapsids (R. M. Krug, M. Shaw, B. Broni, G. Shapiro, and O. Haller, J. Virol. 56:201-206, 1985). We tested two possible mechanisms for this inhibition. First, we determined whether the transport of parental nucleocapsids into the nucleus was...

Recombinant measles virus vaccine expressing the Nipah virus glycoprotein protects against lethal Nipah virus challenge.

Directory of Open Access Journals (Sweden)

Misako Yoneda

Full Text Available Nipah virus (NiV is a member of the genus Henipavirus, which emerged in Malaysia in 1998. In pigs, infection resulted in a predominantly non-lethal respiratory disease; however, infection in humans resulted in over 100 deaths. Nipah virus has continued to re-emerge in Bangladesh and India, and person-to-person transmission appeared in the outbreak. Although a number of NiV vaccine studies have been reported, there are currently no vaccines or treatments licensed for human use. In this study, we have developed a recombinant measles virus (rMV vaccine expressing NiV envelope glycoproteins (rMV-HL-G and rMV-Ed-G. Vaccinated hamsters were completely protected against NiV challenge, while the mortality of unvaccinated control hamsters was 90%. We trialed our vaccine in a non-human primate model, African green monkeys. Upon intraperitoneal infection with NiV, monkeys showed several clinical signs of disease including severe depression, reduced ability to move and decreased food ingestion and died at 7 days post infection (dpi. Intranasal and oral inoculation induced similar clinical illness in monkeys, evident around 9 dpi, and resulted in a moribund stage around 14 dpi. Two monkeys immunized subcutaneously with rMV-Ed-G showed no clinical illness prior to euthanasia after challenge with NiV. Viral RNA was not detected in any organ samples collected from vaccinated monkeys, and no pathological changes were found upon histopathological examination. From our findings, we propose that rMV-NiV-G is an appropriate NiV vaccine candidate for use in humans.

CD147/EMMPRIN Acts as a Functional Entry Receptor for Measles Virus on Epithelial Cells▿

Science.gov (United States)

Watanabe, Akira; Yoneda, Misako; Ikeda, Fusako; Terao-Muto, Yuri; Sato, Hiroki; Kai, Chieko

2010-01-01

Measles is a highly contagious human disease caused by measles virus (MeV) and remains the leading cause of death in children, particularly in developing countries. Wild-type MeV preferentially infects lymphocytes by using signaling lymphocytic activation molecule (SLAM), whose expression is restricted to hematopoietic cells, as a receptor. MeV also infects other epithelial and neuronal cells that do not express SLAM and causes pneumonia and diarrhea and, sometimes, serious symptoms such as measles encephalitis and subacute sclerosing panencephalitis. The discrepancy between the tissue tropism of MeV and the distribution of SLAM-positive cells suggests that there are unknown receptors other than SLAM for MeV. Here we identified CD147/EMMPRIN (extracellular matrix metalloproteinase inducer), a transmembrane glycoprotein, which acts as a receptor for MeV on epithelial cells. Furthermore, we found the incorporation of cyclophilin B (CypB), a cellular ligand for CD147, in MeV virions, and showed that inhibition of CypB incorporation significantly attenuated SLAM-independent infection on epithelial cells, while it had no effect on SLAM-dependent infection. To date, MeV infection was considered to be triggered by binding of its hemagglutinin (H) protein and cellular receptors. Our present study, however, indicates that MeV infection also occurs via CD147 and virion-associated CypB, independently of MeV H. Since CD147 is expressed in a variety of cells, including epithelial and neuronal cells, this molecule possibly functions as an entry receptor for MeV in SLAM-negative cells. This is the first report among members of the Mononegavirales that CD147 is used as a virus entry receptor via incorporated CypB in the virions. PMID:20147391

BM61 of Bombyx mori nucleopolyhedrovirus: its involvement in the egress of nucleocapsids from the nucleus.

Science.gov (United States)

Shen, Hongxing; Chen, Keping

2012-04-05

All lepidopteran baculovirus genomes sequenced encode a homolog of the Bombyx mori nucleopolyhedrovirus orf61 gene (Bm61). To determine the role of Bm61 in the baculoviral life cycle, we constructed a Bm61 knockout virus and characterized it in cells. We observed that the Bm61 deletion bacmid led to a defect in production of infectious budded virus (BV). Quantitative PCR analysis of BV in the media culturing the transfected cell indicated that BV was not produced due to Bm61 deletion. Electron microscope analysis showed that in the knockout of Bm61, nucleocapsids were not transported from the nucleus to the cytoplasm. From these results we concluded that BM61 is required in the BV pathway for the egress of nucleocapsids from the nucleus to the cytoplasm. Copyright © 2012 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

The Herpes Simplex Virus Protein pUL31 Escorts Nucleocapsids to Sites of Nuclear Egress, a Process Coordinated by Its N-Terminal Domain.

Directory of Open Access Journals (Sweden)

Christina Funk

2015-06-01

Full Text Available Progeny capsids of herpesviruses leave the nucleus by budding through the nuclear envelope. Two viral proteins, the membrane protein pUL34 and the nucleo-phosphoprotein pUL31 form the nuclear egress complex that is required for capsid egress out of the nucleus. All pUL31 orthologs are composed of a diverse N-terminal domain with 1 to 3 basic patches and a conserved C-terminal domain. To decipher the functions of the N-terminal domain, we have generated several Herpes simplex virus mutants and show here that the N-terminal domain of pUL31 is essential with basic patches being critical for viral propagation. pUL31 and pUL34 entered the nucleus independently of each other via separate routes and the N-terminal domain of pUL31 was required to prevent their premature interaction in the cytoplasm. Unexpectedly, a classical bipartite nuclear localization signal embedded in this domain was not required for nuclear import of pUL31. In the nucleus, pUL31 associated with the nuclear envelope and newly formed capsids. Viral mutants lacking the N-terminal domain or with its basic patches neutralized still associated with nucleocapsids but were unable to translocate them to the nuclear envelope. Replacing the authentic basic patches with a novel artificial one resulted in HSV1(17+Lox-UL31-hbpmp1mp2, that was viable but delayed in nuclear egress and compromised in viral production. Thus, while the C-terminal domain of pUL31 is sufficient for the interaction with nucleocapsids, the N-terminal domain was essential for capsid translocation to sites of nuclear egress and a coordinated interaction with pUL34. Our data indicate an orchestrated sequence of events with pUL31 binding to nucleocapsids and escorting them to the inner nuclear envelope. We propose a common mechanism for herpesviral nuclear egress: pUL31 is required for intranuclear translocation of nucleocapsids and subsequent interaction with pUL34 thereby coupling capsid maturation with primary

Measles: What we have learned from non-human primate models

NARCIS (Netherlands)

R.L. de Swart (Rik)

2018-01-01

textabstractStudies in non-human primates (NHPs) have been crucial for our understanding of measles as a high impact viral disease of humans. Over a century ago, inoculations of NHPs with filtered secretions from measles patients first identified a virus as the causative agent of this disease. In

Structure and assembly of a paramyxovirus matrix protein.

Science.gov (United States)

Battisti, Anthony J; Meng, Geng; Winkler, Dennis C; McGinnes, Lori W; Plevka, Pavel; Steven, Alasdair C; Morrison, Trudy G; Rossmann, Michael G

2012-08-28

Many pleomorphic, lipid-enveloped viruses encode matrix proteins that direct their assembly and budding, but the mechanism of this process is unclear. We have combined X-ray crystallography and cryoelectron tomography to show that the matrix protein of Newcastle disease virus, a paramyxovirus and relative of measles virus, forms dimers that assemble into pseudotetrameric arrays that generate the membrane curvature necessary for virus budding. We show that the glycoproteins are anchored in the gaps between the matrix proteins and that the helical nucleocapsids are associated in register with the matrix arrays. About 90% of virions lack matrix arrays, suggesting that, in agreement with previous biological observations, the matrix protein needs to dissociate from the viral membrane during maturation, as is required for fusion and release of the nucleocapsid into the host's cytoplasm. Structure and sequence conservation imply that other paramyxovirus matrix proteins function similarly.

Epidemiological and molecular investigation of a measles outbreak in Punjab, Pakistan, 2013-2015.

Science.gov (United States)

Zaidi, Syed Sohail Zahoor; Hameed, Abdul; Ali, Naeem; Rana, Muhammad Suleman; Umair, Massab; Alam, Muhammad Masroor; Aamir, Uzma Bashir; Khurshid, Adnan; Sharif, Salmaan; Shaukat, Shahzad; Angez, Mehar; Mujtaba, Ghulam; Arshad, Yasir; Akthar, Ribqa; Sufian, Mian Muhammad; Mehmood, Nayab

2018-04-28

Despite the availability of an effective vaccine, the measles virus continues to cause significant morbidity and mortality in children worldwide. Molecular characterization of wild-type measles strains is an invaluable component of epidemiological studies or surveillance systems that provides important information pertinent to outbreak linkages and transmission pathways. Serum samples and throat swabs were collected from suspected measles cases from the Punjab province of Pakistan (2013-2015) and further tested for measles immunoglobulin M (IgM) through enzyme-linked immunosorbent assay and reverse-transcriptase polymerase chain reaction for molecular characterization. Among the total of 5415 blood samples, 59% tested positive for measles IgM. Males had a higher infection rate (55%) than females (45%), and the highest frequency of positive cases (63%) was found in the age group of 0 to 5 years. Partial sequencing of the nucleoprotein gene showed that 27 strains belonged to the B3 genotype, whereas 2 viruses were identified as D4. On phylogenetic analysis, Pakistani B3 strains were found to be closely related to previously reported indigenous strains and those from neighboring countries of Iran and Qatar. This is the first report on the detection of the measles B3 genotype from Punjab, Pakistan. The current study shows a high burden of measles infections in Punjab province owing to poor routine immunization coverage in major cities. It is imperative that national health authorities adopt strategic steps on an urgent basis for improvement of routine immunization coverage. Molecular epidemiology of the measles viruses circulating in different parts of the country can provide useful data to manage future outbreaks. © 2018 Wiley Periodicals, Inc.

A Review of Measles

Science.gov (United States)

Dardis, Melissa R.

2012-01-01

Measles, once a common childhood illness that many older school nurses could recognize without difficulty, needs review again after reemerging from Europe and other continents. A highly contagious disease, which has been referenced since the seventh century, the virus can cause serious illness and death, despite the fact that it is vaccine…

Aerosol measles vaccination in macaques: Preclinical studies of immune responses and safety

NARCIS (Netherlands)

R.L. de Swart (Rik); T. Kuiken (Thijs); J. Fernandez-de Castro (Jorge); M.J. Papania (Mark); J.V. Bennett (John); J.L. Valdespino (José); P.D. Minor; C.L. Witham (Clyde); S. Yüksel (Selma); H.W. Vos (Helma); G. van Amerongen (Geert); A.D.M.E. Osterhaus (Albert)

2006-01-01

textabstractThe comparative efficacy and safety of measles vaccination via the aerosol route versus subcutaneous injection has not been fully resolved. We vaccinated cynomolgus monkeys (Macaca fascicularis) with the live-attenuated Edmonston-Zagreb measles virus (MV) vaccine and compared different

Successful public health response to four cases of imported measles in Panama.

Science.gov (United States)

Sosa, Nestor; Guerra, Ilka; Abrego, Leyda; Cisneros, Julio; Castillo, Juan; Nieto-Guevara, Javier; Gálvez, Carlos; Moltó, Yadira; Smith, Rebecca E; Pascale, Juan Miguel

2012-08-21

In Panama, the last endemic cases of measles occurred in 1995. In this paper, we report four cases of imported measles in three girls and one boy after they returned from a trip to Poland and Israel between 28 April and 11 May 2011. The etiologic diagnosis of the four cases was confirmed by detection of IgM antibodies against measles virus and positive polymerase chain reaction using measles-specific primers. All cases had genotype D4 with close genetic similarity to virus reported from Poland. Public health interventions included isolation of the cases in their homes and an extensive search for and vaccination of contacts of the four cases, regardless of their vaccination status. A nationwide vaccination campaign was also implemented after the first case was identified. A total of 70,950 measles vaccine doses were administered in Panama in the two months following the identification of these cases. In addition, 94,179 persons were confirmed to have their immunization schedule up-to-date and did not receive the vaccine. No secondary cases were detected in Panama in the following six months.

Oncolytic measles virus enhances antitumour responses of adoptive CD8+NKG2D+ cells in hepatocellular carcinoma treatment.

Science.gov (United States)

Chen, Aiping; Zhang, Yonghui; Meng, Gang; Jiang, Dengxu; Zhang, Hailin; Zheng, Meihong; Xia, Mao; Jiang, Aiqin; Wu, Junhua; Beltinger, Christian; Wei, Jiwu

2017-07-12

There is an urgent need for novel effective treatment for hepatocellular carcinoma (HCC). Oncolytic viruses (OVs) not only directly lyse malignant cells, but also induce potent antitumour immune responses. The potency and precise mechanisms of antitumour immune activation by attenuated measles virus remain unclear. In this study, we investigated the potency of the measles virus vaccine strain Edmonston (MV-Edm) in improving adoptive CD8 + NKG2D + cells for HCC treatment. We show that MV-Edm-infected HCC enhanced the antitumour activity of CD8 + NKG2D + cells, mediated by at least three distinct mechanisms. First, MV-Edm infection compelled HCC cells to express the specific NKG2D ligands MICA/B, which may contribute to the activation of CD8 + NKG2D + cells. Second, MV-Edm-infected HCC cells stimulated CD8 + NKG2D + cells to express high level of FasL resulting in enhanced induction of apoptosis. Third, intratumoural administration of MV-Edm enhanced infiltration of intravenously injected CD8 + NKG2D + cells. Moreover, we found that MV-Edm and adoptive CD8 + NKG2D + cells, either administered alone or combined, upregulated the immune suppressive enzyme indoleamine 2,3-dioxygenase 1 (IDO1) in HCC. Elimination of IDO1 by fludarabine enhanced antitumour responses. Taken together, our data provide a novel and clinically relevant strategy for treatment of HCC.

Charge neutralization as the major factor for the assembly of nucleocapsid-like particles from C-terminal truncated hepatitis C virus core protein.

Science.gov (United States)

de Souza, Theo Luiz Ferraz; de Lima, Sheila Maria Barbosa; Braga, Vanessa L de Azevedo; Peabody, David S; Ferreira, Davis Fernandes; Bianconi, M Lucia; Gomes, Andre Marco de Oliveira; Silva, Jerson Lima; de Oliveira, Andréa Cheble

2016-01-01

Hepatitis C virus (HCV) core protein, in addition to its structural role to form the nucleocapsid assembly, plays a critical role in HCV pathogenesis by interfering in several cellular processes, including microRNA and mRNA homeostasis. The C-terminal truncated HCV core protein (C124) is intrinsically unstructured in solution and is able to interact with unspecific nucleic acids, in the micromolar range, and to assemble into nucleocapsid-like particles (NLPs) in vitro . The specificity and propensity of C124 to the assembly and its implications on HCV pathogenesis are not well understood. Spectroscopic techniques, transmission electron microscopy and calorimetry were used to better understand the propensity of C124 to fold or to multimerize into NLPs when subjected to different conditions or in the presence of unspecific nucleic acids of equivalent size to cellular microRNAs. The structural analysis indicated that C124 has low propensity to self-folding. On the other hand, for the first time, we show that C124, in the absence of nucleic acids, multimerizes into empty NLPs when subjected to a pH close to its isoelectric point (pH ≈ 12), indicating that assembly is mainly driven by charge neutralization. Isothermal calorimetry data showed that the assembly of NLPs promoted by nucleic acids is enthalpy driven. Additionally, data obtained from fluorescence correlation spectroscopy show that C124, in nanomolar range, was able to interact and to sequester a large number of short unspecific nucleic acids into NLPs. Together, our data showed that the charge neutralization is the major factor for the nucleocapsid-like particles assembly from C-terminal truncated HCV core protein. This finding suggests that HCV core protein may physically interact with unspecific cellular polyanions, which may correspond to microRNAs and mRNAs in a host cell infected by HCV, triggering their confinement into infectious particles.

Measles Virus Suppresses RIG-I-like Receptor Activation in Dendritic Cells via DC-SIGN-Mediated Inhibition of PP1 Phosphatases

NARCIS (Netherlands)

Mesman, Annelies W.; Zijlstra-Willems, Esther M.; Kaptein, Tanja M.; de Swart, Rik L.; Davis, Meredith E.; Ludlow, Martin; Duprex, W. Paul; Gack, Michaela U.; Gringhuis, Sonja I.; Geijtenbeek, Teunis B. H.

2014-01-01

Dendritic cells (DCs) are targets of measles virus (MV) and play central roles in viral dissemination. However, DCs express the RIG-I-like receptors (RLRs) RIG-I and Mda5 that sense MV and induce type I interferon (IFN) production. Given the potency of this antiviral response, RLRs are tightly

Measles virus suppresses RIG-I-like receptor activation in dendritic cells via DC-SIGN-mediated inhibition of PP1 phosphatases

NARCIS (Netherlands)

A.W. Mesman (Annelies ); E.M. Zijlstra-Willems (Esther); T.M. Kaptein (Tanja); R.L. de Swart (Rik); M.E. Davis (Meredith); M. Ludlow (Martin); W.P. Duprex (Paul); M.U. Gack (Michaela); S.I. Gringhuis (Sonja); T.B.H. Geijtenbeek (Teunis)

2014-01-01

textabstractDendritic cells (DCs) are targets of measles virus (MV) and play central roles in viral dissemination. However, DCs express the RIG-I-like receptors (RLRs) RIG-I and Mda5 that sense MV and induce type I interferon (IFN) production. Given the potency of this antiviral response, RLRs are

Association between seroprevalence of measles and various social determinants in the year following a measles outbreak in Turkey.

Science.gov (United States)

Emek, M; Islek, D; Atasoylu, G; Ozbek, O A; Ceylan, A; Acikgoz, A; Tay, Z; Demiral, Y; Oktem, M A; Unal, B

2017-06-01

Despite an ongoing measles elimination programme, a measles outbreak occurred in 2013 in Turkey. Population-based seroprevalence studies are needed to determine seronegativity and explore the reasons for this outbreak. This study aimed to explore the seroprevalence of measles and its association with various social determinants in a provincial population in Turkey in the year following a measles outbreak. Cross-sectional study. This study was conducted in Manisa Province in 2014 in a sample of 1740 people aged >2 years. The dependent variable was the seroprevalence of measles. Independent variables were sex, age, migration, household size, household density, income, education level, existence of chronic disease and occupational class. Blood samples were collected from participants at family health centres. The presence of specific measles antibodies in serum samples was determined using an anti-measles virus IgG enzyme-linked immunosorbent assay test. Chi-squared test and logistic regression analysis were performed. Overall, data from 1250 people were analysed. The seroprevalence of measles in the whole study population was 82.2% (95% confidence interval 80.0-84.2). Seroprevalence was 55.4% among subjects aged 2-9 years, 48.7% among subjects aged 10-19 years, 74.1% among subjects aged 20-29 years and 93.6% among subjects aged 30-39 years (P 40 years was >95%. The lowest seroprevalence was found in primary school children (40.2%), followed by those below the age for primary education (69.8%) and secondary school graduates (75.1%). The prevalence of measles seronegativity was not associated with any of the social determinants when adjusted for age. The seroprevalence of measles was lower than expected in the study population and was particularly low in subjects aged measles elimination targets, suggesting that it may be necessary to re-evaluate the need for an extra dose of measles vaccine. Copyright © 2017 The Royal Society for Public Health. Published by Elsevier

Progress Toward Regional Measles Elimination - Worldwide, 2000-2016.

Science.gov (United States)

Dabbagh, Alya; Patel, Minal K; Dumolard, Laure; Gacic-Dobo, Marta; Mulders, Mick N; Okwo-Bele, Jean-Marie; Kretsinger, Katrina; Papania, Mark J; Rota, Paul A; Goodson, James L

2017-10-27

The fourth United Nations Millennium Development Goal, adopted in 2000, set a target to reduce child mortality by two thirds by 2015. One indicator of progress toward this target was measles vaccination coverage (1). In 2010, the World Health Assembly (WHA) set three milestones for measles control by 2015: 1) increase routine coverage with the first dose of a measles-containing vaccine (MCV1) among children aged 1 year to ≥90% at the national level and to ≥80% in every district; 2) reduce global annual measles incidence to measles mortality by 95% from the 2000 estimate (2).* In 2012, WHA endorsed the Global Vaccine Action Plan, † with the objective of eliminating measles in four World Health Organization (WHO) regions by 2015 and in five regions by 2020. Countries in all six WHO regions have adopted goals for measles elimination by or before 2020. Measles elimination is defined as the absence of endemic measles virus transmission in a region or other defined geographic area for ≥12 months, in the presence of a high quality surveillance system that meets targets of key performance indicators. This report updates a previous report (3) and describes progress toward global measles control milestones and regional measles elimination goals during 2000-2016. During this period, annual reported measles incidence decreased 87%, from 145 to 19 cases per million persons, and annual estimated measles deaths decreased 84%, from 550,100 to 89,780; measles vaccination prevented an estimated 20.4 million deaths. However, the 2015 milestones have not yet been met; only one WHO region has been verified as having eliminated measles. Improved implementation of elimination strategies by countries and their partners is needed, with focus on increasing vaccination coverage through substantial and sustained additional investments in health systems, strengthening surveillance systems, using surveillance data to drive programmatic actions, securing political commitment, and raising

Identification of a High Affinity Nucleocapsid Protein Binding Element from The Bovine Leukemia Virus Genome

Science.gov (United States)

Yildiz, F. Zehra; Babalola, Kathleen; Summers, Michael F.

2012-01-01

Retroviral genome recognition is mediated by interactions between the nucleocapsid (NC) domain of the virally encoded Gag polyprotein and cognate RNA packaging elements that, for most retroviruses, appear to reside primarily within the 5′-untranslated region (5′-UTR) of the genome. Recent studies suggest that a major packaging determinant of Bovine Leukemia Virus (BLV), a member of the human T-cell leukemia virus (HTLV)/BLV family and a non-primate animal model for HTLV-induced leukemogenesis, resides within the gag open reading frame. We have prepared and purified the recombinant BLV NC protein and conducted electrophoretic mobility shift and isothermal titration calorimetry studies with RNA fragments corresponding to these proposed packaging elements. The gag-derived RNAs did not exhibit significant affinity for NC, suggesting an alternate role in packaging. However, an 83-nucleotide fragment of the 5′-UTR that resides just upstream of the gag start codon binds NC stoichiometrically and with high affinity (Kd = 136 ± 21 nM). These nucleotides were predicted to form tandem hairpin structures, and studies with smaller fragments indicate that the NC binding site resides exclusively within the distal hairpin (residues G369- U399, Kd = 67 ± 8 nM at physiological ionic strength). Unlike all other structurally characterized retroviral NC binding RNAs, this fragment is not expected to contain exposed guanosines, suggesting that RNA binding may be mediated by a previously uncharacterized mechanism. PMID:22846919

Transmission of measles among healthcare Workers in Hospital W, Xinjiang Autonomous Region, China, 2016.

Science.gov (United States)

Jia, Haimei; Ma, Chao; Lu, Mengting; Fu, Jianping; Rodewald, Lance E; Su, Qiru; Wang, Huaqin; Hao, Lixin

2018-01-12

As China approaches the elimination of measles, outbreaks of measles continue to occur. Healthcare workers (HCWs) are known to be at high risk of infection and transmission of measles virus. A measles outbreak occurred in a hospital in Xinjiang Uighur Autonomous Region of the People's Republic of China. We report an investigation of this outbreak and its implications for measles elimination and outbreak preparedness. We conducted a retrospective search for measles cases using hospital records. Information on cases was collected by interview, and was used to determine epidemiological linkages. We surveyed HCWs to determine their demographic characteristics, disease history and vaccination status, and knowledge about measles. We identified 19 cases, ages 18 to 45 years, in Hospital W between December 2015 and January 2016; 14 were laboratory-confirmed, and 5 were epidemiologically linked. The primary case was a 25-year-old neurology department nurse who developed a rash on 22 December 2015 that was reported on 11 January 2016. She continued working and living with her workmates in a dormitory during her measles transmission period. Among the 19 infected HCWs, 2 had received a dose of measles-containing vaccine (MCV) before the outbreak, and 16 had unknown vaccination status. Outbreak response immunization activities were started on 8 January in a non-selective manner by offering vaccine regardless of vaccination history; 605(68%) of 890 HCWs were vaccinated. The HCW survey had a 73% response rate (646/890); 41% of HCWs reported that they had received MCV before outbreak, and 56% exhibited good knowledge of measles symptoms, transmission, complications, and vaccination. Low MCV coverage, low measles knowledge among HCWs, delayed reporting of measles cases, and absence of proper case management were associated with this outbreak. Training and vaccinating HCWs against measles are essential activities to prevent measles virus transmission among HCWs.

Trials of Edmonston-Zagreb measles vaccine in Guinea-Bissau

DEFF Research Database (Denmark)

Jensen, T G; Whittle, H; Mordhorst, Camilla

1994-01-01

In two trials of measles vaccination in Guinea-Bissau, children were randomized to receive either the Edmonston-Zagreb (EZ) virus at age 4-8 months or, as a control group, a standard dose (5000 p.f.u.) of the Schwarz (SW) virus at 9-12 months. In the first trial a medium dose of EZ virus (40,000 p...

Nosocomial measles cluster in Denmark following an imported case, December 2008-January 2009

DEFF Research Database (Denmark)

Groth, C; Bottiger, Be; Plesner, A

2009-01-01

A cluster of six confirmed cases with identical measles virus genotype was reported in Denmark between December 2008 and January 2009. The findings highlight the importance of vaccination before travelling and adherence to the routine vaccination schedule.......A cluster of six confirmed cases with identical measles virus genotype was reported in Denmark between December 2008 and January 2009. The findings highlight the importance of vaccination before travelling and adherence to the routine vaccination schedule....

Measles outbreak in the Republic of the Marshall Islands, 2003.

Science.gov (United States)

Hyde, Terri B; Dayan, Gustavo H; Langidrik, Justina R; Nandy, Robin; Edwards, Russell; Briand, Kennar; Konelios, Mailynn; Marin, Mona; Nguyen, Huong Q; Khalifah, Anthony P; O'leary, Michael J; Williams, Nobia J; Bellini, William J; Bi, Daoling; Brown, Cedric J; Seward, Jane F; Papania, Mark J

2006-04-01

Measles is a highly contagious viral infection. Measles transmission can be prevented through high population immunity (>or=95%) achieved by measles vaccination. In the Republic of the Marshall Islands (RMI), no measles cases were reported during 1989-2002; however, a large measles outbreak occurred in 2003. Reported 1-dose measles vaccine coverage among children aged 12-23 months varied widely (52-94%) between 1990 and 2000. RMI is a Pacific island nation (1999 population: 50,840). A measles case was defined as fever, rash, and cough, or coryza, or conjunctivitis, in an RMI resident between July 13 and November 7, 2003. A vaccination campaign was used for outbreak control. Of the 826 reported measles cases, 766 (92%) occurred in the capital (Majuro). There were 186 (23%) cases in infants aged or=15 years. The attack rate was highest among infants (Majuro atoll: 213 cases/1,000 infants). Among cases aged 1-14 years, 281 (59%) reported no measles vaccination before July 2003. There were 100 hospitalizations and 3 deaths. The measles H1 genotype was identified. The vaccination campaign resulted in 93% coverage among persons aged 6 months to 40 years. Interpretation Populations without endemic measles transmission can accumulate substantial susceptibility and be at risk for large outbreaks when measles virus is imported. 'Islands' of measles susceptibility may develop in infants, adults, and any groups with low vaccine coverage. To prevent outbreaks, high population immunity must be sustained by maintaining and documenting high vaccine coverage.

The significance for epidemiological studies anti-measles antibody detection examined by enzyme immunoassay (EIA) and plaque reduction neutralization test (PRNT).

Science.gov (United States)

Siennicka, Joanna; Częścik, Agnieszka; Trzcińska, Agnieszka

2014-01-01

The paper discusses the role of anti-measles antibodies for protection and significance for epidemiological studies determination of antibodies by different serological methods. The comparison of anti-measles virus antibodies levels measured by enzyme immunoassay (EIA) and Plaque Reduction Neutralization Test (PRNT) was described. It was found that the 200 mIU/ml of anti-measles activity measured by PRNT (level protection against symp- tomatic disease) is equivalent of 636 mIU/ml measured by EIA (Enzygnost®Anti-Measles Virus/IgG, Simens).

Biased hypermutation occurred frequently in a gene inserted into the IC323 recombinant measles virus during its persistence in the brains of nude mice

Energy Technology Data Exchange (ETDEWEB)

Otani, Sanae [Department of Virology and Graduate School of Medicine, Osaka City University, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585 (Japan); Department of Pediatrics, Graduate School of Medicine, Osaka City University, Osaka (Japan); Ayata, Minoru, E-mail: maverick@med.osaka-cu.ac.jp [Department of Virology and Graduate School of Medicine, Osaka City University, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585 (Japan); Takeuchi, Kaoru [Laboratory of Environmental Microbiology, Division of Biomedical Science, Faculty of Medicine, University of Tsukuba, Ibaraki (Japan); Takeda, Makoto [Department of Virology 3, National Institute of Infectious Diseases, Tokyo (Japan); Shintaku, Haruo [Department of Pediatrics, Graduate School of Medicine, Osaka City University, Osaka (Japan); Ogura, Hisashi [Department of Virology and Graduate School of Medicine, Osaka City University, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585 (Japan)

2014-08-15

Measles virus (MV) is the causative agent of measles and its neurological complications, subacute sclerosing panencephalitis (SSPE) and measles inclusion body encephalitis (MIBE). Biased hypermutation in the M gene is a characteristic feature of SSPE and MIBE. To determine whether the M gene is the preferred target of hypermutation, an additional transcriptional unit containing a humanized Renilla reniformis green fluorescent protein (hrGFP) gene was introduced into the IC323 MV genome, and nude mice were inoculated intracerebrally with the virus. Biased hypermutation occurred in the M gene and also in the hrGFP gene when it was inserted between the leader and the N gene, but not between the H and L gene. These results indicate that biased hypermutation is usually found in a gene whose function is not essential for viral proliferation in the brain and that the location of a gene in the MV genome can affect its mutational frequency. - Highlights: • Wild-type MV can cause persistent infections in nude mice. • Biased hypermutation occurred in the M gene. • Biased hypermutation occurred in an inessential gene inserted between the leader and the N gene.

Biased hypermutation occurred frequently in a gene inserted into the IC323 recombinant measles virus during its persistence in the brains of nude mice

International Nuclear Information System (INIS)

Otani, Sanae; Ayata, Minoru; Takeuchi, Kaoru; Takeda, Makoto; Shintaku, Haruo; Ogura, Hisashi

2014-01-01

Measles virus (MV) is the causative agent of measles and its neurological complications, subacute sclerosing panencephalitis (SSPE) and measles inclusion body encephalitis (MIBE). Biased hypermutation in the M gene is a characteristic feature of SSPE and MIBE. To determine whether the M gene is the preferred target of hypermutation, an additional transcriptional unit containing a humanized Renilla reniformis green fluorescent protein (hrGFP) gene was introduced into the IC323 MV genome, and nude mice were inoculated intracerebrally with the virus. Biased hypermutation occurred in the M gene and also in the hrGFP gene when it was inserted between the leader and the N gene, but not between the H and L gene. These results indicate that biased hypermutation is usually found in a gene whose function is not essential for viral proliferation in the brain and that the location of a gene in the MV genome can affect its mutational frequency. - Highlights: • Wild-type MV can cause persistent infections in nude mice. • Biased hypermutation occurred in the M gene. • Biased hypermutation occurred in an inessential gene inserted between the leader and the N gene

Measles and canine distemper virus antibodies in patients with multiple sclerosis determined by radioimmunoassay

International Nuclear Information System (INIS)

Arnadottir, T.

1980-01-01

Antibodies against measles virus (MV) and canine distemper virus (CDV) were measured by solid-phase radioimmunoassay (RIA) of sera and cerebrospinal fluid (CSF) from 28 patients with multiple sclerosis (MS) and matched neurological controls. When the groups were compared for MV antibody titers and CDV antibody titers of sera and MV/CDV serum antibody titer ratios, no significant difference was found. The CDV antibody titers and the MV antibody titers were in good correlation. CDV antibodies showed RIA titration curves typical of low avidity antibodies. In tests for MV antibodies in CSF, 82% of the MS patients and 19% of the controls were positive, whereas 36% of the MS patients and 4% of the controls were positive in CDV RIA. The correlation between MV and CDV antibody levels, the low avidity of CDV antibodies and the fact that absorption of the specimens with MV antigen abolished all CDV antibody activity suggest that the CDV antibodies are MV antibodies cross-reacting with CDV. It is concluded that canine distemper virus is unlikely to be involved in the etiology of multiple sclerosis. (author)

Peptide domains involved in the localization of the porcine reproductive and respiratory syndrome virus nucleocapsid protein to the nucleolus

International Nuclear Information System (INIS)

Rowland, Raymond R.R.; Schneider, Paula; Fang Ying; Wootton, Sarah; Yoo, Dongwan; Benfield, David A.

2003-01-01

The nucleocapsid (N) protein of porcine reproductive and respiratory syndrome virus (PRRSV) is the principal component of the viral nucleocapsid and localizes to the nucleolus. Peptide sequence analysis of the N protein of several North American isolates identified two potential nuclear localization signal (NLS) sequences located at amino acids 10-13 and 41-42, which were labeled NLS-1 and NLS-2, respectively. Peptides containing NLS-1 or NLS-2 were sufficient to accumulate enhanced green fluorescent protein (EGFP) in the nucleus. The inactivation of NLS-1 by site-directed mutagenesis or the deletion of the first 14 amino acids did not affect N protein localization to the nucleolus. The substitution of key lysine residues with uncharged amino acids in NLS-2 blocked nuclear/nucleolar localization. Site-directed mutagenesis within NLS-2 identified the sequence, KKNKK, as forming the core localization domain within NLS-2. Using an in vitro pull-down assay, the N protein was able to bind importin-α, importin-β nuclear transport proteins. The localization pattern of N-EGFP fusion peptides represented by a series of deletions from the C- and N-terminal ends of the N protein identified a region covering amino acids 41-72, which contained a nucleolar localization signal (NoLS) sequence. The 41-72 N peptide when fused to EGFP mimicked the nucleolar-cytoplasmic distribution of native N. These results identify a single NLS involved in the transport of N from the cytoplasm and into nucleus. An additional peptide sequence, overlapping NLS-2, is involved in the further targeting of N to the nucleolus

ANALISIS GEN HAEMAGGLUTININ PADA VIRUS CAMPAK LIAR

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Subangkit Subangkit

2015-05-01

Full Text Available AbstrakPenyakit Campak disebabkan oleh virus campak yang termasuk genus Morbilivirus dan Family Paramyxoviridae. Penyakit campak masih menjadi masalah kesehatan karena masih ditemukan Kejadian Luar Biasa (KLB di Indonesia. Salah satu penyebab terjadinya KLB tersebut diduga sebagaiakibat perbedaan antigenesitas antara strain vaksin yang digunakan dengan strain virus campak liar yang beredar di Indonesia. Penelitian ini bertujuan mendapatkan gambaran tentang karakteristik genetik gen Haemagglutinin virus campak liar yang ada di Indonesia. Spesimen yang digunakan sebanyak 27 isolat virus penyebab KLB dari 17 propinsi selama periode tahun 2003-2010. Isolat virus dilakukan pemeriksaan secara RT-PCR dan sekuensing dengan metode Sanger. Hasil sekuensing dianalisis dengan menggunakan perangkat lunak Bioedit 7.0 dan MEGA 4.0. Hasil penelitian didapatkan perbedaan 10 asam amino antara virus campak strain vaksin CAM-70 dan virus campak liar pada posisi D416N; K424T; V451M; N455T; V466I; I473T; F476L; Y481S atau Y481N; H495N; G505D. Kesimpulan penelitian ini adalah terdapat perbedaan karakteristik genetik antara virus campak liar di Indonesia berbeda dengan strain virus vaksin CAM-70.Kata kunci : Campak, Analisis Molekuler, Hemagglutinin, CD46AbstractMeasles is caused by virus belonging to the genus Morbilivirus and Family Paramyxoviridae. Measles is still a public health problem because outbreak of measles still found in Indonesia. Outbreak is suspected as a result of differences in antigenicity between vaccine strains used with wild-type measles virus strains circulating in Indonesia. This study aims to get genetic characteristics of wild-type measles virus haemagglutinin gene in Indonesia. The specimens were used 27 viral isolates from 17 provinces period 2003-2010. Viral isolates examined by RT-PCR and sequencing with Sanger method. Sequencing analysis were conducted using Bioedit 7.0 and MEGA 4.0 software. The results showed 10 amino acid differences

Autographa californica multiple nucleopolyhedrovirus PK-1 is essential for nucleocapsid assembly

Energy Technology Data Exchange (ETDEWEB)

Liang, Changyong, E-mail: cyliang@yzu.edu.cn [College of Bioscience and Biotechnology, Yangzhou University, Yangzhou 225009 (China); Li, Min; Dai, Xuejuan; Zhao, Shuling; Hou, Yanling; Zhang, Yongli; Lan, Dandan [College of Bioscience and Biotechnology, Yangzhou University, Yangzhou 225009 (China); Wang, Yun; Chen, Xinwen [State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071 (China)

2013-09-01

PK-1 (Ac10) is a baculovirus-encoded serine/threonine kinase and its function is unclear. Our results showed that a pk-1 knockout AcMNPV failed to produce infectious progeny, while the pk-1 repair virus could rescue this defect. qPCR analysis demonstrated that pk-1 deletion did not affect viral DNA replication. Analysis of the repaired recombinants with truncated pk-1 mutants demonstrated that the catalytic domain of protein kinases of PK-1 was essential to viral infectivity. Moreover, those PK-1 mutants that could rescue the infectious BV production defect exhibited kinase activity in vitro. Therefore, it is suggested that the kinase activity of PK-1 is essential in regulating viral propagation. Electron microscopy revealed that pk-1 deletion affected the formation of normal nucleocapsids. Masses of electron-lucent tubular structures were present in cell transfected with pk-1 knockout bacmid. Therefore, PK-1 appears to phosphorylate some viral or cellular proteins that are essential for DNA packaging to regulate nucleocapsid assembly. - Highlights: • A pk-1 knockout AcMNPV failed to produce infectious progeny. • The pk-1 deletion did not affect viral DNA replication. • The catalytic domain of protein kinases (PKc) of PK-1 was essential to viral infectivity. • The kinase activity of PK-1 is essential in regulating viral propagation. • PK-1 appears to phosphorylate some viral proteins that are essential for DNA packaging to regulate nucleocapsid assembly.

