One
of the challenging features of the hepatitis C virus
(HCV) is its rapid mutation rate, which helps it to escape immune system detection
and enables it to quickly develop resistance to targeted antiviral
drugs.
Some investigators have suggested that HIV-related immune suppression
may alter interactions between the host and HCV, resulting in fewer amino acid
substitutions in HCV viral variants. A group of researchers from Johns Hopkins
University and Montefiore Medical Center tested this hypothesis in a study published
September 2, 2008 in the online edition of the Journal of Acquired Immune Deficiency
Syndromes.
Higher HCV RNA levels in HIV-HCV
coinfected individuals compared to those with HCV
infection alone suggest increased viral replication, the authors noted as
background. If this increase is dependent on decreased selective pressure from
a weakened immune system, then a reduced rate of viral nucleotide changes would
be expected.
The study authors analyzed HCV envelope sequences over time
from 79 chronic hepatitis C patients who were HIV negative, HIV positive without
advanced disease, or HIV positive with severe
immune deficiency.
They amplified and performed direct sequence analysis
on a 1026-nt region of the HCV genome, which encodes a portion of the envelope
glycoproteins E1 and E2, including hypervariable region-1.
They found
that the overall divergence between the paired sequences dS, dN, and dN/dS all
showed no significant differences among the 3 groups. There was no observed difference
between HIV positive and HIV negative individuals, nor between HIV positive patients
with minimal or severe immune deficiency.
"By measuring nucleotide
substitutions in HCV sequences over time," the study authors concluded, "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."
Departments of Medicine and
Oncology, Johns Hopkins Medical Institutions, Baltimore, MD; Departments of Medicine
and Epidemiology & Population Health, Montefiore Medical Center, Albert Einstein
College of Medicine, Bronx, NY.
9/19/08
Reference
DM
Netski, Q Mao, SC Ray, and others. Genetic divergence of hepatitis C virus: the
role of HIV-related immunosuppression. Journal of Acquired Immune Deficiency Syndromes.
September 2, 2008 [Epub ahead of print].
(Abstract).
