Effect of immunosuppression on composition of quasispecies population of hepatitis C virus in patients with chronic hepatitis C coinfected with human immunodeficiency virus.
OBJECTIVE
To study the effects of the immunosuppression caused by the reduction of CD4 activity on the composition of hepatitis C virus (HCV) populations, we analyzed the number of HCV quasispecies clones and the nucleotide diversity of the hypervariable region 1 (HVR1) of HCV in 37 patients with hemophilia with persistent HCV infection, with or without human immunodeficiency virus (HIV).


METHODS
The numbers of HCV quasispecies clones were measured by fluorescence single-strand conformation polymorphism analysis. Direct sequencing was used to analyze the degree of diversity of HVR1. We compared these values according to coinfection with HIV, and CD4 counts of patients.


RESULTS
There were no differences in either the number of HCV clones or the diversity between patients with and without HIV coinfection. In HIV coinfected patients the diversity decreased in association with the decrease in CD4 count while the number of HCV clones did not. The diversity of HVR1 was 3.64 +/- 5.03% in patients with a CD4 count < 50/microliters and 14.92 +/- 6.03% in patients with a CD4 count > or = 50/microliters; it was significantly lower in the former (p = 0.0002).


CONCLUSIONS
A severe reduction in the CD4 count, which is considered to cause a decline in the activity of helper T-lymphocytes, induced changes in the composition of HCV populations; one or a few quasispecies clones are predominant in the HCV population in the serum of individual patients.
Toyoda
H
H
Second Department of Internal Medicine, Nagoya University School of Medicine, Japan.
Fukuda
Y
Y
Koyama
Y
Y
Takamatsu
J
J
Saito
H
H
Hayakawa
T
T
D000328:Adult; D015704:CD4 Antigens / Q000032:analysis; D002908:Chronic Disease; D005260:Female; D014644:Genetic Variation; D015658:HIV Infections / Q000150:complications* / Q000276:immunology* / Q000821:virology; D016174:Hepacivirus / Q000235:genetics*; D006526:Hepatitis C / Q000150:complications* / Q000821:virology*; D006801:Humans; D007108:Immune Tolerance; D008297:Male; D009994:Osmolar Concentration; D018807:Polymorphism, Single-Stranded Conformational; D012367:RNA, Viral / Q000032:analysis
D015704:CD4 Antigens; D012367:RNA, Viral