Measles mimicking HIV seroconversion syndrome: a case report

Directory of Open Access Journals (Sweden)

Brook Gary

2010-02-01

Full Text Available Abstract Introduction Measles is on the rise in the United Kingdom and must be considered in the differential diagnosis of any patient presenting with fever and rash. As a highly infectious disease, identified patients must be isolated in the hospital setting. Case presentation A 28-year-old Polish woman presented ill to the accident and emergency department of a district general hospital. She had painful genital ulceration, oral soreness, fever, and a facial rash. She became hypoxic within 24 hours of presentation and began to tire, thus requiring noninvasive ventilation. Her respiratory symptoms were out of proportion to the findings of her chest radiograph, which remained virtually normal. Human immunodeficiency virus seroconversion syndrome complicated by Pneumocystis carinii pneumonia was high among the differential diagnoses. She was given cotrimoxazole, high-dose steroids, broad spectrum antibiotics, and anti fungal cover. Human immunodeficiency virus polymerase chain reaction came back as negative and her symptoms resolved within 10 days of presentation. She was taken off all treatment and discharged home feeling well. Serological measles was confirmed as part of a viral screen, but its clinical suspicion was low. Conclusion The presentation of measles in this patient was unique and atypical. With its incidence rising in the United Kingdom, measles must be increasingly considered as a differential diagnosis in patients presenting with fever and rash.

Acute measles encephalitis in partially vaccinated adults.

Directory of Open Access Journals (Sweden)

Annette Fox

Full Text Available The pathogenesis of acute measles encephalitis (AME is poorly understood. Treatment with immune-modulators is based on theories that post-infectious autoimmune responses cause demyelination. The clinical course and immunological parameters of AME were examined during an outbreak in Vietnam.Fifteen measles IgM-positive patients with confusion or Glasgow Coma Scale (GCS score below 13, and thirteen with uncomplicated measles were enrolled from 2008-2010. Standardized clinical exams were performed and blood collected for lymphocyte and measles- and auto-antibody analysis. The median age of AME patients was 21 years, similar to controls. Eleven reported receiving measles vaccination when aged one year. Confusion developed a median of 4 days after rash. Six patients had GCS <8 and four required mechanical ventilation. CSF showed pleocytosis (64% and proteinorrhachia (71% but measles virus RNA was not detected. MRI revealed bilateral lesions in the cerebellum and brain stem in some patients. Most received dexamethasone +/- IVIG within 4 days of admission but symptoms persisted for ≥3 weeks in five. The concentration of voltage gated calcium channel-complex-reactive antibodies was 900 pM in one patient, and declined to 609 pM ∼ 3 months later. Measles-reactive IgG antibody avidity was high in AME patients born after vaccine coverage exceeded 50% (∼ 25 years earlier. AME patients had low CD4 (218/µl, p = 0.029 and CD8 (200/µl, p = 0.012 T-cell counts compared to controls.Young adults presenting with AME in Vietnam reported a history of one prior measles immunization, and those aged <25 years had high measles-reactive IgG avidity indicative of prior vaccination. This suggests that one-dose measles immunization is not sufficient to prevent AME in young adults and reinforces the importance of maintaining high coverage with a two-dose measles immunization schedule. Treatment with corticosteroids and IVIG is common practice, and should be

An increasing, potentially measles-susceptible population over time after vaccination in Korea.

Science.gov (United States)

Kang, Hae Ji; Han, Young Woo; Kim, Su Jin; Kim, You-Jin; Kim, A-Reum; Kim, Joo Ae; Jung, Hee-Dong; Eom, Hye Eun; Park, Ok; Kim, Sung Soon

2017-07-24

In Korea, measles occurs mainly in infants measles infection. Age-specific measles seroprevalence was evaluated by performing enzyme immunoassays and plaque reduction-neutralization tests on 3050 subjects aged 0-50years (birth cohort 1964-2014) and 480 subjects aged 2-30years (birth cohort 1984-2012). The overall seropositivity and measles antibody concentrations were 71.5% and 1366mIU/mL, respectively. Progressive decline in antibody levels and seropositivity were observed over time after vaccination in infants, adolescents, and young adults. The accumulation of potentially susceptible individuals in the population was confirmed by comparing data from 2010 and 2014 seroprevalence surveys. The statistical correlation between measles incidence and measles seronegativity was determined. Waning levels of measles antibodies with increasing time post-vaccination suggests that measles susceptibility is potentially increasing in Korea. This trend may be related to limitations of vaccine-induced immunity in the absence of natural boosting by the wild virus, compared to naturally acquired immunity triggered by measles infection. This study provides an important view into the current measles herd immunity in Korea. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

[Monitoring of implementation of international programs of poliomyelitis eradication and measles and rubella elimination in the Republic of Belarus].

Science.gov (United States)

2012-01-01

Monitoring of implementation of international programs of poliomyelitis eradication, and measles and rubella elimination in the Republic of Belarus based on results of molecular-epidemiologic studies of 2009 - 2010. 271 viral agents isolated from children with acute flaccid paralysis syndrome, other diseases, healthy children and from sewage water within the framework of poliomyelitis control implementation were identified by serological and molecular methods. Blood sera of 528 patients with fever and rash were examined for the presence of IgM to measles and rubella virus, 418 - for the presence of IgM to parvovirus B19 and parvovirus DNA. Blood sera of 33 pregnant women and 64 children with signs of intrauterine infection were studied for IgM and IgG antibodies to rubella virus. Measles virus was isolated, N-gene sequence and phylogenetic analysis carried out. The studies performed confirmed that indigenous wild polioviruses in the country do not circulate, imported wild or vaccine-related polioviruses were also not detected. Measles and rubella morbidity in the Republic of Belarus was less than 1 in 1 000 000. 2 cases of rubella (2009) and 1 case of measles (2010) was detected during adequate control level: the rate of detection of patients with fever and rash, in whom measles and rubella diagnosis was excluded by the results of laboratory examination, was more than 2 in 100 000 of the population. The etiologic agent in more than 20% of diseases with fever and rash was parvovirus B19. A single case of measles was caused by genotype D8 virus imported from India. The data obtained give evidence to conformance of the poliomyelitis, measles, rubella, innate rubella syndrome control implemented in the Republic of Belarus to WHO recommendations; maintenance of status of country as free from poliomyelitis and achievement of main criteria of elimination of both measles and rubella by 2010.

Interaction of measles virus vectors with Auger electron emitting radioisotopes

International Nuclear Information System (INIS)

Dingli, David; Peng, K.-W.; Harvey, Mary E.; Vongpunsawad, Sompong; Bergert, Elizabeth R.; Kyle, Robert A.; Cattaneo, Roberto; Morris, John C.; Russell, Stephen J.

2005-01-01

A recombinant measles virus (MV) expressing the sodium iodide symporter (NIS) is being considered for therapy of advanced multiple myeloma. Auger electrons selectively damage cells in which the isotope decays. We hypothesized that the Auger electron emitting isotope 125 I can be used to control viral proliferation. MV was engineered to express both carcinoembryonic antigen and NIS (MV-NICE). Cells were infected with MV-NICE and exposed to 125 I with appropriate controls. MV-NICE replication in vitro is inhibited by the selective uptake of 125 I by cells expressing NIS. Auger electron damage is partly mediated by free radicals and abrogated by glutathione. In myeloma xenografts, control of MV-NICE with 125 I was not possible under the conditions of the experiment. MV-NICE does not replicate faster in the presence of radiation. Auger electron emitting isotopes effectively stop propagation of MV vectors expressing NIS in vitro. Additional work is necessary to translate these observations in vivo

Attenuated Salmonella enterica serovar Typhi and Shigella flexneri 2a strains mucosally deliver DNA vaccines encoding measles virus hemagglutinin, inducing specific immune responses and protection in cotton rats.

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

2003-05-01

Measles remains a leading cause of child mortality in developing countries. Residual maternal measles antibodies and immunologic immaturity dampen immunogenicity of the current vaccine in young infants. Because cotton rat respiratory tract is susceptible to measles virus (MV) replication after intranasal (i.n.) challenge, this model can be used to assess the efficacy of MV vaccines. Pursuing a new measles vaccine strategy that might be effective in young infants, we used attenuated Salmonella enterica serovar Typhi CVD 908-htrA and Shigella flexneri 2a CVD 1208 vaccines to deliver mucosally to cotton rats eukaryotic expression plasmid pGA3-mH and Sindbis virus-based DNA replicon pMSIN-H encoding MV hemagglutinin (H). The initial i.n. dose-response with bacterial vectors alone identified a well-tolerated dosage (1 x 10(9) to 7 x 10(9) CFU) and a volume (20 micro l) that elicited strong antivector immune responses. Animals immunized i.n. on days 0, 28, and 76 with bacterial vectors carrying DNA plasmids encoding MV H or immunized parenterally with these naked DNA vaccine plasmids developed MV plaque reduction neutralizing antibodies and proliferative responses against MV antigens. In a subsequent experiment of identical design, cotton rats were challenged with wild-type MV 1 month after the third dose of vaccine or placebo. MV titers were significantly reduced in lung tissue of animals immunized with MV DNA vaccines delivered either via bacterial live vectors or parenterally. Since attenuated serovar Typhi and S. flexneri can deliver measles DNA vaccines mucosally in cotton rats, inducing measles immune responses (including neutralizing antibodies) and protection, boosting strategies can now be evaluated in animals primed with MV DNA vaccines.

Epidemiology and genetic characterization of measles strains in Senegal, 2004-2013.

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Dia, Ndongo; Fall, Ameth; Ka, Rouguiyatou; Fall, Amary; Kiori, David E; Goudiaby, Deborah G; Fall, Aichatou D; Faye, El Hadj Abdourahmane; Dosseh, Annick; Ndiaye, Kader; Diop, Ousmane M; Niang, Mbayame Nd

2015-01-01

In Senegal, with the variable routine vaccination coverage, the risk for illness and death from measles still exists as evidenced by the measles epidemic episode in 2009. Since 2002 a laboratory-based surveillance system of measles was established by the Ministry of Health and the Institut Pasteur de Dakar. The present study analysed the data collected over the 10 years inclusive between 2004-2013 in order to define a measles epidemiological profile in Senegal, and we carried out a phylogenetic analysis of measles virus circulating in Senegal over the period 2009-2012. A total number of 4580 samples were collected from suspected cases, with the most cases between 2008 and 2010 (2219/4580; 48.4%). The majority of suspected cases are found in children from 4-6 years old (29%). 981 (21.4%) were measles laboratory-confirmed by IgM ELISA. The measles confirmation rate per year is very high during 2009-2010 periods (48.5% for each year). Regarding age groups, the highest measles IgM-positivity rate occurred among persons aged over 15 years with 39.4% (115/292) followed by 2-3 years old age group with 30.4% (323/1062) and 30% (148/494) in children under one year old group. The majority of suspected cases were collected between February and June and paradoxically confirmed cases rates increased from July (77/270; 28.6%) and reached a peak in November with 60% (93/155). Phylogenetic analysis showed that all the 29 sequences from strains that circulated in Senegal between 2009 and 2012 belong to the B3 genotype and they are clustered in B3.1 (2011-2012) and B3.3 (2009-2011) sub-genotypes according to a temporal parameter. Improvements in the measles surveillance in Senegal are required and the introduction of oral fluid and FTA cards as an alternative to transportation of sera should be investigated to improve surveillance. The introduction of a national vaccine database including number of doses of measles-containing vaccine will greatly improve efforts to interrupt and

A Recombinant Measles Vaccine with Enhanced Resistance to Passive Immunity.

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Julik, Emily; Reyes-Del Valle, Jorge

2017-09-21

Current measles vaccines suffer from poor effectiveness in young infants due primarily to the inhibitory effect of residual maternal immunity on vaccine responses. The development of a measles vaccine that resists such passive immunity would strongly contribute to the stalled effort toward measles eradication. In this concise communication, we show that a measles virus (MV) with enhanced hemagglutinin (H) expression and incorporation, termed MVvac2-H2, retained its enhanced immunogenicity, previously established in older mice, when administered to very young, genetically modified, MV-susceptible mice in the presence of passive anti-measles immunity. This immunity level mimics the sub-neutralizing immunity prevalent in infants too young to be vaccinated. Additionally, toward a more physiological small animal model of maternal anti-measles immunity interference, we document vertical transfer of passive anti-MV immunity in genetically-modified, MV susceptible mice and show in this physiological model a better MVvac2-H2 immunogenic profile than that of the parental vaccine strain. In sum, these data support the notion that enhancing MV hemagglutinin incorporation can circumvent in vivo neutralization. This strategy merits additional exploration as an alternative pediatric measles vaccine.

Detection of Measles Virus Genotypes B3, D4, D5, D8, and H1 in the Surveillance System in Hokkaido, Japan, 2006-2015, the Last Decade toward the Elimination.

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Miyoshi, Masahiro; Komagome, Rika; Yamaguchi, Hiroki; Ohnishi, Asami; Kikuchi, Masayuki; Ishida, Setsuko; Nagano, Hideki; Okano, Motohiko

2017-05-24

Measles is an acute and highly contagious disease caused by measles virus (MeV). The government of Japan, following the last epidemic in 2007 and 2008, which was caused by genotype D5 strains, introduced a catch-up-vaccination program for teenagers during Japan fiscal years 2008-2012 and a mandatory case-based reporting system for the nationwide elimination. Furthermore, laboratory confirmation of measles cases by genotyping of isolates has been performed to clarify the source of infection and support the interruption of measles cases. Owing to these preventive measures, the number of measles cases has been steadily decreasing after the last epidemic. In March 2015, Japan was internationally verified as having achieved measles elimination by the World Health Organization Regional Office for the Western Pacific. The continuous elimination of measles and high levels of vaccination coverage for MeV have been maintained nationally. However, imported or import-associated cases of measles have sporadically occurred during this time. After the last nationwide epidemic, 17 imported or import-associated measles cases (MeV strains identified as genotypes H1, D4, D8, and B3) were reported in Hokkaido, the northern islands of Japan. In this study, we present the occurrence of measles and surveillance activities in Hokkaido during 2006-2015.

A simple sandwich ELISA (WELYSSA) for the detection of lyssavirus nucleocapsid in rabies suspected specimens using mouse monoclonal antibodies.

Science.gov (United States)

Xu, Gelin; Weber, Patrick; Hu, Qiaoling; Xue, Honggang; Audry, Laurent; Li, Chengping; Wu, Jie; Bourhy, Herve

2007-10-01

Monoclonal antibody (MAb)-based capture enzyme-linked immunosorbent assays (ELISA) were developed for the diagnosis of rabies-suspect specimens. A combination of four mouse monoclonal antibodies directed against the rabies virus nucleocapsid was selected and used for the detection. The test was optimized and standardized so that maximum concordance could be maintained with the standard procedures of rabies diagnosis recommended by the WHO expert committee. Using prototype viruses from the different genotypes of lyssavirus and from various geographic origins and phylogenetic lineages, this paper presents a reliable, rapid and transferable diagnostic method, named WELYSSA that readily permits the detection of lyssaviruses belonging to the 7 genotypes of lyssavirus circulating in Europe, Africa, Asia and Oceania. The threshold of detection of lyssavirus nucleocapsids is low (0.8 ng/ml). With a panel of 1030 specimens received for rabies diagnostic testing, this test was found to be highly specific (0.999) and sensitive (0.970) when compared to other recommended rabies diagnostic methods.

Prevalence of measles neutralizing antibody in children under 15 ...

African Journals Online (AJOL)

The immune status of children under 15 years in the Southwestern region of Nigeria against measles virus was determined using the neutralization test with a view to assessing the herd immunity to the virus in these communities. A total of 256 serum samples collected from children were tested by the beta method of ...

Charge neutralization as the major factor for the assembly of nucleocapsid-like particles from C-terminal truncated hepatitis C virus core protein

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Theo Luiz Ferraz de Souza

2016-11-01

Full Text Available Background Hepatitis C virus (HCV core protein, in addition to its structural role to form the nucleocapsid assembly, plays a critical role in HCV pathogenesis by interfering in several cellular processes, including microRNA and mRNA homeostasis. The C-terminal truncated HCV core protein (C124 is intrinsically unstructured in solution and is able to interact with unspecific nucleic acids, in the micromolar range, and to assemble into nucleocapsid-like particles (NLPs in vitro. The specificity and propensity of C124 to the assembly and its implications on HCV pathogenesis are not well understood. Methods Spectroscopic techniques, transmission electron microscopy and calorimetry were used to better understand the propensity of C124 to fold or to multimerize into NLPs when subjected to different conditions or in the presence of unspecific nucleic acids of equivalent size to cellular microRNAs. Results The structural analysis indicated that C124 has low propensity to self-folding. On the other hand, for the first time, we show that C124, in the absence of nucleic acids, multimerizes into empty NLPs when subjected to a pH close to its isoelectric point (pH ≈ 12, indicating that assembly is mainly driven by charge neutralization. Isothermal calorimetry data showed that the assembly of NLPs promoted by nucleic acids is enthalpy driven. Additionally, data obtained from fluorescence correlation spectroscopy show that C124, in nanomolar range, was able to interact and to sequester a large number of short unspecific nucleic acids into NLPs. Discussion Together, our data showed that the charge neutralization is the major factor for the nucleocapsid-like particles assembly from C-terminal truncated HCV core protein. This finding suggests that HCV core protein may physically interact with unspecific cellular polyanions, which may correspond to microRNAs and mRNAs in a host cell infected by HCV, triggering their confinement into infectious particles.

Meeting measles elimination indicators: surveillance performance in a regional area of Australia

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David N Durrheim

2011-08-01

Full Text Available The World Health Organization (WHO Western Pacific Region has established specific measles elimination surveillance indicators. There has been concern in Australia that these indicators may be too stringent and that measles elimination can occur without all surveillance prerequisites being met, in particular the minimum fever and rash clinician-suspected measles reporting rate with subsequent laboratory exclusion of measles. A regional public health unit in northern New South Wales, Australia, prompted local general practitioners to report fever and rash presentations that met the measles case definition or that they considered to be clinical measles. These notifications from July 2006 to June 2008 were reviewed to determine whether measles indicators for monitoring progress towards measles elimination could be achieved in Australia. Results confirmed that the surveillance indicators of “>2 reported suspected measles cases per 100 000 population,” “at least 80% of suspected cases adequately investigated within 48 hours” and “greater than 80% of cases had adequate blood samples collected” could be met. Only half the cases had virology that would allow genotyping of measles virus. Special efforts to engage and convince Australian medical doctors about the public health value of reporting clinically suggestive measles cases and collecting confirmatory blood tests, resulted in the current WHO Western Pacific Region indicators for progress towards measles elimination being met in a regional area of Australia.

Low titers of measles antibody in mothers whose infants suffered from measles before eligible age for measles vaccination

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Wu Qiaozhen

2010-05-01

Full Text Available Abstract Background Resurgence or outbreak of measles recently occurred in both developed and developing countries despite long-standing widespread use of measles vaccine. Measles incidence in China has increased since 2002, particularly in infants and in persons ≥ 15 years of age. It is speculated that infants may acquire fewer measles IgG from their mothers, resulting in the reduced duration of protection during their early months of life. This study aimed to clarify the reason of increased susceptibility to measles in young infants in China. Measles IgG in 24 measles infants ≤ 9 months of age and their vaccinated mothers was quantitatively measured. The mean measles neutralizing titer in the vaccinated mothers and in 13 age-match women with the histories of clinical measles were compared. Results All the mothers were confirmed to be vaccinated successfully by the presence of measles IgG. Six vaccinated mothers were positive for measles IgM and had high concentrations of measles IgG and the neutralizing antibody, indicating underwent natural boosting. The mean measles neutralizing titer in 18 vaccinated mothers without natural boosting were significantly lower than that in 13 age-match women with the histories of clinical measles (1:37 vs 1:182, P Conclusions Our results suggest that infants born to mothers who acquired immunity to measles by vaccination may get a relatively small amount of measles antibody, resulting in loss of the immunity to measles before the vaccination age. Measures to improve the immunity in young infants not eligible for measles vaccination would be critical to interrupt the measles transmission in China.

Rubella (German Measles, Three-Day Measles) Photos

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... Controls Cancel Submit Search The CDC Rubella (German Measles, Three-Day Measles) Note: Javascript is disabled or is not supported ... child's back. Distribution is similar to that of measles, but the lesions are less intensely red. This ...

Patterns of measles transmission among airplane travelers.

Science.gov (United States)

Edelson, Paul J

2012-09-01

With advanced air handling systems on modern aircraft and the high level of measles immunity in many countries, measles infection in air travelers may be considered a low-risk event. However, introduction of measles into countries where transmission has been controlled or eliminated can have substantial consequences both for the use of public health resources and for those still susceptible. In an effort to balance the relatively low likelihood of disease transmission among largely immune travelers and the risk to the public health of the occurrence of secondary cases resulting from importations, criteria in the United States for contact investigations for measles exposures consider contacts to be those passengers who are seated within 2 rows of the index case. However, recent work has shown that cabin air flow may not be as reliable a barrier to the spread of measles virus as previously believed. Along with these new studies, several reports have described measles developing after travel in passengers seated some distance from the index case. To understand better the potential for measles virus to spread on an airplane, reports of apparent secondary cases occurring in co-travelers of passengers with infectious cases of measles were reviewed. Medline™ was searched for articles in all languages from 1946 to week 1 of March 2012, using the search terms "measles [human] or rubeola" and ("aircraft" or "airplane" or "aeroplane" or "aviation" or "travel" or "traveler" or "traveller"); 45 citations were returned. Embase™ was searched from 1988 to week 11 2012, using the same search strategy; 95 citations were returned. Papers were included in this review if they reported secondary cases of measles occurring in persons traveling on an airplane on which a person or persons with measles also flew, and which included the seating location of both the index case(s) and the secondary case(s) on the plane. Nine reports, including 13 index cases and 23 apparent secondary cases

Photos of Measles and People with Measles

Science.gov (United States)

... Spanish Resources Related Links Measles and Rubella Initiative World Health Organization Pan American Health Organization Photos of Measles and ... Library (PHIL) Related Links Measles and Rubella Initiative World Health Organization Pan American Health Organization Language: English (US) Español ( ...

Correlation between live attenuated measles viral load and growth inhibition percentage in non-small cell lung cancer cell line

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Rasha Fadhel Obaid

2018-03-01

Conclusion Live attenuated measles virus strain induced cytotoxic effect against human lung cancer cell line (A549 by induction of apoptosis as an important mechanism of anti-tumor activity, in addition, it indicates a correlation between the quantity of MV genomesand percentage of growth inhibition. This relation  has proved that measles virus had anticancer effect.

Measles IgG antibody index correlates with T2 lesion load on MRI in patients with early multiple sclerosis.

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Berit Rosche

Full Text Available BACKGROUND: B cells and humoral immune responses play an important role in the pathogenesis and diagnosis of multiple sclerosis (MS. A characteristic finding in patients with MS is a polyspecific intrathecal B cell response against neurotropic viruses, specifically against measles virus, rubella virus, and varicella zoster virus, also known as an MRZ reaction (MRZR. Here, we correlated from the routine clinical diagnostics individual IgG antibody indices (AIs of MRZR with magnetic resonance imaging (MRI findings in patients with first MS diagnosis. METHODS/RESULTS: MRZR was determined in 68 patients with a clinically isolated syndrome (CIS or early relapsing-remitting MS (RRMS. Absolute AI values for measles virus, rubella virus, and varicella zoster virus were correlated with T2 lesion load and gadolinium enhancing lesions on cerebral MRI (cMRI and cMRI combined with spinal MRI (sMRI. Measles virus AI correlated significantly with T2 lesion load on cMRI (p = 0.0312, Mann-Whitney U test and the sum of lesions on cMRI and sMRI (p = 0.0413. Varicella zoster virus AI also showed a correlation with T2 lesion load on cMRI but did not reach statistical significance (p = 0.2893. CONCLUSION: The results confirm MRZR as part of the polyspecific immune reaction in MS with possible prognostic impact on MRI and clinical parameters. Furthermore, the data indicate that intrathecal measles virus IgG production correlates with disease activity on cMRI and sMRI in patients with early MS.

In Vitro Measles Virus Infection of Human Lymphocyte Subsets Demonstrates High Susceptibility and Permissiveness of both Naive and Memory B Cells.

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Laksono, Brigitta M; Grosserichter-Wagener, Christina; de Vries, Rory D; Langeveld, Simone A G; Brem, Maarten D; van Dongen, Jacques J M; Katsikis, Peter D; Koopmans, Marion P G; van Zelm, Menno C; de Swart, Rik L

2018-04-15

Measles is characterized by a transient immune suppression, leading to an increased risk of opportunistic infections. Measles virus (MV) infection of immune cells is mediated by the cellular receptor CD150, expressed by subsets of lymphocytes, dendritic cells, macrophages, and thymocytes. Previous studies showed that human and nonhuman primate memory T cells express higher levels of CD150 than naive cells and are more susceptible to MV infection. However, limited information is available about the CD150 expression and relative susceptibility to MV infection of B-cell subsets. In this study, we assessed the susceptibility and permissiveness of naive and memory T- and B-cell subsets from human peripheral blood or tonsils to in vitro MV infection. Our study demonstrates that naive and memory B cells express CD150, but at lower frequencies than memory T cells. Nevertheless, both naive and memory B cells proved to be highly permissive to MV infection. Furthermore, we assessed the susceptibility and permissiveness of various functionally distinct T and B cells, such as helper T (T H ) cell subsets and IgG- and IgA-positive memory B cells, in peripheral blood and tonsils. We demonstrated that T H 1T H 17 cells and plasma and germinal center B cells were the subsets most susceptible and permissive to MV infection. Our study suggests that both naive and memory B cells, along with several other antigen-experienced lymphocytes, are important target cells of MV infection. Depletion of these cells potentially contributes to the pathogenesis of measles immune suppression. IMPORTANCE Measles is associated with immune suppression and is often complicated by bacterial pneumonia, otitis media, or gastroenteritis. Measles virus infects antigen-presenting cells and T and B cells, and depletion of these cells may contribute to lymphopenia and immune suppression. Measles has been associated with follicular exhaustion in lymphoid tissues in humans and nonhuman primates, emphasizing the

The sf32 unique gene of Spodoptera frugiperda multiple nucleopolyhedrovirus (SfMNPV is a non-essential gene that could be involved in nucleocapsid organization in occlusion-derived virions.

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Inés Beperet

Full Text Available A recombinant virus lacking the sf32 gene (Sf32null, unique to the Spodoptera frugiperda multiple nucleopolyhedrovirus (SfMNPV, was generated by homologous recombination from a bacmid comprising the complete viral genome (Sfbac. Transcriptional analysis revealed that sf32 is an early gene. Occlusion bodies (OBs of Sf32null contained 62% more genomic DNA than viruses containing the sf32 gene, Sfbac and Sf32null-repair, although Sf32null DNA was three-fold less infective when injected in vivo. Sf32null OBs were 18% larger in diameter and contained 17% more nucleocapsids within ODVs than those of Sfbac. No significant differences were detected in OB pathogenicity (50% lethal concentration, speed-of-kill or budded virus production in vivo. In contrast, the production of OBs/larva was reduced by 39% in insects infected by Sf32null compared to those infected by Sfbac. The SF32 predicted protein sequence showed homology (25% identity, 44% similarity to two adhesion proteins from Streptococcus pyogenes and a single N-mirystoylation site was predicted. We conclude that SF32 is a non-essential protein that could be involved in nucleocapsid organization during ODV assembly and occlusion, resulting in increased numbers of nucleocapsids within ODVs.

Neurokinin-1 enables measles virus trans-synaptic spread in neurons

International Nuclear Information System (INIS)

Makhortova, Nina R.; Askovich, Peter; Patterson, Catherine E.; Gechman, Lisa A.; Gerard, Norma P.; Rall, Glenn F.

2007-01-01

Measles virus (MV), a morbillivirus that remains a significant human pathogen, can infect the central nervous system, resulting in rare but often fatal diseases, such as subacute sclerosing panencephalitis. Previous work demonstrated that MV was transmitted trans-synaptically and that, while a cellular receptor for the hemagglutinin (H) protein was required for MV entry, it was dispensable for subsequent cell-to-cell spread. Here, we explored what role the other envelope protein, fusion (F), played in trans-synaptic transport. We made the following observations: (1) MV-F expression in infected neurons was similar to that seen in infected fibroblasts; (2) fusion inhibitory peptide (FIP), an inhibitor of MV fusion, prevented both infection and spread in primary neurons; (3) Substance P, a neurotransmitter with the same active site as FIP, also blocked neuronal MV spread; and (4) both genetic deletion and pharmacological inhibition of the Substance P receptor, neurokinin-1 (NK-1), reduced infection of susceptible mice. Together, these data implicate a role for NK-1 in MV CNS infection and spread, perhaps serving as an MV-F receptor or co-receptor on neurons

A virus of hyperthermophilic archaea with a unique architecture among DNA viruses.

Science.gov (United States)

Rensen, Elena Ilka; Mochizuki, Tomohiro; Quemin, Emmanuelle; Schouten, Stefan; Krupovic, Mart; Prangishvili, David

2016-03-01

Viruses package their genetic material in diverse ways. Most known strategies include encapsulation of nucleic acids into spherical or filamentous virions with icosahedral or helical symmetry, respectively. Filamentous viruses with dsDNA genomes are currently associated exclusively with Archaea. Here, we describe a filamentous hyperthermophilic archaeal virus, Pyrobaculum filamentous virus 1 (PFV1), with a type of virion organization not previously observed in DNA viruses. The PFV1 virion, 400 ± 20 × 32 ± 3 nm, contains an envelope and an inner core consisting of two structural units: a rod-shaped helical nucleocapsid formed of two 14-kDa major virion proteins and a nucleocapsid-encompassing protein sheath composed of a single major virion protein of 18 kDa. The virion organization of PFV1 is superficially similar to that of negative-sense RNA viruses of the family Filoviridae, including Ebola virus and Marburg virus. The linear dsDNA of PFV1 carries 17,714 bp, including 60-bp-long terminal inverted repeats, and contains 39 predicted ORFs, most of which do not show similarities to sequences in public databases. PFV1 is a lytic virus that completely disrupts the host cell membrane at the end of the infection cycle.

Do HIV-positive adult immigrants need to be screened for measles-mumps-rubella and varicella zoster virus immunization?

Science.gov (United States)

Llenas-García, Jara; Rubio, Rafael; Hernando, Asunción; Arrazola, Pilar; Pulido, Federico

2013-08-01

A systematic screening for measles, mumps, rubella (MMR) and varicella zoster virus (VZV) in HIV-positive adult immigrants in Spain was evaluated, and factors associated with MMR and VZV vaccines' indication were studied. Every HIV-positive immigrant was tested for VZV and MMR-IgG. MMR vaccine was indicated to patients with lymphocytes CD4+ >200 cells/mm³ and a negative measles-IgG, a negative mumps-IgG and/or a negative rubella-IgG. VZV vaccine was indicated to every VZV-IgG negative patient with CD4+ >400 cells/mm³. In total, 289 patients were screened; seroprevalence was 95.2%, 92.2%, 70.3% and 89.3% for VZV, measles, mumps and rubella IgG, respectively. Having a negative VZV-IgG was statistically associated with coming from sub-Saharan Africa (prevalence ratio [PR]: 6.52; 95% CI: 1.71-24.84; p=0.006), while having secondary education was a protective factor (PR: 0.25; 95% CI: 0.07-0.97; p=0.045). Fourteen patients (4.8%) had indication of VZV vaccine; vaccination was feasible in 21.4% of them at first visit. Eighty-one patients (29.7%) had indication of MMR vaccine, most of them due to mumps-IgG negative (53.1%) or rubella-IgG negative (24.7%). Age Especial attention should be given to immigrant women of childbearing age.

Epidemiology of two large measles virus outbreaks in Catalonia: what a difference the month of administration of the first dose of vaccine makes.

Science.gov (United States)

Torner, Núria; Anton, Andres; Barrabeig, Irene; Lafuente, Sara; Parron, Ignasi; Arias, César; Camps, Neus; Costa, Josep; Martínez, Ana; Torra, Roser; Godoy, Pere; Minguell, Sofia; Ferrús, Glòria; Cabezas, Carmen; Domínguez, Ángela; Spain

2013-03-01

Measles cases in the European Region have been increasing in the last decade; this illustrates the challenge of what we are now encountering in the form of pediatric preventable diseases. In Catalonia, autochthonous measles was declared eliminated in the year 2000 as the result of high measles-mumps-rubella vaccine (MMR) coverage for first and second dose (15 mo and 4 y) since the mid-1990s. From then on, sporadic imported cases and small outbreaks appeared, until in 2006-2007 a large measles outbreak affecting mostly unvaccinated toddlers hit the Barcelona Health Region. Consequently, in January 2008, first dose administration of MMR was lowered from 15 to 12 mo of age. A new honeymoon period went by until the end of 2010, when several importations of cases triggered new sustained transmission of different wild measles virus genotypes, but this time striking young adults. The aim of this study is to show the effect of a change in MMR vaccination schedule policy, and the difference in age incidence and hospitalization rates of affected individuals between both outbreaks.   Epidemiologic data were obtained by case interviews and review of medical records. Samples for virological confirmation and genotyping of cases were collected as established in the Measles Elimination plan guidelines. Incidence rate (IR), rate ratio (RR) and their 95% CI and hospitalization rate (HR) by age group were determined. Statistic z was used for comparing proportions. Total number of confirmed cases was 305 in the 2010 outbreak and 381 in the 2006-2007 outbreak; mean age 20 y (SD 14.8 y; 3 mo to 51 y) vs. 15 mo (SD 13.1 y; 1 mo to 50 y). Highest proportion of cases was set in ≥ 25 y (47%) vs. 24.2% in 2006 (p < 0.001). Differences in IR for ≤ 15 mo (49/100,000 vs. 278.2/100,000; RR: 3,9; 95%CI 2,9-5.4) and in overall HR 29.8% vs. 15.7% were all statistically significant (p < 0.001). The change of the month of age for the administration of the first MMR dose proved successful to

Autographa californica multiple nucleopolyhedrovirus ac66 is required for the efficient egress of nucleocapsids from the nucleus, general synthesis of preoccluded virions and occlusion body formation

International Nuclear Information System (INIS)

Ke Jianhao; Wang Jinwen; Deng Riqiang; Wang Xunzhang

2008-01-01

Although orf66 (ac66) of Autographa californica multiple nucleopolyhedrovirus (AcMNPV) is conserved in all sequenced lepidopteran baculovirus genomes, its function is not known. This paper describes generation of an ac66 knockout AcMNPV bacmid mutant and analyses of the influence of ac66 deletion on the virus replication in Sf-9 cells so as to determine the role of ac66 in the viral life cycle. Results indicated that budded virus (BV) yields were reduced over 99% in ac66-null mutant infected cells in comparison to that in wild-type virus infected cells. Optical microscopy revealed that occlusion body synthesis was significantly reduced in the ac66 knockout bacmid-transfected cells. In addition, ac66 deletion interrupted preoccluded virion synthesis. The mutant phenotype was rescued by an ac66 repair bacmid. On the other hand, real-time PCR analysis indicated that ac66 deletion did not affect the levels of viral DNA replication. Electron microscopy revealed that ac66 is not essential for nucleocapsid assembly, but for the efficient transport of nucleocapsids from the nucleus to the cytoplasm. These results suggested that ac66 plays an important role for the efficient exit of nucleocapsids from the nucleus to the cytoplasm for BV synthesis as well as for preoccluded virion and occlusion synthesis

Dendritic Cell Targeted Chitosan Nanoparticles for Nasal DNA Immunization against SARS CoV Nucleocapsid Protein

OpenAIRE

Raghuwanshi, Dharmendra; Mishra, Vivek; Das, Dipankar; Kaur, Kamaljit; Suresh, Mavanur R.

2012-01-01

This work investigates the formulation and in vivo efficacy of dendritic cell (DC) targeted plasmid DNA loaded biotinylated chitosan nanoparticles for nasal immunization against nucleocapsid (N) protein of severe acute respiratory syndrome coronavirus (SARS-CoV) as antigen. The induction of antigen-specific mucosal and systemic immune response at the site of virus entry is a major challenge for vaccine design. Here, we designed a strategy for non-invasive receptor mediated gene delivery to na...

Epstein–Barr Virus, but Not Cytomegalovirus, Latency Accelerates the Decay of Childhood Measles and Rubella Vaccine Responses—A 10-Year Follow-up of a Swedish Birth Cohort

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Gintare Lasaviciute

2017-12-01

Full Text Available BackgroundEpstein–Barr virus (EBV and cytomegalovirus (CMV are ubiquitous and persistent herpesviruses commonly acquired during childhood. Both viruses have a significant impact on the immune system, especially through mediating the establishment of cellular immunity, which keeps these viruses under control for life. Far less is known about how these viruses influence B-cell responses.ObjectivesTo evaluate the impact of latent EBV and CMV infection on rubella- and measles-specific antibody responses as well as on the B-cell compartment in a prospective birth cohort followed during the first 10 years of life.MethodsIgG titers against rubella and measles vaccines were measured in plasma obtained from the same donors at 2, 5, and 10 years of age. Peripheral B-cell subsets were evaluated ex vivo at 2 and 5 years of age. Factors related to optimal B-cell responses including IL-21 and CXCL13 levels in plasma were measured at all-time points.ResultsEBV carriage in the absence of CMV associated with an accelerated decline of rubella and measles-specific IgG levels (p = 0.003 and p = 0.019, respectively, linear mixed model analysis, while CMV carriage in the absence of EBV associated with delayed IgG decay over time for rubella (p = 0.034. At 5 years of age, EBV but not CMV latency associated with a lower percentage of plasmablasts, but higher IL-21 levels in the circulation.ConclusionOur findings suggest that EBV carriage in the absence of CMV influences the B-cell compartment and the dynamics of antibody responses over time during steady state in the otherwise healthy host.

Etiology of maculopapular rash in measles and rubella suspected patients from Belarus.

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Marina A Yermalovich

Full Text Available As a result of successful implementation of the measles/rubella elimination program, the etiology of more and more double negative cases remains elusive. The present study determined the role of different viruses as causative agents in measles or rubella suspected cases in Belarus. A total of 856 sera sent to the WHO National Laboratory between 2009 and 2011 were tested for specific IgM antibodies to measles virus (MV, rubella virus (RV and human parvovirus B19 (B19V. The negatives were further investigated for antibodies to enterovirus (EV and adenovirus (AdV. Children of up to 3 years were tested for IgM antibodies to human herpesvirus 6 (HHV6. A viral etiology was identified in 451 (52.7% cases, with 6.1% of the samples being positive for MV; 2.6% for RV; 26.2% for B19V; 9.7% for EV; 4.6% for AdV; and 3.6% for HHV6. Almost all measles and rubella cases occurred during limited outbreaks in 2011 and nearly all patients were at least 15 years old. B19V, EV and AdV infections were prevalent both in children and adults and were found throughout the 3 years. B19V occurred mainly in 3-10 years old children and 20-29 years old adults. EV infection was most common in children up to 6 years of age and AdV was confirmed mainly in 3-6 years old children. HHV6 infection was mostly detected in 6-11 months old infants. Laboratory investigation of measles/rubella suspected cases also for B19V, EV, AdV and HHV6 allows diagnosing more than half of all cases, thus strengthening rash/fever disease surveillance in Belarus.

