Los Alamos Hepatitis C Virus Sequence and Human Immunology Databases: An Expanding Resource for Antiviral Research

Hraber, Peter; Leach, Robert W.; Reilly, Lee Philip; Thurmond, Jim; Yusim, Karina; Kuiken, Carla

doi:10.1177/095632020701800301

Cited by 10 publications

(5 citation statements)

References 28 publications

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“…A previous study in 1997 [40] reported that subtype 1b was the most prevalent subtype (76%), followed by subtype 3a (19%) and single cases of subtypes 1a and 2a, which suggests that the prevalence of subtype 3a has increased and that fewer subtype 1b strains are now circulating. Subtypes 1b and 3a are also dominant over other subtypes in Russia, Estonia and western Europe [41]. While both subtypes have a similar prevalence (45%) in Russia, the relative prevalence of subtype 1b over subtype 3a is three‐fold greater in Estonia (71% vs. 24%; [30]) and 6.5‐fold higher in western Europe (58% vs. 9%).…”

Section: Resultsmentioning

confidence: 99%

Multiple genotypes and subtypes of hepatitis B and C viruses in Belarus: similarities with Russia and western European influences

Olinger¹,

Lazouskaya

2008

Clinical Microbiology and Infection

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The Republic of Belarus reports a seroprevalence of 4.8% for hepatitis B virus (HBV) and 1.26% for hepatitis C virus (HCV), but little is known about the molecular characteristics of the circulating viruses. This study analysed 69 HBV surface antigen (HBsAg)-positive and 113 anti-HCV-positive donors attending a national reference hospital in Minsk. Among the HCV patients, 70% were co-infected with human immunodeficiency virus (HIV). Phylogenetic analysis of 12 complete genomes and 31 partial HBV sequences, as well as 78 core/E1 HCV sequences, revealed that multiple genotypes and subtypes of both viruses were circulating in Belarus. Of the HBV strains, 11.6% were genotype A2 and 88.6% were genotype D. The genotype D strains segregated into four recently described subtypes, with D2 being the most prevalent (58.1%), followed by D3 (16.3%), D1 (11.6%) and D4 (2.3%), but with inter-subtypic distances lower than the minimal 4% distance proposed to define subtypes. The 78 HCV strains belonged to subtypes 1b (53.8%), 3a (38.5%), 1a (5.1%), 4a (1.3%) and 4d (1.3%). Subtype 1b was less prevalent (45.1% vs. 70.4%) among HCV/HIV co-infected donors, while subtype 3a was more prevalent (29.6% vs. 43.1%). The relative prevalence of HBV and HCV genotypes in Belarus corresponded to the prevalence in Russia, although with a clear European influence that reflected the socio-political context of the country.

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Section: Resultsmentioning

confidence: 99%

Multiple genotypes and subtypes of hepatitis B and C viruses in Belarus: similarities with Russia and western European influences

Olinger¹,

Lazouskaya

2008

Clinical Microbiology and Infection

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“…In the two cases where mutations did occur, these were novel mutations not found in sequence databases (Combet et al , 2007; Hraber et al , 2007) and both were associated with a functional impact on T-cell recognition. In the absence of the infecting strain, it is not possible to prove that the mutations occurred within the donors.…”

Section: Discussionmentioning

confidence: 99%

Virological footprint of CD4+ T-cell responses during chronic hepatitis C virus infection

