Molecular epidemiology of hepatitis C virus infection amongst intravenous drug users in rural communities

Majid, Ayaz; R, Holmes; Desselberger, Ulrich; Simmonds, Peter; Mckee, Thomas Alexander

doi:10.1002/jmv.1890460111

Cited by 34 publications

(23 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…1. The excess of clusters of genotype 1 is in accordance with the prevalence of HCV genotypes in the United Kingdom (21,25,44). The only exception was recipient 2 of cluster 3, whose genotype differed from the implicated donor and the other recipient in the cluster.…”

Section: Discussionsupporting

confidence: 56%

Evolutionary Rate and Genetic Drift of Hepatitis C Virus Are Not Correlated with the Host Immune Response: Studies of Infected Donor-Recipient Clusters

Allain¹,

Dong²,

Vandamme

et al. 2000

J Virol

View full text Add to dashboard Cite

Six donor-recipient clusters of hepatitis C virus (HCV)-infected individuals were studied. For five clusters the period of infection of the donor could be estimated, and for all six clusters the time of infection of the recipients from the donor via blood transfusion was also precisely known. Detailed phylogenetic analyses were carried out to investigate the genomic evolution of the viral quasispecies within infected individuals in each cluster. The molecular clock analysis showed that HCV quasispecies within a patient are evolving at the same rate and that donors that have been infected for longer time tend to have a lower evolutionary rate. Phylogenetic analysis based on the split decomposition method revealed different evolutionary patterns in different donor-recipient clusters. Reactivity of antibody against the first hypervariable region (HVR1) of HCV in donor and recipient sera was evaluated and correlated to the calculated evolutionary rate. Results indicate that anti-HVR1 reactivity was related more to the overall level of humoral immune response of the host than to the HVR1 sequence itself, suggesting that the particular sequence of the HVR1 peptides is not the determinant of reactivity. Moreover, no correlation was found between the evolutionary rate or the heterogeneity of the viral quasispecies in the patients and the strength of the immune response to HVR1 epitopes. Rather, the results seem to imply that genetic drift is less dependent on immune pressure than on the rate of evolution and that the genetic drift of HCV is independent of the host immune pressure.Hepatitis C virus (HCV) causes persistent infection in a majority of infected individuals. Among the possible mechanisms explaining persistence are the relatively poor immunogenicity of the virus, particularly of the envelope glycoproteins; the low level of viremia outside the preseroconversion period; and the considerable variability of the viral genome, leading to substantial changes in the viral epitopes over time in the same individual (22,36). One of the main contributors to these genomic changes is the hypervariable region 1 (HVR1) located at the N terminus of the major envelope glycoprotein E2. Mutations in HVR1, which is critical for virus interaction with target cells (34, 48), produce escape mutants, a likely contributing factor to viral persistence (24,38,46).The host of HCV, primate or human, seems in most cases unable to generate an effective immune response, whether humoral, as levels of antibody to the E2 protein or HVR1 are typically low or undetectable, or cellular, as no evidence of a specific T-cell response to E2 epitopes has been provided (3,16,17,37). This feature was supported by data collected in vivo indicating that neither natural defenses nor passive immunotherapy was able to prevent reinfection of a chronically infected patient or animal with the same or related viruses (7,30).Some studies of HCV evolution over time, in the same infected individual or in different individuals infected with the same viral quasispecies...

show abstract

Section: Discussionsupporting

confidence: 56%

Evolutionary Rate and Genetic Drift of Hepatitis C Virus Are Not Correlated with the Host Immune Response: Studies of Infected Donor-Recipient Clusters

Allain¹,

Dong²,

Vandamme

et al. 2000

J Virol

View full text Add to dashboard Cite

show abstract

“…Such data would indicate that VSV-expressed HCV glycoproteins may generate humoral responses that could be effective at preventing bona fide HCV infection, at least against similar genotypes. Furthermore, our findings that VSV-induced anti-HCV E2 antibodies were cross-reactive between genotypes 1a and 1b is encouraging for vaccine purposes, since these genotypes are the most prevalent worldwide (45). Interestingly, nonpropagating VSV⌬G-C/E1/E2 was found to stimulate humoral and cellular immune responses in mice that were comparable to those of live VSV-C/E1/E2 without the prerequisite for adjuvant enhancement.…”