Polio and Measles Down the Drain: Environmental Enterovirus Surveillance in the Netherlands, 2005 to 2015.

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Benschop, Kimberley S M; van der Avoort, Harrie G; Jusic, Edin; Vennema, Harry; van Binnendijk, Rob; Duizer, Erwin

2017-07-01

Polioviruses (PVs) are members of the genus Enterovirus In the Netherlands, the exclusion of PV circulation is based on clinical enterovirus (EV) surveillance (CEVS) of EV-positive cases and routine environmental EV surveillance (EEVS) conducted on sewage samples collected in the region of the Netherlands where vaccination coverage is low due to religious reasons. We compared the EEVS data to those of the CEVS to gain insight into the relevance of EEVS for poliovirus and nonpolio enterovirus surveillance. Following the polio outbreak in Syria, EEVS was performed at the primary refugee center in Ter Apel in the Netherlands, and data were compared to those of CEVS and EEVS. Furthermore, we assessed the feasibility of poliovirus detection by EEVS using measles virus detection in sewage during a measles outbreak as a proxy. Two Sabin-like PVs were found in routine EEVS, 11 Sabin-like PVs were detected in the CEVS, and one Sabin-like PV was found in the Ter Apel sewage. We observed significant differences between the three programs regarding which EVs were found. In 6 sewage samples collected during the measles outbreak in 2013, measles virus RNA was detected in regions where measles cases were identified. In conclusion, we detected PVs, nonpolio EVs, and measles virus in sewage and showed that environmental surveillance is useful for poliovirus detection in the Netherlands, where live oral poliovirus vaccine is not used and communities with lower vaccination coverage exist. EEVS led to the detection of EV types not seen in the CEVS, showing that EEVS is complementary to CEVS. IMPORTANCE We show that environmental enterovirus surveillance complements clinical enterovirus surveillance for poliovirus detection, or exclusion, and for nonpolio enterovirus surveillance. Even in the presence of adequate surveillance, only a very limited number of Sabin-like poliovirus strains were detected in a 10-year period, and no signs of transmission of oral polio vaccine (OPV) strains

Tyrosine 110 in the measles virus phosphoprotein is required to block STAT1 phosphorylation

International Nuclear Information System (INIS)

Devaux, Patricia; Messling, Veronika von; Songsungthong, Warangkhana; Springfeld, Christoph; Cattaneo, Roberto

2007-01-01

The measles virus (MV) P gene encodes three proteins: P, an essential polymerase cofactor, and C and V, which have multiple functions including immune evasion. We show here that the MV P protein also contributes to immune evasion, and that tyrosine 110 is required to block nuclear translocation of the signal transducer and activator of transcription factors (STAT) after interferon type I treatment. In particular, MV P inhibits STAT1 phosphorylation. This is shown not only by transient expression but also by reverse genetic analyses based on a new functional infectious cDNA derived from a MV vaccine vial (Moraten strain). Our study also identifies a conserved sequence around P protein tyrosine 110 as a candidate interaction site with a cellular protein

Measles outbreak reveals measles susceptibility among adults in ...

African Journals Online (AJOL)

Background. The World Health Organization, African Region, set the goal of achieving measles elimination by 2020. Namibia was one of seven African countries to implement an accelerated measles control strategy beginning in 1996. Following implementation of this strategy, measles incidence decreased; however, ...

High Concentrations of Measles Neutralizing Antibodies and High-Avidity Measles IgG Accurately Identify Measles Reinfection Cases

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Rota, Jennifer S.; Hickman, Carole J.; Mercader, Sara; Redd, Susan; McNall, Rebecca J.; Williams, Nobia; McGrew, Marcia; Walls, M. Laura; Rota, Paul A.; Bellini, William J.

2016-01-01

In the United States, approximately 9% of the measles cases reported from 2012 to 2014 occurred in vaccinated individuals. Laboratory confirmation of measles in vaccinated individuals is challenging since IgM assays can give inconclusive results. Although a positive reverse transcription (RT)-PCR assay result from an appropriately timed specimen can provide confirmation, negative results may not rule out a highly suspicious case. Detection of high-avidity measles IgG in serum samples provides laboratory evidence of a past immunologic response to measles from natural infection or immunization. High concentrations of measles neutralizing antibody have been observed by plaque reduction neutralization (PRN) assays among confirmed measles cases with high-avidity IgG, referred to here as reinfection cases (RICs). In this study, we evaluated the utility of measuring levels of measles neutralizing antibody to distinguish RICs from noncases by receiver operating characteristic curve analysis. Single and paired serum samples with high-avidity measles IgG from suspected measles cases submitted to the CDC for routine surveillance were used for the analysis. The RICs were confirmed by a 4-fold rise in PRN titer or by RT-quantitative PCR (RT-qPCR) assay, while the noncases were negative by both assays. Discrimination accuracy was high with serum samples collected ≥3 days after rash onset (area under the curve, 0.953; 95% confidence interval [CI], 0.854 to 0.993). Measles neutralizing antibody concentrations of ≥40,000 mIU/ml identified RICs with 90% sensitivity (95% CI, 74 to 98%) and 100% specificity (95% CI, 82 to 100%). Therefore, when serological or RT-qPCR results are unavailable or inconclusive, suspected measles cases with high-avidity measles IgG can be confirmed as RICs by measles neutralizing antibody concentrations of ≥40,000 mIU/ml. PMID:27335386

Computational Analysis of the Interaction Energies between Amino Acid Residues of the Measles Virus Hemagglutinin and Its Receptors

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Fengqi Xu

2018-05-01

Full Text Available Measles virus (MV causes an acute and highly devastating contagious disease in humans. Employing the crystal structures of three human receptors, signaling lymphocyte-activation molecule (SLAM, CD46, and Nectin-4, in complex with the measles virus hemagglutinin (MVH, we elucidated computationally the details of binding energies between the amino acid residues of MVH and those of the receptors with an ab initio fragment molecular orbital (FMO method. The calculated inter-fragment interaction energies (IFIEs revealed a number of significantly interacting amino acid residues of MVH that played essential roles in binding to the receptors. As predicted from previously reported experiments, some important amino-acid residues of MVH were shown to be common but others were specific to interactions with the three receptors. Particularly, some of the (non-polar hydrophobic residues of MVH were found to be attractively interacting with multiple receptors, thus indicating the importance of the hydrophobic pocket for intermolecular interactions (especially in the case of Nectin-4. In contrast, the electrostatic interactions tended to be used for specific molecular recognition. Furthermore, we carried out FMO calculations for in silico experiments of amino acid mutations, finding reasonable agreements with virological experiments concerning the substitution effect of residues. Thus, the present study demonstrates that the electron-correlated FMO method is a powerful tool to search exhaustively for amino acid residues that contribute to interactions with receptor molecules. It is also applicable for designing inhibitors of MVH and engineered MVs for cancer therapy.

[Drug clinics. Drug of the month. A new measles-rubella-mumps vaccine (Priorix)].

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Senterre, J

1999-02-01

A novel measles-mumps-rubella vaccine (Priorix) has been marketed by SmithKline Beecham. It contains live attenuated virus with measles and mumps strains slightly different from those present in MMR VAX (Pasteur Merieux MSD). The indications and contraindications are similar for both vaccines. Immunogenicity is also equivalent as well as general reactogenicity. By contrast local symptoms were reported significantly less frequently after Priorix.

Combination of Vaccine-Strain Measles and Mumps Viruses Enhances Oncolytic Activity against Human Solid Malignancies.

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Son, Ho Anh; Zhang, LiFeng; Cuong, Bui Khac; Van Tong, Hoang; Cuong, Le Duy; Hang, Ngo Thu; Nhung, Hoang Thi My; Yamamoto, Naoki; Toan, Nguyen Linh

2018-02-07

Oncolytic measles and mumps viruses (MeV, MuV) have a potential for anti-cancer treatment. We examined the anti-tumor activity of MeV, MuV, and MeV-MuV combination (MM) against human solid malignancies (HSM). MeV, MuV, and MM targeted and significantly killed various cancer cell lines of HSM but not normal cells. MM demonstrated a greater anti-tumor effect and prolonged survival in a human prostate cancer xenograft tumor model compared to MeV and MuV. MeV, MuV, and MM significantly induced the expression of immunogenic cell death markers and enhanced spleen-infiltrating immune cells. In conclusion, MM combination significantly improves the treatment of human solid malignancies.

Identification of a novel canine distemper virus B-cell epitope using a monoclonal antibody against nucleocapsid protein.

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Yi, Li; Cheng, Yuening; Zhang, Miao; Cao, Zhigang; Tong, Mingwei; Wang, Jianke; Zhao, Hang; Lin, Peng; Cheng, Shipeng

2016-02-02

Canine distemper virus (CDV) is a member of the genus Morbillivirus within the family Paramyxoviridae and has caused severe economic losses in China. Nucleocapsid protein (N) is the major structural viral protein and can be used to diagnose CDV and other morbilliviruses. In this study, a specific monoclonal antibody, 1N8, was produced against the CDV N protein (amino acids 277-471). A linear N protein epitope was identified by subjecting a series of partially overlapping synthesized peptides to enzyme-linked immunosorbent assay (ELISA) analysis. The results indicated that (350)LNFGRSYFDPA(360) was the minimal linear epitope that could be recognized by mAb 1N8. ELISA assays revealed that mouse anti-CDV sera could also recognize the minimal linear epitope. Alignment analysis of the amino acid sequences indicated that the epitope was highly conserved among CDV strains. Furthermore, the epitope was conserved among other morbilliviruses, which was confirmed with PRRV using western blotting. Taken together, the results of this study may have potential applications in the development of suitable diagnostic techniques for CDV or other morbilliviruses. Copyright © 2015 Elsevier B.V. All rights reserved.

Resting lymphocyte transduction with measles virus glycoprotein pseudotyped lentiviral vectors relies on CD46 and SLAM

International Nuclear Information System (INIS)

Zhou Qi; Schneider, Irene C.; Gallet, Manuela; Kneissl, Sabrina; Buchholz, Christian J.

2011-01-01

The measles virus (MV) glycoproteins hemagglutinin (H) and fusion (F) were recently shown to mediate transduction of resting lymphocytes by lentiviral vectors. MV vaccine strains use CD46 or signaling lymphocyte activation molecule (SLAM) as receptor for cell entry. A panel of H protein mutants derived from vaccine strain or wild-type MVs that lost or gained CD46 or SLAM receptor usage were investigated for their ability to mediate gene transfer into unstimulated T lymphocytes. The results demonstrate that CD46 is sufficient for efficient vector particle association with unstimulated lymphocytes. For stable gene transfer into these cells, however, both MV receptors were found to be essential.

Phase I Trial of Intratumoral Administration of NIS-Expressing Strain of Measles Virus in Unresectable or Recurrent Malignant Peripheral Nerve Sheath Tumor

Science.gov (United States)

2017-10-01

AWARD NUMBER: W81XWH-15-1-0115 TITLE: Phase I Trial of Intratumoral Administration of NIS-Expressing Strain of Measles Virus in Unresectable or...Fort Detrick, Maryland 21702-5012 DISTRIBUTION STATEMENT: Approved for Public Release; Distribution Unlimited REPORT DOCUMENTATION PAGE Form...Approved OMB No. 0704-0188 Public reporting burden for this collection of information is estimated to average 1 hour per response, including the time

Measles immune suppression: lessons from the macaque model.

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Rory D de Vries

Full Text Available Measles remains a significant childhood disease, and is associated with a transient immune suppression. Paradoxically, measles virus (MV infection also induces robust MV-specific immune responses. Current hypotheses for the mechanism underlying measles immune suppression focus on functional impairment of lymphocytes or antigen-presenting cells, caused by infection with or exposure to MV. We have generated stable recombinant MVs that express enhanced green fluorescent protein, and remain virulent in non-human primates. By performing a comprehensive study of virological, immunological, hematological and histopathological observations made in animals euthanized at different time points after MV infection, we developed a model explaining measles immune suppression which fits with the "measles paradox". Here we show that MV preferentially infects CD45RA(- memory T-lymphocytes and follicular B-lymphocytes, resulting in high infection levels in these populations. After the peak of viremia MV-infected lymphocytes were cleared within days, followed by immune activation and lymph node enlargement. During this period tuberculin-specific T-lymphocyte responses disappeared, whilst strong MV-specific T-lymphocyte responses emerged. Histopathological analysis of lymphoid tissues showed lymphocyte depletion in the B- and T-cell areas in the absence of apoptotic cells, paralleled by infiltration of T-lymphocytes into B-cell follicles and reappearance of proliferating cells. Our findings indicate an immune-mediated clearance of MV-infected CD45RA(- memory T-lymphocytes and follicular B-lymphocytes, which causes temporary immunological amnesia. The rapid oligoclonal expansion of MV-specific lymphocytes and bystander cells masks this depletion, explaining the short duration of measles lymphopenia yet long duration of immune suppression.

The central globular domain of the nucleocapsid protein of human immunodeficiency virus type 1 is critical for virion structure and infectivity.

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Ottmann, M; Gabus, C; Darlix, J L

1995-03-01

The nucleocapsid protein NCp7 of human immunodeficiency virus type 1 (HIV-1) is a 72-amino-acid peptide containing two CCHC-type zinc fingers linked by a short basic sequence, 29RAPRKKG35, which is conserved in HIV-1 and simian immunodeficiency virus. The complete three-dimensional structure of NCp7 has been determined by 1H-nuclear magnetic resonance spectroscopy (N. Morellet, H. de Rocquigny, Y. Mely, N. Jullian, H. Demene, M. Ottmann, D. Gerard, J. L. Darlix, M. C. Fournié-Zaluski, and B. P. Roques, J. Mol. Biol. 235:287-301, 1994) and revealed a central globular domain where the two zinc fingers are brought in close proximity by the RAPRKKG linker. To examine the role of this globular structure and more precisely of the RAPRKKG linker in virion structure and infectivity, we generated HIV-1 DNA mutants in the RAPRKK sequence of NCp7 and analyzed the mutant virions produced by transfected cells. Mutations that probably alter the structure of NCp7 structure led to the formation of very poorly infectious virus (A30P) or noninfectious virus (P31L and R32G). In addition, the P31L mutant did not contain detectable amounts of reverse transcriptase and had an immature core morphology, as determined by electron microscopy. On the other hand, mutations changing the basic nature of NCp7 had poor effect. R29S had a wild-type phenotype, and the replacement of 32RKK34 by SSS (S3 mutant) resulted in a decrease by no more than 100-fold of the virus titer. These results clearly show that the RAPRKKG linker contains residues that are critical for virion structure and infectivity.

Measles Outbreak among Unvaccinated Children in Bajura

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S Sitaula

2010-12-01

CFR of this outbreak is higher than the national CFR. Vaccine efficacy of 50% points towards the need for investigation of vaccine logistics and cold chain system. Moreover, this laboratory test confirmed an outbreak showing that the measles virus could be imported from an endemic region and rapidly spread through a susceptible population who were previously not immunized.

Viral RNA annealing activities of human immunodeficiency virus type 1 nucleocapsid protein require only peptide domains outside the zinc fingers.

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De Rocquigny, H; Gabus, C; Vincent, A; Fournié-Zaluski, M C; Roques, B; Darlix, J L

1992-07-15

The nucleocapsid (NC) of human immunodeficiency virus type 1 consists of a large number of NC protein molecules, probably wrapping the dimeric RNA genome within the virion inner core. NC protein is a gag-encoded product that contains two zinc fingers flanked by basic residues. In human immunodeficiency virus type 1 virions, NCp15 is ultimately processed into NCp7 and p6 proteins. During virion assembly the retroviral NC protein is necessary for core formation and genomic RNA encapsidation, which are essential for virus infectivity. In vitro NCp15 activates viral RNA dimerization, a process most probably linked in vivo to genomic RNA packaging, and replication primer tRNA(Lys,3) annealing to the initiation site of reverse transcription. To characterize the domains of human immunodeficiency virus type 1 NC protein necessary for its various functions, the 72-amino acid NCp7 and several derived peptides were synthesized in a pure form. We show here that synthetic NCp7 with or without the two zinc fingers has the RNA annealing activities of NCp15. Further deletions of the N-terminal 12 and C-terminal 8 amino acids, leading to a 27-residue peptide lacking the finger domains, have little or no effect on NC protein activity in vitro. However deletion of short sequences containing basic residues flanking the first finger leads to a complete loss of NC protein activity. It is proposed that the basic residues and the zinc fingers cooperate to select and package the genomic RNA in vivo. Inhibition of the viral RNA binding and annealing activities associated with the basic residues flanking the first zinc finger of NC protein could therefore be used as a model for the design of antiviral agents.

In Vivo Efficacy of Measles Virus Fusion Protein-Derived Peptides Is Modulated by the Properties of Self-Assembly and Membrane Residence

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Figueira, T. N.; Palermo, L. M.; Veiga, A. S.; Huey, D.; Alabi, C. A.; Santos, N. C.; Welsch, J. C.; Mathieu, C.; Niewiesk, S.; Moscona, A.

2016-01-01

ABSTRACT Measles virus (MV) infection is undergoing resurgence and remains one of the leading causes of death among young children worldwide despite the availability of an effective measles vaccine. MV infects its target cells by coordinated action of the MV hemagglutinin (H) and fusion (F) envelope glycoproteins; upon receptor engagement by H, the prefusion F undergoes a structural transition, extending and inserting into the target cell membrane and then refolding into a postfusion structure that fuses the viral and cell membranes. By interfering with this structural transition of F, peptides derived from the heptad repeat (HR) regions of F can inhibit MV infection at the entry stage. In previous work, we have generated potent MV fusion inhibitors by dimerizing the F-derived peptides and conjugating them to cholesterol. We have shown that prophylactic intranasal administration of our lead fusion inhibitor efficiently protects from MV infection in vivo. We show here that peptides tagged with lipophilic moieties self-assemble into nanoparticles until they reach the target cells, where they are integrated into cell membranes. The self-assembly feature enhances biodistribution and the half-life of the peptides, while integration into the target cell membrane increases fusion inhibitor potency. These factors together modulate in vivo efficacy. The results suggest a new framework for developing effective fusion inhibitory peptides. IMPORTANCE Measles virus (MV) infection causes an acute illness that may be associated with infection of the central nervous system (CNS) and severe neurological disease. No specific treatment is available. We have shown that fusion-inhibitory peptides delivered intranasally provide effective prophylaxis against MV infection. We show here that specific biophysical properties regulate the in vivo efficacy of MV F-derived peptides. PMID:27733647

Development of new therapy for canine mammary cancer with recombinant measles virus

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Koichiro Shoji

2016-01-01

Full Text Available Oncolytic virotherapy is a promising treatment strategy for cancer. We previously generated a recombinant measles virus (rMV-SLAMblind that selectively uses a poliovirus receptor-related 4 (PVRL4/Nectin4 receptor, but not signaling lymphocyte activation molecule (SLAM. We demonstrated that the virus exerts therapeutic effects against human breast cancer cells. Here, we examined the applicability of rMV-SLAMblind to treating canine mammary cancers (CMCs. We found that the susceptibilities of host cells to rMV-SLAMblind were dependent on canine Nectin-4 expression. Nectin-4 was detected in four of nine CMC cell lines. The rMV-SLAMblind efficiently infected those four Nectin-4-positive cell lines and was cytotoxic for three of them (CF33, CHMm, and CTBm. In vivo experiment showed that the administration of rMV-SLAMblind greatly suppressed the progression of tumors in mice xenografted with a CMC cell line (CF33. Immunohistochemistry revealed that canine Nectin-4 was expressed in 45% of canine mammary tumors, and the tumor cells derived from one clinical specimen were efficiently infected with rMV-SLAMblind. These results suggest that rMV-SLAMblind infects CMC cells and displays antitumor activity in vitro, in xenografts, and ex vivo. Therefore, oncolytic virotherapy with rMV-SLAMblind can be a novel method for treating CMCs.

Crimean-Congo Hemorrhagic Fever Virus Nucleocapsid Protein Augments mRNA Translation.

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Jeeva, Subbiah; Cheng, Erdong; Ganaie, Safder S; Mir, Mohammad A

2017-08-01

Crimean-Congo hemorrhagic fever virus (CCHFV) is a tick-borne Nairovirus of the Bunyaviridae family, causing severe illness with high mortality rates in humans. Here, we demonstrate that CCHFV nucleocapsid protein (CCHFV-NP) augments mRNA translation. CCHFV-NP binds to the viral mRNA 5' untranslated region (UTR) with high affinity. It facilitates the translation of reporter mRNA both in vivo and in vitro with the assistance of the viral mRNA 5' UTR. CCHFV-NP equally favors the translation of both capped and uncapped mRNAs, demonstrating the independence of this translation strategy on the 5' cap. Unlike the canonical host translation machinery, inhibition of eIF4F complex, an amalgam of three initiation factors, eIF4A, eIF4G, and eIF4E, by the chemical inhibitor 4E1RCat did not impact the CCHFV-NP-mediated translation mechanism. However, the proteolytic degradation of eIF4G alone by the human rhinovirus 2A protease abrogated this translation strategy. Our results demonstrate that eIF4F complex formation is not required but eIF4G plays a critical role in this translation mechanism. Our results suggest that CCHFV has adopted a unique translation mechanism to facilitate the translation of viral mRNAs in the host cell cytoplasm where cellular transcripts are competing for the same translation apparatus. IMPORTANCE Crimean-Congo hemorrhagic fever, a highly contagious viral disease endemic to more than 30 countries, has limited treatment options. Our results demonstrate that NP favors the translation of a reporter mRNA harboring the viral mRNA 5' UTR. It is highly likely that CCHFV uses an NP-mediated translation strategy for the rapid synthesis of viral proteins during the course of infection. Shutdown of this translation mechanism might selectively impact viral protein synthesis, suggesting that an NP-mediated translation strategy is a target for therapeutic intervention against this viral disease. Copyright © 2017 American Society for Microbiology.

Antecedent causes of a measles resurgence in the Democratic Republic of the Congo

Science.gov (United States)

Scobie, Heather Melissa; Ilunga, Benoît Kebela; Mulumba, Audry; Shidi, Calixte; Coulibaly, Tiekoura; Obama, Ricardo; Tamfum, Jean-Jacques Muyembe; Simbu, Elisabeth Pukuta; Smit, Sheilagh Brigitte; Masresha, Balcha; Perry, Robert Tyrrell; Alleman, Mary Margaret; Kretsinger, Katrina; Goodson, James

2015-01-01

Introduction Despite accelerated measles control efforts, a massive measles resurgence occurred in the Democratic Republic of the Congo (DRC) starting in mid-2010, prompting an investigation into likely causes. Methods We conducted a descriptive epidemiological analysis using measles immunization and surveillance data to understand the causes of the measles resurgence and to develop recommendations for elimination efforts in DRC. Results During 2004-2012, performance indicator targets for case-based surveillance and routine measles vaccination were not met. Estimated coverage with the routine first dose of measles-containing vaccine (MCV1) increased from 57% to 73%. Phased supplementary immunization activities (SIAs) were conducted starting in 2002, in some cases with sub-optimal coverage (≤95%). In 2010, SIAs in five of 11 provinces were not implemented as planned, resulting in a prolonged interval between SIAs, and a missed birth cohort in one province. During July 1, 2010-December 30, 2012, high measles attack rates (>100 cases per 100,000 population) occurred in provinces that had estimated MCV1 coverage lower than the national estimate and did not implement planned 2010 SIAs. The majority of confirmed case-patients were aged measles virus strains that were previously identified in the region. Conclusion The resurgence was likely caused by an accumulation of unvaccinated, measles-susceptible children due to low MCV1 coverage and suboptimal SIA implementation. To achieve the regional goal of measles elimination by 2020, efforts are needed in DRC to improve case-based surveillance and increase two-dose measles vaccination coverage through routine services and SIAs. PMID:26401224

An amino-terminal segment of hantavirus nucleocapsid protein presented on hepatitis B virus core particles induces a strong and highly cross-reactive antibody response in mice

International Nuclear Information System (INIS)

Geldmacher, Astrid; Skrastina, Dace; Petrovskis, Ivars; Borisova, Galina; Berriman, John A.; Roseman, Alan M.; Crowther, R. Anthony; Fischer, Jan; Musema, Shamil; Gelderblom, Hans R.; Lundkvist, Aake; Renhofa, Regina; Ose, Velta; Krueger, Detlev H.; Pumpens, Paul; Ulrich, Rainer

2004-01-01

Previously, we have demonstrated that hepatitis B virus (HBV) core particles tolerate the insertion of the amino-terminal 120 amino acids (aa) of the Puumala hantavirus nucleocapsid (N) protein. Here, we demonstrate that the insertion of 120 amino-terminal aa of N proteins from highly virulent Dobrava and Hantaan hantaviruses allows the formation of chimeric core particles. These particles expose the inserted foreign protein segments, at least in part, on their surface. Analysis by electron cryomicroscopy of chimeric particles harbouring the Puumala virus (PUUV) N segment revealed 90% T = 3 and 10% T = 4 shells. A map computed from T = 3 shells shows additional density splaying out from the tips of the spikes producing the effect of an extra shell of density at an outer radius compared with wild-type shells. The inserted Puumala virus N protein segment is flexibly linked to the core spikes and only partially icosahedrally ordered. Immunisation of mice of two different haplotypes (BALB/c and C57BL/6) with chimeric core particles induces a high-titered and highly cross-reactive N-specific antibody response in both mice strains

Enhanced lysis by bispecific oncolytic measles viruses simultaneously using HER2/neu or EpCAM as target receptors

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Jan RH Hanauer

2016-01-01

Full Text Available To target oncolytic measles viruses (MV to tumors, we exploit the binding specificity of designed ankyrin repeat proteins (DARPins. These DARPin-MVs have high tumor selectivity while maintaining excellent oncolytic potency. Stability, small size, and efficacy of DARPins allowed the generation of MVs simultaneously targeted to tumor marker HER2/neu and cancer stem cell (CSC marker EpCAM. For optimization, the linker connecting both DARPins was varied in flexibility and length. Flexibility had no impact on fusion helper activity whereas length had. MVs with bispecific MV-H are genetically stable and revealed the desired double-target specificity. In vitro, the cytolytic activity of bispecific MVs was superior or comparable to mono-targeted viruses depending on the target cells. In vivo, therapeutic efficacy of the bispecific viruses was validated in an orthotopic ovarian carcinoma model revealing an effective reduction of tumor mass. Finally, the power of bispecific targeting was demonstrated on cocultures of different tumor cells thereby mimicking tumor heterogeneity in vitro, more closely reflecting real tumors. Here, bispecific excelled monospecific viruses in efficacy. DARPin-based targeting domains thus allow the generation of efficacious oncolytic viruses with double specificity, with the potential to handle intratumoral variation of antigen expression and to simultaneously target CSCs and the bulk tumor mass.

Biological characterization and variability of the nucleocapsid protein gene of Groundnut bud necrosis virus isolates infecting pea from India

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Mohammad AKRAM

2012-09-01

Full Text Available A disease of pea characterized by browning in veins, leaves and stems, mostly in growing tips, and brown circular spots on pods, was recorded in four districts of Uttar Pradesh, India. The causal agent of this disease was detected by reverse transcription-polymerase chain reaction (RT-PCR using primers pair HRP 26/HRP 28 and identified as Groundnut bud necrosis virus (GBNV on the basis of nucleocapsid protein (NP gene sequence. Virus isolates from Bareilly (BRY, Kanpur (KNP, Udham Singh Nagar (USN and Shahjahanpur (SJP were designated as GBNV-[Pea_BRY], GBNV-[Pea_KNP], GBNV-[Pea_USN] and GBNV-[Pea_SJP] and their NP genes sequenced. The sequence data of each isolate were deposited at NCBI database (JF281101-JF281104. The complete nucleotide sequence of the NP genes of all the GBNV isolates had a single open reading frame of 831 nucleotides and 276 amino acids. The isolates had among them 2% variability at amino acid level and 2‒3 variability at nucleotide level, but had variability with other GBNV isolates of fabaceous hosts in the range of 0‒6% at amino acid level and 1‒8% at nucleotide level. Though this variation in nucleotide sequences of GBNV isolates from fabaceous hosts is within the limits of species demarcation for tospoviruses, formation of a separate cluster within the GBNV isolates indicates the possibility of distinct variants in GBNV.

Functional interactions of nucleocapsid protein of feline immunodeficiency virus and cellular prion protein with the viral RNA.

Science.gov (United States)

Moscardini, Mila; Pistello, Mauro; Bendinelli, M; Ficheux, Damien; Miller, Jennifer T; Gabus, Caroline; Le Grice, Stuart F J; Surewicz, Witold K; Darlix, Jean-Luc

2002-04-19

All lentiviruses and oncoretroviruses examined so far encode a major nucleic-acid binding protein (nucleocapsid or NC* protein), approximately 2500 molecules of which coat the dimeric RNA genome. Studies on HIV-1 and MoMuLV using in vitro model systems and in vivo have shown that NC protein is required to chaperone viral RNA dimerization and packaging during virus assembly, and proviral DNA synthesis by reverse transcriptase (RT) during infection. The human cellular prion protein (PrP), thought to be the major component of the agent causing transmissible spongiform encephalopathies (TSE), was recently found to possess a strong affinity for nucleic acids and to exhibit chaperone properties very similar to HIV-1 NC protein in the HIV-1 context in vitro. Tight binding of PrP to nucleic acids is proposed to participate directly in the prion disease process. To extend our understanding of lentiviruses and of the unexpected nucleic acid chaperone properties of the human prion protein, we set up an in vitro system to investigate replication of the feline immunodeficiency virus (FIV), which is functionally and phylogenetically distant from HIV-1. The results show that in the FIV model system, NC protein chaperones viral RNA dimerization, primer tRNA(Lys,3) annealing to the genomic primer-binding site (PBS) and minus strand DNA synthesis by the homologous FIV RT. FIV NC protein is able to trigger specific viral DNA synthesis by inhibiting self-priming of reverse transcription. The human prion protein was found to mimic the properties of FIV NC with respect to primer tRNA annealing to the viral RNA and chaperoning minus strand DNA synthesis. Copyright 2002 Elsevier Science Ltd.

Immunoglobulin GM and KM genes and measles vaccine-induced humoral immunity.

Science.gov (United States)

Ovsyannikova, Inna G; Larrabee, Beth R; Schaid, Daniel J; Poland, Gregory A

2017-10-04

Identifying genetic polymorphisms that explain variations in humoral immunity to live measles virus vaccine is of great interest. Immunoglobulin GM (heavy chain) and KM (light chain) allotypes are genetic markers known to be associated with susceptibility to several infectious diseases. We assessed associations between GM and KM genotypes and measles vaccine humoral immunity (neutralizing antibody titers) in a combined cohort (n=1796) of racially diverse healthy individuals (age 18-41years). We did not discover any significant associations between GM and/or KM genotypes and measles vaccine-induced neutralizing antibody titers. African-American subjects had higher neutralizing antibody titers than Caucasians (1260mIU/mL vs. 740mIU/mL, p=7.10×10 -13 ), and those titers remained statistically significant (p=1.68×10 -09 ) after adjusting for age at enrollment and time since last vaccination. There were no statistically significant sex-specific differences in measles-induced neutralizing antibody titers in our study (p=0.375). Our data indicate a surprising lack of evidence for an association between GM and KM genotypes and measles-specific neutralizing antibody titers, despite the importance of these immune response genes. Copyright © 2017 Elsevier Ltd. All rights reserved.

Disneyland Measles Outbreak

OpenAIRE

Palladino, Erica

2015-01-01

This media information sheet analyzes print and online coverage of the 2015 Disneyland measles outbreak. The frameworks that the media used to report on the outbreak presented vaccination as the only viable option from preventing the spread of measles. Reporting also failed to mention that the 2015 Disneyland measles outbreak was smaller than U.S. measles outbreaks in 2013 and 2014.

Measles (lecture, continuing

Directory of Open Access Journals (Sweden)

Shostakovych-Koretsraya L.R.

2013-12-01

Full Text Available The second part of the article discusses differential diagnosis during different measles periods. Routine and confirmatory laboratory diagnosis, including cytological, serological and molecular genetic methods is outlined. Criteria of suspected, probable and proved diagnosis of measles cases are provided. Principles of diagnosis formulation according to WHO criteria are described. Complications of measles ac¬cording to cause (viral and bacterial, by different systems and particularities in high risk patients are considered. Complications of measles from central nervous system are described in details. Therapeutic management of measles is described in details, including indications for hospital admission, etiotropic therapy, strict indications for steroids and immunoglobulins prescription, vitamin A in dosages, therapy of complications, indications for antibiotics usage and other pathogenetic therapy. Specific therapy of measles complications from central nervous system is outlined. Active and passive immunization, anti-epidemic activities, patient follow-up after episode of measles and disease prognosis are described. The literature reference list consists of 121 items, including Cyrillic, Latin articles and electronic resources.

Girls may have lower levels of maternal measles antibodies and higher risk of subclinical measles infection before the age of measles vaccination.

Science.gov (United States)

Martins, Cesario; Bale, Carlitos; Garly, May-Lill; Rodrigues, Amabelia; Lisse, Ida M; Andersen, Andreas; Eriksson, Mia; Benn, Christine S; Whittle, Hilton; Aaby, Peter

2009-08-20

Previous studies have suggested that girls may have lower maternal measles antibody levels than boys. Girls might therefore be more likely to contract measles infection before the normal age of measles vaccination at 9 months of age. In connection with a clinical trial of different measles vaccination strategies, we collected pre-measles vaccination blood samples at 4.5 months of age from two subgroups of children. Samples from these children were used to assess possible differences in maternal antibody levels for boys and girls. At 9 months of age another subgroup of children was sampled before the normal measles vaccination; these samples were used to assess the frequency of subclinical measles infection among boys and girls. We determined measles-specific antibody levels for 812 children at 4.5 months of age and for 896 children at 9 months of age. At 4.5 months of age girls were less likely to have protective maternal antibody levels, the male-female ratio for protective antibody level being 1.23 (1.00-1.51). Among children sampled at 9 months of age, girls were more likely to have protective levels, the female-male ratio for having protective antibody levels being 1.65 (0.98-2.78) (p=0.054) and the geometric mean titre was significantly higher for girls (p=0.007). Children who lived in houses with known measles cases were more likely to have protective levels at 9 months of age even though they had not reported measles infection. Since we had excluded children with known measles infection, girls may have been more likely to have had subclinical measles infection. Combining clinical and possible subclinical measles infection, girls tended to be more likely than boys to contract measles infection before 9 months of age, the RR being 1.36 (0.97-1.90). Girls lost maternal measles antibodies more rapidly than boys and well before 9 months of age. They may be more likely to contract subclinical measles infection before the current age of measles vaccination.

Characteristics of patients with measles admitted to allied hospital rawalpindi

International Nuclear Information System (INIS)

Sultana, A.; Sabir, S.A.; Awan, A.

2015-01-01

Measles, a virus borne droplet infection, is one of the leading causes of death among young children worldwide despite presence of a safe and cost-effective vaccine. Objective of our study was to identify the characteristics of measles patients admitted to Allied Hospitals, Rawalpindi. Methods: This cross-sectional study was conducted amongst patients admitted with measles in paediatric units of Rawalpindi Medical College Allied Hospitals, Rawalpindi. A standard proforma was used to collect data from the respondents. Results: A total of 55 patients (mean age-29.36 months) with measles were included in the study. 65.5% children were vaccinated while 34.5% were not vaccinated. Among those vaccinated 14 were male. Out of the vaccinated children 52.6% were residents of middle class areas, 31.6% lower middle class area, 10.5% upper middle class areas and 5.3% rural areas. In 55.0% of patients who were vaccinated with at least one dose of measles at nine month of age the estimated calendar months of vaccination was March to April while in 30% the overall climatic period of vaccination was of summer (May to September). Twenty one study subjects were exposed to a case of measles in the family and thirty five out of all developed at least one known complication of the disease. Pneumonia was the most common complication reported in patients (63.6%) followed by diarrhoea (27.3%). Conclusion: Majority of the patients suffering from measles were not vaccinated and the most common reason for failure to immunize children was lack of awareness. Educated and well off fathers were more likely to get their children immunized. The vaccinated children who developed measles majority were vaccinated during months of March, April and May. (author)

Antigenic analysis of some Nigerian street rabies virus using ...

African Journals Online (AJOL)

The authors studied 12 street rabies virus isolates from 3 states of Nigeria using both the anti-nucleocapsid and anti-glycoprotein monoclonal antibodies and cross-protection tests. It was observed that all the viruses were rabies having divergent antigenic presentation. Also noticed was an antigenic shift when the viruses ...

Measles vaccination using a microneedle patch☆

Science.gov (United States)

Edens, Chris; Collins, Marcus L.; Ayers, Jessica; Rota, Paul A.; Prausnitz, Mark R.

2013-01-01

Measles vaccination programs would benefit from delivery methods that decrease cost, simplify logistics, and increase safety. Conventional subcutaneous injection is limited by the need for skilled healthcare professionals to reconstitute and administer injections, and by the need for safe needle handling and disposal to reduce the risk of disease transmission through needle re-use and needlestick injury. Microneedles are micron-scale, solid needles coated with a dry formulation of vaccine that dissolves in the skin within minutes after patch application. By avoiding the use of hypodermic needles, vaccination using a microneedle patch could be carried out by minimally trained personnel with reduced risk of blood-borne disease transmission. The goal of this study was to evaluate measles vaccination using a microneedle patch to address some of the limitations of subcutaneous injection. Viability of vaccine virus dried onto a microneedle patch was stabilized by incorporation of the sugar, trehalose, and loss of viral titer was less than 1 log10(TCID50) after storage for at least 30 days at room temperature. Microneedle patches were then used to immunize cotton rats with the Edmonston-Zagreb measles vaccine strain. Vaccination using microneedles at doses equaling the standard human dose or one-fifth the human dose generated neutralizing antibody levels equivalent to those of a subcutaneous immunization at the same dose. These results show that measles vaccine can be stabilized on microneedles and that vaccine efficiently reconstitutes in vivo to generate a neutralizing antibody response equivalent to that generated by subcutaneous injection. PMID:23044406

Measles transmission following the tsunami in a population with a high one-dose vaccination coverage, Tamil Nadu, India 2004–2005

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Wairgkar Niteen S

2006-09-01

Full Text Available Abstract Background On 26 December 2004, a tsunami struck the coast of the state of Tamil Nadu, India, where one-dose measles coverage exceeded 95%. On 29 December, supplemental measles immunization activities targeted children 6 to 60 months of age in affected villages. On 30 December, Cuddalore, a tsunami-affected district in Tamil Nadu reported a cluster of measles cases. We investigated this cluster to estimate the magnitude of the problem and to propose recommendations for control. Methods We received notification of WHO-defined measles cases through stimulated passive surveillance. We collected information regarding date of onset, age, sex, vaccination status and residence. We collected samples for IgM antibodies and genotype studies. We modeled the accumulation of susceptible individuals over the time on the basis of vaccination coverage, vaccine efficacy and birth rate. Results We identified 101 measles cases and detected IgM antibodies against measles virus in eight of 11 sera. Cases were reported from tsunami-affected (n = 71 and unaffected villages (n = 30 with attack rates of 1.3 and 1.7 per 1000, respectively. 42% of cases in tsunami-affected villages had an onset date within 14 days of the tsunami. The median ages of case-patients in tsunami-affected and un-affected areas were 54 months and 60 months respectively (p = 0.471. 36% of cases from tsunami-affected areas were above 60 months of age. Phylogenetic analyses indicated that the sequences of virus belonged to genotype D8 that circulated in Tamil Nadu. Conclusion Measles virus circulated in Cuddalore district following the tsunami, although there was no association between the two events. Transmission despite high one-dose vaccination coverage pointed to the limitations of this vaccination strategy. A second opportunity for measles immunization may help reducing measles mortality and morbidity in such areas. Children from 6 month to 14 years of age must be targeted for

First large scale chemical synthesis of the 72 amino acid HIV-1 nucleocapsid protein NCp7 in an active form.

