Trends for genetic variation of Hepatitis C Virus quasispecies in Human Immunodeficiency virus-1 coinfected patients

Abstract

Chronic infection by Hepatitis C Virus (HCV) causes liver fibrosis, which is accelerated by unknown mechanisms in patients with HIV-1 coinfection. The evolution of HCV quasispecies in this setting of coinfection is not fully understood. To compare HCV quasispecies between HIV-HCV coinfection and HCV monoinfection, we sequenced 340 HCV clones from the HVR-1 and NS3 regions at two different time points in two groups of treatment-naïve patients with HCV-1a infection: (1) HIV-HCV positive (n=6); and (2) HIV negative-HCV positive (n=3). In HCV/HIV coinfection, we found a trend for reduced HCV genetic complexity and diversity, and a trend towards reduced dN/dS ratios in the HVR-1 region, especially in those patients with CD4<200cells/mm(3), who lost positive selective immune pressure in the HVR-1 region. Differences in immune regulation of HCV quasispecies in HIV coinfected individuals deserve further exploration to clarify the different outcomes of chronic hepatitis C noted between the immunocompromised and the immunocompetent host.

Figure 1. HCV HVR-1 and NS3 phylogenetic analyses

Panel (a): Neighbour-Joining phylogenetic tree obtained with all HCV HVR-1 sequences from the study subjects at the two time points. (Left) Viral isolates from patient group 1 (HIV-HCV coinfected). Branches corresponding to isolates from patient group 2 are shown collapsed for clarity. (Right) Viral isolates from patient group 2 (HIV negative). Branches corresponding to isolates from patient group 1 are shown collapsed for clarity. Panel (b): Neighbour-Joining phylogenetic tree obtained with all HCV NS3 sequences from the study subjects at the two time points. (Left) Viral isolates from patient group 1 (HIV-HCV coinfected). Branches corresponding to isolates from patient group 2 are shown collapsed for clarity. (Right) Viral isolates from patient group 2 (HIV negative). Branches corresponding to isolates from patient group 1 are shown collapsed for clarity. NOTE: Symbols: empty squares: HCV-HIV CD4<200 T0; filled squares: HCV-HIV CD4<200 T1; empty diamonds: HCV-HIV CD4>200 T0; filled diamonds: HCV-HIV CD4>200 T1; empty circles: HCV monoinfection T0; filled circles: HCV monoinfection T1; grey boxes: newly emerged variants after one-year follow-up, with bootstrap values >50 (indicated in the corresponding branches). HCV variants with bootstrap support >50% were considered divergent because the phylogenetic signal in the HCV genomic regions sequenced was relatively low.

Figure 1. HCV HVR-1 and NS3 phylogenetic analyses

Panel (a): Neighbour-Joining phylogenetic tree obtained with all HCV HVR-1 sequences from the study subjects at the two time points. (Left) Viral isolates from patient group 1 (HIV-HCV coinfected). Branches corresponding to isolates from patient group 2 are shown collapsed for clarity. (Right) Viral isolates from patient group 2 (HIV negative). Branches corresponding to isolates from patient group 1 are shown collapsed for clarity. Panel (b): Neighbour-Joining phylogenetic tree obtained with all HCV NS3 sequences from the study subjects at the two time points. (Left) Viral isolates from patient group 1 (HIV-HCV coinfected). Branches corresponding to isolates from patient group 2 are shown collapsed for clarity. (Right) Viral isolates from patient group 2 (HIV negative). Branches corresponding to isolates from patient group 1 are shown collapsed for clarity. NOTE: Symbols: empty squares: HCV-HIV CD4<200 T0; filled squares: HCV-HIV CD4<200 T1; empty diamonds: HCV-HIV CD4>200 T0; filled diamonds: HCV-HIV CD4>200 T1; empty circles: HCV monoinfection T0; filled circles: HCV monoinfection T1; grey boxes: newly emerged variants after one-year follow-up, with bootstrap values >50 (indicated in the corresponding branches). HCV variants with bootstrap support >50% were considered divergent because the phylogenetic signal in the HCV genomic regions sequenced was relatively low.