Section: Discussionmentioning

confidence: 58%

“…Major sources of transmission include infected blood transfusions or intravenous drug abuse, but lower-risk exposures follow vertical, sexual, and occupational exposure to blood (35,45,49). Screening measures with improved diagnostic technologies have lowered the risks of contaminated blood transmission, but annual estimates suggest that 100,000 new infections still occur in the United States alone due to the seronegative "window" period of HCV infection (47).…”

mentioning

confidence: 99%

Evaluating Replication-Defective Vesicular Stomatitis Virus as a Vaccine Vehicle

Majid

Ezelle

et al. 2006

J Virol

View full text Add to dashboard Cite

We have generated replication-competent (VSV-C/E1/E2) and nonpropagating (VSV⌬G-C/E1/E2) vesicular stomatitis virus (VSV) contiguously expressing the structural proteins of hepatitis C virus (HCV; core [C] and glycoproteins E1 and E2) and report on their immunogenicity in murine models. VSV-C/E1/E2 and VSV⌬G-C/E1/E2 expressed high levels of HCV C, E1, and E2, which were authentically posttranslationally processed. Both VSV-expressed HCV E1-E2 glycoproteins were found to form noncovalently linked heterodimers and appeared to be correctly folded, as confirmed by coimmunoprecipitation analysis using conformationally sensitive anti-HCV-E2 monoclonal antibodies (MAbs). Intravenous or intraperitoneal immunization of BALB/c mice with VSV-C/E1/E2 or VSV⌬G-C/E1/E2 resulted in significant and surprisingly comparable HCV core or E2 antibody responses compared to those of control mice. In addition, both virus types generated HCV C-, E1-, or E2-specific gamma interferon (IFN-␥)-producing CD8 ؉ T cells, as determined by enzyme-linked immunospot (ELISPOT) analysis. Mice immunized with VSV⌬G-C/E1/E2 were also protected against the formation of tumors expressing HCV E2 (CT26-hghE2t) and exhibited CT26-hghE2t-specific IFN-␥-producing and E2-specific CD8 ؉ T-cell activity. Finally, recombinant vaccinia virus (vvHCV.S) expressing the HCV structural proteins replicated at significantly lower levels when inoculated into mice immunized with VSV-C/E1/E2 or VSV⌬G-C/E1/E2, but not with control viruses. Our data therefore illustrate that potentially safer replication-defective VSV can be successfully engineered to express high levels of antigenically authentic HCV glycoproteins. In addition, this strategy may therefore serve in effective vaccine and immunotherapy-based approaches to the treatment of HCV-related disease.

show abstract

“…O uso de drogas intravenosas é um importante fator de risco para a aquisição do VHC 5 , assim como a utilização do canudinho, já que a principal via de transmissão do VHC é a parenteral. O mais provável, portanto, é que este paciente tenha se infectado neste período.…”

unclassified

Detecção do genótipo 4 do vírus da hepatite C em Salvador, BA

Zarife

Oliveira²,

Romeu³

et al. 2006

Rev. Soc. Bras. Med. Trop.

View full text Add to dashboard Cite

2 RESUMOÉ descrito o primeiro caso de detecção do genótipo 4 do vírus da hepatite C (VHC) em Salvador, BA. Foram utilizados os testes de RT-PCR para detecção do VHC-RNA, e o LIPA para genotipagem. O genótipo 4 responde mal ao tratamento, sendo portanto importante a busca ativa dos contactantes. Palavras-chaves: Vírus da hepatite C. VHC-RNA. Genotipagem. ABSTRACTThe first detected case of genotype 4 of the hepatitis C virus (HCV) in Salvador, Bahia, is described. RT-PCR tests were used to detect HCV-RNA, and LIPA was used for genotyping. Genotype 4 responds poorly to treatment, and it is therefore important to actively search for people who have been in contact with it. Key-words: Hepatitis C virus. HCV-RNA. Genotyping.

show abstract

Molecular epidemiology of hepatitis C virus infection amongst intravenous drug users in rural communities

Cited by 34 publications

References 29 publications

Evolutionary Rate and Genetic Drift of Hepatitis C Virus Are Not Correlated with the Host Immune Response: Studies of Infected Donor-Recipient Clusters

Evolutionary Rate and Genetic Drift of Hepatitis C Virus Are Not Correlated with the Host Immune Response: Studies of Infected Donor-Recipient Clusters

Evaluating Replication-Defective Vesicular Stomatitis Virus as a Vaccine Vehicle

Detecção do genótipo 4 do vírus da hepatite C em Salvador, BA

Contact Info

Product

Resources

About