Science.gov (United States)

de Rocquigny, H; Ficheux, D; Gabus, C; Fournié-Zaluski, M C; Darlix, J L; Roques, B P

1991-10-31

The nucleocapsid protein (NC) of the human immunodeficiency virus type 1 plays a crucial role in the formation of infectious viral particles and therefore should be a major target for the development of antiviral agents. This requires an investigation of NC protein structure and of its interactions with both primer tRNA(Lys,3) and genomic RNA. Nucleocapsid protein NCp7, which results from the maturation of NCp15, contains two zinc fingers flanked by sequences rich in basic and proline residues. Here we report the first synthesis of large quantities of NCp7 able to activate HIV-1 RNA dimerization and replication primer tRNA(Lys,3) annealing to the initiation site of reverse transcription. In addition UV spectroscopic analyses performed to characterize the Co2+ binding properties of each zinc finger suggest that the two fingers probably interact in NCp7.

Cell-to-Cell Measles Virus Spread between Human Neurons Is Dependent on Hemagglutinin and Hyperfusogenic Fusion Protein.

Science.gov (United States)

Sato, Yuma; Watanabe, Shumpei; Fukuda, Yoshinari; Hashiguchi, Takao; Yanagi, Yusuke; Ohno, Shinji

2018-03-15

Measles virus (MV) usually causes acute infection but in rare cases persists in the brain, resulting in subacute sclerosing panencephalitis (SSPE). Since human neurons, an important target affected in the disease, do not express the known MV receptors (signaling lymphocyte activation molecule [SLAM] and nectin 4), how MV infects neurons and spreads between them is unknown. Recent studies have shown that many virus strains isolated from SSPE patients possess substitutions in the extracellular domain of the fusion (F) protein which confer enhanced fusion activity. Hyperfusogenic viruses with such mutations, unlike the wild-type MV, can induce cell-cell fusion even in SLAM- and nectin 4-negative cells and spread efficiently in human primary neurons and the brains of animal models. We show here that a hyperfusogenic mutant MV, IC323-F(T461I)-EGFP (IC323 with a fusion-enhancing T461I substitution in the F protein and expressing enhanced green fluorescent protein), but not the wild-type MV, spreads in differentiated NT2 cells, a widely used human neuron model. Confocal time-lapse imaging revealed the cell-to-cell spread of IC323-F(T461I)-EGFP between NT2 neurons without syncytium formation. The production of virus particles was strongly suppressed in NT2 neurons, also supporting cell-to-cell viral transmission. The spread of IC323-F(T461I)-EGFP was inhibited by a fusion inhibitor peptide as well as by some but not all of the anti-hemagglutinin antibodies which neutralize SLAM- or nectin-4-dependent MV infection, suggesting the presence of a distinct neuronal receptor. Our results indicate that MV spreads in a cell-to-cell manner between human neurons without causing syncytium formation and that the spread is dependent on the hyperfusogenic F protein, the hemagglutinin, and the putative neuronal receptor for MV. IMPORTANCE Measles virus (MV), in rare cases, persists in the human central nervous system (CNS) and causes subacute sclerosing panencephalitis (SSPE) several

[Ophthalmological symptoms of measles and their treatment].

Science.gov (United States)

Végh, Mihály; Hári-Kovács, András; Roth, Hans-Walter; Facskó, Andrea

2017-10-01

Measles, caused by the Morbilli virus, is a highly (about 95 %) contagious disease affecting primarily children, but without proper immunisation, adults can also be infected. The leading symptoms of the disease are high fever that presents after an incubation period of 9-10 days and the red rash that begins several days after the fever starts. Beyond specific generalized symptoms, measles may have ocular symptoms. The most commonly occurring conjunctivitis, the so-called "red eye symptom", is not characteristic only for measles infection, however, by taking the generalized symptoms it can suggest the diagnosis at the beginning of the disease. Conjunctivitis of varying severity is noticed in the half of the cases without using ophthalmological instrumentation. Using ophthalmological instrumentation, the mild forms of conjunctivitis can be diagnosed, by meticulous ophthalmological examination, further eye diseases can be discovered. The viral conjunctivitis can progress to keratitis and bacterial superinfection can occur. If the infection presents in childhood it can affect the posterior segment. The fight against measles is very effective in Hungary since the vaccination has been introduced, and the lack of vaccination is also the primary cause of the risk to the disease. In the diagnosis, symptomatic treatment of the disease and the curbing of possible mass infections, the practicing physician (general practitioner) has a key role. The correct care of the infected patient in Hungary is provided by a methodological letter, professional information and legal guides. Orv Hetil. 2017; 158(39): 1523-1527.

Routine vitamin A supplementation for the prevention of blindness due to measles infection in children

DEFF Research Database (Denmark)

Bello, Segun; Meremikwu, Martin M; Ejemot-Nwadiaro, Regina I

2016-01-01

BACKGROUND: Reduced vitamin A concentration increases the risk of blindness in children infected with the measles virus. Promoting vitamin A supplementation in children with measles contributes to the control of blindness in children, which is a high priority within the World Health Organization...... (WHO) VISION 2020 The Right to Sight Program. OBJECTIVES: To assess the efficacy of vitamin A in preventing blindness in children with measles without prior clinical features of vitamin A deficiency. SEARCH METHODS: We searched CENTRAL 2015, Issue 11, MEDLINE (1950 to December week 3, 2015), Embase...... (1974 to December 2015) and LILACS (1985 to December 2015). SELECTION CRITERIA: Randomised controlled trials (RCTs) assessing the efficacy of vitamin A in preventing blindness in well-nourished children diagnosed with measles but with no prior clinical features of vitamin A deficiency. DATA COLLECTION...

Girls may have lower levels of maternal measles antibodies and higher risk of subclinical measles infection before the age of measles vaccination

DEFF Research Database (Denmark)

Martins, Cesario; Bale, Carlitos; Garly, May-Lill

2009-01-01

BACKGROUND: Previous studies have suggested that girls may have lower maternal measles antibody levels than boys. Girls might therefore be more likely to contract measles infection before the normal age of measles vaccination at 9 months of age. METHODS: In connection with a clinical trial...... of different measles vaccination strategies, we collected pre-measles vaccination blood samples at 4.5 months of age from two subgroups of children. Samples from these children were used to assess possible differences in maternal antibody levels for boys and girls. At 9 months of age another subgroup...... of children was sampled before the normal measles vaccination; these samples were used to assess the frequency of subclinical measles infection among boys and girls. RESULTS: We determined measles-specific antibody levels for 812 children at 4.5 months of age and for 896 children at 9 months of age. At 4...

The organisation of Ebola virus reveals a capacity for extensive, modular polyploidy.

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Daniel R Beniac

Full Text Available BACKGROUND: Filoviruses, including Ebola virus, are unusual in being filamentous animal viruses. Structural data on the arrangement, stoichiometry and organisation of the component molecules of filoviruses has until now been lacking, partially due to the need to work under level 4 biological containment. The present study provides unique insights into the structure of this deadly pathogen. METHODOLOGY AND PRINCIPAL FINDINGS: We have investigated the structure of Ebola virus using a combination of cryo-electron microscopy, cryo-electron tomography, sub-tomogram averaging, and single particle image processing. Here we report the three-dimensional structure and architecture of Ebola virus and establish that multiple copies of the RNA genome can be packaged to produce polyploid virus particles, through an extreme degree of length polymorphism. We show that the helical Ebola virus inner nucleocapsid containing RNA and nucleoprotein is stabilized by an outer layer of VP24-VP35 bridges. Elucidation of the structure of the membrane-associated glycoprotein in its native state indicates that the putative receptor-binding site is occluded within the molecule, while a major neutralizing epitope is exposed on its surface proximal to the viral envelope. The matrix protein VP40 forms a regular lattice within the envelope, although its contacts with the nucleocapsid are irregular. CONCLUSIONS: The results of this study demonstrate a modular organization in Ebola virus that accommodates a well-ordered, symmetrical nucleocapsid within a flexible, tubular membrane envelope.

Molecular surveillance of measles and rubella in the WHO European Region: new challenges in the elimination phase.

Science.gov (United States)

Santibanez, S; Hübschen, J M; Ben Mamou, M C; Muscat, M; Brown, K E; Myers, R; Donoso Mantke, O; Zeichhardt, H; Brockmann, D; Shulga, S V; Muller, C P; O'Connor, P M; Mulders, M N; Mankertz, A

2017-08-01

The WHO European Region (EUR) has adopted the goal of eliminating measles and rubella but individual countries perform differently in achieving this goal. Measles virus spread across the EUR by mobile groups has recently led to large outbreaks in the insufficiently vaccinated resident population. As an instrument for monitoring the elimination process and verifying the interruption of endemic virus transmission, molecular surveillance has to provide valid and representative data. Irrespective of the country's specific situation, it is required to ensure the functionality of the laboratory surveillance that is supported by the WHO Global Measles and Rubella Laboratory Network. To investigate whether the molecular surveillance in the EUR is adequate for the challenges in the elimination phase, we addressed the quality assurance of molecular data, the continuity and intensity of molecular monitoring, and the analysis of transmission chains. Published articles, the molecular External Quality Assessment Programme of the WHO, the Centralized Information System for Infectious Diseases of the WHO EUR and the WHO Measles and Rubella Nucleotide Surveillance databases served as information sources. Molecular proficiency testing conducted by the WHO in 2016 has shown that the expertise for measles and rubella virus genotyping exists in all parts of the EUR. The analysis of surveillance data reported nationally to the WHO in 2013-2016 has revealed some countries with outbreaks but not sufficiently representative molecular data. Long-lasting supranational MV transmission chains were identified. A more systematic molecular monitoring and recording of the transmission pattern for the whole EUR could help to create a meaningful picture of the elimination process. Copyright © 2017 European Society of Clinical Microbiology and Infectious Diseases. All rights reserved.

[Production of monoclonal antibodies against a wild strain of rabies virus].

Science.gov (United States)

Akacem, O; Benmansour, A; Coulon, P; Brahimi, M; Benhassine, M

1992-01-01

Production of monoclonal antibodies against a wild strain of rabies virus. Cell fusion of SP 2/O, a murine myeloma against a wild strain of rabies virus has originated five monoclonal antibodies (M.A.) specific for virus nucleocapsid , one M.A. specific for virus glycoprotein and one M.A. specific for a viral membrane protein.

[Difficulties in the epidemiological surveillance of measles in Africa: exemplified by the Ivory Coast].

Science.gov (United States)

Rey, J L; Trolet, C; Soro, B; Cunin, P; Merouze, F

1991-06-01

In tropical areas measles cases often are under-reported but the authors comment here two epidemics which had at first been considered as outbreaks of measles but were not. The first epidemic resembled a Chikungunya virus outbreak with important rashes, hyperthermia and pain attacks and was due to Igbo-Ora arbovirus. In the second epidemic children were having rashes with hyperthermia and adenopathy evoking rubella. The authors consider the possibility of over-reporting in view of the surveillance of measles, the target-disease in EPI (Expanded Programme on Immunization). This hypothesis is confirmed by the distribution of reported cases at national level with a high rate of out-season cases and among adults.

Laboratory safe detection of nucleocapsid protein of Rift Valley fever virus in human and animal specimens by a sandwich ELISA.

Science.gov (United States)

Jansen van Vuren, P; Paweska, J T

2009-04-01

A safe laboratory procedure, based on a sandwich ELISA (sAg-ELISA), was developed and evaluated for the detection of nucleocapsid protein (NP) of Rift Valley fever virus (RVFV) in specimens inactivated at 56 degrees C for 1h in the presence of 0.5% Tween-20 (v/v) before testing. Polyclonal capture and detection immune sera were generated respectively in sheep and rabbits immunized with recombinant NP antigen. The assay was highly repeatable and specific; it detected strains of RVFV from the entire distributional range of the disease, isolated over a period of 53 years; no cross-reactivity with genetically related African phleboviruses or other members of the family Bunyaviridae was observed. In specimens spiked with RVFV, including human and animal sera, homogenates of liver and spleen tissues of domestic ruminants, and Anopheles mosquito homogenates, the sAg-ELISA detection limit ranged from log(10)10(2.2) to 10(3.2) TCID(50)/reaction volume. The ELISA detected NP antigen in spiked bovine and sheep liver homogenates up to at least 8 days of incubation at 37 degrees C whereas infectious virus could not be detected at 48h incubation in these adverse conditions. Compared to virus isolation from sera from RVF patients and sheep infected experimentally, the ELISA had 67.7% and 70% sensitivity, and 97.97% and 100% specificity, respectively. The assay was 100% accurate when testing tissues of various organs from mice infected experimentally and buffalo foetuses infected naturally. The assay was able to detect NP antigen in infective culture supernatants 16-24h before cytopathic effects were observed microscopically and as early as 8h after inoculation with 10(5.8) TCID(50)/ml of RVFV. This ability renders the assay for rapid identification of the virus when its primary isolation is attempted in vitro. As a highly specific, safe and simple assay format, the sAg-ELISA represents a valuable diagnostic tool for use in less equipped laboratories in Africa, and for routine

Immune responses against SARS-coronavirus nucleocapsid protein induced by DNA vaccine

International Nuclear Information System (INIS)

Zhao Ping; Cao Jie; Zhao Lanjuan; Qin Zhaolin; Ke Jinshan; Pan Wei; Ren Hao; Yu Jianguo; Qi Zhongtian

2005-01-01

The nucleocapsid (N) protein of SARS-coronavirus (SARS-CoV) is the key protein for the formation of the helical nucleocapsid during virion assembly. This protein is believed to be more conserved than other proteins of the virus, such as spike and membrane glycoprotein. In this study, the N protein of SARS-CoV was expressed in Escherichia coli DH5α and identified with pooled sera from patients in the convalescence phase of SARS. A plasmid pCI-N, encoding the full-length N gene of SARS-CoV, was constructed. Expression of the N protein was observed in COS1 cells following transfection with pCI-N. The immune responses induced by intramuscular immunization with pCI-N were evaluated in a murine model. Serum anti-N immunoglobulins and splenocytes proliferative responses against N protein were observed in immunized BALB/c mice. The major immunoglobulin G subclass recognizing N protein was immunoglobulin G2a, and stimulated splenocytes secreted high levels of gamma interferon and IL-2 in response to N protein. More importantly, the immunized mice produced strong delayed-type hypersensitivity (DTH) and CD8 + CTL responses to N protein. The study shows that N protein of SARS-CoV not only is an important B cell immunogen, but also can elicit broad-based cellular immune responses. The results indicate that the N protein may be of potential value in vaccine development for specific prophylaxis and treatment against SARS

IMPROVEMENT OF THE QUALITY CONTROL OF ELISA TESTING FOR THE LABORATORY CONFIRMATION OF MEASLES AND RUBELLA INFECTIONS AT THE STAGE OF THE MEASLES/ RUBELLA ELIMINATION PROGRAM

Directory of Open Access Journals (Sweden)

T. A. Mamaeva

2017-01-01

Full Text Available To estimate ELISA serological studies results of IgM and IgG specific Measles and Rubella Viruses (MRV antibodies detection the “in-house” laboratory controls (ILC including the specific markers of MRV infections were for the first time commercially prepared by the Vector Best PLC (Russia: “Measles-IgM, ser.1”, “Measles-IgM, ser.2”, “Rubella-IgM”, Measles-IgG” and “Rubella-IgG”. This task was realized under the special Executive Order of the Government of Russia N 523-r, 2014, April, 4. According to passport characteristics ILC samples are the lyophilized human sera, inactivated by heating (1 hour at 56°C and stabilized by the mixture of sucrose (5% and ProClin-3000 as the conservation agent. Samples are free of HBs Ag, anti-HVC, T.Pallidum, HIV-1/2, HIV-1Ag р24.The aim of the study was to evaluate the possibility of using the ILC for detection of the MRV IgM and IgG antibodies by ELISA with commercial ELISA kits used in Russia and CIS countries. In the process of detecting the specific activity of “Measles-IgM, ser.1”, “Measles-IgM, ser.2” and “Rubella-IgM” by ELISA kits of different formats (Vector Best, EcoLab and Siemens Companies the statistically different results were received (p < 0.05. The optical density (OD values of IgM in the “Measles-IgM, ser.1” and “Measles-IgM, ser.2” ILC, obtained by ELISA “VectoMeasles IgM” (Vector Best were significantly higher than those obtained by ELISA IgEnzygnost®Anti-MeaslesVirus/IgМ. These values consisted for the ser. 1–1.33±0.02 о.u. vs. 0.18±0.01 о.u. (р < 0.05 and for the ser. 2–2.83±0.03 о.u. vs. 0.7±0.02 о.е. (р < 0.05 in the Vector Best and Siemens ELISA kits correspondently. In the “Rubella-IgM” ILC the OD values of the specific IgM by the “ELISA-Rubella IgM” EcoLab were also higher than those obtained by IgEnzygnost®Anti-RubellaVirus/IgМ ELISA kit. These values consisted 2.92±0.04 о.u. vs. 0.88±0.03 �

Protective immunity provided by HLA-A2 epitopes for fusion and hemagglutinin proteins of measles virus

International Nuclear Information System (INIS)

Oh, Sang Kon; Stegman, Brian; Pendleton, C. David; Ota, Martin O.; Pan, C.-H.; Griffin, Diane E.; Burke, Donald S.; Berzofsky, Jay A.

2006-01-01

Natural infection and vaccination with a live-attenuated measles virus (MV) induce CD8 + T-cell-mediated immune responses that may play a central role in controlling MV infection. In this study, we show that newly identified human HLA-A2 epitopes from MV hemagglutinin (H) and fusion (F) proteins induced protective immunity in HLA-A2 transgenic mice challenged with recombinant vaccinia viruses expressing F or H protein. HLA-A2 epitopes were predicted and synthesized. Five and four peptides from H and F, respectively, bound to HLA-A2 molecules in a T2-binding assay, and four from H and two from F could induce peptide-specific CD8 + T cell responses in HLA-A2 transgenic mice. Further experiments proved that three peptides from H (H9-567, H10-250, and H10-516) and one from F protein (F9-57) were endogenously processed and presented on HLA-A2 molecules. All peptides tested in this study are common to 5 different strains of MV including Edmonston. In both A2K b and HHD-2 mice, the identified peptide epitopes induced protective immunity against recombinant vaccinia viruses expressing H or F. Because F and H proteins induce neutralizing antibodies, they are major components of new vaccine strategies, and therefore data from this study will contribute to the development of new vaccines against MV infection

Two-dimensional polyacrylamide gel analysis of Plodia interpunctella granulosis virus

International Nuclear Information System (INIS)

Russell, D.L.; Consigli, R.A.

1986-01-01

The structural polypeptides of purified Plodia interpunctella granulosis virus were analyzed by three different two-dimensional gel systems. Isoelectric focusing followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis allowed resolution of 53 acidic polypeptides in the enveloped nucleocapsid of the virus ranging in molecular weight from 97,300 to 8000. Nine of these polypeptides were shown to be glycoproteins by the technique of radiolabeled lectin blotting. Separation of the granulin in this system allowed resolution of five species, all of which have identical tryptic peptide maps. This matrix protein was demonstrated to be a phosphoglycoprotein by radiolabeled lectin blotting and acid phosphatase dephosphorylation. Nonequilibrium pH gel electrophoresis followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis allowed resolution of the major basic protein of the virus, VP12, from a more acidic protein of the same molecular weight. Tryptic peptide analysis demonstrated that these two proteins were indeed different and acid urea gels followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis allowed localization of the acidic protein to the envelope and the basic protein to the nucleocapsid of the virus. Finally, probing of the separated envelope nucleocapsid proteins in both the isoelectric focusing and nonequilibrium pH gel electrophoresis two-dimensional systems after transfer to nitrocellulose with iodinated, purified viral proteins allowed further insight into reactions which may be important in the maintenance of the virion structure

VIRUS FAMILIES – contd

Indian Academy of Sciences (India)

First page Back Continue Last page Overview Graphics. VIRUS FAMILIES – contd. Minus strand RNA viruses. Rhabdovirus e.g. rabies. Paramyxovirus e.g. measles, mumps. Orthomyxovirus e.g. influenza. Retroviruses. RSV, HTLV, MMTV, HIV. Notes:

ICTV virus taxonomy profile

NARCIS (Netherlands)

García, María Laura; Bó, Dal Elena; Graça, da John V.; Gago-Zachert, Selma; Hammond, John; Moreno, Pedro; Natsuaki, Tomohide; Pallás, Vicente; Navarro, Jose A.; Reyes, Carina A.; Luna, Gabriel Robles; Sasaya, Takahide; Tzanetakis, Ioannis E.; Vaira, Anna María; Verbeek, Martin; Lefkowitz, Elliot J.; Davison, Andrew J.; Siddell, Stuart G.; Simmonds, Peter; Adams, Michael J.; Smith, Donald B.; Orton, Richard J.; Sanfaçon, Hélène

2017-01-01

The Ophioviridae is a family of filamentous plant viruses, with single-stranded negative, and possibly ambisense, RNA genomes of 11.3-12.5 kb divided into 3-4 segments, each encapsidated separately. Virions are naked filamentous nucleocapsids, forming kinked circles of at least two different contour

Post-Ebola Measles Outbreak in Lola, Guinea, January-June 2015(1).

Science.gov (United States)

Suk, Jonathan E; Paez Jimenez, Adela; Kourouma, Mamadou; Derrough, Tarik; Baldé, Mamadou; Honomou, Patric; Kolie, Nestor; Mamadi, Oularé; Tamba, Kaduono; Lamah, Kalaya; Loua, Angelo; Mollet, Thomas; Lamah, Molou; Camara, Amara Nana; Prikazsky, Vladimir

2016-06-01

During public health crises such as the recent outbreaks of Ebola virus disease in West Africa, breakdowns in public health systems can lead to epidemics of vaccine-preventable diseases. We report here on an outbreak of measles in the prefecture of Lola, Guinea, which started in January 2015.

Structural and Functional Studies on the Fusion and Attachment Envelope Glycoproteins of Nipah Virus and Hendra Virus

Science.gov (United States)

2003-01-01

including measles virus (MeV), mumps virus, Sendai virus (SeV), Newcastle disease virus (NDV), rinderpest virus, canine distemper virus (CDV), human...Institute of Health, Bethesda, MD. Hut 102, MT2, MT4, and CEM human T cell lines were provided by Chou-Zen Giam, USUHS, Bethesda, MD. The human osteosarcoma

Resurgence of measles in a country of elimination: interim assessment and current control measures in the Republic of Korea in early 2014

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Tae Un Yang

2015-04-01

Full Text Available Since the beginning of 2014, the Republic of Korea has experienced a resurgence of measles cases. Among the 220 cases confirmed as measles during epidemiological weeks 1–20 (December 29, 2013 to May 17, 2014, 10 imported cases were identified. The predominant genotype was B3, which reflects the circulating measles virus in adjacent countries. Even with the verification of measles elimination in March 2014 by the World Health Organization, recent importation has been related to international travel. Targeted control measures have been implemented in addition to proper isolation and patient care. A vigilant surveillance system and high levels of vaccine coverage should be maintained to sustain the measles elimination status.

Biological Feasibility of Measles Eradication

Science.gov (United States)

Strebel, Peter

2011-01-01

Recent progress in reducing global measles mortality has renewed interest in measles eradication. Three biological criteria are deemed important for disease eradication: (1) humans are the sole pathogen reservoir; (2) accurate diagnostic tests exist; and (3) an effective, practical intervention is available at reasonable cost. Interruption of transmission in large geographical areas for prolonged periods further supports the feasibility of eradication. Measles is thought by many experts to meet these criteria: no nonhuman reservoir is known to exist, accurate diagnostic tests are available, and attenuated measles vaccines are effective and immunogenic. Measles has been eliminated in large geographical areas, including the Americas. Measles eradication is biologically feasible. The challenges for measles eradication will be logistical, political, and financial. PMID:21666201

Measles burden in urban settings: characteristics of measles cases in Addis Ababa city administration, Ethiopia, 2004-2014.

Science.gov (United States)

Mersha, Amare Mengistu; Braka, Fiona; Gallagher, Kathleen; Tegegne, Aysheshim Ademe; Argay, Aron Kassahun; Mekonnen, Mekonnen Admassu; Aragaw, Merawi; Abegaz, Debritu Mengesha; Worku, Etsehiwot Zeamlak; Baynesagn, Mekonen Getahun

2017-01-01

In developing countries, measles was a major cause of morbidity and mortality before the wide spread use of measles vaccine. The purpose of this study was to describe measles burden in an urban setting, Addis Ababa- since the implementation of measles case-based surveillance in Ethiopia. We analyzed measles surveillance data for 2004 -2014. Incidence of measles was described by sub city, by year and by age groups. Age specific incidence rate were calculated. Logistic regression was used to identify the predictors of confirmed measles cases. Of 4220 suspected measles cases 39% were confirmed cases. Males and females were equally affected. The mean affected age was 7.59 years. Measles cases peaked in 2010 and 2013-2014. Incidence of measles is higher among children less than five years old. Outer sub cities were more affected by measles in all years. Sub cities bordering with Oromia Regional State were more affected by measles. Older age groups were more affected than younger age groups (age ≤ five years old). Efforts to close immunity gaps against measles and further strengthen surveillance in urban settings, particularly among children below five years old, should be prioritized.

Priming T-cell responses with recombinant measles vaccine vector in a heterologous prime-boost setting in non-human primates

NARCIS (Netherlands)

Bolton, Diane L.; Santra, Sampa; Swett-Tapia, Cindy; Custers, Jerome; Song, Kaimei; Balachandran, Harikrishnan; Mach, Linh; Naim, Hussein; Kozlowski, Pamela A.; Lifton, Michelle; Goudsmit, Jaap; Letvin, Norman; Roederer, Mario; Radošević, Katarina

2012-01-01

Licensed live attenuated virus vaccines capable of expressing transgenes from other pathogens have the potential to reduce the number of childhood immunizations by eliciting robust immunity to multiple pathogens simultaneously. Recombinant attenuated measles virus (rMV) derived from the Edmonston

Measles in vaccinated children 1.5 to 3 years of age in rural community of district peshawar, pakistan

International Nuclear Information System (INIS)

Khan, A.; Ullah, O.; Ahmad, I.

2015-01-01

In many developing countries measles is a leading cause of childhood morbidity and mortality. Despite of vaccination thousands of children have been infected by measles virus during last couple of years in Pakistan. The objective of this study was to determine the measles vaccination coverage rate and frequency of measles among vaccinated children of age 1.5-3 years in rural community of district Peshawar. Methods: The cross-sectional study was carried out among 385 children aged 1.5-3 year of rural community of Peshawar. After taking informed consent from parents/guardians a predesigned questionnaire was filled. Evidence of vaccination and measles history was taken by vaccination card, doctor prescription and parent/guardian recall. Data was gathered and analysed by using SPSS-16. Results: Of the 385 children, 361 (93.7%) were vaccinated against measles at 9 month. It was found that 27 (7.48%) vaccinated children had measles history of which 23 (6.74%) were infected after 9 month vaccination. One hundred and ninety-two (49.8%) children were vaccinated both at 9 and 15 months, and 14 (7.29%) dual vaccinated children had a measles history, 9 among them (4.68%) were infected after taking both measles doses. Conclusion: The occurrence of measles among vaccinated children and low coverage rate of second dose of measles vaccine raises many questions about vaccination program and its efficacy. Further studies are needed to evaluate the influence of other predisposing factors like vaccine quality, manufacturer, supply, cold chain, handling, nutritional status of children and technical approach, on measles vaccine efficacy. (author)

Is early measles vaccination better than later measles vaccination?

DEFF Research Database (Denmark)

Aaby, Peter; Martins, Cesário L; Ravn, Henrik

2015-01-01

WHO recommends delaying measles vaccination (MV) until maternal antibody has waned. However, early MV may improve child survival by reducing mortality from conditions other than measles infection. We tested whether early MV improves child survival compared with later MV. We found 43 studies compa...

Case Based Measles Surveillance in Pune: Evidence to Guide Current and Future Measles Control and Elimination Efforts in India

Science.gov (United States)

Bose, Anindya Sekhar; Jafari, Hamid; Sosler, Stephen; Narula, Arvinder Pal Singh; Kulkarni, V. M.; Ramamurty, Nalini; Oommen, John; Jadi, Ramesh S.; Banpel, R. V.; Henao-Restrepo, Ana Maria

2014-01-01

Background According to WHO estimates, 35% of global measles deaths in 2011 occurred in India. In 2013, India committed to a goal of measles elimination by 2020. Laboratory supported case based measles surveillance is an essential component of measles elimination strategies. Results from a case-based measles surveillance system in Pune district (November 2009 through December 2011) are reported here with wider implications for measles elimination efforts in India. Methods Standard protocols were followed for case identification, investigation and classification. Suspected measles cases were confirmed through serology (IgM) or epidemiological linkage or clinical presentation. Data regarding age, sex, vaccination status were collected and annualized incidence rates for measles and rubella cases calculated. Results Of the 1011 suspected measles cases reported to the surveillance system, 76% were confirmed measles, 6% were confirmed rubella, and 17% were non-measles, non-rubella cases. Of the confirmed measles cases, 95% were less than 15 years of age. Annual measles incidence rate was more than 250 per million persons and nearly half were associated with outbreaks. Thirty-nine per cent of the confirmed measles cases were vaccinated with one dose of measles vaccine (MCV1). Conclusion Surveillance demonstrated high measles incidence and frequent outbreaks in Pune where MCV1 coverage in infants was above 90%. Results indicate that even high coverage with a single dose of measles vaccine was insufficient to provide population protection and prevent measles outbreaks. An effective measles and rubella surveillance system provides essential information to plan, implement and evaluate measles immunization strategies and monitor progress towards measles elimination. PMID:25290339

Measles transmission from an anthroposophic community to the general population, Germany 2008

Science.gov (United States)

2011-01-01

measles virus into a pocket of susceptible persons (e.g. vaccination opponents or sceptics) may lead to large outbreaks in the general population, if the general population's vaccination coverage is below the WHO recommended level. Education on the safety of measles vaccine needs to be strengthened to increase measles vaccination coverage. Early intervention may limit spread in schools or kindergartens. Suspected measles has to be reported immediately to the local health authorities in order to allow intervention as early as possible. PMID:21676265

Expression of measles virus nucleoprotein induces apoptosis and modulates diverse functional proteins in cultured mammalian cells.

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Ashima Bhaskar

Full Text Available BACKGROUND: Measles virus nucleoprotein (N encapsidates the viral RNA, protects it from endonucleases and forms a virus specific template for transcription and replication. It is the most abundant protein during viral infection. Its C-terminal domain is intrinsically disordered imparting it the flexibility to interact with several cellular and viral partners. PRINCIPAL FINDINGS: In this study, we demonstrate that expression of N within mammalian cells resulted in morphological transitions, nuclear condensation, DNA fragmentation and activation of Caspase 3 eventuating into apoptosis. The rapid generation of intracellular reactive oxygen species (ROS was involved in the mechanism of cell death. Addition of ascorbic acid (AA or inhibitor of caspase-3 in the extracellular medium partially reversed N induced apoptosis. We also studied the protein profile of cells expressing N protein. MS analysis revealed the differential expression of 25 proteins out of which 11 proteins were up regulated while 14 show signs of down regulation upon N expression. 2DE results were validated by real time and semi quantitative RT-PCR analysis. CONCLUSION: These results show the pro-apoptotic effects of N indicating its possible development as an apoptogenic tool. Our 2DE results present prima facie evidence that the MV nucleoprotein interacts with or causes differential expression of a wide range of cellular factors. At this stage it is not clear as to what the adaptive response of the host cell is and what reflects a strategic modulation exerted by the virus.

Treatment of medulloblastoma using an oncolytic measles virus encoding the thyroidal sodium iodide symporter shows enhanced efficacy with radioiodine

International Nuclear Information System (INIS)

Hutzen, Brian; Pierson, Christopher R; Russell, Stephen J; Galanis, Evanthia; Raffel, Corey; Studebaker, Adam W

2012-01-01

Medulloblastoma is the most common malignant brain tumor of childhood. Although the clinical outcome for medulloblastoma patients has improved significantly, children afflicted with the disease frequently suffer from debilitating side effects related to the aggressive nature of currently available therapy. Alternative means for treating medulloblastoma are desperately needed. We have previously shown that oncolytic measles virus (MV) can selectively target and destroy medulloblastoma tumor cells in localized and disseminated models of the disease. MV-NIS, an oncolytic measles virus that encodes the human thyroidal sodium iodide symporter (NIS), has the potential to deliver targeted radiotherapy to the tumor site and promote a localized bystander effect above and beyond that achieved by MV alone. We evaluated the efficacy of MV-NIS against medulloblastoma cells in vitro and examined their ability to incorporate radioiodine at various timepoints, finding peak uptake at 48 hours post infection. The effects of MV-NIS were also evaluated in mouse xenograft models of localized and disseminated medulloblastoma. Athymic nude mice were injected with D283med-Luc medulloblastoma cells in the caudate putamen (localized disease) or right lateral ventricle (disseminated disease) and subsequently treated with MV-NIS. Subsets of these mice were given a dose of 131 I at 24, 48 or 72 hours later. MV-NIS treatment, both by itself and in combination with 131 I, elicited tumor stabilization and regression in the treated mice and significantly extended their survival times. Mice given 131 I were found to concentrate radioiodine at the site of their tumor implantations. In addition, mice with localized tumors that were given 131 I either 24 or 48 hours after MV-NIS treatment exhibited a significant survival advantage over mice given MV-NIS alone. These data suggest MV-NIS plus radioiodine may be a potentially useful therapy for the treatment of medulloblastoma

Treatment of medulloblastoma using an oncolytic measles virus encoding the thyroidal sodium iodide symporter shows enhanced efficacy with radioiodine

Directory of Open Access Journals (Sweden)

Hutzen Brian

2012-11-01

Full Text Available Abstract Background Medulloblastoma is the most common malignant brain tumor of childhood. Although the clinical outcome for medulloblastoma patients has improved significantly, children afflicted with the disease frequently suffer from debilitating side effects related to the aggressive nature of currently available therapy. Alternative means for treating medulloblastoma are desperately needed. We have previously shown that oncolytic measles virus (MV can selectively target and destroy medulloblastoma tumor cells in localized and disseminated models of the disease. MV-NIS, an oncolytic measles virus that encodes the human thyroidal sodium iodide symporter (NIS, has the potential to deliver targeted radiotherapy to the tumor site and promote a localized bystander effect above and beyond that achieved by MV alone. Methods We evaluated the efficacy of MV-NIS against medulloblastoma cells in vitro and examined their ability to incorporate radioiodine at various timepoints, finding peak uptake at 48 hours post infection. The effects of MV-NIS were also evaluated in mouse xenograft models of localized and disseminated medulloblastoma. Athymic nude mice were injected with D283med-Luc medulloblastoma cells in the caudate putamen (localized disease or right lateral ventricle (disseminated disease and subsequently treated with MV-NIS. Subsets of these mice were given a dose of 131I at 24, 48 or 72 hours later. Results MV-NIS treatment, both by itself and in combination with 131I, elicited tumor stabilization and regression in the treated mice and significantly extended their survival times. Mice given 131I were found to concentrate radioiodine at the site of their tumor implantations. In addition, mice with localized tumors that were given 131I either 24 or 48 hours after MV-NIS treatment exhibited a significant survival advantage over mice given MV-NIS alone. Conclusions These data suggest MV-NIS plus radioiodine may be a potentially useful therapy for

A random PCR screening system for the identification of type 1 human herpes simplex virus.

Science.gov (United States)

Yu, Xuelian; Shi, Bisheng; Gong, Yan; Zhang, Xiaonan; Shen, Silan; Qian, Fangxing; Gu, Shimin; Hu, Yunwen; Yuan, Zhenghong

2009-10-01

Several viral diseases exhibit measles-like symptoms. Differentiation of suspected cases of measles with molecular epidemiological techniques in the laboratory is useful for measles surveillance. In this study, a random PCR screening system was undertaken for the identification of isolates from patients with measles-like symptoms who exhibited cytopathic effects, but who had negative results for measles virus-specific reverse transcription (RT)-PCR and indirect immunofluorescence assays. Sequence analysis of random amplified PCR products showed that they were highly homologous to type 1 human herpes simplex virus (HSV-1). The results were further confirmed by an HSV-1-specific TaqMan real-time PCR assay. The random PCR screening system described in this study provides an efficient procedure for the identification of unknown viral pathogens. Measles-like symptoms can also be caused by HSV-1, suggesting the need to include HSV-1 in differential diagnoses of measles-like diseases.

Synergistic Effects of Sulfated Polysaccharides from Mexican Seaweeds against Measles Virus

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Karla Morán-Santibañez

2016-01-01

Full Text Available Sulfated polysaccharides (SPs extracted from five seaweed samples collected or cultivated in Mexico (Macrocystis pyrifera, Eisenia arborea, Pelvetia compressa, Ulva intestinalis, and Solieria filiformis were tested in this study in order to evaluate their effect on measles virus in vitro. All polysaccharides showed antiviral activity (as measured by the reduction of syncytia formation and low cytotoxicity (MTT assay at inhibitory concentrations. SPs from Eisenia arborea and Solieria filiformis showed the highest antiviral activities (confirmed by qPCR and were selected to determine their combined effect. Their synergistic effect was observed at low concentrations (0.0274 μg/mL and 0.011 μg/mL of E. arborea and S. filiformis SPs, resp., which exhibited by far a higher inhibitory effect (96% syncytia reduction in comparison to the individual SP effects (50% inhibition with 0.275 μg/mL and 0.985 μg/mL of E. arborea and S. filiformis, resp.. Time of addition experiments and viral penetration assays suggest that best activities of these SPs occur at different stages of infection. The synergistic effect would allow reducing the treatment dose and toxicity and minimizing or delaying the induction of antiviral resistance; sulfated polysaccharides of the tested seaweed species thus appear as promising candidates for the development of natural antiviral agents.