Fleming

Harcourt

Barnes

et al. 2010

Journal of General Virology

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Human and animal model evidence suggests that CD4+ T cells play a critical role in the control of chronic hepatitis C virus (HCV) infection. However, despite their importance, the mechanism behind the failure of such populations in chronic disease is not understood and the contribution of viral mutation is not known. To address this, this study defined the specificity and virological footprint of CD4+ T cells in chronic infection. CD8+ T-cell-depleted peripheral blood mononuclear cells from 61 HCV genotype 1-infected patients were analysed against a panel of peptides covering the HCV genotype 1 core – a region where CD4+ T-cell responses may be reproducibly obtained. In parallel, the core region and E2 protein were sequenced. Gamma interferon-secreting CD4+ T-cell responses directed against multiple epitopes were detected in 53 % of individuals, targeting between one and four peptides in the HCV core. Viral sequence evaluation revealed that these CD4+ T-cell responses were associated with mutants in 2/21 individuals. In these two cases, the circulating sequence variant was poorly recognized by host CD4+ T cells. Bioinformatics analyses revealed no overall evidence of selection in the target epitopes and no differences between the groups with and without detectable CD4+ T-cell responses. It was concluded that sustained core peptide-specific CD4+ T-cell responses may be reproducibly measured during chronic HCV infection and that immune escape may occur in specific instances. However, overall the virological impact of such responses is limited and other causes for CD4+ T-cell failure in HCV must be sought.

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“…A total of 82 Brazilian sequences belonging to subtype 1a and 161 sequences of subtype 1b were obtained with the in silico search of Brazilian HCV polymerase fragment sequences on Los Alamos HCV database (https://hcv.lanl.gov/content/index) and Genbank (https://www.ncbi.nlm.nih.gov/genbank/). Datasets of subtypes 1a and 1b with in silico and target sequences obtained on that work were used to obtain a more detailed genetic reconstruction analysis with local geographical information.…”

Section: Methodsmentioning

confidence: 99%

Molecular characterization of hepatitis C virus in end‐stage renal disease patients under hemodialysis

Silva

Todão

Kamitani

et al. 2017

Journal of Medical Virology

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New direct-acting antiviral (DAA) agents are in development or already approved for the treatment of chronic hepatitis C virus (HCV) infection. The effectiveness of these drugs is related to the previous existence of resistant variants. Certain clinical conditions can allow changes in immunological characteristics of the host and even modify genetic features of viral populations. The aim of this study was to perform HCV molecular characterization from samples of end-stage renal disease patients on hemodialysis (ESRD-HD). Nested PCR and Sanger sequencing were used to obtain genetic information from the NS5B partial region of a cohort composed by 86 treatment-naïve patients. Genomic sequences from the Los Alamos databank were employed for comparative analysis. Bioinformatics methodologies such as phylogenetic reconstructions, informational entropy, and mutation analysis were used to analyze datasets separated by geographical location, HCV genotype, and renal function status. ESRD-HD patients presented HCV genotypes 1a (n = 18), 1b (n = 16), 2a (n = 2), 2b (n = 2), and 3a (n = 4). Control subjects were infected with genotypes 1a (n = 11), 1b (n = 21), 2b (n = 4), and 3a (n = 8). Dataset phylogenetic reconstruction separated HCV subtype 1a into two distinct clades. The entropy analysis from the ESRD-HD group revealed two amino acid positions related to an epitope for cytotoxic T lymphocytes and T helper cells. Genotype 1a was found to be more diverse than subtype 1b. Also, genotype 1a ERSD-HD patients had a higher mean of amino acids changes in comparison to control group patients. The identification of specific mutations on epitopes and high genetic diversity within the NS5B HCV partial protein in hemodialysis patients can relate to host immunological features and geographical distribution patterns. This genetic diversity can affect directly the new DAA's resistance mechanisms.

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Los Alamos Hepatitis C Virus Sequence and Human Immunology Databases: An Expanding Resource for Antiviral Research

Cited by 10 publications

References 28 publications

Multiple genotypes and subtypes of hepatitis B and C viruses in Belarus: similarities with Russia and western European influences

Multiple genotypes and subtypes of hepatitis B and C viruses in Belarus: similarities with Russia and western European influences

Virological footprint of CD4+ T-cell responses during chronic hepatitis C virus infection

Molecular characterization of hepatitis C virus in end‐stage renal disease patients under hemodialysis

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