Analysis of a non‐structural gene reveals evidence of possible hepatitis C virus (HCV) compartmentalization

Abstract

Viral diversity is a hallmark of hepatitis C virus (HCV) infection; however, only limited data are available regarding HCV variability in extrahepatic sites, and none have systematically compared diversity in non-structural and structural genomic regions. Therefore, HCV diversity in the NS5B and envelope 1 (E1) hypervariable region 1 (HVR1) genes was evaluated in matched sera and peripheral blood mononuclear cells (PBMCs) obtained from 13 HCV-infected women. Multiple clonal sequences were compared to evaluate quasispecies diversity and viral compartmentalization in PBMCs. Genetic distances were higher for E1/HVR1 compared to NS5B in both the sera and PBMCs (p = 0.0511 and p = 0.0284). Genetic distances were higher in serum NS5B compared to PBMC NS5B (p = 0.0003); however, they were not different when comparing E1/HVR1 in sera to PBMCs. By phylogenetic analysis of NS5B, evidence of possible PBMC compartmentalization was observed for 1 woman, while statistical methods were consistent with PBMC compartmentalization for 6 women. Evidence of compartmentalization within a non-structural genomic region may suggest that viral adaptation to a unique extracellular microenvironment(s) may be required for efficient replication and could contribute to HCV persistence.

Hepatitis B virus full‐length genomic mutations and quasispecies in hepatocellular carcinoma

“…The distinct quasispecies characteristics between tumor and non‐tumor tissues further indicate the existence of compartmentalization, which was confirmed by using both phylogenetic analysis and correlation coefficient tests. Different principle for assessing compartmentalization is responsible for the disparity between phylogenetic and statistical analyses, and such disparity has also been noted in previous HCV and HIV studies in which multiple methods have been utilized to detect compartmentalization . Similarly, in the present study, we provided a reliable assessment of viral compartmentalization by utilizing two complementary strategies.…”

“…Different principle for assessing compartmentalization is responsible for the disparity between phylogenetic and statistical analyses, and such disparity has also been noted in previous HCV and HIV studies in which multiple methods have been utilized to detect compartmentalization. 22,23 Similarly, in the present study, we provided a reliable assessment of viral compartmentalization by utilizing two complementary strategies. The compartmentalization of viral quasispecies reflects the interaction between viral population and microenvironment from host.…”

Evidence of distinct populations of hepatitis C virus in the liver and plasma of patients co‐infected with HIV and HCV

“…Similarly, NS5B variability impacts HCV RNA levels and treatment outcome in vivo [Lohmann et al, ; Lévêque and Wang, ; Hamano et al, ; Itakura et al, ; Le Pogam et al, ; Blackard et al, ]. We identified previously NS5B compartmentalization in PBMCs even when E1/E2 compartmentalization was absent [Blackard et al, ].…”

HCV resistance compartmentalization within tumoral and non‐tumoral liver in transplanted patients with hepatocellular carcinoma

“…1 The HCV infection has an extraordinarily ability to persist in up to 80.0% of individuals. 2 Chronic HCV infection is closely associated with cirrhosis and hepatocellular carcinoma (HCC) development (15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30).0% of cases within 20 years, and 2-4% risk/year respectively), 3,4 both leading causes of liver transplantation (LT) or liver-related deaths. 5 Chronic HCV infection may also occur in patients with the hepatitis B virus (HBV) infection, since they share the same transmission modes.…”

“…12 Even though the HCV infection is curable 13 its quasispecies nature and high genetic variability influence the rates of therapeutic success, especially in patients with cirrhosis/HCC, whose liver anatomy is profoundly compromised and for whom DAA pharmacokinetics may be affected. [14][15][16] Although HCV is predominantly a hepatotropic-virus, evidence of its replication and/or presence also in other compartments may in turn imply a differential tropism for other cell types [17][18][19][20] and persistence mechanisms over time.…”