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

Abstract

Viral diversity is an important predictor of hepatitis C virus (HCV) treatment response and may influence viral pathogenesis. HIV influences HCV variability in the plasma; however, limited data on viral variability are available from distinct tissue/cell compartments in patients co-infected with HIV and HCV. Thus, this exploratory study evaluated diversity of the hypervariable region 1 (HVR1) of HCV in the plasma and liver for 14 patients co-infected with HIV and HCV. Median intra-patient genetic distances and entropy values were similar in the plasma and liver compartments. Positive immune selection pressure was observed in the plasma for five individuals and in the liver for three individuals. Statistical evidence supporting viral compartmentalization was found in five individuals. Linear regression identified ALT (P = 0.0104) and AST (P = 0.0130) as predictors of viral compartmentalization. A total of 12 signature amino acids that distinguish liver from plasma E1/HVR1 were identified. One signature amino acid was shared by at least two individuals. These findings suggest that HCV compartmentalization is relatively common among patients co-infected with HIV and HCV. These data also imply that evaluating viral diversity, including drug resistance patterns, in the serum/plasma only may not adequately represent viruses replicating with in the liver and, thus, deserves careful consideration in future studies.

Characterization of Hepatitis C Virus (HCV) Envelope Diversification from Acute to Chronic Infection within a Sexually Transmitted HCV Cluster by Using Single-Molecule, Real-Time Sequencing

“…This complex pattern of within-host envelope gene evolution during chronic HCV infection supports the findings of previous studies (32, 51, 52) that used sequencing technologies with a lower depth. Here, we show that even with a greater sequencing depth, not all HCV lineages are detected at all times, which is consistent with the hypothesis of compartmentalization in the liver or in extrahepatic tissues giving rise to distinct HCV subpopulations (53)(54)(55)(56)(57).…”

Compartmentalization of hepatitis C virus variants in patients with hepatocellular carcinoma

“…In particular, a clear serum compartmentalization was observed for the patients having pre‐transplant samples. This result is in accordance with other studies which showed different viral populations between serum and liver . This finding could be attributed, among other causes, to: (i) the existence of slow replication or defective variants in the liver that would be less represented among circulating variants, (ii) a difference in HCV variant clearance rates, and/or (iii) the contribution of the extrahepatic viral replication.…”

“…The characteristics of the four patients analyzed are expressed in Table 1. A total of 414 cloned sequences were obtained and an average of 17 (11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24) sequences from each sample for both of the genomic regions analyzed (Table 1).…”

“…samples. Although circulating virus is thought to represent liver population, some studies have shown evidences that plasma variants differed from those in the liver [18,19]. Moreover, a few studies have found different viral variants according to tumoral or nontumoral tissue sub-localization within the liver of HCC patients [20][21][22][23][24][25].…”

Hepatitis B virus (HBV) variants fluctuate in paired plasma and peripheral blood mononuclear cells among patient cohorts during different chronic hepatitis B (CHB) disease phases

“…In the woodchuck model, it was demonstrated that at low replication rates, the virus is predisposed to invade the PBMC compartment leading to occult viral infection and even primary hepatocellular carcinoma in 20% of infected animals [17,18,43]. Viral infection of immune cells is a well-recognized immune escape strategy, and due to lower levels of viral replication as well as unique cellular and biological conditions, the virus may evolve differently, as was found in studies of other hepatotropic and lymphotropic viruses such as hepatitis C virus [44] and the human immunodeficiency virus [45][46][47][48]. These studies highlight the potential clinical impact of HBV variability in plasma vs PBMC warranting further investigation.…”