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Самохвалов, Е И; Hijikata, Makoto; Gylka, Rodica I.; Lvov, D. K.; Mishiro, Shunji

doi:10.1023/a:1008182901274

Cited by 29 publications

(1 citation statement)

References 27 publications

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“…Besides the 11 isolates from the current study, the tree also included 47 sequences retrieved from the HCV database. Among them, 19 belonged to subtype 2a (12 from Japan, seven with unknown origin), 25 belonged to subtype 2b (23 from Japan and two from the USA), and one belonged to each of subtype 2c (from an Italian patient) (Nakao et al , 1996), subtype 2k (Samokhvalov et al , 2000) and subtype 2i (Noppornpanth et al , 2006). The tree showed that the 11 isolates were distinct from each other and from subtypes 2a, 2b, 2c, 2k and 2i.…”

Section: Resultsmentioning

confidence: 99%

Full-length sequences of 11 hepatitis C virus genotype 2 isolates representing five subtypes and six unclassified lineages with unique geographical distributions and genetic variation patterns

Cao

Lü

et al. 2012

Journal of General Virology

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In this study, we characterized full-length hepatitis C virus (HCV) genome sequences for 11 genotype 2 isolates. They were isolated from the sera of 11 patients residing in Canada, of whom four had an African origin. Full-length genomes, each with 18-25 overlapping fragments, were obtained by PCR amplification. Five isolates represent the first complete genomes of subtypes 2d, 2e, 2j, 2m and 2r, while the other six correspond to variants that do not group within any assigned subtypes. These sequences had lengths of 9508-9825 nt and each contained a single ORF encoding 3012-3106 aa. Predicted amino acids were carefully inspected and unique variation patterns were recognized, especially for a 2e isolate, QC64. Phylogenetic analysis of complete genome sequences provides evidence that there are a total of 16 subtypes, of which 11 have been described here. Co-analysis with 68 partial NS5B sequences also differentiated 18 assigned subtypes, 2a-2r, and eight additional lineages within genotype 2, which is consistent with the analysis of complete genome sequences. The data from this study will now allow 10 assigned subtypes and six additional lineages of HCV genotype 2 to have their full-length genomes defined. Further analysis with 2021 genotype 2 sequences available in the HCV database indicated that the geographical distribution of these subtypes is consistent with an African origin, with particular subtypes having spread to Asia and the Americas.

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Section: Resultsmentioning

confidence: 99%

Full-length sequences of 11 hepatitis C virus genotype 2 isolates representing five subtypes and six unclassified lineages with unique geographical distributions and genetic variation patterns

Cao

Lü

et al. 2012

Journal of General Virology

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Consensus proposals for a unified system of nomenclature of hepatitis C virus genotypes

et al. 2005

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International standardization and coordination of the nomenclature of variants of hepatitis C virus (HCV) is increasingly needed as more is discovered about the scale of HCV-related liver disease and important biological and antigenic differences that exist between variants. A group of scientists expert in the field of HCV genetic variability, and those involved in development of HCV sequence databases, the Hepatitis Virus Database (Japan), euHCVdb (France), and Los Alamos (United States), met to re-examine the status of HCV genotype nomenclature, resolve conflicting genotype or subtype names among described variants of HCV, and draw up revised criteria for the assignment of new genotypes as they are discovered in the future. A comprehensive listing of all currently classified variants of HCV incorporates a number of agreed genotype and subtype name reassignments to create consistency in nomenclature. The paper also contains consensus proposals for the classification of new variants into genotypes and subtypes, which recognizes and incorporates new knowledge of HCV genetic diversity and epidemiology. A proposal was made that HCV variants be classified into 6 genotypes (representing the 6 genetic groups defined by phylogenetic analysis). Subtype name assignment will be either confirmed or provisional, depending on the availability of complete or partial nucleotide sequence data, or remain unassigned where fewer than 3 examples of a new subtype have been described. In conclusion, these proposals provide the framework by which the HCV databases store and provide access to data on HCV, which will internationally coordinate the assignment of new genotypes and subtypes in the future. (HEPATOLOGY 2005;42:962-973.)

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Neutralization resistance of hepatitis C virus can be overcome by recombinant human monoclonal antibodies

et al. 2013

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Immunotherapy and vaccine development for hepatitis C virus (HCV) will depend on broadly reactive neutralizing antibodies. However, studies in infectious JFH1-based culture systems expressing patient derived Core-NS2 proteins have suggested neutralization resistance for specific HCV strains, in particular of genotype 2. To further examine this phenomenon, we developed a panel of HCV genotype 2 recombinants for testing of sensitivity to neutralization by chronic-phase patient sera and lead human monoclonal antibodies. The novel Core-NS2 recombinants, with patient derived genotype 2a (strain T9), 2b (strains DH8 and DH10), and 2c (strain S83) consensus sequences, were viable in Huh7.5 hepatoma cells without requirement for adaptive mutations, reaching HCV infectivity titers of 3.9–4.5 log10 focus-forming units per mL. In in vitro neutralization assays, we demonstrated that the novel genotype 2 viruses as well as prototype strains J6(2a) and J8(2b), all with authentic envelope proteins, were resistant to neutralization by genotype 2a, 2b, 2c, 2j, 2i, and 2q patient sera. These patient sera, however, had high titers of HCV-specific neutralizing antibodies, since they efficiently reduced the infectivity of J6(2a) and J8(2b) with deleted hypervariable region 1. The genotype 2a, 2b, and 2c viruses, found resistant to polyclonal patient sera neutralization, were efficiently neutralized by two lead human monoclonal antibodies, AR4A and HC84.26. Conclusion: Using novel 2a, 2b, and 2c cell culture systems, expressing authentic envelope proteins, we demonstrated resistance of HCV to patient-derived polyclonal high-titer neutralizing antibodies. However, the same genotype 2 culture viruses were all sensitive to human monoclonal HCV antibodies recognizing conformational epitopes, indicating that neutralization resistance of HCV can be overcome by applying recombinant antibodies. These findings have important implications for HCV immunotherapy and vaccine development.

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Cited by 29 publications

References 27 publications

Full-length sequences of 11 hepatitis C virus genotype 2 isolates representing five subtypes and six unclassified lineages with unique geographical distributions and genetic variation patterns

Full-length sequences of 11 hepatitis C virus genotype 2 isolates representing five subtypes and six unclassified lineages with unique geographical distributions and genetic variation patterns

Consensus proposals for a unified system of nomenclature of hepatitis C virus genotypes

Neutralization resistance of hepatitis C virus can be overcome by recombinant human monoclonal antibodies

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