VHS virus - present situation

DEFF Research Database (Denmark)

Skall, Helle Frank; Olesen, Niels Jørgen

2015-01-01

of the worldwide distribution of the disease will be given. Virus evolution: Recent studies indicate that only a few amino acid changes in the structural proteins of VHSV can change the virulence patterns significantly, thereby coming closer to assessing the risk of none to low virulent viruses becoming high...... virulent. Virulence factors both depend on the ability of VHSV to enter a cell and on the speed and efficiencyof virus replication in the cells. Apparently the viral nucleocapsid protein plays a very important role for the later and seems to be the target for determination of a virulence marker....

[Measles in Poland in 2004].

Science.gov (United States)

Czarkowski, Mirosław P; Kondej, Barbara; Paweł, Stefanoff

2006-01-01

In Poland 11 measles cases were registered in 2004 (0.03 per 100,000 population), of which 3 were cases imported from Chechnya. Of 8 local cases, 3 cases occurred in unvaccinated persons, 2 in persons vaccinated with one dose and 3 in vaccinated with two doses of measles vaccine (administered at the age of 13-15 months and 7 years). The most affected age groups were 1-year old children (0.29 per 100,000 population) and 6-year olds (0.25). Out of 11 reported cases 2 were hospitalized. There were no deaths attributed to measles. Poland participates in the WHO Measles Elimination Strategy. Presently, the most important is the maintenance of a sensitive and timely surveillance of measles and measles-compatible cases, with serologic testing of one suspect case per 100,000 population. The performance of the surveillance system was insufficient with only 44 measles-compatible cases reported in 2004 (12% of expected reports). Serologic confirmation of cases was also insufficient, with 5 cases confirmed in WHO accredited laboratory. These results indicate the need to maintain the high immunisation coverage and improve measles surveillance system.

FastStats: Measles

Science.gov (United States)

... Women’s Health State and Territorial Data Reproductive Health Contraceptive Use Infertility Reproductive Health Notice Regarding FastStats Mobile ... measles, mumps, rubella: 91.9% (2015) Percent of adolescents aged 13-17 years vaccinated against measles, mumps, ...

The measles virus phosphoprotein interacts with the linker domain of STAT1

International Nuclear Information System (INIS)

Devaux, Patricia; Priniski, Lauren; Cattaneo, Roberto

2013-01-01

The measles virus (MV) phosphoprotein (P) and V proteins block the interferon (IFN) response by impeding phosphorylation of the signal transducer and activator of transcription 1 (STAT1) by the Janus kinase 1 (JAK1). We characterized how STAT1 mutants interact with P and JAK1 phosphorylation. Certain mutants of the linker, the Src-homology 2 domain (SH2), or the transactivation domain had reduced or abolished phosphorylation through JAK1 after IFN treatment. Other mutants, mainly localized in the linker, failed to interact with P as documented by the lack of interference with nuclear translocation. Thus the functional footprint of P on STAT1 localizes mainly to the linker domain; there is also some overlap with the STAT1 phosphorylation functional footprint on the SH2 domain. Based on these observations, we discuss how the MV-P might operate to inhibit the JAK/STAT pathway. - Highlights: • Residue in the linker and SH2 domains of STAT1 are important for MV-P interaction. • Residue in the linker and SH2 domains of STAT1 are important for STAT1 phosphorylation. • Residues interferring with both functions have similar location on STAT1. • The viral P and V proteins may operate in concert to inhibit the JAK/STAT pathway

The measles virus phosphoprotein interacts with the linker domain of STAT1

Energy Technology Data Exchange (ETDEWEB)

Devaux, Patricia, E-mail: devaux.patricia@mayo.edu; Priniski, Lauren; Cattaneo, Roberto

2013-09-15

The measles virus (MV) phosphoprotein (P) and V proteins block the interferon (IFN) response by impeding phosphorylation of the signal transducer and activator of transcription 1 (STAT1) by the Janus kinase 1 (JAK1). We characterized how STAT1 mutants interact with P and JAK1 phosphorylation. Certain mutants of the linker, the Src-homology 2 domain (SH2), or the transactivation domain had reduced or abolished phosphorylation through JAK1 after IFN treatment. Other mutants, mainly localized in the linker, failed to interact with P as documented by the lack of interference with nuclear translocation. Thus the functional footprint of P on STAT1 localizes mainly to the linker domain; there is also some overlap with the STAT1 phosphorylation functional footprint on the SH2 domain. Based on these observations, we discuss how the MV-P might operate to inhibit the JAK/STAT pathway. - Highlights: • Residue in the linker and SH2 domains of STAT1 are important for MV-P interaction. • Residue in the linker and SH2 domains of STAT1 are important for STAT1 phosphorylation. • Residues interferring with both functions have similar location on STAT1. • The viral P and V proteins may operate in concert to inhibit the JAK/STAT pathway.

ICTV virus taxonomy profile: Baculoviridae

Science.gov (United States)

The Baculoviridae is a family of large viruses with circular dsDNA genomes ranging from 80 to 180 kbp. Virions consist of enveloped rod-shaped nucleocapsids and are embedded in distinctive occlusion bodies measuring 0.15 to 15 µm. The occlusion bodies consist of a matrix composed of a single viral...

Chemovirotherapy for head and neck squamous cell carcinoma with EGFR-targeted and CD/UPRT-armed oncolytic measles virus.

Science.gov (United States)

Zaoui, K; Bossow, S; Grossardt, C; Leber, M F; Springfeld, C; Plinkert, P K; Kalle, C von; Ungerechts, G

2012-03-01

First-line treatment of recurrent and/or refractory head and neck squamous cell carcinoma (HNSCC) is based on platinum, 5-fluorouracil (5-FU) and the monoclonal antiEGFR antibody cetuximab. However, in most cases this chemoimmunotherapy does not cure the disease, and more than 50% of HNSCC patients are dying because of local recurrence of the tumors. In the majority of cases, HNSCC overexpress the epidermal growth factor receptor (EGFR), and its presence is associated with a poor outcome. In this study, we engineered an EGFR-targeted oncolytic measles virus (MV), armed with the bifunctional enzyme cytosine deaminase/uracil phosphoribosyltransferase (CD/UPRT). CD/UPRT converts 5-fluorocytosine (5-FC) into the chemotherapeutic 5-FU, a mainstay of HNSCC chemotherapy. This virus efficiently replicates in and lyses primary HNSCC cells in vitro. Arming with CD/UPRT mediates efficient prodrug activation with high bystander killing of non-infected tumor cells. In mice bearing primary HNSCC xenografts, intratumoral administration of MV-antiEGFR resulted in statistically significant tumor growth delay and prolongation of survival. Importantly, combination with 5-FC is superior to virus-only treatment leading to significant tumor growth inhibition. Thus, chemovirotherapy with EGFR-targeted and CD/UPRT-armed MV is highly efficacious in preclinical settings with direct translational implications for a planned Phase I clinical trial of MV for locoregional treatment of HNSCC.

Mitigating measles outbreaks in West Africa post-Ebola.

Science.gov (United States)

Truelove, Shaun A; Moss, William J; Lessler, Justin

2015-01-01

The Ebola outbreak in 2014-2015 devastated the populations, economies and healthcare systems of Guinea, Liberia and Sierra Leone. With this devastation comes the impending threat of outbreaks of other infectious diseases like measles. Strategies for mitigating these risks must include both prevention, through vaccination, and case detection and management, focused on surveillance, diagnosis and appropriate clinical care and case management. With the high transmissibility of measles virus, small-scale reactive vaccinations will be essential to extinguish focal outbreaks, while national vaccination campaigns are needed to guarantee vaccination coverage targets are reached in the long term. Rapid and multifaceted strategies should carefully navigate challenges present in the wake of Ebola, while also taking advantage of current Ebola-related activities and international attention. Above all, resources and focus currently aimed at these countries must be utilized to build up the deficit in infrastructure and healthcare systems that contributed to the extent of the Ebola outbreak.

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.

Interaction study of rice stripe virus proteins reveals a region of the nucleocapsid protein (NP) required for NP self-interaction and nuclear localization.

Science.gov (United States)

Lian, Sen; Cho, Won Kyong; Jo, Yeonhwa; Kim, Sang-Min; Kim, Kook-Hyung

2014-04-01

Rice stripe virus (RSV), which belongs to the genus Tenuivirus, is an emergent virus problem. The RSV genome is composed of four single-strand RNAs (RNA1-RNA4) and encodes seven proteins. We investigated interactions between six of the RSV proteins by yeast-two hybrid (Y2H) assay in vitro and by bimolecular fluorescence complementation (BiFC) in planta. Y2H identified self-interaction of the nucleocapsid protein (NP) and NS3, while BiFC revealed self-interaction of NP, NS3, and NCP. To identify regions(s) and/or crucial amino acid (aa) residues required for NP self-interaction, we generated various truncated and aa substitution mutants. Y2H assay showed that the N-terminal region of NP (aa 1-56) is necessary for NP self-interaction. Further analysis with substitution mutants demonstrated that additional aa residues located at 42-47 affected their interaction with full-length NP. These results indicate that the N-terminal region (aa 1-36 and 42-47) is required for NP self-interaction. BiFC and co-localization studies showed that the region required for NP self-interaction is also required for NP localization at the nucleus. Overall, our results indicate that the N-terminal region (aa 1-47) of the NP is important for NP self-interaction and that six aa residues (42-47) are essential for both NP self-interaction and nuclear localization. Copyright © 2014 Elsevier B.V. All rights reserved.

Measles (Rubeola) Cases and Outbreaks

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... Address What’s this? Submit What's this? Submit Button Measles Cases and Outbreaks Language: English (US) Español (Spanish) ... Español: Casos y brotes de sarampión Number of measles cases by year since 2010 Measles cases per ...

Zika virus infection.

Science.gov (United States)

Pougnet, Laurence; Thill, Chloé; Pougnet, Richard; Auvinet, Henri; Giacardi, Christophe; Drouillard, Isabelle

2016-12-01

A 21-year old woman from New-Caledonia had 40 ̊C fever with vomiting, arthralgia, myalgia, and measles-like rash. Etiological analyses showed primary infection with Zika virus. Because of severe clinical presentation, she was hospitalized in the intensive care unit of the Brest military Hospital. Zika virus is mainly transmitted by Aedes mosquitoes. If they settle in Metropolitan France, Zika virus might also spread there.

Occurrence of different types of infectious hematopoietic necrosis virus in fish

International Nuclear Information System (INIS)

Hsu, Y.; Engelking, H.M.; Leong, J.C.

1986-01-01

The virion protein patterns of 71 isolates of infectious hematopoietic necrosis virus (IHNV) from the Pacific Northwest were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis of [ 35 S]-methionine-labeled virus. This analysis led to the classification of these virus isolates into four or more types. Type 1 virus was characterized by a nucleocapsid protein with an approximate molecular weight of 40,500. Type 2 and type 3 viruses have nucleocapsid proteins with molecular weights of 42,800 and 43,250, respectively. Type 2 virus was responsible for the recent epizootics of IHNV among fish in the lower Columbia River. The California IHNV isolates were type 3 with the exception of some of those isolated from fish at the Coleman Hatchery on the Sacramento River. These Coleman Hatchery isolates belonged to a type 4 virus group characterized by a larger glycoprotein of approximately 70,000 molecular weight. All other viruses examined had glycoproteins of 67,000 molecular weight. The type 5 virus isolates were grouped together because they were not sufficiently distinct to warrant classification into a separate type. These findings have been useful in determining that (i) a particular virus type is characteristic for a geographic area and will infect many different salmonid species in that area and (ii) the same type isolated from parental fish is responsible for the subsequent outbreak of the diseases in progeny

Measles: summary of worldwide impact.

Science.gov (United States)

Assaad, F

1983-01-01

Nearly every measles infection results in well-recognized clinical disease. In nonimmunized populations almost every child will get measles early in life. The universality of the disease in nonimmunized communities, particularly those in the developing world, has led to a more or less passive acceptance of measles as an unavoidable risk of early life. The clinical spectrum of measles ranges from a mild, self-limiting illness to a fatal disease. Conditions encountered mainly in the developing world, e.g., unfavorable nutrition, high risk of concurrent infection, and inadequate case management -- particularly at home -- favor the development of complications and adverse outcome. Conversely, good clinical management of an otherwise healthy child, a situation seen mostly in the developed world, greatly influences the course of the disease. Hence many in the medical profession believe that measles is a mild disease except among populations living under particularly unfavorable conditions. Measles vaccine is effective in preventing disease in the individual and in controlling it in the community if it is given at the critical age when maternal antibodies wane and the risk of natural infection increases sharply and if a high immunization rate is maintained in the target population. The experience with immunization, particularly in sub-saharan Africa, is rewarding: mothers who had previously accepted measles as an unavoidable risk clamour for immunization of their children once its effectiveness has been demonstrated. No reason exists for measles to claim its present toll of morbidity and mortality. With extension of the Expanded Programme on Immunization of the World Health Organization, the impact of measles should progressively decline.

Measles hectic in Pakistan; Upsurge versus the lurking vaccination.

Science.gov (United States)

2015-02-01

Measles has claimed more lives than anticipated, as the outbreaks hit Pakistan severely in 2013 as compared to 2012. Claiming 350 lives through the year 2013, Measles became a headache for the health agencies, authorities and common people. The sudden appearance of the virus in different parts of the country both rural and urban at the same time can be linked to more than one cause. The notable being corruption in health system, poor health infrastructure, destabilized routine immunization, shortage in number of vaccinators, negligence among parents, and floods. As a consequence of these causative factors, the unclear picture of immunization coverage can be presumed as the ultimate etiology of outbreaks in such numbers. Therefore, there is an urgent need to draw out the actual data of immunisation coverage and focus on elimination of hurdles in the road to success in fully coverage with vaccines.

Measles elimination and immunisation: national surveillance trends in Japan, 2008-2015.

Science.gov (United States)

Inaida, S; Matsuno, S; Kobune, F

2017-08-01

Measles elimination relies on vaccination programmes. In Japan, a major outbreak started in 2007. In response, 5-year two-dose catch-up vaccination programme was initiated in April 2008 for children 13-16-years-old. In this study, we analysed the epidemic curves, incidence rates for each age group, virus genotype, vaccination coverage and ratio of measles gelatin particle agglutination (PA) antibody using surveillance data for 2008-2015. Monthly case counts markedly decreased as vaccination coverage increased. D5, which is the endemic virus type, disappeared after 2011, with the following epidemic caused by imported viruses. Most cases were confirmed to have a no-dose or single-dose vaccination status. Although the incidence rate among all age groups ⩾5-years-old decreased during the study period, for children <5-years-old, the incidence rate remained relatively high and increased in 2014. The ratio of PA antibody (⩾1:128 titres) increased for the majority of age groups, but with a decrease for specific age groups: the 0-5 months and the 2-4, 14, 19 and most of the 26-55- and the 60-year-old groups (-1 to -9%). This seems to be the result of higher vaccination coverage, which would result in decreasing natural immunity booster along with decreasing passive immunity in infants whose mothers did not have the natural immunity booster. The 20-29- and 30-39-year-old age groups had higher number of cases, suggesting that vaccination within these age groups might be important for eliminating imported viruses.

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

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

2012-02-01

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

Characterization of a single-nucleocapsid nucleopolyhedrovirus of Thysanoplusia orichalcea L. (Lepidoptera: Noctuidae) from Indonesia.

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Cheng, X W; Carner, G R

2000-05-01

A single-nucleocapsid nucleopolyhedrovirus (NPV) isolated from Thysanoplusia orichalcea L. (Lepidoptera:Noctuidae) (ThorNPV) in Indonesia has tetrahedral occlusion bodies (OBs) with a width of 1. 22 microm (range = 0.803-1.931 microm). The length of the virion with an envelope averaged 0.29 and 0.23 microm without an envelope. ThorNPV was propagated in Pseudoplusia includens (Walker) and its authenticity was confirmed by sequence analysis of the polyhedrin gene of the ThorNPV produced in T. orichalcea and P. includens. Polyhedrin amino acid sequence analysis revealed that ThorNPV belongs to Group II of baculoviruses and is closely related to Trichoplusia ni single nucleocapsid NPV, sharing 97.6% sequence identity. Infectivity of ThorNPV against third instar P. includens was low, with a LD(50) value of 65,636 OBs/larva. Electron microscopy of infected tissues showed many polyhedra without virions embedded, which might explain the low virulence against P. includens. Differences in virion occlusion rates between individual cells in the same tissue suggested that the inoculum consisted of at least two variants that differed in the gene(s) controlling virion occlusion. In a host range test using the LD(50) value to P. includens against Spodoptera exigua, S. frugiperda, S. eridania, Anticarsia gemmatalis, Helicoverpa zea, Trichoplusia ni, and P. includens, P. includens was the only species infected. The virus infected primarily the fat body, tracheal epithelium, and hypodermis. The genomic size of the ThorNPV is 135 kb. Copyright 2000 Academic Press.

Intracellular HIV-1 Gag localization is impaired by mutations in the nucleocapsid zinc fingers

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Muriaux Delphine

2007-08-01

Full Text Available Abstract Background The HIV-1 nucleocapsid protein (NC is formed of two CCHC zinc fingers flanked by highly basic regions. HIV-1 NC plays key roles in virus structure and replication via its nucleic acid binding and chaperoning properties. In fact, NC controls proviral DNA synthesis by reverse transcriptase (RT, gRNA dimerization and packaging, and virion assembly. Results We previously reported a role for the first NC zinc finger in virion structure and replication 1. To investigate the role of both NC zinc fingers in intracellular Gag trafficking, and in virion assembly, we generated series of NC zinc fingers mutations. Results show that all Zinc finger mutations have a negative impact on virion biogenesis and maturation and rendered defective the mutant viruses. The NC zinc finger mutations caused an intracellular accumulation of Gag, which was found either diffuse in the cytoplasm or at the plasma membrane but not associated with endosomal membranes as for wild type Gag. Evidences are also provided showing that the intracellular interactions between NC-mutated Gag and the gRNA were impaired. Conclusion These results show that Gag oligomerization mediated by gRNA-NC interactions is required for correct Gag trafficking, and assembly in HIV-1 producing cells and the release of infectious viruses.

[Measles in Poland in 2003].

Science.gov (United States)

Stefanoff, Paweł; Czarkowski, Mirosław P

2005-01-01

In Poland 48 measles cases were registered in 2003 (0.13 per 100,000 population)--of which 65% were cases imported from Chechnya and Afghanistan. Measles outbreaks occurred in 3 centers for immigrants. In total, 31 cases were reported, of which 96.8% were unvaccinated, and 93.5% were under 15 years of age. Of 17 local cases, 5 (29.4%) cases occurred in unvaccinated persons, 3 (17.6%) in persons vaccinated with one dose and 7 (41.2%) in those vaccinated with two doses of measles vaccine (administered at the age of 13-15 months and 7 years). Among 12 vaccinated cases only one 2-year old child was recently vaccinated. The remaining cases were in the 3-7 and 10-24 age ranges. The most affected were infants (incidence 0.57 per 100,000), 1-year old (0.28) and 2-year old children (incidence 0.27). Cases among adolescents and adults over 15 years of age increased from 23.5% in 2002 to 47.1% in 2003. The increasing age of locally-acquired cases, together with constantly high immunization coverage indicates high effectiveness of vaccinations in Poland. Out of all reported cases 13 (38%) were hospitalized. There were no deaths due to measles in Poland in 2003. Poland participates in the WHO Measles Elimination Strategy. Presently, the most important is the maintenance of a sensitive and timely surveillance of measles and measles-compatible cases, with serologic confirmation of one rash-like illness per 100 000 population. The performance of the surveillance system is insufficient with only 55 measles-compatible cases reported in 2003 (15% of expected reports). Serologic confirmation of cases was also insufficient, with 22 cases (40.0%) confirmed by IgM ELISA test. These results indicate the need to maintain the high immunisation coverage and improve measles surveillance system.

The roentgenological study of measles pneumonia

International Nuclear Information System (INIS)

Shin, U.; Song, C. H.; Lee, H. Y.; Chung, H. K.; Joo, K. B.

1983-01-01

Measles is important infectious disease of pediatrics and pneumonia is the most commonest complication of measles. We have experienced 20 cases of pneumonia among 31 cases of measles in infant nursing home of Chae Chun during of December. 1981. The results a are as follows; 1. The incidence of measles pneumonia is 64.5%. 2. The patterns of pneumonic infiltration is : The pneumonia may have a bronchopneumonia (60%), Lobar pneumonia (15%), or combined form (35%). 3. Both lungs are involved by measles pneumonia: Right lung only (30%), Left lung only (5%), or Bilateral (65%). 4. Hilar lymphadenopathy (51.6%). Hilar lymphadenopathy with pneumonia (82.2%) and hilar lymphadenopathy without pneumonia (17.8%). 5. There is no pulmonary nodule which is noted frequently in atypical measles pneumonia as a seguale

Determining infants' age for measles vaccination based on persistence of protective level of maternal measles antibody.

Science.gov (United States)

Shilpi, Tanjida; Sattar, Humayun; Miah, Md Ruhul Amin

2009-12-01

The present study was conducted over a period of one year to find the right time for measles vaccination when maternal antibody titer in infants was decayed rendering them susceptible to wild virus infection. Blood samples were collected from the cord of new born (147), 2-5 months (47) and 5 to 7.5 months (24) of age. The mean measles IgG antibody titer detected in cord blood at birth (0 months) was 348.8 mlU/mL which steeply decreased to 155.6 mlU/mL by the age of 2-3 months. After that the fall in antibody becomes relatively slower and decreased to 101.6 mIU/mL by the age of 3-5 months and 38.8 mlU/mL by the age of 5-6 months and to 19.2 mIU/mL between the age of 6 to 7.5 months. The fall in antibody level with the advance of age was statistically significant (p < 0.001 ). Majority of the subjects (97.6%) exhibited protective level of antibody at birth. But only a little above one-quarter (25.5%) of them persisted the protective level between the age of 2-5 months and none had protective level from 5 months onwards.

Central nervous system virion detection in acute measles: histopathological, ultrastructural and pathogenetic aspects Detecção de partículas virais no SNC no sarampo agudo: aspectos histopatológicos, ultraestruturais e patogenéticos

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C.L.P. Lancellotti

1995-04-01

Full Text Available Histopathological and ultrastructural studies of 23 patients who died with clinical diagnosis of measles were carried out. In 12 cases viral nucleocapsids were searched by electron microscopy and detected in 100% of the cases in the lungs and in 50% of the cases in the central nervous system. They were mostly intranuclear. Histopathological changes associated to neurological alterations and the detection of virion are discussed in relation to acute and delayed clinical manifestations.Foram realizados estudos histopatológicos e ultraestruturais de 23 pacientes que morreram com diagnóstico clínico de sarampo. Presença de nucleo-capsides virais foi pesquisada em 12 casos e detectada em 50% destes casos no SNC. Eram, na maioria dos casos, intranucleares. As alterações histopatológicas associadas a manifestações neurológicas e à detecção do vírus são discutidas em relação às manifestações clínicas agudas e tardias.

Factors Influencing University Nursing Students' Measles Vaccination Rate During a Community Measles Outbreak

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Ji Soo Kim, RN, PhD

2016-03-01

Conclusions: A systematic measles vaccination program targeting nursing students upon their entry to university is needed. In order to increase the measles vaccination rate, application of effective promotion campaigns and education programs is necessary.

White spot syndrome virus envelope protein VP28 is involved in the systemic infection of shrimp

NARCIS (Netherlands)

Hulten, van M.C.W.; Witteveldt, J.; Snippe, M.; Vlak, J.M.

2001-01-01

White spot syndrome virus (WSSV) is a large DNA virus infecting shrimp and other crustaceans. The virus particles contain at least five major virion proteins, of which three (VP26, VP24, and VP15) are present in the rod-shaped nucleocapsid and two (VP28 and VP19) reside in the envelope. The mode of

Dengue Virus Genome Uncoating Requires Ubiquitination.

Science.gov (United States)

Byk, Laura A; Iglesias, Néstor G; De Maio, Federico A; Gebhard, Leopoldo G; Rossi, Mario; Gamarnik, Andrea V

2016-06-28

The process of genome release or uncoating after viral entry is one of the least-studied steps in the flavivirus life cycle. Flaviviruses are mainly arthropod-borne viruses, including emerging and reemerging pathogens such as dengue, Zika, and West Nile viruses. Currently, dengue virus is one of the most significant human viral pathogens transmitted by mosquitoes and is responsible for about 390 million infections every year around the world. Here, we examined for the first time molecular aspects of dengue virus genome uncoating. We followed the fate of the capsid protein and RNA genome early during infection and found that capsid is degraded after viral internalization by the host ubiquitin-proteasome system. However, proteasome activity and capsid degradation were not necessary to free the genome for initial viral translation. Unexpectedly, genome uncoating was blocked by inhibiting ubiquitination. Using different assays to bypass entry and evaluate the first rounds of viral translation, a narrow window of time during infection that requires ubiquitination but not proteasome activity was identified. In this regard, ubiquitin E1-activating enzyme inhibition was sufficient to stabilize the incoming viral genome in the cytoplasm of infected cells, causing its retention in either endosomes or nucleocapsids. Our data support a model in which dengue virus genome uncoating requires a nondegradative ubiquitination step, providing new insights into this crucial but understudied viral process. Dengue is the most significant arthropod-borne viral infection in humans. Although the number of cases increases every year, there are no approved therapeutics available for the treatment of dengue infection, and many basic aspects of the viral biology remain elusive. After entry, the viral membrane must fuse with the endosomal membrane to deliver the viral genome into the cytoplasm for translation and replication. A great deal of information has been obtained in the last decade

In Vitro-Assembled Alphavirus Core-Like Particles Maintain a Structure Similar to That of Nucleocapsid Cores in Mature Virus

OpenAIRE

Mukhopadhyay, Suchetana; Chipman, Paul R.; Hong, Eunmee M.; Kuhn, Richard J.; Rossmann, Michael G.

2002-01-01

In vitro-assembled core-like particles produced from alphavirus capsid protein and nucleic acid were studied by cryoelectron microscopy. These particles were found to have a diameter of 420 Å with 240 copies of the capsid protein arranged in a T=4 icosahedral surface lattice, similar to the nucleocapsid core in mature virions. However, when the particles were subjected to gentle purification procedures, they were damaged, preventing generation of reliable structural information. Similarly, pu...

Dimerization Efficiency of Canine Distemper Virus Matrix Protein Regulates Membrane-Budding Activity.

Science.gov (United States)

Bringolf, Fanny; Herren, Michael; Wyss, Marianne; Vidondo, Beatriz; Langedijk, Johannes P; Zurbriggen, Andreas; Plattet, Philippe

2017-08-15

Paramyxoviruses rely on the matrix (M) protein to orchestrate viral assembly and budding at the plasma membrane. Although the mechanistic details remain largely unknown, structural data suggested that M dimers and/or higher-order oligomers may facilitate membrane budding. To gain functional insights, we employed a structure-guided mutagenesis approach to investigate the role of canine distemper virus (CDV) M protein self-assembly in membrane-budding activity. Three six-alanine-block (6A-block) mutants with mutations located at strategic oligomeric positions were initially designed. While the first one includes residues potentially residing at the protomer-protomer interface, the other two display amino acids located within two distal surface-exposed α-helices proposed to be involved in dimer-dimer contacts. We further focused on the core of the dimeric interface by mutating asparagine 138 (N138) to several nonconservative amino acids. Cellular localization combined with dimerization and coimmunopurification assays, performed under various denaturing conditions, revealed that all 6A-block mutants were impaired in self-assembly and cell periphery accumulation. These phenotypes correlated with deficiencies in relocating CDV nucleocapsid proteins to the cell periphery and in virus-like particle (VLP) production. Conversely, all M-N138 mutants remained capable of self-assembly, though to various extents, which correlated with proper accumulation and redistribution of nucleocapsid proteins at the plasma membrane. However, membrane deformation and VLP assays indicated that the M-N138 variants exhibiting the most reduced dimerization propensity were also defective in triggering membrane remodeling and budding, despite proper plasma membrane accumulation. Overall, our data provide mechanistic evidence that the efficiency of CDV M dimerization/oligomerization governs both cell periphery localization and membrane-budding activity. IMPORTANCE Despite the availability of

Priming T-cell responses with recombinant measles vaccine vector in a heterologous prime-boost setting in non-human primates

OpenAIRE

Bolton, Diane L.; Santra, Sampa; Swett, Cindy; Custers, Jerome; Song, Kaimei; Balachandran, Harikrishnan; Kozlowski, Pamela A.; Letvin, Norman; Roederer, Mario; Radošević, Katarina

2012-01-01

Licensed live attenuated virus vaccines capable of expressing transgenes from other pathogens have the potential to reduce the number of childhood immunizations by eliciting robust immunity to multiple pathogens simultaneously. Recombinant attenuated measles virus (rMV) derived from the Edmonston Zagreb vaccine strain was engineered to express simian immunodeficiency virus (SIV) Gag protein for the purpose of evaluating the immunogenicity of rMV as a vaccine vector in rhesus macaques. rMV-Gag...

Epstein-Barr virus but not cytomegalovirus is associated with reduced vaccine antibody responses in Gambian infants.

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Beth Holder

2010-11-01

Full Text Available Epstein-Barr virus (EBV and cytomegalovirus (CMV are persistent herpesviruses that have various immunomodulatory effects on their hosts. Both viruses are usually acquired in infancy in Sub-Saharan Africa, a region where childhood vaccines are less effective than in high income settings. To establish whether there is an association between these two observations, we tested the hypothesis that infection with one or both viruses modulate antibody responses to the T-cell independent meningococcal polysaccharide vaccine and the T-cell dependent measles vaccines.Infection with EBV and CMV was diagnosed by the presence of virus-specific IgM in the peripheral blood or by the presence of IgG at higher levels than that found in umbilical cord blood. Anti-meningococcus IgG and IgM were quantified by ELISA. Anti-measles antibody responses were quantified by haemagglutinin antibody inhibition assay. Infants infected with EBV had reduced IgG and IgM antibody responses to meningococcal polysaccharides and to measles vaccine. Infection with CMV alone predicted no changes in the response to meningococcal polysaccharide. While CMV alone had no discernable effect on the antibody response to measles, the response of infants infected with both CMV and EBV was similar to that of infants infected with neither, suggesting that the effects of CMV infection countered the effects of EBV on measles antibody responses.The results of this exploratory study indicate that infection with EBV is associated with reduced antibody responses to polysaccharides and to measles vaccine, but suggest that the response to T-cell dependent antigens such as measles haemagglutinin may be restored by infection with CMV.

Differential miRNA expression in B cells is associated with inter-individual differences in humoral immune response to measles vaccination.

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Haralambieva, Iana H; Kennedy, Richard B; Simon, Whitney L; Goergen, Krista M; Grill, Diane E; Ovsyannikova, Inna G; Poland, Gregory A

2018-01-01

MicroRNAs are important mediators of post-transcriptional regulation of gene expression through RNA degradation and translational repression, and are emerging biomarkers of immune system activation/response after vaccination. We performed Next Generation Sequencing (mRNA-Seq) of intracellular miRNAs in measles virus-stimulated B and CD4+ T cells from high and low antibody responders to measles vaccine. Negative binomial generalized estimating equation (GEE) models were used for miRNA assessment and the DIANA tool was used for gene/target prediction and pathway enrichment analysis. We identified a set of B cell-specific miRNAs (e.g., miR-151a-5p, miR-223, miR-29, miR-15a-5p, miR-199a-3p, miR-103a, and miR-15a/16 cluster) and biological processes/pathways, including regulation of adherens junction proteins, Fc-receptor signaling pathway, phosphatidylinositol-mediated signaling pathway, growth factor signaling pathway/pathways, transcriptional regulation, apoptosis and virus-related processes, significantly associated with neutralizing antibody titers after measles vaccination. No CD4+ T cell-specific miRNA expression differences between high and low antibody responders were found. Our study demonstrates that miRNA expression directly or indirectly influences humoral immunity to measles vaccination and suggests that B cell-specific miRNAs may serve as useful predictive biomarkers of vaccine humoral immune response.

Biological characterization of clones derived from the edmonston strain of measles virus in comparison with schwarz and CAM-70 vaccine strains

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Maria Beatriz Junqueira Borges

1996-08-01

Full Text Available Four virus clones were derived from the Edmonston strain of measles virus by repeated plaque purification. These clones were compared with the vaccine strains Schwarz and CAM-70 in terms of biological activities including plaque formation, hemagglutination, hemolysis and replication in Vero cells and chick embryo fibroblasts (CEF. Two clones of intermediate plaque yielded mixed plaque populations on subcultivation whereas the other two, showing small and large plaque sizes, showed stable plaque phenotypes. The vaccine strains showed consistent homogeneous plaque populations. All the Edmonston clones showed agglutination of monkey erythrocytes in isotonic solution while both vaccine strains hemagglutinated only in the presence of high salt concentrations. Variation in the hemolytic activity was observed among the four clones but no hemolytic activity was detected for the vaccine virus strains. Vaccine strains replicated efficiently both in Vero cells and CEF. All four clones showed efficient replication in Vero cells but different replication profiles in CEF. Two of them replicated efficiently, one was of intermediate efficiency and the other showed no replication in CEF. Two of the clones showed characteristics similar to vaccine strains. One in terms of size and homogeneity of plaques, the other for a low hemolytic activity and both for the efficiency of propagation in CEF.

Diagnosis of measles by clinical case definition in dengue-endemic areas: implications for measles surveillance and control.

OpenAIRE

Dietz, V. J.; Nieburg, P.; Gubler, D. J.; Gomez, I.

1992-01-01

In many countries, measles surveillance relies heavily on the use of a standard clinical case definition; however, the clinical signs and symptoms of measles are similar to those of dengue. For example, during 1985, in Puerto Rico, 22 (23%) of 94 cases of illnesses with rashes that met the measles clinical case definition were serologically confirmed as measles, but 32 (34%) others were serologically confirmed as dengue. Retrospective analysis at the San Juan Laboratories of the Centers for D...

Lack of association between measles virus vaccine and autism with enteropathy: a case-control study.

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Mady Hornig

2008-09-01

Full Text Available The presence of measles virus (MV RNA in bowel tissue from children with autism spectrum disorders (ASD and gastrointestinal (GI disturbances was reported in 1998. Subsequent investigations found no associations between MV exposure and ASD but did not test for the presence of MV RNA in bowel or focus on children with ASD and GI disturbances. Failure to replicate the original study design may contribute to continued public concern with respect to the safety of the measles, mumps, and rubella (MMR vaccine.The objective of this case-control study was to determine whether children with GI disturbances and autism are more likely than children with GI disturbances alone to have MV RNA and/or inflammation in bowel tissues and if autism and/or GI episode onset relate temporally to receipt of MMR. The sample was an age-matched group of US children undergoing clinically-indicated ileocolonoscopy. Ileal and cecal tissues from 25 children with autism and GI disturbances and 13 children with GI disturbances alone (controls were evaluated by real-time reverse transcription (RT-PCR for presence of MV RNA in three laboratories blinded to diagnosis, including one wherein the original findings suggesting a link between MV and ASD were reported. The temporal order of onset of GI episodes and autism relative to timing of MMR administration was examined. We found no differences between case and control groups in the presence of MV RNA in ileum and cecum. Results were consistent across the three laboratory sites. GI symptom and autism onset were unrelated to MMR timing. Eighty-eight percent of ASD cases had behavioral regression.This study provides strong evidence against association of autism with persistent MV RNA in the GI tract or MMR exposure. Autism with GI disturbances is associated with elevated rates of regression in language or other skills and may represent an endophenotype distinct from other ASD.

Nucleocapsid Gene-Mediated Transgenic Resistance Provides Protection Against Tomato spotted wilt virus Epidemics in the Field.

Science.gov (United States)

Herrero, S; Culbreath, A K; Csinos, A S; Pappu, H R; Rufty, R C; Daub, M E

2000-02-01

ABSTRACT Transformation of plants with the nucleocapsid (N) gene of Tomato spotted wilt tospovirus (TSWV) provides resistance to disease development; however, information is lacking on the response of plants to natural inoculum in the field. Three tobacco cultivars were transformed with the N gene of a dahlia isolate of TSWV (TSWV-D), and plants were evaluated over several generations in the greenhouse. The resistant phenotype was more frequently observed in 'Burley 21' than in 'KY-14' or 'K-326', but highly resistant 'Burley 21' transgenic lines were resistant to only 44% of the heterologous TSWV isolates tested. Advanced generation (R(3) and R(4)) transgenic resistant lines of 'Burley 21' and a 'K-326' F(1) hybrid containing the N genes of two TSWV isolates were evaluated in the field near Tifton, GA, where TSWV is endemic. Disease development was monitored by symptom expression and enzyme-linked immunosorbent assay (ELISA) analysis. Whereas incidence of TSWV infection in 'Burley 21' susceptible controls was 20% in 1996 and 62% in 1997, the mean incidence in transgenic lines was reduced to 4 and 31%, respectively. Three transgenic 'Burley 21' lines were identified that had significantly lower incidence of disease than susceptible controls over the two years of the study. In addition, the rate of disease increase at the onset of the 1997 epidemic was reduced for all the 'Burley 21' transgenic lines compared with the susceptible controls. The 'K-326' F(1) hybrid was as susceptible as the 'K-326' nontransformed control. ELISA analysis demonstrated that symptomless plants from the most resistant 'Burley 21' transgenic lines accumulated detectable nucleocapsid protein, whereas symptomless plants from more susceptible lines did not. We conclude that transgenic resistance to TSWV is effective in reducing incidence of the disease in the field, and that accumulation of transgene protein may be important in broad-spectrum resistance.

Measles - Educational Resources for Parents and Childcare Providers

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... Search Form Controls Cancel Submit Search the CDC Measles (Rubeola) Note: Javascript is disabled or is not ... message, please visit this page: About CDC.gov . Measles Home About Measles History of Measles Signs and ...

Development of the Global Measles Laboratory Network.

Science.gov (United States)

Featherstone, David; Brown, David; Sanders, Ray

2003-05-15

The routine reporting of suspected measles cases and laboratory testing of samples from these cases is the backbone of measles surveillance. The Global Measles Laboratory Network (GMLN) has developed standards for laboratory confirmation of measles and provides training resources for staff of network laboratories, reference materials and expertise for the development and quality control of testing procedures, and accurate information for the Measles Mortality Reduction and Regional Elimination Initiative. The GMLN was developed along the lines of the successful Global Polio Laboratory Network, and much of the polio laboratory infrastructure was utilized for measles. The GMLN has developed as countries focus on measles control activities following successful eradication of polio. Currently more than 100 laboratories are part of the global network and follow standardized testing and reporting procedures. A comprehensive laboratory accreditation process will be introduced in 2002 with six quality assurance and performance indicators.

