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Genetic divergence of hepatitis C virus: the role of HIV-related immunosuppression.

ABSTRACT: BACKGROUND:We tested the hypothesis that HIV-related immunosuppression alters the host-hepatitis C virus (HCV) interaction, resulting in fewer amino acid-changing substitutions in HCV viral variants. Higher HCV RNA levels in persons coinfected with HIV compared with HCV infection alone suggest increased viral replication. If this increase is dependent on decreased immune selective pressure, then a reduced rate of nucleotide changes resulting in amino acid replacements (nonsynonymous changes, dN) would be expected. METHODS:We investigated HCV envelope sequences over time in 79 persons with chronic HCV infection who were HIV negative (group 1) or HIV positive with (group 3) or without (group 2) severe immunodeficiency. We amplified a 1026-nt region of the HCV genome, which encodes a portion of the envelope glycoproteins E1 and E2, including hypervariable region-1 for direct sequence analysis. RESULTS:The overall divergence between paired sequences, dS, dN, and dN/dS, all showed no significant differences among the 3 groups. CONCLUSIONS:By measuring nucleotide substitutions in HCV sequences over time, we found no significant differences in the genetic divergence between HCV-monoinfected control subjects and HIV/HCV-coinfected subjects with various levels of immunodeficiency as measured by CD4+ T-cell counts.

SUBMITTER: Netski DM

PROVIDER: S-EPMC3071283 | biostudies-literature | 2008 Oct

REPOSITORIES: biostudies-literature

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Genetic divergence of hepatitis C virus: the role of HIV-related immunosuppression.

Netski Dale M DM Mao Qing Q Ray Stuart C SC Klein Robert S RS

Journal of acquired immune deficiency syndromes (1999) 20081001 2

<h4>Background</h4>We tested the hypothesis that HIV-related immunosuppression alters the host-hepatitis C virus (HCV) interaction, resulting in fewer amino acid-changing substitutions in HCV viral variants. Higher HCV RNA levels in persons coinfected with HIV compared with HCV infection alone suggest increased viral replication. If this increase is dependent on decreased immune selective pressure, then a reduced rate of nucleotide changes resulting in amino acid replacements (nonsynonymous chan ...[more]

PMID: 18769357

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Project description:OBJECTIVE:To estimate the risk of cervical intraepithelial neoplasia grade 2, 2-3, 3, adenocarcinoma in situ, or cancer (CIN 2 or worse) among women with human immunodeficiency virus (HIV)- and non-HIV-associated immunosuppression. METHODS:We performed a case-control study of 20,146 women with incident CIN 2 or worse and 5:1 age-matched, incidence-density selected women in a control group (n=100,144) enrolled in an integrated health care system from 1996 to 2014. Adjusted rate ratios (RRs) from conditional logistic regression were obtained for HIV status (stratified by CD4 T-cells), solid organ transplant history, and immunosuppressive medication use. RESULTS:Risk of CIN 2 or worse was increased among women with HIV (n=36 women in the case group and 79 women in the control group; adjusted RR 2.0, 95% CI 1.3-3.0) compared with those without HIV and in solid organ transplant recipients (n=51 women in the case group and 68 women in the control group; RR 3.3, 95% CI 2.3-4.8) compared with women without a prior transplant. The highest risks were among women with HIV and less than 200 CD4 T-cells/microliter (n=9 women in the case group and eight women in the control group; RR 5.6, 95% CI 2.1-14.7) compared with those without HIV and in solid organ transplant recipients prescribed three or greater immunosuppressive medication classes (n=32 women in the case group and 33 women in the control group; RR 4.1, 95% CI 2.5-6.8) compared with women without a prior transplant and zero medication classes. No increased risks were observed for women with HIV and 500 or greater CD4 T-cells/microliter (n=9 women in the case group and 43 women in the control group; RR 0.8, 95% CI 0.4-1.7) compared with those without HIV or women without prior solid organ transplantation prescribed two or fewer immunosuppressive medication classes (n=1,262 women in the case group and 6,100 women in the control group; RR 0.95, 95% CI 0.89-1.01) compared with women without and a prior transplant and zero medication classes. CONCLUSION:Risk of CIN 2 or worse is increased in women with a prior solid organ transplant or who have HIV and CD4 cells/microliter less than 500 but not in women with HIV and higher CD4 levels or in women without a prior solid organ transplant but who are prescribed only one or two immunosuppressive medication classes.

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Genetic divergence of hepatitis C virus: the role of HIV-related immunosuppression.

Publications

Genetic divergence of hepatitis C virus: the role of HIV-related immunosuppression.

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