Genetic divergence of hepatitis C virus: the role of HIV-related immunosuppression.
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.
Netski
Dale M
DM
Department of Medicine, Johns Hopkins Medical Institutions, 855 N. Wolfe Street, Baltimore, MD 21205, USA.
Mao
Qing
Q
Ray
Stuart C
SC
Klein
Robert S
RS