Molecular architecture of the nucleoprotein C-terminal domain from the Ebola and Marburg viruses.

Science.gov (United States)

Baker, Laura E; Ellena, Jeffrey F; Handing, Katarzyna B; Derewenda, Urszula; Utepbergenov, Darkhan; Engel, Daniel A; Derewenda, Zygmunt S

2016-01-01

The Filoviridae family of negative-sense, single-stranded RNA (ssRNA) viruses is comprised of two species of Marburgvirus (MARV and RAVV) and five species of Ebolavirus, i.e. Zaire (EBOV), Reston (RESTV), Sudan (SUDV), Taï Forest (TAFV) and Bundibugyo (BDBV). In each of these viruses the ssRNA encodes seven distinct proteins. One of them, the nucleoprotein (NP), is the most abundant viral protein in the infected cell and within the viral nucleocapsid. It is tightly associated with the viral RNA in the nucleocapsid, and during the lifecycle of the virus is essential for transcription, RNA replication, genome packaging and nucleocapsid assembly prior to membrane encapsulation. The structure of the unique C-terminal globular domain of the NP from EBOV has recently been determined and shown to be structurally unrelated to any other known protein [Dziubańska et al. (2014), Acta Cryst. D70, 2420-2429]. In this paper, a study of the C-terminal domains from the NP from the remaining four species of Ebolavirus, as well as from the MARV strain of Marburgvirus, is reported. As expected, the crystal structures of the BDBV and TAFV proteins show high structural similarity to that from EBOV, while the MARV protein behaves like a molten globule with a core residual structure that is significantly different from that of the EBOV protein.

Risk Factors for Measles Virus Infection Among Adults During a Large Outbreak in Postelimination Era in Mongolia, 2015.

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Hagan, José E; Takashima, Yoshihiro; Sarankhuu, Amarzaya; Dashpagma, Otgonbayar; Jantsansengee, Baigalmaa; Pastore, Roberta; Nyamaa, Gunregjav; Yadamsuren, Buyanjargal; Mulders, Mick N; Wannemuehler, Kathleen A; Anderson, Raydel; Bankamp, Bettina; Rota, Paul; Goodson, James L

2017-12-05

In 2015, a large nationwide measles outbreak occurred in Mongolia, with very high incidence in the capital city of Ulaanbaatar and among young adults. We conducted an outbreak investigation including a matched case-control study of risk factors for laboratory-confirmed measles among young adults living in Ulaanbaatar. Young adults with laboratory-confirmed measles, living in the capital city of Ulaanbaatar, were matched with 2-3 neighborhood controls. Conditional logistic regression was used to estimate adjusted matched odds ratios (aMORs) for risk factors, with 95% confidence intervals. During March 1-September 30, 2015, 20 077 suspected measles cases were reported; 14 010 cases were confirmed. Independent risk factors for measles included being unvaccinated (adjusted matched odds ratio [aMOR] 2.0, P < .01), being a high school graduate without college education (aMOR 2.6, P < .01), remaining in Ulaanbaatar during the outbreak (aMOR 2.5, P < .01), exposure to an inpatient healthcare facility (aMOR 4.5 P < .01), and being born outside of Ulaanbaatar (aMOR 1.8, P = .02). This large, nationwide outbreak shortly after verification of elimination had high incidence among young adults, particularly those born outside the national capital. In addition, findings indicated that nosocomial transmission within health facilities helped amplify the outbreak. Published by Oxford University Press for the Infectious Diseases Society of America 2017. This work is written by (a) US Government employee(s) and is in the public domain in the US.

MEASLES IN INFANTS

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V. N. Timchenko

2015-01-01

Full Text Available A clinical observation and treatment of 36 children between the ages of 5 months up to 3 years old with measles. In 34 persons. (94.4% diagnosed with typical moderate forms, from 2 people (5.6% — atypical (mitigirovannaya a mild form of the disease. All children are vaccinated against measles. Typical measles char-acterized by moderate forms of cyclical flow with the change of the classical period and the presence of characteristic clinical syndromes. Pathognomonic symptom found: spots Belsky — Filatov — Koplik (67.7%, stages a rash (100%, stages of pigmentation (100%. Causal therapy was VIFERON®. Revealed the rapid disappearance of intoxication and normalization of body temperature, the early decline in the severity and duration of catarrhal syndrome, reducing the severity and frequency of complications, no stratification of SARS.

Patchwork structure-function analysis of the Sendai virus matrix protein.

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Mottet-Osman, Geneviève; Miazza, Vincent; Vidalain, Pierre-Olivier; Roux, Laurent

2014-09-01

Paramyxoviruses contain a bi-lipidic envelope decorated by two transmembrane glycoproteins and carpeted on the inner surface with a layer of matrix proteins (M), thought to bridge the glycoproteins with the viral nucleocapsids. To characterize M structure-function features, a set of M domains were mutated or deleted. The genes encoding these modified M were incorporated into recombinant Sendai viruses and expressed as supplemental proteins. Using a method of integrated suppression complementation system (ISCS), the functions of these M mutants were analyzed in the context of the infection. Cellular membrane association, localization at the cell periphery, nucleocapsid binding, cellular protein interactions and promotion of viral particle formation were characterized in relation with the mutations. At the end, lack of nucleocapsid binding go together with lack of cell surface localization and both features definitely correlate with loss of M global function estimated by viral particle production. Copyright © 2014 Elsevier Inc. All rights reserved.

The Role of the Hendra Virus and Nipah Virus Attachment Glycoproteins in Receptor Binding and Antibody Neutralization

Science.gov (United States)

2014-01-31

of important human (measles (MeV), mumps, human parainfluenza and respiratory syncytial virus (RSV)) and animal ( canine distemper virus (CDV...occurrence of a natural canine infection (6; 7). Since the emergence of HeV there have been a total of 86 horse fatalities, 2 canine infections and 7...Infectious Diseases 6. Anonymous. 2011. HENDRA VIRUS, EQUINE - AUSTRALIA (21): (QUEENSLAND) CANINE . Pro-Med-mail, Archive No. 20110802.2324

Measles Virus: Identification in the M Protein Primary Sequence of a Potential Molecular Marker for Subacute Sclerosing Panencephalitis

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Hasan Kweder

2015-01-01

Full Text Available Subacute Sclerosing Panencephalitis (SSPE, a rare lethal disease of children and young adults due to persistence of measles virus (MeV in the brain, is caused by wild type (wt MeV. Why MeV vaccine strains never cause SSPE is completely unknown. Hypothesizing that this phenotypic difference could potentially be represented by a molecular marker, we compared glycoprotein and matrix (M genes from SSPE cases with those from the Moraten vaccine strain, searching for differential structural motifs. We observed that all known SSPE viruses have residues P64, E89, and A209 (PEA in their M proteins whereas the equivalent residues for vaccine strains are either S64, K89, and T209 (SKT as in Moraten or PKT. Through the construction of MeV recombinants, we have obtained evidence that the wt MeV-M protein PEA motif, in particular A209, is linked to increased viral spread. Importantly, for the 10 wt genotypes (of 23 that have had their M proteins sequenced, 9 have the PEA motif, the exception being B3, which has PET. Interestingly, cases of SSPE caused by genotype B3 have yet to be reported. In conclusion, our results strongly suggest that the PEA motif is a molecular marker for wt MeV at risk to cause SSPE.

Immunohistochemical detection of virus through its nuclear cytopathic effect in idiopathic interstitial pneumonia other than acute exacerbation

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G.C. dos Santos

2013-11-01

Full Text Available Idiopathic interstitial pneumonias include complex diseases that have a strong interaction between genetic makeup and environmental factors. However, in many cases, no infectious agent can be demonstrated, and these clinical diseases rapidly progress to death. Theoretically, idiopathic interstitial pneumonias could be caused by the Epstein-Barr virus, cytomegalovirus, adenovirus, hepatitis C virus, respiratory syncytial virus, and herpesvirus, which may be present in such small amounts or such configuration that routine histopathological analysis or viral culture techniques cannot detect them. To test the hypothesis that immunohistochemistry provides more accurate results than the mere histological demonstration of viral inclusions, this method was applied to 37 open lung biopsies obtained from patients with idiopathic interstitial pneumonias. As a result, immunohistochemistry detected measles virus and cytomegalovirus in diffuse alveolar damage-related histological patterns of acute exacerbation of idiopathic pulmonary fibrosis and nonspecific interstitial pneumonia in 38 and 10% of the cases, respectively. Alveolar epithelium infection by cytomegalovirus was observed in 25% of organizing pneumonia patterns. These findings were coincident with nuclear cytopathic effects but without demonstration of cytomegalovirus inclusions. These data indicate that diffuse alveolar damage-related cytomegalovirus or measles virus infections enhance lung injury, and a direct involvement of these viruses in diffuse alveolar damage-related histological patterns is likely. Immunohistochemistry was more sensitive than the histological demonstration of cytomegalovirus or measles virus inclusions. We concluded that all patients with diffuse alveolar damage-related histological patterns should be investigated for cytomegalovirus and measles virus using sensitive immunohistochemistry in conjunction with routine procedures.

Measles epidemic in Brazil in the post-elimination period: Coordinated response and containment strategies.

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Lemos, Daniele Rocha Queiroz; Franco, Aidée Ramirez; de Sá Roriz, Maria Lúcia Feitosa; Carneiro, Ana Karine Borges; de Oliveira Garcia, Márcio Henrique; de Souza, Fábia Lidiana; Duron Andino, Regina; de Góes Cavalcanti, Luciano Pamplona

2017-03-23

The measles virus circulation was halted in Brazil in 2001 and the country has a routine vaccination coverage against measles, mumps and rubella higher than 95%. In Ceará, the last confirmed case was in 1999. This article describes the strategies adopted and the effectiveness of surveillance and control measures implemented during a measles epidemic in the post-elimination period. The epidemic started in December 2013 and lasted 20 months, reaching 38 cities and 1,052 confirmed cases. The D8 genotype was identified. More than 50,000 samples were tested for measles and 86.4% of the confirmed cases had a laboratory diagnosis. The beginning of an campaign vaccination was delayed in part by the availability of vaccine. The classic control measures were not enough to control the epidemic. The creation of a committee of experts, the agreement signed between managers of the three spheres of government, the conducting of an institutional active search of suspected cases, vaccination door to door at alternative times, the use of micro planning, a broad advertising campaign at local media and technical operative support contributed to containing the epidemic. It is important to recognize the possibility of epidemics at this stage of post-elimination and prepare a sensitive surveillance system for timely response. Copyright © 2017 Elsevier Ltd. All rights reserved.

Interacting partners of M-PMV nucleocapsid-dUTPase

Czech Academy of Sciences Publication Activity Database

Németh-Pongrácz, V.; Snášel, Jan; Rumlová, Michaela; Pichová, Iva; Vértessy, B. G.

2006-01-01

Roč. 25, č. 9/11 (2006), s. 1197-1200 ISSN 1525-7770 R&D Projects: GA MŠk 1M0508; GA ČR GP203/05/P557 Institutional research plan: CEZ:AV0Z40550506 Keywords : dUTPase * nucleocapsid * fusion protein * preintegration complex Subject RIV: CE - Biochemistry Impact factor: 0.671, year: 2006

Antibody levels to tetanus, diphtheria, measles and varicella in patients with primary immunodeficiency undergoing intravenous immunoglobulin therapy: a prospective study.

Science.gov (United States)

Nobre, Fernanda Aimée; Gonzalez, Isabela Garrido da Silva; Simão, Raquel Maria; de Moraes Pinto, Maria Isabel; Costa-Carvalho, Beatriz Tavares

2014-06-21

Patients with antibody deficiencies depend on the presence of a variety of antibody specificities in intravenous immunoglobulin (IVIG) to ensure continued protection against pathogens. Few studies have examined levels of antibodies to specific pathogens in IVIG preparations and little is known about the specific antibody levels in patients under regular IVIG treatment. The current study determined the range of antibodies to tetanus, diphtheria, measles and varicella in IVIG products and the levels of these antibodies in patients undergoing IVIG treatment. We selected 21 patients with primary antibody deficiencies who were receiving regular therapy with IVIG. Over a period of one year, we collected four blood samples from each patient (every 3 months), immediately before immunoglobulin infusion. We also collected samples from the IVIG preparation the patients received the month prior to blood collection. Antibody levels to tetanus, diphtheria, measles and varicella virus were measured in plasma and IVIG samples. Total IgG levels were determined in plasma samples. Antibody levels to tetanus, diphtheria, varicella virus and measles showed considerable variation in different IVIG lots, but they were similar when compared between commercial preparations. All patients presented with protective levels of antibodies specific for tetanus, measles and varicella. Some patients had suboptimal diphtheria antibody levels. There was a significant correlation between serum and IVIG antibodies to all pathogens, except tetanus. There was a significant correlation between diphtheria and varicella antibodies with total IgG levels, but there was no significant correlation with antibodies to tetanus or measles. The study confirmed the variation in specific antibody levels between batches of the same brand of IVIG. Apart from the most common infections to which these patients are susceptible, health care providers must be aware of other vaccine preventable diseases, which still exist

Emergency measles control activities--Darfur, Sudan, 2004.

Science.gov (United States)

2004-10-01

The Darfur region of Sudan, composed of three states with a population of approximately six million, has experienced civil conflict during the previous year, resulting in the internal displacement of approximately one million residents and an exodus of an estimated 170,000 persons to neighboring Chad. The conflict has left a vulnerable population with limited access to food, health care, and other basic necessities. In addition, measles vaccination coverage has been adversely affected; in 2003, coverage was reported to be 46%, 57%, and 77% in North, West, and South Darfur, respectively. This report describes measles-control activities in Darfur region conducted by the Federal Ministry of Health (FMOH) in Sudan in collaboration with the United Nations and nongovernmental organizations (NGOs) during March-August 2004. Ongoing measles transmission in camps for internally displaced persons (IDPs) and neighboring communities in Darfur led to a regionwide measles vaccination campaign targeting all children aged 9 months-15 years, resulting in a reduction in reported measles cases. Once security is improved, ongoing efforts to increase measles vaccine coverage will be required to eliminate persistent susceptibility to measles in the Darfur population.

RESPONSE OF VOLTA CHILDREN TO JET INOCULATION OF COMBINED LIVE MEASLES, SMALLPOX AND YELLOW FEVER VACCINES.

Science.gov (United States)

MEYER, H M; HOSTETLER, D D; BERNHEIN, B C; ROGERS, N G; LAMBIN, P; CHASSARY, A; LABUSQUIERE, R; SMADEL, J E

1964-01-01

An earlier study established that Upper Volta children respond to vaccination with the Enders live attenuated measles strain in the same general fashion as do children in the USA. The present report describes a second pilot project carried out in Ouagadougou, Upper Volta. During this investigation various mixtures of live measles, smallpox and 17D yellow fever vaccines were introduced into susceptible infants by jet injection. Combining the attenuated virus vaccines did not alter or accentuate the characteristic clinical reactions elicited by the individual components, nor was there evidence of significant immunological interference. From this experience it is concluded that combined vaccination with these agents may be safely and effectively employed in larger programmes as the need dictates.

Measles seroprevalence, outbreaks, and vaccine coverage in Rwanda.

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Seruyange, Eric; Gahutu, Jean-Bosco; Mambo Muvunyi, Claude; Uwimana, Zena G; Gatera, Maurice; Twagirumugabe, Theogene; Katare, Swaibu; Karenzi, Ben; Bergström, Tomas

2016-01-01

Measles outbreaks are reported after insufficient vaccine coverage, especially in countries recovering from natural disaster or conflict. We compared seroprevalence to measles in blood donors in Rwanda and Sweden and explored distribution of active cases of measles and vaccine coverage in Rwanda. 516 Rwandan and 215 Swedish blood donors were assayed for measles-specific immunoglobulin G (IgG) by enzyme-linked immunosorbent assay (ELISA). Data on vaccine coverage and acute cases in Rwanda from 1980 to 2014 were collected, and IgM on serum samples and polymerase chain reaction (PCR) on nasopharyngeal (NPH) swabs from suspected measles cases during 2010-2011 were analysed. The seroprevalence of measles IgG was significantly higher in Swedish blood donors (92.6%; 95% CI: 89.1-96.1%) compared to Rwandan subjects (71.5%; 95% CI: 67.6-75.4%) and more pronounced Rwanda, with the exception of an outbreak in 1995 following the 1994 genocide. 76/544 serum samples were IgM positive and 21/31 NPH swabs were PCR positive for measles, determined by sequencing to be of genotype B3. Measles seroprevalence was lower in Rwandan blood donors compared to Swedish subjects. Despite this, the number of reported measles cases in Rwanda rapidly decreased during the study period, concomitant with increased vaccine coverage. Taken together, the circulation of measles was limited in Rwanda and vaccine coverage was favourable, but seroprevalence and IgG levels were low especially in younger age groups.

Measles Vaccination in the Presence or Absence of Maternal Measles Antibody: Impact on Child Survival

Science.gov (United States)

Aaby, Peter; Martins, Cesário L.; Garly, May-Lill; Andersen, Andreas; Fisker, Ane B.; Claesson, Mogens H.; Ravn, Henrik; Rodrigues, Amabelia; Whittle, Hilton C.; Benn, Christine S.

2014-01-01

Background. Measles vaccine (MV) has a greater effect on child survival when administered in early infancy, when maternal antibody may still be present. Methods. To test whether MV has a greater effect on overall survival if given in the presence of maternal measles antibody, we reanalyzed data from 2 previously published randomized trials of a 2-dose schedule with MV given at 4–6 months and at 9 months of age. In both trials antibody levels had been measured before early measles vaccination. Results. In trial I (1993–1995), the mortality rate was 0.0 per 1000 person-years among children vaccinated with MV in the presence of maternal antibody and 32.3 per 1000 person-years without maternal antibody (mortality rate ratio [MRR], 0.0; 95% confidence interval [CI], 0–.52). In trial II (2003–2007), the mortality rate was 4.2 per 1000 person-years among children vaccinated in presence of maternal measles antibody and 14.5 per 1000 person-years without measles antibody (MRR, 0.29; 95% CI, .09–.91). Possible confounding factors did not explain the difference. In a combined analysis, children who had measles antibody detected when they received their first dose of MV at 4–6 months of age had lower mortality than children with no maternal antibody, the MRR being 0.22 (95% CI, .07–.64) between 4–6 months and 5 years. Conclusions. Child mortality in low-income countries may be reduced by vaccinating against measles in the presence of maternal antibody, using a 2-dose schedule with the first dose at 4–6 months (earlier than currently recommended) and a booster dose at 9–12 months of age. Clinical Trials Registration. NCT00168558. PMID:24829213

Measles

Science.gov (United States)

... Z Regions » Africa Americas South-East Asia Europe Eastern Mediterranean Western Pacific WHO in countries » Overview Statistics ... of children to receive measles vaccine in north-eastern Nigeria 16 January 2017 WHO strengthens South Sudan’s ...

The C protein of measles virus inhibits the type I interferon response

International Nuclear Information System (INIS)

Shaffer, Jessica A.; Bellini, William J.; Rota, Paul A.

2003-01-01

Type I interferons (IFNα/β) are an important part of innate immunity to viral infections because they induce an antiviral response and limit viral replication until the adaptive response clears the infection. Since the nonstructural proteins of several paramyxoviruses inhibit the IFNα/β response, we chose to explore the role of the C protein of measles virus (MV) in such inhibition. Previous studies have suggested that the MV C protein may serve as a virulence factor, but its role in the pathogenesis of MV remains undefined. In the present study, a recombinant MV strain that does not express the C protein (MV C-) and its parental strain (Ed Tag) were used. Growth of MV C- was restricted in human peripheral blood mononuclear cells and HeLa cells, but in the presence of neutralizing antibodies to IFNα/β, MV C- produced titers that were equivalent to those of Ed Tag. In addition, expression of the MV C protein from plasmid DNA inhibited the production of an IFNα/β responsive reporter gene and, to a lesser extent, inhibited an IFNγ responsive reporter gene. The ability of the MV C protein to suppress the IFNα/β response was confirmed using a biologic assay. After IFNβ stimulation, HeLa cells infected with Ed Tag produced five-fold less IFNα/β than cells infected with MV C-. While the mechanism of inhibition remains unclear, these data suggest that the MV C protein plays an important role in the pathogenesis of MV by inhibiting IFNα/β signaling

Clinical outcome in measles patients hospitalized with complications

International Nuclear Information System (INIS)

Rehman, A.U.; Saeed, T.

2008-01-01

Measles is a highly communicable viral illness and is common cause of childhood mortality and morbidity. Keeping in view the high prevalence of measles in the developing world, we carried out this study to look into the complicated measles cases and clinical outcome in patients admitted in children ward of Ayub Teaching Hospital. Detailed history and physical examination of all the hospitalized patients with complication of measles were recorded in a proforma. Immunization and nutritional status of each admitted patient was assessed and the clinical outcome of measles was compared with demographic profile. one hundred thirty six hospitalized patients with complications of measles were studied. There was 60.3% male and 57.3% of patients were vaccinated against measles. Malnourished patients were 71.35% and had longer hospital stay (>5 days). Pneumonia (39.7%) and diarrhoea (38.2%) were the commonest complications. Seven children died and encephalitis (57.1%) was the commonest cause of death. The most common complications of measles are pneumonia and diarrhoea with dehydration requiring admission. Malnutrition results in more complications and longer hospital stay. Mortality is significantly associated with encephalitis. (author)

HSV-1 nucleocapsid egress mediated by UL31 in association with UL34 is impeded by cellular transmembrane protein 140

Energy Technology Data Exchange (ETDEWEB)

Guan, Ying [Department of Viral Immunology, Institute of Medical Biology, Chinese Academy of Medicine Science, Peking Union Medical College, Kunming 650118 (China); Yunnan Academy of Tobacco Science, Kunming, Yunnan 650106 (China); Guo, Lei; Yang, Erxia; Liao, Yun; Liu, Longding; Che, Yanchun; Zhang, Ying; Wang, Lichun; Wang, Jingjing [Department of Viral Immunology, Institute of Medical Biology, Chinese Academy of Medicine Science, Peking Union Medical College, Kunming 650118 (China); Li, Qihan, E-mail: imbcams.lq@gmail.com [Department of Viral Immunology, Institute of Medical Biology, Chinese Academy of Medicine Science, Peking Union Medical College, Kunming 650118 (China)

2014-09-15

During HSV-1 infection, the viral UL31 protein forms a complex with the UL34 protein at the cellular nuclear membrane, where both proteins play important roles in the envelopment of viral nucleocapsids and their egress into the cytoplasm. To characterize the mechanism of HSV-1 nucleocapsid egress, we screened host proteins to identify proteins that interacted with UL31 via yeast two-hybrid analysis. Transmembrane protein 140 (TMEM140), was identified and confirmed to bind to and co-localize with UL31 during viral infection. Further studies indicated that TMEM140 inhibits HSV-1 proliferation through selectively blocking viral nucleocapsid egress during the viral assembly process. The blockage function of TMEM140 is mediated by impeding the formation of the UL31–UL34 complex due to competitive binding to UL31. Collectively, these data suggest the essentiality of the UL31–UL34 interaction in the viral nucleocapsid egress process and provide a new anti-HSV-1 strategy in viral assembly process of nucleocapsid egress. - Highlights: • Cellular TMEM140 protein interacts with HSV-1 UL31 protein during viral infection. • Increasing expression of TMEM140 leads to inhibition of HSV-1 proliferation. • Increasing expression of TMEM140 blocks HSV-1 nucleocapsid egress process. • Binding to UL31 of TMEM140 impedes formation of HSV-1 UL31–UL34 complex.

The V domain of dog PVRL4 (nectin-4) mediates canine distemper virus entry and virus cell-to-cell spread

International Nuclear Information System (INIS)

Delpeut, Sebastien; Noyce, Ryan S.; Richardson, Christopher D.

2014-01-01

The entry of canine distemper virus (CDV) is a multistep process that involves the attachment of CDV hemagglutinin (H) to its cellular receptor, followed by fusion between virus and cell membranes. Our laboratory recently identified PVRL4 (nectin-4) to be the epithelial receptor for measles and canine distemper viruses. In this study, we demonstrate that the V domain of PVRL4 is critical for CDV entry and virus cell-to-cell spread. Furthermore, four key amino acid residues within the V domain of dog PVRL4 and two within the CDV hemagglutinin were shown to be essential for receptor-mediated virus entry. - Highlights: • PVRL4 (nectin-4) is the epithelial cell receptor for measles and canine distemper viruses. • V domain of PVRL4 is critical for CDV entry, cell-to-cell spread, and syncytia formation. • Chimeric PVRL1 backbone substituted with the V domain of PVRL4 can function as a receptor. • Amino acids (F132/P133/A134/G135) within the V domain are essential for PVRL4 receptor activity. • Amino acids (P493/Y539) within CDV H protein are essential for PVRL4 receptor interaction

The V domain of dog PVRL4 (nectin-4) mediates canine distemper virus entry and virus cell-to-cell spread

Energy Technology Data Exchange (ETDEWEB)

Delpeut, Sebastien; Noyce, Ryan S. [The Department of Microbiology and Immunology, Dalhousie University, Halifax, Nova Scotia, Canada B3H 1X5 (Canada); IWK Health Centre, Canadian Center for Vaccinology, Goldbloom Pavilion, Halifax, Nova Scotia, Canada B3H 1X5 (Canada); Richardson, Christopher D., E-mail: chris.richardson@dal.ca [The Department of Microbiology and Immunology, Dalhousie University, Halifax, Nova Scotia, Canada B3H 1X5 (Canada); IWK Health Centre, Canadian Center for Vaccinology, Goldbloom Pavilion, Halifax, Nova Scotia, Canada B3H 1X5 (Canada); The Department of Pediatrics, Dalhousie University, Halifax, Nova Scotia (Canada)

2014-04-15

The entry of canine distemper virus (CDV) is a multistep process that involves the attachment of CDV hemagglutinin (H) to its cellular receptor, followed by fusion between virus and cell membranes. Our laboratory recently identified PVRL4 (nectin-4) to be the epithelial receptor for measles and canine distemper viruses. In this study, we demonstrate that the V domain of PVRL4 is critical for CDV entry and virus cell-to-cell spread. Furthermore, four key amino acid residues within the V domain of dog PVRL4 and two within the CDV hemagglutinin were shown to be essential for receptor-mediated virus entry. - Highlights: • PVRL4 (nectin-4) is the epithelial cell receptor for measles and canine distemper viruses. • V domain of PVRL4 is critical for CDV entry, cell-to-cell spread, and syncytia formation. • Chimeric PVRL1 backbone substituted with the V domain of PVRL4 can function as a receptor. • Amino acids (F132/P133/A134/G135) within the V domain are essential for PVRL4 receptor activity. • Amino acids (P493/Y539) within CDV H protein are essential for PVRL4 receptor interaction.

Probing Mercaptobenzamides as HIV Inactivators via Nucleocapsid Protein 7.

Science.gov (United States)

Saha, Mrinmoy; Scerba, Michael T; Shank, Nathaniel I; Hartman, Tracy L; Buchholz, Caitlin A; Buckheit, Robert W; Durell, Stewart R; Appella, Daniel H

2017-05-22

Human immunodeficiency virus type 1 (HIV-1) nucleocapsid protein 7 (NCp7), a zinc finger protein, plays critical roles in viral replication and maturation and is an attractive target for drug development. However, the development of drug-like molecules that inhibit NCp7 has been a significant challenge. In this study, a series of novel 2-mercaptobenzamide prodrugs were investigated for anti-HIV activity in the context of NCp7 inactivation. The molecules were synthesized from the corresponding thiosalicylic acids, and they are all crystalline solids and stable at room temperature. Derivatives with a range of amide side chains and aromatic substituents were synthesized and screened for anti-HIV activity. Wide ranges of antiviral activity were observed, with IC 50 values ranging from 1 to 100 μm depending on subtle changes to the substituents on the aromatic ring and side chain. Results from these structure-activity relationships were fit to a probable mode of intracellular activation and interaction with NCp7 to explain variations in antiviral activity. Our strategy to make a series of mercaptobenzamide prodrugs represents a general new direction to make libraries that can be screened for anti-HIV activity. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Measles vaccination in the presence or absence of maternal measles antibody

DEFF Research Database (Denmark)

Aaby, Peter; Martins, Cesário L; Garly, May-Lill

2014-01-01

vaccinated with MV in the presence of maternal antibody and 32.3 per 1000 person-years without maternal antibody (mortality rate ratio [MRR], 0.0; 95% confidence interval [CI], 0-.52). In trial II (2003-2007), the mortality rate was 4.2 per 1000 person-years among children vaccinated in presence of maternal...... mortality than children with no maternal antibody, the MRR being 0.22 (95% CI, .07-.64) between 4-6 months and 5 years. CONCLUSIONS: Child mortality in low-income countries may be reduced by vaccinating against measles in the presence of maternal antibody, using a 2-dose schedule with the first dose at 4......BACKGROUND: Measles vaccine (MV) has a greater effect on child survival when administered in early infancy, when maternal antibody may still be present. METHODS: To test whether MV has a greater effect on overall survival if given in the presence of maternal measles antibody, we reanalyzed data...

Critical epitopes in the nucleocapsid protein of SFTS virus recognized by a panel of SFTS patients derived human monoclonal antibodies.

Directory of Open Access Journals (Sweden)

Li Yu

Full Text Available BACKGROUND: SFTS virus (SFTSV is a newly discovered pathogen to cause severe fever with thrombocytopenia syndrome (SFTS in human. Successful control of SFTSV epidemic requires better understanding of the antigen target in humoral immune responses to the new bunyavirus infection. METHODOLOGY/PRINCIPAL FINDINGS: We have generated a combinatorial Fab antibody phage library from two SFTS patients recovered from SFTSV infection. To date, 94 unique human antibodies have been generated and characterized from over 1200 Fab antibody clones obtained by screening the library with SFTS purified virions. All those monoclonal antibodies (MAbs recognized the nucleocapsid (N protein of SFTSV while none of them were reactive to the viral glycoproteins Gn or Gc. Furthermore, over screening 1000 mouse monoclonal antibody clones derived from SFTSV virions immunization, 462 clones reacted with N protein, while only 16 clones were reactive to glycoprotein. Furthermore, epitope mapping of SFTSV N protein was performed through molecular simulation, site mutation and competitive ELISA, and we found that at least 4 distinct antigenic epitopes within N protein were recognized by those human and mouse MAbs, in particular mutation of Glu10 to Ala10 abolished or significantly reduced the binding activity of nearly most SFTS patients derived MAbs. CONCLUSIONS/SIGNIFICANCE: The large number of human recombinant MAbs derived from SFTS patients recognized the viral N protein indicated the important role of the N protein in humoral responses to SFTSV infection, and the critical epitopes we defined in this study provided molecular basis for detection and diagnosis of SFTSV infection.

Allergic disease and atopic sensitization in children in relation to measles vaccination and measles infection.

NARCIS (Netherlands)

Rosenlund, H.; Bergstrom, A.; Alm, J.; Swartz, J.; Scheynius, A.; van Hage, M.; Johansen, K.; Brunekreef, B.|info:eu-repo/dai/nl/067548180; von Mutius, E.; Ege, M.; Riedler, J.; Braun-Fahrlander, C.; Waser, M.; Pershagen, G.

2009-01-01

OBJECTIVE: Our aim was to investigate the role of measles vaccination and measles infection in the development of allergic disease and atopic sensitization. METHODS: A total of 14 893 children were included from the cross-sectional, multicenter Prevention of Allergy-Risk Factors for Sensitization in

Allergic Disease and Atopic Sensitization in Children in Relation to Measles Vaccination and Measles Infection

NARCIS (Netherlands)

Rosenlund, Helen; Bergstrom, Anna; Alm, Johan S.; Swartz, Jackie; Scheynius, Annika; van Hage, Marianne; Johansen, Kari; Brunekreef, Bert; von Mutius, Erika; Ege, Markus J.; Riedler, Josef; Braun-Fahrlaender, Charlotte; Waser, Marco; Pershagen, Goran

OBJECTIVE. Our aim was to investigate the role of measles vaccination and measles infection in the development of allergic disease and atopic sensitization. METHODS. A total of 14 893 children were included from the cross-sectional, multicenter Prevention of Allergy-Risk Factors for Sensitization in

Genetic and serological typing of European infectious haematopoietic necrosis virus (IHNV) isolates

DEFF Research Database (Denmark)

Johansson, Tove; Einer-Jensen, Katja; Batts, William

2009-01-01

Infectious haematopoietic necrosis virus (IHNV) causes the lethal disease infectious haematopoietic necrosis (IHN) in juvenile salmon and trout. The nucleocapsid (N) protein gene and partial glycoprotein (G) gene (nucleotides 457 to 1061) of the European isolates IT-217A, FR-32/87, DE-DF 13/98 11...

Measles virus envelope pseudotyped lentiviral vectors transduce quiescent human HSCs at an efficiency without precedent.

Science.gov (United States)

Lévy, Camille; Amirache, Fouzia; Girard-Gagnepain, Anais; Frecha, Cecilia; Roman-Rodríguez, Francisco J; Bernadin, Ornellie; Costa, Caroline; Nègre, Didier; Gutierrez-Guerrero, Alejandra; Vranckx, Lenard S; Clerc, Isabelle; Taylor, Naomi; Thielecke, Lars; Cornils, Kerstin; Bueren, Juan A; Rio, Paula; Gijsbers, Rik; Cosset, François-Loïc; Verhoeyen, Els

2017-10-24

Hematopoietic stem cell (HSC)-based gene therapy trials are now moving toward the use of lentiviral vectors (LVs) with success. However, one challenge in the field remains: efficient transduction of HSCs without compromising their stem cell potential. Here we showed that measles virus glycoprotein-displaying LVs (hemagglutinin and fusion protein LVs [H/F-LVs]) were capable of transducing 100% of early-acting cytokine-stimulated human CD34 + (hCD34 + ) progenitor cells upon a single application. Strikingly, these H/F-LVs also allowed transduction of up to 70% of nonstimulated quiescent hCD34 + cells, whereas conventional vesicular stomatitis virus G (VSV-G)-LVs reached 5% at the most with H/F-LV entry occurring exclusively through the CD46 complement receptor. Importantly, reconstitution of NOD/SCIDγc -/- (NSG) mice with H/F-LV transduced prestimulated or resting hCD34 + cells confirmed these high transduction levels in all myeloid and lymphoid lineages. Remarkably, for resting CD34 + cells, secondary recipients exhibited increasing transduction levels of up to 100%, emphasizing that H/F-LVs efficiently gene-marked HSCs in the resting state. Because H/F-LVs promoted ex vivo gene modification of minimally manipulated CD34 + progenitors that maintained stemness, we assessed their applicability in Fanconi anemia, a bone marrow (BM) failure with chromosomal fragility. Notably, only H/F-LVs efficiently gene-corrected minimally stimulated hCD34 + cells in unfractionated BM from these patients. These H/F-LVs improved HSC gene delivery in the absence of cytokine stimulation while maintaining their stem cell potential. Thus, H/F-LVs will facilitate future clinical applications requiring HSC gene modification, including BM failure syndromes, for which treatment has been very challenging up to now.

The sequence of the Helicoverpa armigera single nucleocapsid nucleopolyhedrovirus genome

NARCIS (Netherlands)

Chen, X.; IJkel, W.F.J.; Tarchini, R.; Sun, X.; Sandbrink, H.; Wang, H.; Peters, S.; Zuidema, D.; Klein Lankhorst, R.; Vlak, J.M.; Hu, Z.

2001-01-01

The nucleotide sequence of the Helicoverpa armigera single-nucleocapsid nucleopolyhedrovirus (HaSNPV) DNA genome was determined and analysed. The circular genome encompasses 131 403 bp, has a G C content of 39.1 molnd contains five homologous regions with a unique pattern of repeats.

Measles in Pakistan: Time to make steps towards eradication.

Science.gov (United States)

Rehman, Inayat Ur; Bukhsh, Allah; Khan, Tahir Mehmood

World Health Organization (WHO) measles surveillance data report a reduction in cases of measles globally from 67,524 cases in 2015 to 16,846 in 2016, and a reduction in deaths from 546,800 to 114,900 during period of 2000-14. Pakistan is among the five nations where almost a million children did not receive their first dose of measles vaccination, and outbreaks of the disease resulted in 4386 cases in 2011, 14,687 cases in 2012 with 310 deaths. In 2013, about 25,401 cases of measles were reported and 321 affected children died. The measles vaccination coverage is very low in Pakistan for both 1st dose and booster dose. To prevent outbreaks of measles in Pakistan a national vaccination program should be launched side by side with a polio eradication program in each district and township and a campaign should be launched to educate parents on measles vaccination for childrens to reduce the measles case fatality rate. Copyright © 2017 Elsevier Ltd. All rights reserved.

Stop measles in Switzerland - The importance of travel medicine.

Science.gov (United States)

Bühler, Silja; Lang, Phung; Bally, Bettina; Hatz, Christoph; Jaeger, Veronika K

2017-06-27

In line with the worldwide strive to combat measles, the Swiss Federal Office of Public Heath (FOPH) launched a National Strategy for measles elimination 2011-2015. In this study, we highlight the importance of travel medicine consultations to complement measles vaccination programmes based on data from the Travel Clinic of the University of Zurich. We analysed measles vaccination data from the Zurich Travel Clinic between July 2010 and February 2016 and focused on three groups: (i) all clients who received the measles vaccination, (ii) all clients aged>two years who received the measles vaccination ("catch-up vaccination"), and (iii) all clients aged>two years and born after 1963 ("FOPH recommended catch-up vaccination"). 107,669 consultations were performed from 2010 to 2016. In 12,470 (11.6%) of these, a measles vaccination was administered; 90.9% measles vaccinations were given during a pre-travel consultation, and 99.4% were administered to individuals aged>two years ("catch-up vaccinations"). An "FOPH recommended catch-up vaccination" was received by 13.6% of all Zurich Travel Clinic clients aged >2years and born after 1963. In this study, we highlight the importance of travel medicine consultations to enhance the measles vaccination coverage in the adult Swiss population. Copyright © 2017 Elsevier Ltd. All rights reserved.

