Long-term evolution of the 5'UTR and a region of NS4 containing a CTL epitope of hepatitis C virus in two haemophilic patients.

Abstract

Haemophilic patients exposed to unsterilized clotting factor concentrates prior to 1985 have become infected with hepatitis C virus (HCV). We have studied the sequence evolution of the 5hUTR and a region of NS4 over 12 years in one human immunodeficiency virus (HIV) positive haemophilic patient and 14 years for one HIV negative haemophilic patient. One sample each year from the date of HCV infection to 1994 was analysed for genotype, virus load and nucleotide sequence of the two genetic loci. Both patients were infected with HCV

Impact of Highly Active Antiretroviral Therapy and Immunologic Status on Hepatitis C Virus Quasispecies Diversity in Human Immunodeficiency Virus/Hepatitis C Virus-Coinfected Patients

“…It has been shown previously that HCV quasispecies diversity changes in an oscillatory manner during the natural course of infection in both monoinfected and HIV-coinfected patients (6). Thus, we hypothesized that analyzing the quasispecies at a single time point-a "snapshot in time"-might not accurately reflect the overall quasispecies profile in a patient over time.…”

“…One study showed that coinfected patients with lower CD4 ϩ -cell counts had a greater percentage of new clones over a 1-year study period than did those with higher CD4 ϩ -cell counts (Dove et al, Hepatology 30:456A, 1999); however, this study involved only nine patients, and the authors did not report whether or not there was a change in genetic distance or K a /K s . Two other studies compared HIV/ HCV-coinfected patients with HCV-monoinfected controls and found that coinfected patients had more quasispecies diversity (6,43). One study compared only two patients (6), and neither study addressed the effect of CD4 ϩ -cell count differences within the coinfected population (6,43).…”

“…When comparing HIV/HCV-coinfected patients with HCV-monoinfected controls, two studies have found that coinfected patients have more quasispecies diversity (6,43). If HIV infection were a surrogate marker for immunosuppression, this would imply that quasispecies diversity increases with immunosuppression.…”

Contribution of Taq polymerase-induced errors to the estimation of RNA virus diversity.

“…In experiments designed to distinguish significant differences in nucleotide diversity over time, poor sampling may lead to ambiguous results. For instance, Devereux et al (1997) performed a decade-long evolutionary study of hepatitis C virus in two infected patients by sampling five clones of a 132 nucleotide portion of the NS4 gene each year (a total of 660 nucleotides per year). The oscillatory pattern of diversity over time observed in their study better reflects stochastic behaviour of sampling rather than real changes in the trends of average divergences between years.…”

Longitudinal Evaluation of the Structure of Replicating and Circulating Hepatitis C Virus Quasispecies in Nonprogressive Chronic Hepatitis C Patients

“…In longitudinal studies, the nucleotide complexity of the hypervariable domain of the HCV E2 region (HVR1) did not increase cumulatively over time but fluctuated in consecutive serum samples (2). Similarly, at more conserved regions of the genome, an oscillatory pattern of quasispecies complexity over time has been observed in long-term studies with frequent serum sampling (7). The factors that drive these fluctuations and their relative contributions are not defined, and, to further complicate the interpretation of the biological meaning of circulating quasispecies complexity, it has been proven that within an infected patient the composition of the circulating viral population does not necessarily reflect that of the hepatic population (4,15,28,34,38).…”