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Journal of Virology, April 2001, p. 3259-3267, Vol. 75, No. 7
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

Qing Mao,1,2 Stuart C. Ray,1 Oliver Laeyendecker,1 John R. Ticehurst,3,4 Steffanie A. Strathdee,5 David Vlahov,5 and David L. Thomas1,5,*

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.

* 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.

Journal of Virology, April 2001, p. 3259-3267, Vol. 75, No. 7
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.7.3259-3267.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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