Implication of health care personnel in measles transmission

Science.gov (United States)

Torner, Núria; Solano, Ruben; Rius, Cristina; Domínguez, Angela; Surveillance Network of Catalonia, Spain, the Measles Elimination Program

2014-01-01

Healthcare personnel (HCP) play an important role in transmission of highly contagious diseases such as measles. Current immunization guidelines in Catalonia include Measles-Mumps-Rubella (MMR) immunization for HCP born after 1967 without evidence of immunity. Despite high vaccination coverage (90%) a high burden of measles cases related to outbreaks have occurred. The aim of this study was to assess the implication of HCP in measles transmission related to healthcare setting. A review of surveillance case data from 2001 to 2013 gathered through the Measles Elimination Program in Catalonia was performed. Twenty six outbreaks involving 797 cases were reported, 52 (6.5%) were HCP aged 21–41 years, 72,5% (38) patient were care personnel (doctors and nurses) and 22,5% (14) other health care related personnel. Forty six 87%) were unvaccinated, 4(10%) had only one dose and 2 had two doses of MMR. In community outbreaks 30 clusters with HCP involved were observed, yet none were identified as index cases. Non-vaccinated HCPs against measles were all under 45 years of age. Vaccination is the only reliable protection against nosocomial spread of measles from HCPs. Assessing vaccination status of HCPs and implementing a 2 dose vaccination in those lacking evidence of immunity is needed in order to set to zero the risk of acquiring and spreading measles in healthcare (HC) settings. PMID:25483548

Measles Virus Hemagglutinin epitopes immunogenic in natural infection and vaccination are targeted by broad or genotype-specific neutralizing monoclonal antibodies.

Science.gov (United States)

Muñoz-Alía, Miguel Angel; Casasnovas, José M; Celma, María Luisa; Carabaña, Juan; Liton, Paloma B; Fernandez-Muñoz, Rafael

2017-05-15

Measles virus (MV) remains a leading cause of vaccine-preventable deaths in children. Protection against MV is associated with neutralizing antibodies that preferentially recognize the viral hemagglutinin (MV-H), and to a lesser extent, the fusion protein (MV-F). Although MV is serologically monotypic, 24 genotypes have been identified. Here we report three neutralization epitopes conserved in the more prevalent circulating MV genotypes, two located in the MV-H receptor binding site (RBS) (antigenic site III) and a third in MV-H/MV-F interphase (antigenic site Ia) which are essential for MV multiplication. In contrast, two MV-H neutralization epitopes, showed a genotype-specific neutralization escape due to a single amino acid change, that we mapped in the "noose" antigenic site, or an enhanced neutralization epitope (antigenic site IIa). The monoclonal antibody (mAb) neutralization potency correlated with its binding affinity and was mainly driven by kinetic dissociation rate (k off ). We developed an immunoassay for mAb binding to MV-H in its native hetero-oligomeric structure with MV-F on the surface of a MV productive steady-state persistently infected (p.i.) human cell lines, and a competitive-binding assay with serum from individuals with past infection by different MV genotypes. Binding assays revealed that a broad neutralization epitope, in RBS antigenic site, a genotype specific neutralization epitopes, in noose and IIa sites, were immunogenic in natural infection and vaccination and may elicit long-lasting humoral immunity that might contribute to explain MV immunogenic stability. These results support the design of improved measles vaccines, broad-spectrum prophylactic or therapeutic antibodies and MV-used in oncolytic therapies. Copyright © 2017 Elsevier B.V. All rights reserved.

Evidence of pestivirus RNA in human virus vaccines.

Science.gov (United States)

Harasawa, R; Tomiyama, T

1994-01-01

We examined live virus vaccines against measles, mumps, and rubella for the presence of pestivirus RNA or of pestiviruses by reverse transcription PCR. Pestivirus RNA was detected in two measles-mumps-rubella combined vaccines and in two monovalent vaccines against mumps and rubella. Nucleotide sequence analysis of the PCR products indicated that a modified live vaccine strain used for immunization of cattle against bovine viral diarrhea is not responsible for the contamination of the vaccines. Images PMID:8077414

Dynamic Phosphorylation of VP30 Is Essential for Ebola Virus Life Cycle.

Science.gov (United States)

Biedenkopf, Nadine; Lier, Clemens; Becker, Stephan

2016-05-15

Ebola virus is the causative agent of a severe fever with high fatality rates in humans and nonhuman primates. The regulation of Ebola virus transcription and replication currently is not well understood. An important factor regulating viral transcription is VP30, an Ebola virus-specific transcription factor associated with the viral nucleocapsid. Previous studies revealed that the phosphorylation status of VP30 impacts viral transcription. Together with NP, L, and the polymerase cofactor VP35, nonphosphorylated VP30 supports viral transcription. Upon VP30 phosphorylation, viral transcription ceases. Phosphorylation weakens the interaction between VP30 and the polymerase cofactor VP35 and/or the viral RNA. VP30 thereby is excluded from the viral transcription complex, simultaneously leading to increased viral replication which is supported by NP, L, and VP35 alone. Here, we use an infectious virus-like particle assay and recombinant viruses to show that the dynamic phosphorylation of VP30 is critical for the cotransport of VP30 with nucleocapsids to the sites of viral RNA synthesis, where VP30 is required to initiate primary viral transcription. We further demonstrate that a single serine residue at amino acid position 29 was sufficient to render VP30 active in primary transcription and to generate a recombinant virus with characteristics comparable to those of wild-type virus. In contrast, the rescue of a recombinant virus with a single serine at position 30 in VP30 was unsuccessful. Our results indicate critical roles for phosphorylated and dephosphorylated VP30 during the viral life cycle. The current Ebola virus outbreak in West Africa has caused more than 28,000 cases and 11,000 fatalities. Very little is known regarding the molecular mechanisms of how the Ebola virus transcribes and replicates its genome. Previous investigations showed that the transcriptional support activity of VP30 is activated upon VP30 dephosphorylation. The current study reveals that

Measles, One of the Re-emerging Diseases

Directory of Open Access Journals (Sweden)

Zeynep Türe

2016-03-01

Full Text Available Objective: The aim of the study is to stand out the measles which is a highly contagious re-emerging viral illness and may cause severe complications in susceptible population. Methods: This retrospective study was conducted on patients who were diagnosed with measles in the department of Infectious Diseases, Erciyes University Hospital, between January 2013 and February 2014. The diagnosis of measles was confirmed by measles specific immunoglobulin M (IgM antibody positivity in serum samples. Results: Nine patients were included the study. Three patients had a co-morbid condition including hematopoietic stem cell transplantation, pregnancy and diabetes mellitus. Four of the patients had hepatitis and one of them had pneumonia as a complication. Conclusion: Susceptible population, especially immunocompromised people are still at risk about measles. Adherence to universal vaccination programs is determinative in terms of breaking out of an outbreak. J Microbiol Infect Dis 2016;6(1: 19-22

Investigation of a measles outbreak in Cordillera, northern Philippines, 2013

Directory of Open Access Journals (Sweden)

Paola Katrina Ching

2016-07-01

Full Text Available Introduction: Measles is a highly infectious viral illness that remains one of the leading causes of death among children worldwide. In the Philippines, decreasing routine vaccination coverage from 2007 to 2011 led to local measles outbreaks. A team investigated a measles outbreak reported in Cordillera of the Philippines in May 2013. Methods: Measles case data with symptom onset from 2 February to 27 May 2013 were obtained from official sources and verified on site. Data included age, sex, residential address, signs and symptoms and vaccination status. Active case-findings were also conducted for contacts of these cases. The living environments of the cases were investigated. A survey was conducted with the cases and caregivers to understand their knowledge and attitudes about measles. Results: There were 50 measles cases identified with an age range from six months to 32 years (median: 16 years. Thirty-two were male (64%. Twenty (40% were hospitalized with one death. Thirty-two (64% cases were laboratory confirmed, and 36 (72% received a single dose of measles vaccine. Overcrowded living environments were observed among many cases. The majority of respondents (46/48, 96% knew about measles, but there were misconceptions about the cause of measles and how it can be prevented and managed. Conclusion: This measles outbreak occurred in an area with low immunization coverage. Achieving 95% measles immunization coverage and strengthening routine immunization strategies to address high-risk populations are recommended. Also, we recommend health education campaigns to include components that address misconceptions about measles.

Efficient cellular release of Rift Valley fever virus requires genomic RNA.

Directory of Open Access Journals (Sweden)

Mary E Piper

2011-03-01

Full Text Available The Rift Valley fever virus is responsible for periodic, explosive epizootics throughout sub-Saharan Africa. The development of therapeutics targeting this virus is difficult due to a limited understanding of the viral replicative cycle. Utilizing a virus-like particle system, we have established roles for each of the viral structural components in assembly, release, and virus infectivity. The envelope glycoprotein, Gn, was discovered to be necessary and sufficient for packaging of the genome, nucleocapsid protein and the RNA-dependent RNA polymerase into virus particles. Additionally, packaging of the genome was found to be necessary for the efficient release of particles, revealing a novel mechanism for the efficient generation of infectious virus. Our results identify possible conserved targets for development of anti-phlebovirus therapies.

Completely assembled virus particles detected by transmission electron microscopy in proximal and mid-axons of neurons infected with herpes simplex virus type 1, herpes simplex virus type 2 and pseudorabies virus

International Nuclear Information System (INIS)

Huang Jialing; Lazear, Helen M.; Friedman, Harvey M.

2011-01-01

The morphology of alphaherpesviruses during anterograde axonal transport from the neuron cell body towards the axon terminus is controversial. Reports suggest that transport of herpes simplex virus type 1 (HSV-1) nucleocapsids and envelope proteins occurs in separate compartments and that complete virions form at varicosities or axon termini (subassembly transport model), while transport of a related alphaherpesvirus, pseudorabies virus (PRV) occurs as enveloped capsids in vesicles (assembled transport model). Transmission electron microscopy of proximal and mid-axons of primary superior cervical ganglion (SCG) neurons was used to compare anterograde axonal transport of HSV-1, HSV-2 and PRV. SCG cell bodies were infected with HSV-1 NS and 17, HSV-2 2.12 and PRV Becker. Fully assembled virus particles were detected intracellularly within vesicles in proximal and mid-axons adjacent to microtubules after infection with each virus, indicating that assembled virions are transported anterograde within axons for all three alphaherpesviruses.

Oral or parenteral administration of replication-deficient adenoviruses expressing the measles virus haemagglutinin and fusion proteins: protective immune responses in rodents.

Science.gov (United States)

Fooks, A R; Jeevarajah, D; Lee, J; Warnes, A; Niewiesk, S; ter Meulen, V; Stephenson, J R; Clegg, J C

1998-05-01

The genes encoding the measles virus (MV) haemagglutinin (H) and fusion (F) proteins were placed under the control of the human cytomegalovirus immediate early promoter in a replication-deficient adenovirus vector. Immunofluorescence and radioimmune precipitation demonstrated the synthesis of each protein and biological activity was confirmed by the detection of haemadsorption and fusion activities in infected cells. Oral as well as parenteral administration of the H-expressing recombinant adenovirus elicited a significant protective response in mice challenged with MV. While the F-expressing adenovirus failed to protect mice, cotton rats immunized with either the H- or F-expressing recombinant showed reduced MV replication in the lungs. Antibodies elicited in mice following immunization with either recombinant had no in vitro neutralizing activity, suggesting a protective mechanism involving a cell-mediated immune response. This study demonstrates the feasibility of using oral administration of adenovirus recombinants to induce protective responses to heterologous proteins.

Unsustainability of a measles immunisation campaign - rise in ...

African Journals Online (AJOL)

The 1990 national mass measles immunisation campaign resulted in a marked reduction in measles incidence in Natal/KwaZulu in the first 6 months after the campaign. Data from the measles ward admissions book at Clairwood Hospital were collated for the period 1 January 1989 to 31 May 1992 to assess the ...

Measles Case Fatality Rate in Bihar, India, 2011–12

Science.gov (United States)

Murhekar, Manoj V.; Ahmad, Mohammad; Shukla, Hemant; Abhishek, Kunwar; Perry, Robert T.; Bose, Anindya S.; Shimpi, Rahul; Kumar, Arun; Kaliaperumal, Kanagasabai; Sethi, Raman; Selvaraj, Vadivoo; Kamaraj, Pattabi; Routray, Satyabrata; Das, Vidya Nand; Menabde, Nata; Bahl, Sunil

2014-01-01

Background Updated estimates of measles case fatality rates (CFR) are critical for monitoring progress towards measles elimination goals. India accounted for 36% of total measles deaths occurred globally in 2011. We conducted a retrospective cohort study to estimate measles CFR and identify the risk factors for measles death in Bihar–one of the north Indian states historically known for its low vaccination coverage. Methods We systematically selected 16 of the 31 laboratory-confirmed measles outbreaks occurring in Bihar during 1 October 2011 to 30 April 2012. All households of the villages/urban localities affected by these outbreaks were visited to identify measles cases and deaths. We calculated CFR and used multivariate analysis to identify risk factors for measles death. Results The survey found 3670 measles cases and 28 deaths (CFR: 0.78, 95% confidence interval: 0.47–1.30). CFR was higher among under-five children (1.22%) and children belonging to scheduled castes/tribes (SC/ST, 1.72%). On multivariate analysis, independent risk factors associated with measles death were age Measles CFR in Bihar was low. To further reduce case fatality, health authorities need to ensure that SC/ST are targeted by the immunization programme and that outbreak investigations target for vitamin A treatment of cases in high risk groups such as SC/ST and young children and ensure regular visits by health-workers in affected villages to administer vitamin A to new cases. PMID:24824641

THE RESULTS OF STUDY OF THE LEVELS OF SPECIFIC ANTIBODIES TO THE COMBINED INJECTION VACCINES AGAINST INFLUENZA, MEASLES, RUBELLA AND MUMPS AND DT IN CHILDREN WITH CHRONIC PHYSICAL ILLNESS

Directory of Open Access Journals (Sweden)

S. M. Haritе

2014-01-01

Full Text Available The levels of antibodies to the separate and combined administration of the vaccine plus Grippol® Plus and vaccines against measles, mumps and/or rubella, diphtheria and tetanus (DT in children with chronic medical illnesses, including HIV and organic CNS. Revealed that at low reactogenicity and safety of the vaccine Grippol® Plus, concomitant vaccination does not affect the dynamics of the synthesis (seroprotection, seroconversion, diphtheria, mumps, and rubella antibodies, however, reduces the synthesis of measles antibodies. When combined administration of DT and mumps-measles vaccines + Grippol® Plus suppressed antibody response to a strain of influenza virus A/H3N2. 

Optimising measles virus-guided radiovirotherapy with external beam radiotherapy and specific checkpoint kinase 1 inhibition

International Nuclear Information System (INIS)

Touchefeu, Yann; Khan, Aadil A.; Borst, Gerben; Zaidi, Shane H.; McLaughlin, Martin; Roulstone, Victoria; Mansfield, David; Kyula, Joan; Pencavel, Tim; Karapanagiotou, Eleni M.; Clayton, Jamie; Federspiel, Mark J.; Russell, Steve J.; Garrett, Michelle; Collins, Ian; Harrington, Kevin J.

2013-01-01

Background and purpose: We previously reported a therapeutic strategy comprising replication-defective NIS-expressing adenovirus combined with radioiodide, external beam radiotherapy (EBRT) and DNA repair inhibition. We have now evaluated NIS-expressing oncolytic measles virus (MV-NIS) combined with NIS-guided radioiodide, EBRT and specific checkpoint kinase 1 (Chk1) inhibition in head and neck and colorectal models. Materials and methods: Anti-proliferative/cytotoxic effects of individual agents and their combinations were measured by MTS, clonogenic and Western analysis. Viral gene expression was measured by radioisotope uptake and replication by one-step growth curves. Potential synergistic interactions were tested in vitro by Bliss independence analysis and in in vivo therapeutic studies. Results: EBRT and MV-NIS were synergistic in vitro. Furthermore, EBRT increased NIS expression in infected cells. SAR-020106 was synergistic with EBRT, but also with MV-NIS in HN5 cells. MV-NIS mediated 131 I-induced cytotoxicity in HN5 and HCT116 cells and, in the latter, this was enhanced by SAR-020106. In vivo studies confirmed that MV-NIS, EBRT and Chk1 inhibition were effective in HCT116 xenografts. The quadruplet regimen of MV-NIS, virally-directed 131 I, EBRT and SAR-020106 had significant anti-tumour activity in HCT116 xenografts. Conclusion: This study strongly supports translational and clinical research on MV-NIS combined with radiation therapy and radiosensitising agents

Effects of supplemental measles immunization on cases of measles ...

African Journals Online (AJOL)

2014-03-01

Mar 1, 2014 ... Background: Measles is a highly contagious vaccine-preventable infection which continues to be a significant cause of .... other exanthematous childhood illnesses not in con- .... Sixty-third World Health Assembly Agenda pro-.

Two short basic sequences surrounding the zinc finger of nucleocapsid protein NCp10 of Moloney murine leukemia virus are critical for RNA annealing activity.

Science.gov (United States)

De Rocquigny, H; Ficheux, D; Gabus, C; Allain, B; Fournie-Zaluski, M C; Darlix, J L; Roques, B P

1993-02-25

The 56 amino acid nucleocapsid protein (NCp10) of Moloney Murine Leukemia Virus, contains a CysX2CysX4HisX4Cys zinc finger flanked by basic residues. In vitro NCp10 promotes genomic RNA dimerization, a process most probably linked to genomic RNA packaging, and replication primer tRNA(Pro) annealing to the initiation site of reverse transcription. To characterize the amino-acid sequences involved in the various functions of NCp10, we have synthesized by solid phase method the native protein and a series of derived peptides shortened at the N- or C-terminus with or without the zinc finger domain. In the latter case, the two parts of the protein were linked by a Glycine - Glycine spacer. The in vitro studies of these peptides show that nucleic acid annealing activities of NCp10 do not require a zinc finger but are critically dependent on the presence of specific sequences located on each side of the CCHC domain and containing proline and basic residues. Thus, deletion of 11R or 49PRPQT, of the fully active 29 residue peptide 11RQGGERRRSQLDRDGGKKPRGPRGPRPQT53 leads to a complete loss of NCp10 activity. Therefore it is proposed that in NCp10, the zinc finger directs the spatial recognition of the target RNAs by the basic domains surrounding the zinc finger.

PrPC has nucleic acid chaperoning properties similar to the nucleocapsid protein of HIV-1.

Science.gov (United States)

Derrington, Edmund; Gabus, Caroline; Leblanc, Pascal; Chnaidermann, Jonas; Grave, Linda; Dormont, Dominique; Swietnicki, Wieslaw; Morillas, Manuel; Marck, Daniel; Nandi, Pradip; Darlix, Jean-Luc

2002-01-01

The function of the cellular prion protein (PrPC) remains obscure. Studies suggest that PrPC functions in several processes including signal transduction and Cu2+ metabolism. PrPC has also been established to bind nucleic acids. Therefore we investigated the properties of PrPC as a putative nucleic acid chaperone. Surprisingly, PrPC possesses all the nucleic acid chaperoning properties previously specific to retroviral nucleocapsid proteins. PrPC appears to be a molecular mimic of NCP7, the nucleocapsid protein of HIV-1. Thus PrPC, like NCP7, chaperones the annealing of tRNA(Lys) to the HIV-1 primer binding site, the initial step of retrovirus replication. PrPC also chaperones the two DNA strand transfers required for production of a complete proviral DNA with LTRs. Concerning the functions of NCP7 during budding, PrPC also mimices NCP7 by dimerizing the HIV-1 genomic RNA. These data are unprecedented because, although many cellular proteins have been identified as nucleic acid chaperones, none have the properties of retroviral nucleocapsid proteins.

Isolation of Ganjam virus from ticks collected off domestic animals around Pune, Maharashtra, India.

Science.gov (United States)

Joshi, M V; Geevarghese, G; Joshi, G D; Ghodke, Y S; Mourya, D T; Mishra, A C

2005-03-01

Studies on viruses of zoonotic importance in certain villages around Pune were undertaken between December 2000 and January 2002. A total of 1,138 adult ticks belonging to six different species were collected off domestic animals and processed for virus isolation. Six virus isolates were obtained. All six isolates were identified as Ganjam virus by Quick Complement Fixation test and reverse transcriptase-polymerase chain reaction using RNA nucleocapsid gene amplification. Five isolates were from the pools of adult Hemaphysalis intermedia ticks, and one isolate was from a pool of adult Rhipecephalus hemaphysaloides. This is the first report of isolation of Ganjam virus from Maharashtra state of India.

Measles vaccine: a 27-year follow-up.

LENUS (Irish Health Repository)

Ramsay, M E

1994-04-01

In 1964, the Medical Research Council undertook a trial of measles vaccine in over 36,000 United Kingdom children; 9577 of whom received live vaccine, 10,625 received inactivated followed by live vaccines, and 16,328 acted as unvaccinated controls. Participants in this study have been followed to determine the long term protection from measles vaccine and follow-up data were available on 4194, 4638 and 274 respectively. During the 5-year period 1986-90, the protective efficacy of live measles vaccine has remained high at 87%, but the 95% confidence interval was wide (-43 to 99%) due to the small numbers of cases. Between 1976 and 1990, however, the overall efficacy of the live vaccine was 92% (95% confidence interval 86 to 95%) and there was no evidence of a decline in efficacy (P = 0.13) over the 15-year period. This study suggests that the protection from live measles vaccine persists for up to 27 years after vaccination, and that no change in the current United Kingdom measles immunization policy should be made on the grounds of waning immunity.

Priming T-cell responses with recombinant measles vaccine vector in a heterologous prime-boost setting in non-human primates.

Science.gov (United States)

Bolton, Diane L; Santra, Sampa; Swett-Tapia, Cindy; Custers, Jerome; Song, Kaimei; Balachandran, Harikrishnan; Mach, Linh; Naim, Hussein; Kozlowski, Pamela A; Lifton, Michelle; Goudsmit, Jaap; Letvin, Norman; Roederer, Mario; Radošević, Katarina

2012-09-07

Licensed live attenuated virus vaccines capable of expressing transgenes from other pathogens have the potential to reduce the number of childhood immunizations by eliciting robust immunity to multiple pathogens simultaneously. Recombinant attenuated measles virus (rMV) derived from the Edmonston Zagreb vaccine strain was engineered to express simian immunodeficiency virus (SIV) Gag protein for the purpose of evaluating the immunogenicity of rMV as a vaccine vector in rhesus macaques. rMV-Gag immunization alone elicited robust measles-specific humoral and cellular responses, but failed to elicit transgene (Gag)-specific immune responses, following aerosol or intratracheal/intramuscular delivery. However, when administered as a priming vaccine to a heterologous boost with recombinant adenovirus serotype 5 expressing the same transgene, rMV-Gag significantly enhanced Gag-specific T lymphocyte responses following rAd5 immunization. Gag-specific humoral responses were not enhanced, however, which may be due to either the transgene or the vector. Cellular response priming by rMV against the transgene was highly effective even when using a suboptimal dose of rAd5 for the boost. These data demonstrate feasibility of using rMV as a priming component of heterologous prime-boost vaccine regimens for pathogens requiring strong cellular responses. Copyright © 2012 Elsevier Ltd. All rights reserved.

Antecedent causes of a measles resurgence in the Democratic ...

African Journals Online (AJOL)

Introduction: Despite accelerated measles control efforts, a massive measles resurgence occurred in the Democratic Republic of the Congo (DRC) starting in mid-2010, prompting an investigation into likely causes. Methods: We conducted a descriptive epidemiological analysis using measles immunization and surveillance ...

Measles trends and vaccine effectiveness in Nairobi, Kenya | Borus ...

African Journals Online (AJOL)

Objectives: To determine morbidity and mortality from measles and to estimate measles vaccine effectiveness among children hospitalised with measles in two hospitals in Nairobi. Design: A review of hospital records (index cards). Setting: Kenyatta National Hospital and Mbagathi District Hospitals covering the years ...

A general measles vaccination campaign in urban Guinea-Bissau

DEFF Research Database (Denmark)

Byberg, S.; Thysen, S. M.; Rodrigues, A.

2017-01-01

Background Measles vaccination campaigns targeting children aged 9–59 months are conducted every three years in Guinea-Bissau. Studies have demonstrated beneficial non-specific effects of measles vaccine. We compared mortality one year after the December 2012 measles vaccination campaign in Bissa...

Measles outbreak--California, December 2014-February 2015.

Science.gov (United States)

Zipprich, Jennifer; Winter, Kathleen; Hacker, Jill; Xia, Dongxiang; Watt, James; Harriman, Kathleen

2015-02-20

On January 5, 2015, the California Department of Public Health (CDPH) was notified about a suspected measles case. The patient was a hospitalized, unvaccinated child, aged 11 years with rash onset on December 28. The only notable travel history during the exposure period was a visit to one of two adjacent Disney theme parks located in Orange County, California. On the same day, CDPH received reports of four additional suspected measles cases in California residents and two in Utah residents, all of whom reported visiting one or both Disney theme parks during December 17-20. By January 7,seven California measles cases had been confirmed, and CDPH issued a press release and an Epidemic Information Exchange (Epi-X) notification to other states regarding this outbreak. Measles transmission is ongoing.

Measles in Italy, laboratory surveillance activity during 2010

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Claudia Fortuna

2014-12-01

Full Text Available INTRODUCTION: The European Regional Office of the World Health Organization (WHO/Europe developed a strategic approach to stop the indigenous transmission of measles in its 53 Member States by 2015. This study describes the measles laboratory surveillance activity performed by the National Reference Laboratory for Measles and Rubella at the Italian National Institute of Health (Istituto Superiore di Sanità during 2010. METHODS: Urine, oral fluid and capillary blood samples from 211 suspected measles cases arrived to the NRL from different regions of Italy for confirmation of the clinical diagnosis. Serological and/or molecular assays were performed; after molecular detection, positive samples were sequenced and genotyped. RESULTS AND DISCUSSION: 85% (180/211 of the specimens were confirmed as measles cases and 139 of these were analyzed phylogenetically. The phylogenetic analysis revealed a co-circulation of D4 and D8 genotypes for the reviewed period.

measles case-based surveillance and outbreak response in nigeria

African Journals Online (AJOL)

of the existing national technical guideline on measles case- based surveillance and outbreak response in Nigeria in ... according to the revised national measles technical guideline9. However, with the strengthening of the ... involves immediate reporting and investigating any suspected case of measles by clinicians using ...

A Global Perspective of Vaccination of Healthcare Personnel against Measles: Systematic Review

Science.gov (United States)

Fiebelkorn, Amy Parker; Seward, Jane F.; Orenstein, Walter

2015-01-01

Measles transmission has been well documented in healthcare facilities. Healthcare personnel who are unvaccinated and who lack other evidence of measles immunity put themselves and their patients at risk for measles. We conducted a systematic literature review of measles vaccination policies and their implementation in healthcare personnel, measles seroprevalence among healthcare personnel, measles transmission and disease burden in healthcare settings, and impact/costs incurred by healthcare facilities for healthcare-associated measles transmission. Five database searches yielded 135 relevant articles; 47 additional articles were found through cross-referencing. The risk of acquiring measles is estimated to be 2 to 19 times higher for susceptible healthcare personnel than for the general population. Fifty-three articles published worldwide during 1989–2013 reported measles transmission from patients to healthcare personnel; many of the healthcare personnel were unvaccinated or had unknown vaccination status. Eighteen articles published worldwide during 1982–2013 described examples of transmission from healthcare personnel to patients or to other healthcare personnel. Half of European countries have no measles vaccine policies for healthcare personnel. There is no global policy recommendation for the vaccination of healthcare personnel against measles. Even in countries such as the United States or Finland that have national policies, the recommendations are not uniformly implemented in healthcare facilities. Measles serosusceptibility in healthcare personnel varied widely across studies (median 6.5%, range 0%-46%) but was consistently higher among younger healthcare personnel. Deficiencies in documentation of two doses of measles vaccination or other evidence of immunity among healthcare personnel presents challenges in responding to measles exposures in healthcare settings. Evaluating and containing exposures and outbreaks in healthcare settings can be

Risk factors for measles death: Kyegegwa District, western Uganda, February-September, 2015.

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Mafigiri, Richardson; Nsubuga, Fred; Ario, Alex Riolexus

2017-07-03

On 18 August 2015, Kyegegwa District reported eight deaths during a measles outbreak to the Uganda Ministry of Health (MoH). We investigated this death cluster to verify the cause, identify risk factors, and inform public health interventions. We defined a probable measles case as onset of fever and generalised rash in a Kyegegwa District resident from 1 February - 15 September 2015, plus ≥1 of the following: coryza, conjunctivitis, and cough. A confirmed measles case was a probable case with measles-specific IgM positivity. A measles death was a death of a probable or confirmed case-person. We conducted an active case-finding to identify measles patients who survived or died. In a case-control study, we compared risk factors between 16 measles patients who died (cases) and 48 who survived (controls), matched by age (±4 years) and village of residence. We identified 94 probable measles cases, 10 (11%) were confirmed by positive measles-specific IgM. Of the 64 probable measles patients aged measles was found in 94% (15/16) among the case-persons (i.e., measles patients who died) and 54% (26/48) among the controls (i.e., measles patients who survived) (OR M-H  = 12; 95% CI = 1.6-104), while 56% (9/16) of case-persons and 67% (17/48) of controls (OR M-H  = 2.3; 95% CI =0.74-7.4) did not receive vitamin A supplementation during illness. 63% (10/16) among the case-persons and 6.3% (3/48) of the controls (OR M-H  = 33; 95% CI = 6.8-159) were not treated for measles illness at a health facility (a proxy for more appropriate treatment), while 38% (6/16) of the case-persons and 25% (12/48) of the controls (OR M-H  = 2.5; 95% CI = 0.67-9.1) were malnourished. Lack of vaccination and no treatment in a health facility increased the risk for measles deaths. The one-dose measles vaccination currently in the national vaccination schedule had a protective effect against measles death. We recommended enhancing measles vaccination and adherence to measles treatment

Measles outbreak in adults: A changing epidemiological pattern

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Swati Bajaj

2017-01-01

Full Text Available Background: Thirty-one cases of fever with rash were reported among students of a college in Pune, India, from March to May 2014. The clinical profile was similar to that of measles and 7 of them tested positive for measles-specific immunoglobulin M (IgM. An outbreak of measles was declared, and epidemiological investigation was carried out to assess the situation and suggest preventive measures. Methods: An epidemiological case sheet filled for each case to identify the source and likely contacts. Medical and administrative authorities were sensitized about the increase in incidence and clustering of cases. A surveillance system was set up for detection of new cases and follow-up of contacts. Throat swabs and blood samples from 12 cases were tested by ELISA method for commonly occurring viral exanthematous fevers to confirm the diagnosis and 7 were positive for measles-specific IgM antibody. Preventive measures were advised to control the outbreak. Results: A total of 31 cases of fever with rashes were reported among students of a college in Pune, India, during the months of March–May 2014. Most of the students were in the age group of 18–24 years. Samples from 12 cases were sent for testing and 7 tested positive for measles-specific IgM antibodies. Seven cases were epidemiologically linked to a lab-confirmed case. All cases had fever, maculopapular rash, and sore throat and gave a history of vaccination for measles in childhood. Conclusion: An epidemiological investigation was carried out for outbreak of measles in a young adult population of college students from Pune. It is reported that, with increase in overall coverage of vaccination, there is a rise in incidence of measles in vaccinated individuals. The age profile also shifts to higher age groups. Investigation of such outbreaks provides an opportunity to identify high-risk groups, changes in measles epidemiology and weaknesses in the routine immunization programs.

Measles Outbreak in Pediatric Hematology and Oncology Patients in Shanghai, 2015

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Ge, Yan-Ling; Zhai, Xiao-Wen; Zhu, Yan-Feng; Wang, Xiang-Shi; Xia, Ai-Mei; Li, Yue-Fang; Zeng, Mei

2017-01-01

Background: Despite substantial progress toward measles control are making in China, measles outbreaks in immunocompromised population still pose a challenge to interrupt endemic transmission. This study aimed to investigate the features of measles in pediatric hematology and oncology patients and explore the reasons behind the outbreak. Methods: We collected demographic, epidemiological, and clinical data of immunocompromised measles children. All suspected measles cases were laboratory-confirmed based on the presence of measles IgM and/or identification of measles RNA. The clinical data were statistically analyzed by t-test for continuous variables and Fisher's exact test for categorical variables. Results: From March 9 to July 25 in 2015, a total of 23 children with malignancies and post hematopoietic stem cell transplantation (post-HSCT) were notified to develop measles in Shanghai. Of these 23 patients with the median age of 5.5 years (range: 11 months–14 years), 20 (87.0%) had received 1–3 doses of measles vaccine previously; all patients had fever with the median fever duration of 8 days; 21 (91.3%) had cough; 18 (78.3%) had rash; 13 (56.5%) had Koplik's spot; 13 (56.5%) had complications including pneumonia and acute liver failure; and five (21.7%) vaccinated patients died from severe pneumonia or acute liver failure. Except the first patient, all patients had hospital visits within 7–21 days before measles onset and 20 patients were likely to be exposed to each other. Conclusions: The outcome of measles outbreak in previously vaccinated oncology and post-HSCT pediatric patients during chemotherapy and immunosuppressant medication was severe. Complete loss of protective immunity induced by measles vaccine during chemotherapy was the potential reason. Improved infection control practice was critical for the prevention of measles in malignancy patients and transplant recipients. PMID:28524832

Strawberry crinkle virus, a Cytorhabdovirus needing more attention from virologists.

Science.gov (United States)

Posthuma, K I; Adams, A N; Hong, Y

2000-11-01

Summary Taxonomic relationship: A member of nonsegmented, negative-sense, single-stranded RNA viruses of the genus Cytorhabdovirus (type member: Lettuce necrotic yellows virus), family Rhabdoviridae, order Mononegavirales. Members of the family Rhabdoviridae can infect vertebrates, invertebrates and plants. Physical properties: Virions are bacilliform, 74-88 nm in diameter and 163-383 nm in length with surface projections probably composed of trimers of the glycoprotein G, occurring in the cytoplasm in either the coated or the uncoated form (Fig. 1). The nucleocapsid is enclosed in a host-derived envelope. Within the virion, the SCV genome consists of a single negative-sense single-stranded RNA molecule of approximately 13 kb. Viral proteins: The SCV genome encodes at least five proteins: the nucleocapsid (N) protein (45 kDa), the matrix (M) protein (77 kDa), the nonstructural protein [Ns, 55 kDa, also known as phosphoprotein (P)], the glycoprotein (G, 23 kDa) and the large (L) protein. Hosts: The natural host range of SCV is limited to species of the genus Fragaria L. Experimental hosts include Physalis pubescens L., P. floridana Rydb., Nicotiana occidentalis, N. glutinosa L. and N. clevelandi Gray. SCV also replicates in its insect vectors Chaetosiphon fragaefolii Cockerell and C. jacobi Hille Ris Lamberts. When injected as purified virus, SCV replicates in aphids Hyperomyzus lactucae (L.), Macrosiphon euphorbiae Thomas, Myzus ornatus Laing, Megoura viciae Buckton, and Acyrthosiphoa pisum (Harris).

Adding interventions to mass measles vaccinations in India.

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Johri, Mira; Verguet, Stéphane; Morris, Shaun K; Sharma, Jitendar K; Ram, Usha; Gauvreau, Cindy; Jones, Edward; Jha, Prabhat; Jit, Mark

2016-10-01

To quantify the impact on mortality of offering a hypothetical set of technically feasible, high-impact interventions for maternal and child survival during India's 2010-2013 measles supplementary immunization activity. We developed Lives Saved Tool models for 12 Indian states participating in the supplementary immunization, based on state- and sex-specific data on mortality from India's Million Deaths Study and on health services coverage from Indian household surveys. Potential add-on interventions were identified through a literature review and expert consultations. We quantified the number of lives saved for a campaign offering measles vaccine alone versus a campaign offering measles vaccine with six add-on interventions (nutritional screening and complementary feeding for children, vitamin A and zinc supplementation for children, multiple micronutrient and calcium supplementation in pregnancy, and free distribution of insecticide-treated bednets). The measles vaccination campaign saved an estimated 19 016 lives of children younger than 5 years. A hypothetical campaign including measles vaccine with add-on interventions was projected to save around 73 900 lives (range: 70 200-79 300), preventing 73 700 child deaths (range: 70 000-79 000) and 300 maternal deaths (range: 200-400). The most effective interventions in the whole package were insecticide-treated bednets, measles vaccine and preventive zinc supplementation. Girls accounted for 66% of expected lives saved (12 712/19 346) for the measles vaccine campaign, and 62% of lives saved (45 721/74 367) for the hypothetical campaign including add-on interventions. In India, a measles vaccination campaign including feasible, high-impact interventions could substantially increase the number of lives saved and mitigate gender-related inequities in child mortality.

Prolonged hospital stay in measles patients | Ashir | Sahel Medical ...

African Journals Online (AJOL)

Background: Measles is still a major cause of childhood morbidity and mortality in Nigeria despite the availability of safe and effective vaccines. The burden of measles using length of hospital stay as a result of complications in hospitalised children with measles is reported. Methods: We carried out a two year retrospective ...

Measles control in the urbanising environment

African Journals Online (AJOL)

1991-04-20

Apr 20, 1991 ... measles infection in childhood is characterised by a high risk between 5 and 11 months of age, soon after loss of ... urban areas compared with 10% in rural areas are infected with measles before 8 months of age. ... magnitude of in- and out-migration, and the respective vac- cination coverage rates.15In ...

Modelling the effects of treatment and quarantine on measles

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Beay, Lazarus Kalvein

2018-03-01

Treatment and quarantine are efforts to cure as well as to overcome the spread of diseases including measles. The spread of measles can be expressed by mathematical modelling in the form of nonlinear dynamical systems. In this study was conducted on the spread of measles by considering the effect of treatment and quarantine on the infected individuals. By using the basic reproduction number of the model, can be analyzed the effects of treatment and quarantine to reduce the spread of measles. Basic reproduction number of models is monotonically descreasing as treatment and quarantine increasing. Numerical simulations conducted on the analysis of the results. The results showed that treatment and quarantine was given to infected individuals who were infectious has a major influence to eliminate measles from the system.

Is there enough vaccine to eradicate measles? An integrated analysis of measles-containing vaccine supply and demand.

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Smith, Graegar; Michelson, Joshua; Singh, Rohit; Dabbagh, Alya; Hoekstra, Edward; van den Ent, Maya; Mallya, Apoorva

2011-07-01

Responding to regional advancements in combating measles, the World Health Organization in May 2008 called for an assessment of the feasibility of measles eradication, including whether sufficient vaccine supply exists. Interviews with international health officials and vaccine-makers provided data for a detailed model of worldwide demand and supply for measles-containing vaccine (MCV). The study projected global MCV demand through 2025 with and without a global eradication goal. The study found that 5.2 billion MCV doses must be administered during 2010-2025 to maintain current measles programs, and 5.9 billion doses would likely be needed with a 2020 eradication goal; in the most intensive scenario, demand could increase to 7.5 billion doses. These volumes are within existing and planned MCV-manufacturing capacity, although there are risks. In some markets, capacity is concentrated: Supply-chain disruptions could reduce supply or increase prices. Mitigation strategies could include stockpiling, long-term contracts, and further coordination with manufacturers. © The Author 2011. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved.

Effects of supplemental measles immunization on cases of measles ...

