TY - JOUR
T1 - Genetic divergence of hepatitis C virus
T2 - The role of HIV-related immunosuppression
AU - Netski, Dale M.
AU - Mao, Qing
AU - Ray, Stuart C.
AU - Klein, Robert S.
PY - 2008/10
Y1 - 2008/10
N2 - 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, d N) 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 El and E2, including hypervariable region-1 for direct sequence analysis. Results: The overall divergence between paired sequences, d s, d N, and d N/d s, 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.
AB - 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, d N) 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 El and E2, including hypervariable region-1 for direct sequence analysis. Results: The overall divergence between paired sequences, d s, d N, and d N/d s, 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.
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U2 - 10.1097/QAI.0b013e3181869a6f
DO - 10.1097/QAI.0b013e3181869a6f
M3 - Article
C2 - 18769357
AN - SCOPUS:55249106625
SN - 1525-4135
VL - 49
SP - 136
EP - 141
JO - Journal of Acquired Immune Deficiency Syndromes
JF - Journal of Acquired Immune Deficiency Syndromes
IS - 2
ER -