Evolutionary study of HVR1 of E2 in chronic hepatitis C virus infection

Alfonso, Victoria; Flichman, Diego Martín; Sookoian, Silvia; Mbayed, Viviana Andrea; Campos, Rodolfo Héctor

doi:10.1099/vir.0.19403-0

Cited by 20 publications

(16 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The antigenic domain towards the carboxyl terminal was stable however the one towards amino terminus was variable between samples. In other study antigenic characteristics at the amino terminus differed between lineages [25]. Our study confirmed the presence of a non antigenic domain in genotype 3a samples as reported in genotype 1b [24].…”

Section: Discussionsupporting

confidence: 89%

Characterization of Hepatitis C Virus genotype 3a Hypervariable region 1 in patients achieved rapid virological response to alpha interferon and Ribavirin Combination therapy

Akram

Idrees

Hussain

et al. 2011

Virol J

View full text Add to dashboard Cite

BackgroundHepatitis C virus roots a chronic liver disease. Currently approved treatment strategy includes administration of alpha interferon and ribavirin combined therapy for 24-48 weeks. One of the predictor of sustained virological response is an early virological response to treatment characterized as rapid response. Hyper variable region 1 (HVR1) of E2 protein is responsible for viral entry and acts as a target for neutralizing antibodies. Any mutation in this region would effect virus interaction with target cell and viral persistence.MethodsThirty one clones of six pre-treatment samples subjected to combination therapy were investigated. Three of the patients were rapid responders (R1, R2 and R3) and two were breakthrough responders (BT1 and BT2). Envelope 2 gene was amplified, cloned and sequenced. Amino acid substitution, frequency, composition and antigenic properties of HVR 1 of E2 protein were studied.ResultsIn both rapid responders (R.R) (14 amino acid sites) and breakthrough responders (BT.R) (13 amino acid sites) half of the amino acid sites were either conserved or resistant to any physiochemical change due to amino acid substitution. It also indicated that average composition of hydrophilic and basic amino acids were comparatively lower in rapid responders than other samples affecting probable interaction of virus with target cells. A central non antigenic region was constant among the breakthrough responders but differed in length significantly among rapid responders reflecting the adaptive nature of HVR1 to the immune response.ConclusionsWe observed that although HVR1is quite variable region in HCV 3a patients responding differently to treatment it still maintains its physiochemical properties for its proper functioning and viability.

show abstract

Section: Discussionsupporting

confidence: 89%

Characterization of Hepatitis C Virus genotype 3a Hypervariable region 1 in patients achieved rapid virological response to alpha interferon and Ribavirin Combination therapy

Akram

Idrees

Hussain

et al. 2011

Virol J

View full text Add to dashboard Cite

show abstract

“…constrain it to conserve its conformation to ensure receptor recognition [Penin et al, 2001;Gaudy et al, 2003]. IFN-a therapy has been shown to induce an HVR1 quasispecies shift pattern of evolution [Pawlotsky et al, 1999;Sarrazin et al, 2001;Alfonso et al, 2004]. In the present study, the NS3 quasispecies evolution after combination therapy has not been investigated.…”

Section: Discussionmentioning

confidence: 92%

Genetic heterogeneity of the NS3 protease gene in hepatitis C virus genotype 1 from untreated infected patients

Vallet

Gouriou

Nousbaum

et al. 2005

Journal of Medical Virology

View full text Add to dashboard Cite

NS3 protease is essential for hepatitis C Virus (HCV) replication, and is one of the most promising targets for specific anti-HCV therapy. Its natural polymorphism has not been studied at the quasispecies level. In the present work, the genetic heterogeneity of the NS3 protease gene was analyzed in 17 HCV genotype 1 (5 subtypes 1a and 12 subtypes 1b) samples collected from infected patients before anti-viral therapy. A total of 294 clones were sequenced. Although the protease NS3 is considered to be one of the less variable genes in the HCV genome, variability of both nucleotide and amino acid sequences was found. In variants belonging to 1a and 1b subtypes, 224 and 267 of 543 positions showed one or more nucleotide substitutions, respectively. Forty and 74 of the 181 NS3 amino acid positions showed at least one mutation in HCV-1a and HCV-1b isolates, respectively. Most substitutions were conservative. This substantial polymorphism of the NS3 protease produced by HCV-1a and HCV-1b suggests that, despite the numerous functional and structural constraints, the enzyme is sufficiently flexible to tolerate substitutions.

show abstract

“…All sequences were truncated to the E1 coding region spanning the nucleotide sites 1 to 399. We also obtained 346 published population-based RT-PCR sequences from Genbank (see Accession Numbers) spanning the hyper-variable region HVR1 of HCV envelope protein E2 [54–57]. …”

Section: Methodsmentioning

confidence: 99%

Adaptation to Human Populations Is Revealed by Within-Host Polymorphisms in HIV-1 and Hepatitis C Virus

et al. 2007

View full text Add to dashboard Cite

CD8+ cytotoxic T-lymphocytes (CTLs) perform a critical role in the immune control of viral infections, including those caused by human immunodeficiency virus type 1 (HIV-1) and hepatitis C virus (HCV). As a result, genetic variation at CTL epitopes is strongly influenced by host-specific selection for either escape from the immune response, or reversion due to the replicative costs of escape mutations in the absence of CTL recognition. Under strong CTL-mediated selection, codon positions within epitopes may immediately “toggle” in response to each host, such that genetic variation in the circulating virus population is shaped by rapid adaptation to immune variation in the host population. However, this hypothesis neglects the substantial genetic variation that accumulates in virus populations within hosts. Here, we evaluate this quantity for a large number of HIV-1– (n ≥ 3,000) and HCV-infected patients (n ≥ 2,600) by screening bulk RT-PCR sequences for sequencing “mixtures” (i.e., ambiguous nucleotides), which act as site-specific markers of genetic variation within each host. We find that nonsynonymous mixtures are abundant and significantly associated with codon positions under host-specific CTL selection, which should deplete within-host variation by driving the fixation of the favored variant. Using a simple model, we demonstrate that this apparently contradictory outcome can be explained by the transmission of unfavorable variants to new hosts before they are removed by selection, which occurs more frequently when selection and transmission occur on similar time scales. Consequently, the circulating virus population is shaped by the transmission rate and the disparity in selection intensities for escape or reversion as much as it is shaped by the immune diversity of the host population, with potentially serious implications for vaccine design.

show abstract

Evolutionary study of HVR1 of E2 in chronic hepatitis C virus infection

Cited by 20 publications

References 43 publications

Characterization of Hepatitis C Virus genotype 3a Hypervariable region 1 in patients achieved rapid virological response to alpha interferon and Ribavirin Combination therapy

Characterization of Hepatitis C Virus genotype 3a Hypervariable region 1 in patients achieved rapid virological response to alpha interferon and Ribavirin Combination therapy

Genetic heterogeneity of the NS3 protease gene in hepatitis C virus genotype 1 from untreated infected patients

Adaptation to Human Populations Is Revealed by Within-Host Polymorphisms in HIV-1 and Hepatitis C Virus

Contact Info

Product

Resources

About