African Journals Online (AJOL)

Background: Measles is a highly contagious vaccine-preventable infection which continues to be a significant cause of childhood morbidity and mortality in developing countries particularly those with poor routine immunisation coverage. Supplemental immunisation activities (SIAs) were thus introduced to improve vaccine ...

Measles Antibodies in Mother-Infant Dyads in Tianjin, China.

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Boulton, Matthew L; Wang, Xiexiu; Wagner, Abram L; Zhang, Ying; Carlson, Bradley F; Gillespie, Brenda W; Ding, Yaxing

2017-11-27

Many measles cases in Tianjin, China, occur in infants whose mothers were born after widespread vaccination programs. We assessed age-specific decreases in maternal measles antibodies in infants and examined maternal and infant characteristics in relation to infant antibody titers. Infant and mother dyads were enrolled from a sample of immunization clinics in all Tianjin districts. Participants' antibody titers were measured from dried blood spots. A multivariable log-linear model regressed infant antibody titers onto infant and mother characteristics. Among 551 infants aged ≤8 months, protective levels of measles antibodies were observed in infants whose mothers had measles titers ≥800 IU/mL (mean antibody titer, 542.5 IU/mL) or 400 to measles and an accordingly low efficiency of transplacental transmission to a fetus. Current vaccination programs, which target children aged 8 months through adolescence may be ineffective in controlling transmission of measles to infants. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Placental malaria and immunity to infant measles

NARCIS (Netherlands)

Owens, S.; Harper, G.; Amuasi, J.; Offei-Larbi, G.; Ordi, J.; Brabin, B. J.

2006-01-01

The efficiency of transplacental transfer of measles specific antibody was assessed in relation to placental malaria. Infection at delivery was associated with a 30% decrease in expected cord measles antibody titres. Uninfected women who received anti-malarial drugs during pregnancy transmitted 30%

Clinical features of measles pneumonia in adults

International Nuclear Information System (INIS)

Tanaka, Hiroshi; Honma, Shin-ichi; Yamagishi, Masahiko; Honda, Yasuhito; Abe, Shosaku; Igarashi, Tomofumi; Sekine, Kyuichiro.

1993-01-01

The clinical features, chest radiographs and computed tomographic (CT) images were evaluated in 11 cases of serologically proved adult measles complicated with pneumonia (10 were previously healthy and one had sarcoidosis). Pneumonia appeared during the rash period in all cases. Respiratory symptoms were cough (9/11), dyspnea (3/11), and hypoxemia (10/11). Pneumonia manifestations were detected in only 4 cases by chest radiograph; on the other hand, they were seen in all cases by CT scan and consisted of ground-glass opacities (73%), nodular opacities (64%) and consolidation (27%). CT seems to be useful method to detect measles pneumonia if it is suspected. Measles pneumonia in previously healthy patients had a good prognosis, as the hypoxemia disappeared within 6 days in all cases. The sarcoidosis patient showed prolonged pneumonic shadows and period of hypoxemia. Measles pneumonia occurring in a host with cellular immunodeficiency may have a severe clinical course. (author)

The potential for measles transmission in England

Directory of Open Access Journals (Sweden)

Fraser Graham

2008-09-01

Full Text Available Abstract Background Since the schools vaccination campaign in 1994, measles has been eliminated from England. Maintaining elimination requires low susceptibility levels to keep the effective reproduction number R below 1. Since 1995, however, MMR coverage in two year old children has decreased by more than 10%. Methods Quarterly MMR coverage data for children aged two and five years resident in each district health authority in England were used to estimate susceptibility to measles by age. The effective reproduction numbers for each district and strategic health authority were calculated and possible outbreak sizes estimated. Results In 2004/05, about 1.9 million school children and 300,000 pre-school children were recorded as incompletely vaccinated against measles in England, including more than 800,000 children completely unvaccinated. Based on this, approximately 1.3 million children aged 2–17 years were susceptible to measles. In 14 of the 99 districts, the level of susceptibility is sufficiently high for R to exceed 1, indicating the potential for sustained measles transmission. Eleven of these districts are in London. Our model suggests that the potential exists for an outbreak of up to 100,000 cases. These results are sensitive to the accuracy of reported vaccination coverage data. Conclusion Our analysis identified several districts with the potential for sustaining measles transmission. Many London areas remain at high risk even allowing for considerable under-reporting of coverage. Primary care trusts should ensure that accurate systems are in place to identify unimmunised children and to offer catch-up immunisation for those not up to date for MMR.

Immunovirotherapy with measles virus strains in combination with anti-PD-1 antibody blockade enhances antitumor activity in glioblastoma treatment.

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Hardcastle, Jayson; Mills, Lisa; Malo, Courtney S; Jin, Fang; Kurokawa, Cheyne; Geekiyanage, Hirosha; Schroeder, Mark; Sarkaria, Jann; Johnson, Aaron J; Galanis, Evanthia

2017-04-01

Glioblastoma (GBM) is the most common primary malignant brain tumor and has a dismal prognosis. Measles virus (MV) therapy of GBM is a promising strategy due to preclinical efficacy, excellent clinical safety, and its ability to evoke antitumor pro-inflammatory responses. We hypothesized that combining anti- programmed cell death protein 1 (anti-PD-1) blockade and MV therapy can overcome immunosuppression and enhance immune effector cell responses against GBM, thus improving therapeutic outcome. In vitro assays of MV infection of glioma cells and infected glioma cells with mouse microglia ± aPD-1 blockade were established to assess damage associated molecular pattern (DAMP) molecule production, migration, and pro-inflammatory effects. C57BL/6 or athymic mice bearing syngeneic orthotopic GL261 gliomas were treated with MV, aPD-1, and combination treatment. T2* weighted immune cell-specific MRI and fluorescence activated cell sorting (FACS) analysis of treated mouse brains was used to examine adaptive immune responses following therapy. In vitro, MV infection induced human GBM cell secretion of DAMP (high-mobility group protein 1, heat shock protein 90) and upregulated programmed cell death ligand 1 (PD-L1). MV infection of GL261 murine glioma cells resulted in a pro-inflammatory response and increased migration of BV2 microglia. In vivo, MV+aPD-1 therapy synergistically enhanced survival of C57BL/6 mice bearing syngeneic orthotopic GL261 gliomas. MRI showed increased inflammatory cell influx into the brains of mice treated with MV+aPD-1; FACS analysis confirmed increased T-cell influx predominantly consisting of activated CD8+ T cells. This report demonstrates that oncolytic measles virotherapy in combination with aPD-1 blockade significantly improves survival outcome in a syngeneic GBM model and supports the potential of clinical/translational strategies combining MV with αPD-1 therapy in GBM treatment. © The Author(s) 2016. Published by Oxford University Press

Measles epidemics of variable lethality in the early 20th century.

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Shanks, G Dennis; Hu, Zheng; Waller, Michael; Lee, Seung-eun; Terfa, Daniel; Howard, Alan; van Heyningen, Elizabeth; Brundage, John F

2014-02-15

Until the mid-20th century, mortality rates were often very high during measles epidemics, particularly among previously isolated populations (e.g., islanders), refugees/internees who were forcibly crowded into camps, and military recruits. Searching for insights regarding measles mortality rates, we reviewed historical records of measles epidemics on the Polynesian island of Rotuma (in 1911), in Boer War concentration camps (in 1900-1902), and in US Army mobilization camps during the First World War (in 1917-1918). Records classified measles deaths by date and clinical causes; by demographic characteristics, family relationships (for Rotuma islanders and Boer camp internees), and prior residences; and by camp (for Boer internees and US Army recruits). During the Rotuman and Boer War epidemics, measles-related mortality rates were high (up to 40%); however, mortality rates differed more than 10-fold across camps/districts, even though conditions were similar. During measles epidemics, most deaths among camp internees/military recruits were due to secondary bacterial pneumonias; in contrast, most deaths among Rotuman islanders were due to gastrointestinal complications. The clinical expressions, courses, and outcomes of measles during first-contact epidemics differ from those during camp epidemics. The degree of isolation from respiratory pathogens other than measles may significantly determine measles-related mortality risk.

Measles vaccination in children with neurological disorders

Directory of Open Access Journals (Sweden)

S. P. Kaplina

2012-01-01

Full Text Available The data on the current vaccination process and specific antibody in 212 children with pathology of nervous systems in age from 1 year to 6 years old, vaccinated against measles. The comparison group consisted of 36 children without neurological disease. 86 children (40,6% were vaccinated measles – mumps vaccine, and 126 children (59,4% only measles vaccine. Post-vaccination period in 77,8% immunized against measles, was uneventful, layering intercurrent infections was noted in 22,2% of vaccine’s, and demonstrated the development of viral respiratory infections, bronchitis, otitis media and exacerbation of underlying disease. It is shown that the level of specific antibody to measles in children with pathology of nervous systems at 30 days after vaccination was 5,04±0,16 log 2, which did not differ from the comparison group (5,88±0,31 log 2. No significant differences in the level of antibody in a smooth and complicated course of vaccination period were found. Immunization of children with disorders of the nervous system of live vaccines is quite effective and leads to the formation of protective antibody titers in all vaccinated.

An Outbreak of Measles in a University in Korea, 2014.

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Choe, Young June; Park, Young Joon; Kim, Ju Whi; Eom, Hye Eun; Park, Ok; Oh, Myoung Don; Lee, Jong Koo

2017-11-01

Measles has been declared eliminated from the Korea since 2006. In April 2014, a measles outbreak occurred at a University in Seoul. A total of 85 measles cases were identified. In order to estimate vaccine effectiveness of measles vaccine, we reviewed the vaccination records of the university students. The vaccine effectiveness of two doses of measles containing vaccine was 60.0% (95% CI, 38.2-74.1; P < 0.05). Transmission was interrupted after the introduction of outbreak-response immunization. The outbreak shows that pockets of under-immunity among college students may have facilitated the disease transmission despite the high 2-dose vaccination coverage in the community. © 2017 The Korean Academy of Medical Sciences.

Perspective on Global Measles Epidemiology and Control and the Role of Novel Vaccination Strategies

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Melissa M. Coughlin

2017-01-01

Full Text Available Measles is a highly contagious, vaccine preventable disease. Measles results in a systemic illness which causes profound immunosuppression often leading to severe complications. In 2010, the World Health Assembly declared that measles can and should be eradicated. Measles has been eliminated in the Region of the Americas, and the remaining five regions of the World Health Organization (WHO have adopted measles elimination goals. Significant progress has been made through increased global coverage of first and second doses of measles-containing vaccine, leading to a decrease in global incidence of measles, and through improved case based surveillance supported by the WHO Global Measles and Rubella Laboratory Network. Improved vaccine delivery methods will likely play an important role in achieving measles elimination goals as these delivery methods circumvent many of the logistic issues associated with subcutaneous injection. This review highlights the status of global measles epidemiology, novel measles vaccination strategies, and describes the pathway toward measles elimination.

Case report: Ribavirin and vitamin A in a severe case of measles.

Science.gov (United States)

Bichon, Amandine; Aubry, Camille; Benarous, Lucas; Drouet, Hortense; Zandotti, Christine; Parola, Philippe; Lagier, Jean-Christophe

2017-12-01

Despite a vaccine being widely available, measles continues to occur frequently, with sometimes lethal consequences. The mortality rate reaches 35% and measles represents 44% of the 1.4 million deaths which are due to preventable diseases. Severe forms of measles are reported, mainly in young, unvaccinated adults, and in specific populations. The risk factors for severe measles include no or incomplete vaccination and vitamin A deficiency. Apart from secondary measles-related infections, severe measles is mainly represented by neurological, respiratory, and digestive symptoms. Strengthening the hypothesis that there is a link between vitamin A deficiency and severe measles in this paper we report the case of a 25-year-old unvaccinated man hospitalized for severe and complicated measles. The evolution was good after administration of intramuscular vitamin A as well as intravenous ribavirin. Measles remains a fatal and serious disease. The early use of ribavirin and vitamin A shows significant improvements regarding morbimortality and should be systematic in severe cases. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

EPIDEMIOLOGICAL FEATURES OF THE MEASLES IN KIROVOGRAD REGION in 2004 – 2015

OpenAIRE

Operchuk, N.I.

2018-01-01

Introduction.The incidence of measles in Ukraine remains an actual problem. Measle is related to vaccine - controled infections. However, low levels of imunization of the child population by planned measles vaccine, insufficient provision of immunobiological drugs (vaccines) in recent years, anti-vaccine companies contribute to the increase of the measles morbidity in Ukraine.Prominent scientist L.V. Gromashevsky spoke about measles, which is a "disease of unique distribution". In the implem...

Controlling measles using supplemental immunization activities: a mathematical model to inform optimal policy.

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Verguet, Stéphane; Johri, Mira; Morris, Shaun K; Gauvreau, Cindy L; Jha, Prabhat; Jit, Mark

2015-03-03

The Measles & Rubella Initiative, a broad consortium of global health agencies, has provided support to measles-burdened countries, focusing on sustaining high coverage of routine immunization of children and supplementing it with a second dose opportunity for measles vaccine through supplemental immunization activities (SIAs). We estimate optimal scheduling of SIAs in countries with the highest measles burden. We develop an age-stratified dynamic compartmental model of measles transmission. We explore the frequency of SIAs in order to achieve measles control in selected countries and two Indian states with high measles burden. Specifically, we compute the maximum allowable time period between two consecutive SIAs to achieve measles control. Our analysis indicates that a single SIA will not control measles transmission in any of the countries with high measles burden. However, regular SIAs at high coverage levels are a viable strategy to prevent measles outbreaks. The periodicity of SIAs differs between countries and even within a single country, and is determined by population demographics and existing routine immunization coverage. Our analysis can guide country policymakers deciding on the optimal scheduling of SIA campaigns and the best combination of routine and SIA vaccination to control measles. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

The V domain of dog PVRL4 (nectin-4) mediates canine distemper virus entry and virus cell-to-cell spread.

Science.gov (United States)

Delpeut, Sebastien; Noyce, Ryan S; Richardson, Christopher D

2014-04-01

The entry of canine distemper virus (CDV) is a multistep process that involves the attachment of CDV hemagglutinin (H) to its cellular receptor, followed by fusion between virus and cell membranes. Our laboratory recently identified PVRL4 (nectin-4) to be the epithelial receptor for measles and canine distemper viruses. In this study, we demonstrate that the V domain of PVRL4 is critical for CDV entry and virus cell-to-cell spread. Furthermore, four key amino acid residues within the V domain of dog PVRL4 and two within the CDV hemagglutinin were shown to be essential for receptor-mediated virus entry. Copyright © 2014 Elsevier Inc. All rights reserved.

Serology indicates cytomegalovirus infection is associated with varicella-zoster virus reactivation.

Science.gov (United States)

Ogunjimi, Benson; Theeten, Heidi; Hens, Niel; Beutels, Philippe

2014-05-01

Varicella-zoster virus (VZV) causes chickenpox after which the virus remains latent in neural ganglia. Subsequent reactivation episodes occur, leading mainly to subclinical detection of VZV, but also to the clinical entity herpes zoster. These reactivations are known to occur most frequently amongst immunocompromised individuals, but the incidence of herpes zoster is also known to increase with age, supposedly as a consequence of immunosenescence. Our analysis aims to explore associations between cytomegalovirus (CMV) infection and VZV reactivation by analyzing VZV-specific antibody titers as a function of age, gender, and CMV serostatus. The analysis was repeated on measles and parvovirus B19 antibody titers. At the time of the observations, measles virus circulation was virtually eliminated, whereas parvovirus B19 circulated at lower levels than VZV. Multiple linear regression analyses, using the log-transformed antibody titers, identified a positive association between ageing and VZV antibody titers suggesting that ageing increasingly stimulates VZV reactivation. CMV infection further amplified the positive association between ageing and the reactivation rate. A negative association between CMV infection and VZV antibody titers was found in young individuals, thereby supporting the hypothesis that CMV infection may have a negative effect on the number of B-cells. However, no associations between CMV infection and measles or parvovirus B19 antibody titers occurred, but ageing tended to be associated with a decrease in the antibody titer against parvovirus B19. The combined results thus suggest that both CMV-dependent and CMV-independent immunosenescence occurs. This is supported by an in-depth analysis of VZV, measles and parvovirus B19 antibody titers. © 2013 Wiley Periodicals, Inc.

What Obstetric Health Care Providers Need to Know About Measles and Pregnancy

Science.gov (United States)

Rasmussen, Sonja A.; Jamieson, Denise J.

2015-01-01

From January 1 to April 3, 2015, 159 people from 18 states and the District of Columbia were reported as having measles. Most cases are part of an outbreak linked to a California amusement park. Because measles was eliminated in the United States in 2000, most U.S. clinicians are unfamiliar with the condition. We reviewed information on the current outbreak, measles manifestations, diagnostic methods, treatment, and infection-control recommendations. To identify information on measles and pregnancy, we reviewed reports with 20 or more measles cases during pregnancy that included data on effects on pregnant women or pregnancy outcomes. These reports were identified through MEDLINE from inception through February 2015 using the following strategy: (((pregnan*) AND measles) AND English[Language]) NOT review[Publication Type]. Reference lists also were reviewed to identify additional articles. Pregnant women infected with measles are more likely to be hospitalized, develop pneumonia, and die than nonpregnant women. Adverse pregnancy outcomes, including pregnancy loss, preterm birth, and low birth weight, are associated with maternal measles; however, the risk of congenital defects does not appear to be increased. No antiviral therapy is available; treatment is supportive. Early identification of possible cases is needed so that appropriate infection control can be instituted promptly. The recent measles outbreak highlights the role that obstetric health care providers play in vaccine-preventable illnesses; obstetrician–gynecologists should ensure that patients are up to date on all vaccines, including measles-containing vaccines, and should recommend and ideally offer a measles-containing vaccine to women without evidence of measles immunity before or after pregnancy. PMID:25899422

An evaluation of the 2012 measles mass vaccination campaign in ...

African Journals Online (AJOL)

Introduction: To estimate the post-campaign level of measles vaccination coverage in Guinea. Method: Interview of parents and observation of measles vaccination cards of children aged 9 to 59 months during the mass measles campaign. A nationwide cluster randomized sample under health District stratification. Results: ...

Don't Let Measles Be Your Travel Souvenir

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... who have never had measles should be vaccinated. International Travel and Measles Traveling abroad for spring or ... site? Adobe PDF file Microsoft PowerPoint file Microsoft Word file Microsoft Excel file Audio/Video file Apple ...

Measles: Make Sure Your Child Is Fully Immunized

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... this? Submit What's this? Submit Button Past Emails Measles: Make Sure Your Child is Fully Immunized Language: ... also become infected if they are not protected. Measles in the U.S. From January 2 to March ...

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.

Measles Antibody Titres In 0-5 Years Children At Aligarh

Directory of Open Access Journals (Sweden)

Kandpal S D

1999-01-01

Full Text Available Research Question: What is the level of measles antibodies in 0-5 year children? Objectives: 1.To assess the pattern of decline of maternal antibodies in 0-9 months infants. 2. To estimate the seropositivity for measles antibodies in vaccinated 9 months infants. Study design: Cross- sectional. Setting: Rural areas of District Aligarh, U.P. Participants: 456 children in the age group of 0-5 years. Statistical analysis: Percentages, correlation coefficient. Results: 1. In all the study subjects below 9 months of age, the transplacentally acquired maternal measles antibodies showed a linear decline with increase in age. Out of 202 study subjects who had been immunized against measles 195(96.50% were seropositive and 7(3.5% were seronegative for measles antibodies.

Measles: who pays the cost?

OpenAIRE

Hastings, A; Hostler, A; Solen, A

1987-01-01

An epidemic of measles resulting in 164 cases in a Leicester group practice was analysed by means of a case-control study and a questionnaire. Estimates were made of the physical, social, and financial costs to children, parents, and family doctors. On average each child was ill for 10.8 days and the illness cost his parents pounds 11.06. His family doctor spent 26 minutes providing care. These results provide an additional stimulus to the primary care team to promote the uptake of measles va...

Characterization of the mode of action of a potent dengue virus capsid inhibitor.

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Scaturro, Pietro; Trist, Iuni Margaret Laura; Paul, David; Kumar, Anil; Acosta, Eliana G; Byrd, Chelsea M; Jordan, Robert; Brancale, Andrea; Bartenschlager, Ralf

2014-10-01

Dengue viruses (DV) represent a significant global health burden, with up to 400 million infections every year and around 500,000 infected individuals developing life-threatening disease. In spite of attempts to develop vaccine candidates and antiviral drugs, there is a lack of approved therapeutics for the treatment of DV infection. We have previously reported the identification of ST-148, a small-molecule inhibitor exhibiting broad and potent antiviral activity against DV in vitro and in vivo (C. M. Byrd et al., Antimicrob. Agents Chemother. 57:15-25, 2013, doi:10 .1128/AAC.01429-12). In the present study, we investigated the mode of action of this promising compound by using a combination of biochemical, virological, and imaging-based techniques. We confirmed that ST-148 targets the capsid protein and obtained evidence of bimodal antiviral activity affecting both assembly/release and entry of infectious DV particles. Importantly, by using a robust bioluminescence resonance energy transfer-based assay, we observed an ST-148-dependent increase of capsid self-interaction. These results were corroborated by molecular modeling studies that also revealed a plausible model for compound binding to capsid protein and inhibition by a distinct resistance mutation. These results suggest that ST-148-enhanced capsid protein self-interaction perturbs assembly and disassembly of DV nucleocapsids, probably by inducing structural rigidity. Thus, as previously reported for other enveloped viruses, stabilization of capsid protein structure is an attractive therapeutic concept that also is applicable to flaviviruses. Dengue viruses are arthropod-borne viruses representing a significant global health burden. They infect up to 400 million people and are endemic to subtropical and tropical areas of the world. Currently, there are neither vaccines nor approved therapeutics for the prophylaxis or treatment of DV infections, respectively. This study reports the characterization of the

The impact of declining vaccination coverage on measles control: a ...

African Journals Online (AJOL)

Introduction: Efforts at immunizing children against measles was intensified in Nigeria with nation-wide measles vaccination campaigns in 2005 - 2006, 2008 and 2011 targeting children between 9 and 59 months. However, there were measles outbreaks in 2010 and 2011in Abia state Nigeria. This study seeks to find out if ...

Measles in Italy: Co-circulation of B3 variants during 2014.

Science.gov (United States)

Magurano, Fabio; Baggieri, Melissa; Bordi, Licia; Lalle, Eleonora; Chironna, Maria; Lazzarotto, Tiziana; Amendola, Antonella; Baldanti, Fausto; Ansaldi, Filippo; Filia, Antonietta; Declich, Silvia; Iannazzo, Stefania; Pompa, Maria Grazia; Bucci, Paola; Marchi, Antonella; Nicoletti, Loredana

2016-06-01

In 2013, the majority of the WHO/EUR countries reported an annual incidence of >1 case per one million population indicating that the elimination target is far from being met. Thus, there is the urgent need to uncover and analyze chains of measles virus (MV) transmission with the objective to identify vulnerable groups and avoid possible routes of introduction of MV variants in the European population. The analysis of molecular epidemiology of MV B3 strains identified in 2014 has shown that four different variants co-circulated in Italy, including the strain that caused a cruise-line ship outbreak at the beginning of the year. © 2015 Wiley Periodicals, Inc.

Measles control and elimination in Somalia: the good, the bad, and the ugly.

Science.gov (United States)

Kamadjeu, Raoul; Assegid, Kebede; Naouri, Boubker; Mirza, Imran Raza; Hirsi, Abdurazak; Mohammed, Abdurahman; Omer, Mohammed; Dualle, Abdi Hassan; Mulugeta, Abraham

2011-07-01

Despite enormous challenges, Somalia has been successfully implementing accelerated measles control activities since 2005. Through innovative strategies and with the support of local and international partners, the country has shown potentials of implementing measles mortality reduction activities in complex emergencies. Measles incidence has been reduced by >80% after the measles catch-up campaigns of 2005-2007, and national reported measles routine immunization coverage with first dose measles containing vaccine has reached 59% for the first time in 2009. However, the near collapse of the health care system and the ongoing insecurity continue to hamper the implementation of recommended measles control and elimination strategies in some parts of the country, making these achievements fragile. Somalia exemplifies the challenges in meeting measles elimination goals in the World Health Organization Eastern Mediterranean region. As the region is entering its 2010 measles elimination goals, it appears necessary to establish realistic and flexible interim goals for measles control in Somalia that will take into consideration the specificities of the country. Maintaining flexibility in conducting field operations, securing financial resources, multiplying opportunities for measles vaccination, and improving disease monitoring systems will remain vital to sustain and improve current achievements. © The Author 2011. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved.

The prion protein has RNA binding and chaperoning properties characteristic of nucleocapsid protein NCP7 of HIV-1.

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Gabus, C; Derrington, E; Leblanc, P; Chnaiderman, J; Dormont, D; Swietnicki, W; Morillas, M; Surewicz, W K; Marc, D; Nandi, P; Darlix, J L

2001-06-01

Transmissible spongiform encephalopathies are fatal neurodegenerative diseases associated with the accumulation of a protease-resistant form of the prion protein (PrP). Although PrP is conserved in vertebrates, its function remains to be identified. In vitro PrP binds large nucleic acids causing the formation of nucleoprotein complexes resembling human immunodeficiency virus type 1 (HIV-1) nucleocapsid-RNA complexes and in vivo MuLV replication accelerates the scrapie infectious process, suggesting possible interactions between retroviruses and PrP. Retroviruses, including HIV-1 encode a major nucleic acid binding protein (NC protein) found within the virus where 2000 NC protein molecules coat the dimeric genome. NC is required in virus assembly and infection to chaperone RNA dimerization and packaging and in proviral DNA synthesis by reverse transcriptase (RT). In HIV-1, 5'-leader RNA/NC interactions appear to control these viral processes. This prompted us to compare and contrast the interactions of human and ovine PrP and HIV-1 NCp7 with HIV-1 5'-leader RNA. Results show that PrP has properties characteristic of NCp7 with respect to viral RNA dimerization and proviral DNA synthesis by RT. The NC-like properties of huPrP map to the N-terminal region of huPrP. Interestingly, PrP localizes in the membrane and cytoplasm of PrP-expressing cells. These findings suggest that PrP is a multifunctional protein possibly participating in nucleic acid metabolism.

Quantitative analysis of the interaction between the envelope protein domains and the core protein of human hepatitis B virus

International Nuclear Information System (INIS)

Choi, Kyoung-Jae; Lim, Chun-Woo; Yoon, Moon-Young; Ahn, Byung-Yoon; Yu, Yeon Gyu

2004-01-01

Interaction between preformed nucleocapsids and viral envelope proteins is critical for the assembly of virus particles in infected cells. The pre-S1 and pre-S2 and cytosolic regions of the human hepatitis B virus envelope protein had been implicated in the interaction with the core protein of nucleocapsids. The binding affinities of specific subdomains of the envelope protein to the core protein were quantitatively measured by both ELISA and BIAcore assay. While a marginal binding was detected with the pre-S1 or pre-S2, the core protein showed high affinities to pre-S with apparent dissociation constants (K D app ) of 7.3 ± 0.9 and 8.2 ± 0.4 μM by ELISA and BIAcore assay, respectively. The circular dichroism analysis suggested that conformational change occurs in pre-S through interaction with core protein. These results substantiate the importance of specific envelope domains in virion assembly, and demonstrate that the interaction between viral proteins can be quantitatively measured in vitro

Antigenic determinants and functional domains in core antigen and e antigen from hepatitis B virus

International Nuclear Information System (INIS)

Salfeld, J.; Pfaff, E.; Noah, M.; Schaller, H.

1989-01-01

The precore/core gene of hepatitis B virus directs the synthesis of two polypeptides, the 21-kilodalton subunit (p21c) forming the viral nucleocapsid (serologically defined as core antigen [HBcAg]) and a secreted processed protein (p17e, serologically defined as HBe antigen [HBeAg]). Although most of their primary amino acid sequences are identical, HBcAg and HBeAg display different antigenic properties that are widely used in hepatitis B virus diagnosis. To locate and to characterize the corresponding determinants, segments of the core gene were expressed in Escherichia coli and probed with a panel of polyclonal or monoclonal antibodies in radioimmunoassays or enzyme-linked immunosorbent assays, Western blots, and competition assays. Three distinct major determinants were characterized. It is postulated that HBcAg and HBeAg share common basic three-dimensional structure exposing the common linear determinant HBe1 but that they differ in the presentation of two conformational determinants that are either introduced (HBc) or masked (HBe2) in the assembled core. The simultaneous presentation of HBe1 and HBc, two distinctly different antigenic determinants with overlapping amino acid sequences, is interpreted to indicate the presence of slightly differently folded, stable conformational states of p21c in the hepatitis virus nucleocapsid

Porcine Reproductive and Respiratory Syndrome Virus Nucleocapsid Protein Interacts with Nsp9 and Cellular DHX9 To Regulate Viral RNA Synthesis.

Science.gov (United States)

Liu, Long; Tian, Jiao; Nan, Hao; Tian, Mengmeng; Li, Yuan; Xu, Xiaodong; Huang, Baicheng; Zhou, Enmin; Hiscox, Julian A; Chen, Hongying

2016-06-01

Porcine reproductive and respiratory syndrome virus (PRRSV) nucleocapsid (N) protein is the main component of the viral capsid to encapsulate viral RNA, and it is also a multifunctional protein involved in the regulation of host cell processes. Nonstructural protein 9 (Nsp9) is the RNA-dependent RNA polymerase that plays a critical role in viral RNA transcription and replication. In this study, we demonstrate that PRRSV N protein is bound to Nsp9 by protein-protein interaction and that the contacting surface on Nsp9 is located in the two predicted α-helixes formed by 48 residues at the C-terminal end of the protein. Mutagenesis analyses identified E646, E608, and E611 on Nsp9 and Q85 on the N protein as the pivotal residues participating in the N-Nsp9 interaction. By overexpressing the N protein binding fragment of Nsp9 in infected Marc-145 cells, the synthesis of viral RNAs, as well as the production of infectious progeny viruses, was dramatically inhibited, suggesting that Nsp9-N protein association is involved in the process of viral RNA production. In addition, we show that PRRSV N interacts with cellular RNA helicase DHX9 and redistributes the protein into the cytoplasm. Knockdown of DHX9 increased the ratio of short subgenomic mRNAs (sgmRNAs); in contrast, DHX9 overexpression benefited the synthesis of longer sgmRNAs and the viral genomic RNA (gRNA). These results imply that DHX9 is recruited by the N protein in PRRSV infection to regulate viral RNA synthesis. We postulate that N and DHX9 may act as antiattenuation factors for the continuous elongation of nascent transcript during negative-strand RNA synthesis. It is unclear whether the N protein of PRRSV is involved in regulation of the viral RNA production process. In this report, we demonstrate that the N protein of the arterivirus PRRSV participates in viral RNA replication and transcription through interacting with Nsp9 and its RdRp and recruiting cellular RNA helicase to promote the production of

Mokola virus infection : description of recent South African cases and a review of the virus epidemiology : case report

Directory of Open Access Journals (Sweden)

B.F. Von Teichman

1998-07-01

Full Text Available Five cases of Mokola virus, a lyssavirus related to rabies, are described. The cases occurred in cats from the East London, Pinetown and Pietermaritzburg areas of South Africa from February 1996 to February 1998. Each of the cats was suspected of being rabid and their brains were submitted for laboratory confirmation. Four of the cases were positive, but with atypical fluorescence, and 1 was negative. Mokola virus infection was identified by anti-lyssavirus nucleocapsid monoclonal antibody typing. As in rabies cases, the predominant clinical signs were of unusual behaviour. Aggression was present, but only during handling. Four of the 5 cats had been vaccinated for rabies, which is consistent with other studies that show that rabies vaccination does not appear to protect against Mokola virus. Since Mokola may be confused with rabies, the incidence of Mokola virus may be more common in Africa than is currently reported. As human infections may be fatal, the emergence of this virus is a potential threat to public health.

Conformational analysis of the partially disordered measles virus N(TAIL)-XD complex by SDSL EPR spectroscopy.

Science.gov (United States)

Kavalenka, Aleh; Urbancic, Iztok; Belle, Valérie; Rouger, Sabrina; Costanzo, Stéphanie; Kure, Sandra; Fournel, André; Longhi, Sonia; Guigliarelli, Bruno; Strancar, Janez

2010-03-17

To characterize the structure of dynamic protein systems, such as partly disordered protein complexes, we propose a novel approach that relies on a combination of site-directed spin-labeled electron paramagnetic resonance spectroscopy and modeling of local rotation conformational spaces. We applied this approach to the intrinsically disordered C-terminal domain of the measles virus nucleoprotein (N(TAIL)) both free and in complex with the X domain (XD, aa 459-507) of the viral phosphoprotein. By comparing measured and modeled temperature-dependent restrictions of the side-chain conformational spaces of 12 SL cysteine-substituted N(TAIL) variants, we showed that the 490-500 region of N(TAIL) is prestructured in the absence of the partner, and were able to quantitatively estimate, for the first time to our knowledge, the extent of the alpha-helical sampling of the free form. In addition, we showed that the 505-525 region of N(TAIL) conserves a significant degree of freedom even in the bound form. The latter two findings provide a mechanistic explanation for the reported rather high affinity of the N(TAIL)-XD binding reaction. Due to the nanosecond timescale of X-band EPR spectroscopy, we were also able to monitor the disordering in the 488-525 region of N(TAIL), in particular the unfolding of the alpha-helical region when the temperature was increased from 281 K to 310 K. Copyright 2010 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Development and evaluation of a blocking enzyme-linked immunosorbent assay and virus neutralization assay to detect antibodies to viral hemorrhagic septicemia virus

Science.gov (United States)

Wilson, Anna; Goldberg, Tony; Marcquenski, Susan; Olson, Wendy; Goetz, Frederick; Hershberger, Paul; Hart, Lucas M.; Toohey-Kurth, Kathy

2014-01-01

Viral hemorrhagic septicemia virus (VHSV) is a target of surveillance by many state and federal agencies in the United States. Currently, the detection of VHSV relies on virus isolation, which is lethal to fish and indicates only the current infection status. A serological method is required to ascertain prior exposure. Here, we report two serologic tests for VHSV that are nonlethal, rapid, and species independent, a virus neutralization (VN) assay and a blocking enzyme-linked immunosorbent assay (ELISA). The results show that the VN assay had a specificity of 100% and sensitivity of 42.9%; the anti-nucleocapsid-blocking ELISA detected nonneutralizing VHSV antibodies at a specificity of 88.2% and a sensitivity of 96.4%. The VN assay and ELISA are valuable tools for assessing exposure to VHSV.

Available studies fail to provide strong evidence of increased risk of diarrhea mortality due to measles in the period 4-26 weeks after measles rash onset.

Science.gov (United States)

Jackson, Bianca D; Black, Robert E

2017-11-07

Measles vaccination effectiveness studies showed dramatic decreases in all-cause mortality in excess of what would be expected from the prevention of measles disease alone. This invited speculation that measles infection may increase the risk of diarrhea morbidity and mortality subsequent to the acute phase of the disease. The aim of the present systematic review is to summarize the existing evidence in the publically available literature pertaining to the putative causal link between measles and diarrhea in the period 4-26 weeks following measles rash onset. We searched the PubMed, Embase, Open Grey and Grey Literature Report databases for relevant literature using broad search terms. Prospective, retrospective and case-control studies in low- and middle-income countries involving children under five wherein relevant evidence were presented were included. Data were extracted from the articles and summarized. Fifty abstracts retrieved through the database searches met the initial screening criteria. Twelve additional documents were identified by review of the references of the documents found in the initial searches. Six documents representing five unique studies that presented evidence relevant to the research question were found. Four of the included studies took place in Bangladesh. One of the included studies took place in Sudan. Some measles vaccine effectiveness studies show lower diarrhea morbidity and mortality among the vaccinated. However, children who received vaccine may have differed in important ways from children who did not, such as health service utilization. Additionally, cohort studies following unvaccinated children showed no difference in diarrhea morbidity and mortality between cases and controls more than 4 weeks after measles rash onset. One study showed some evidence that severe measles may predispose children to gastroenteritis, but was not able to show a corresponding increase in the risk of diarrhea mortality. The available evidence

NuMA and nuclear lamins are cleaved during viral infection - inhibition of caspase activity prevents cleavage and rescues HeLa cells from measles virus-induced but not from rhinovirus 1B-induced cell death

International Nuclear Information System (INIS)

Taimen, Pekka; Berghaell, Heidi; Vainionpaeae, Raija; Kallajoki, Markku

2004-01-01

Nuclear matrix is a structural framework of important nuclear processes. We studied the effect of two different types of viral infections on nuclear matrix. HeLa cells were infected with human rhinovirus 1B (HRV 1B) or measles virus (MV), and Nuclear Mitotic Apparatus protein (NuMA) and lamins A/C and B were used as markers for internal nuclear matrix and peripheral nuclear lamina, respectively. We show that NuMA, lamins, and poly(ADP-ribose) polymerase-1 are cleaved during viral infection in a virus family-specific manner suggesting that these viruses activate different sets of proteases. Morphologically, NuMA was excluded from the condensed chromatin, lamins showed a folded distribution, and both proteins finally remained around the nuclear fragments. A general caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (z-VAD-FMK) prevented the nuclear disintegration and the cleavage of the proteins studied. Interestingly, z-VAD-FMK rescued MV-infected but not HRV 1B-infected cells from cell death. These results show for the first time that NuMA and lamins are specific target proteins during virus-induced programmed cell death

The reduction of measles transmission during school vacations.

NARCIS (Netherlands)

Klinkenberg, Don; Hahné, Susan Jm; Woudenberg, Tom; Wallinga, Jacco

2018-01-01

Historically, measles incidence has shown clear seasonal patterns driven by the school calendar, but since the start of mass vaccination in developed countries there are only occasional outbreaks, which may have changed the effect of school vacations on transmission. In 2013-2014 a large measles

Assessment of coverage levels of single dose measles vaccine

International Nuclear Information System (INIS)

Tariq, P.

2003-01-01

Objective: To study the consequences of low coverage levels of a single dose of measles vaccine. Results: mean age observed in measles cases was 2 years and 8 months with a range from 3 months to 8 years. Maximum number of cases reported were <1 year of age (n=22,32%). Fifty percent of cases were seen among vaccinated children. Seventy-five percent (n=51) had history of contact with a measles case. Pneumonia was the commonest complication followed by acute gastroenteritis, encephalitis, febrile convulsions, oral ulcers, oral thrush, eye changes of vitamin-A deficiency and pulmonary tuberculosis (T.B.) in descending order of frequency. Fifty four cases were successfully treated for complications of measles and discharged. Nine cases left against medical advice. Five patients died all of them had encephalitis either alone (n=1) or in combination with pneumonia and acute gastroenteritis (n=4). Conclusion: There is a dire need to increase the immunization coverage to reduce the rate of vaccine failure and achieve effective control of measles.(author)