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Journal of Virology, April 2001, p. 3259-3267, Vol. 75, No. 7
Departments of
Medicine,1
Pathology,3 and
Epidemiology,5 Johns Hopkins
Medical Institutions, Baltimore, and Center for Devices and
Radiological Health, Food and Drug Administration,
Rockville,4 Maryland, and Southwest
Hospital, Third Military Medical University, Chongqing, Peoples'
Republic of China2
Received 14 September 2000/Accepted 4 January 2001
When chronic hepatitis C virus (HCV) infections are complicated by
acquisition of human immunodeficiency virus (HIV), liver disease
appears to accelerate and serum levels of HCV RNA may rise. We
hypothesized that HIV might affect the HCV quasispecies by decreasing
both complexity (if HIV-induced immunosuppression lessens pressure for
selecting HCV substitutions) and the ratio of nonsynonymous
(dN) to synonymous (dS)
substitutions, because dN may be lower (if
there is less selective pressure). To test this hypothesis, we studied
the evolution of HCV sequences in 10 persons with chronic HCV infection
who seroconverted to HIV and, over the next 3 years, had slow or rapid
progression of HIV-associated disease. From each subject, four serum
specimens were selected with reference to HIV seroconversion: (i) more
than 2 years prior, (ii) less than 2 years prior, (iii) less than 2 years after, and (iv) more than 2 years after. The HCV quasispecies in
these specimens was characterized by generating clones containing 1 kb
of cDNA that spanned the E1 gene and the E2 hypervariable region 1 (HVR1), followed by analysis of clonal frequencies (via electrophoretic migration) and nucleotide sequences. We examined 1,320 cDNA clones (33 per time point) and 287 sequences (median of 7 per time point). We
observed a trend toward lower dN/dS
after HIV seroconversion in 7 of 10 subjects and lower
dN/dS in those with rapid HIV
disease progression. However, the magnitude of these differences was
small. These results are consistent with the hypothesis that HIV
infection alters the HCV quasispecies, but the number of subjects and
observation time may be too low to characterize the full effect.
0022-538X/01/$04.00+0 DOI: 10.1128/JVI.75.7.3259-3267.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
Human Immunodeficiency Virus Seroconversion and
Evolution of the Hepatitis C Virus Quasispecies
*
Corresponding author. Mailing address: 1147 Ross Bldg.,
720 Rutland Ave., Baltimore, MD 21205. Phone: (410) 955-0349. Fax: (410) 614-7564. E-mail: dthomas{at}jhmi.edu.
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