Hepatitis C virus quasispecies: Misunderstood and mistreated?

McCaughan, Geoffrey W.; Laskus, Tomasz; Vargas, Hugo E.

doi:10.1053/jlts.2003.50260

Cited by 6 publications

(4 citation statements)

References 47 publications

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“…Next-generation sequencing technologies facilitate a more complete mining of the quasispecies pool. Our analysis concurs with estimates that variants present at a frequency of Ͼ5% of the sample space are reliably detectable using clonal methods (37,38). Nevertheless, ST and AD phenotype classification was not achievable through clonal analysis, as the true quasispecies spectrum was masked by a few dominant sequences (Table 2).…”

Section: Discussionsupporting

confidence: 85%

Network Analysis of the Chronic Hepatitis C Virome Defines Hypervariable Region 1 Evolutionary Phenotypes in the Context of Humoral Immune Responses

Palmer

Schmidt-Martin

Dimitrova

et al. 2016

J Virol

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Hypervariable region 1 (HVR1) of hepatitis C virus (HCV) comprises the first 27 N-terminal amino acid residues of E2. It is classically seen as the most heterogeneous region of the HCV genome. In this study, we assessed HVR1 evolution by using ultradeep pyrosequencing for a cohort of treatment-naive, chronically infected patients over a short, 16-week period. Organization of the sequence set into connected components that represented single nucleotide substitution events revealed a network dominated by highly connected, centrally positioned master sequences. HVR1 phenotypes were observed to be under strong purifying (stationary) and strong positive (antigenic drift) selection pressures, which were coincident with advancing patient age and cirrhosis of the liver. It followed that stationary viromes were dominated by a single HVR1 variant surrounded by minor variants comprised from conservative single amino acid substitution events. We present evidence to suggest that neutralization antibody efficacy was diminished for stationary-virome HVR1 variants. Our results identify the HVR1 network structure during chronic infection as the preferential dominance of a single variant within a narrow sequence space. IMPORTANCEHCV infection is often asymptomatic, and chronic infection is generally well established in advance of initial diagnosis and subsequent treatment. HVR1 can undergo rapid sequence evolution during acute infection, and the variant pool is typically seen to diverge away from ancestral sequences as infection progresses from the acute to the chronic phase. In this report, we describe HVR1 viromes in chronically infected patients that are defined by a dominant epitope located centrally within a narrow variant pool. Our findings suggest that weakened humoral immune activity, as a consequence of persistent chronic infection, allows for the acquisition and maintenance of host-specific adaptive mutations at HVR1 that reflect virus fitness. Hepatitis C virus (HCV) infection is a global health issue and is recognized as a major etiological agent of liver-related diseases (1). It has been estimated that the current prevalence of HCV represents approximately 2% of the global adult (15 years of age and older) population (2). Following transmission, HCV infection may remain asymptomatic for decades, resulting in the majority of infections initially passing undetected (3). It is estimated that up to 4 million Americans are living with the virus, the majority of whom became infected prior to the isolation and identification of the virus (4, 5). Consequently, the U.S. Centers for Disease Control and Prevention now recommend that Americans born from 1945 to 1965 be screened for the presence of the virus notwithstanding the presence of clinical symptoms (3, 5).HCV is a single-stranded positive-sense RNA virus of considerable genomic heterogeneity. A recent reclassification defined the HCV global distribution into 7 genotypes and 67 subtypes, with genotypes 1 and 3 accounting for the majority of infections worldwide (6...

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Section: Discussionsupporting

confidence: 85%

Network Analysis of the Chronic Hepatitis C Virome Defines Hypervariable Region 1 Evolutionary Phenotypes in the Context of Humoral Immune Responses

Palmer

Schmidt-Martin

Dimitrova

et al. 2016

J Virol

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“…Within a person, the virus exists as quasispecies variants, whose amino acid sequences are very similar but not identical. The most variation occurs in one 27-aa region known as the HVR1, which is in the amino terminal end of the E2 protein [11,12]. The variation in amino acid sequence in the E2 protein is thought to be the result of immunological pressure; however, HVR1 quasispecies can still arise in in vitro cell culture experiments [13].…”

Section: Introductionmentioning

confidence: 99%

Primary Human Hepatocytes in Spheroid Formation to Study Hepatitis C Infection1

Chong¹,

Smith²,

Hughes³

et al. 2006

Journal of Surgical Research

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“…For mutational frequency and entropy analysis, 20–100 clones per sample are recommended (Gretch and Polyak, 1997). It has been estimated that sequencing 99 clones of HVR1 will identify 95% of all variants present at a frequency of at least 3% in the population (McCaughan et al, 2003). Another estimate suggests 20 clones is sufficient to sample 95% of the major variants (those with at least 10% frequency in the population) (Gretch and Polyak, 1997), however most minor variants may be undetected, leaving out useful information (Gretch et al, 1996).…”

Section: Methods Of Quasispecies Analysismentioning

confidence: 99%

The quasispecies nature and biological implications of the hepatitis C virus

Fishman

Branch

2009

Infection, Genetics and Evolution

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Many RNA viruses exist as a cloud of closely related sequence variants called a quasispecies, rather than as a population of identical clones. In this article, we explain the quasispecies nature of RNA viral genomes, and briefly review the principles of quasispecies dynamics and the differences with classical population genetics. We then discuss the current methods for quasispecies analysis and conclude with the biological implications of this phenomenon, focusing on the hepatitis C virus.

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Hepatitis C virus quasispecies: Misunderstood and mistreated?

Cited by 6 publications

References 47 publications

Network Analysis of the Chronic Hepatitis C Virome Defines Hypervariable Region 1 Evolutionary Phenotypes in the Context of Humoral Immune Responses

Network Analysis of the Chronic Hepatitis C Virome Defines Hypervariable Region 1 Evolutionary Phenotypes in the Context of Humoral Immune Responses

Primary Human Hepatocytes in Spheroid Formation to Study Hepatitis C Infection1

The quasispecies nature and biological implications of the hepatitis C virus

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