A panel of 16 full-length HCV genomes was characterized in China belonging to genotypes 1–6 including subtype 2f and two novel genotype 6 variants

Xu, Ru; Tong, Wangxia; Gu, Lin; Li, Chunhua; Fu, Yongshui; Lü, Ling

doi:10.1016/j.meegid.2013.08.014

Cited by 14 publications

(11 citation statements)

References 21 publications

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“…Group B includes only five sequences, each from a different province located in the southern half of China: Shanghai, Fujian, Hubei, Guangdong, and Guangxi [18,28,29]. These mixed geographic origins may indicate a sporadic pattern.…”

Section: Subtype 1amentioning

confidence: 99%

A Unique Pattern of HCV Genotype Distribution on Hainan Island in China Revealed by Evolutionary Analysis

Xiong

Wang

et al. 2016

Cell Physiol Biochem

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Background/Aims:Different genotypes of HCV may differ in both disease progression and response to antiviral therapies. Hainan Island has been inhabited by the “Li” aboriginal minority for centuries. We aimed to provide a better understanding of HCV infection on Hainan Island, so that the information would help improve strategies for HCV prevention and control on the island and in the wider country. Methods: Using RT-PCR and DNA sequencing, we determined HCV sequences from 100 patients living on Hainan Island. Results: Phylogenetic analysis classified these sequences into six subtypes: 6a (n=35), 1b (n=31), 3b (n=16), 2a (n=8), 3a (n=6), and 1a (n=4). By including reference sequences reported from elsewhere in China, phylogeographic trees were reconstructed to indicate their migration patterns. While the predominant 6a isolates were estimated to have origins in Guangdong and Guangxi provinces, the increase in 3b strains must have resulted from IDU network transmission from the southwest. A Bayesian Skyline Plot for subtype 1a, which is rare in China, showed a rapid population growth since 1998. Although slowed in rate around 2005, this growth continued to the present. Not found for any other HCV lineage. Conclusions: Overall, a delayed growth pattern may indicate the unique history of 1a dissemination in China and its recently increasing prevalence, despite measures taken to improve HCV prevention.

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Section: Subtype 1amentioning

confidence: 99%

A Unique Pattern of HCV Genotype Distribution on Hainan Island in China Revealed by Evolutionary Analysis

Xiong

Wang

et al. 2016

Cell Physiol Biochem

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“…Representative sequences from different HCV genotypes were retrieved from the GenBank database (www.nlm.nih.com), including genotype 5a (Gededzha et al, 2014) and China (Xu et al, 2013). For reasons of brevity and clarity, sequences from samples from single patients taken at different time points…”

Section: Phylogenetic Analysesmentioning

confidence: 99%

Naturally occurring resistance mutations within the core and NS5B regions in hepatitis C genotypes, particularly genotype 5a, in South Africa

et al. 2016

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Approximately 1 million South Africans are infected with Hepatitis C virus (HCV). The standard of care (SOC) in South Africa is combination therapy (pegylated interferon and ribavirin). HCV genotypes and/or mutations in the core/ non-structural regions have been associated with response to therapy and/or disease progression. This study examines mutations in the core (29-280 amino acids, including ~90 E1 amino acids) and NS5B (241-306 amino acids) regions on pre-treatment isolates from patients attending Johannesburg hospitals or asymptomatic South African blood donors. Diversity within known CD4+ and CD8+ T-cell epitopes was also explored. Samples grouped into subtypes 1a (N=10) 1b (N=12), 3a(N=5), 4a (N=3) and 5a(N=61). Two mutations, associated with interferon resistance-R70Q and T110N-were present in 29 genotype 5a core sequences. No resistance mutation to NS5B nucleotide inhibitors, sofosbuvir was found. Six putative CD8+ and one CD4+ T-cell epitope sequence in the core region showed binding scores of <300 IC 50 nM to HLA alleles frequently observed in the South African population. No known CD8+ and CD4+ T-cell epitopes were mapped in the NS5B region. The analysis begs the question whether those infected with genotype 5a will benefit better on interferon-free combination therapies. This study provides new insight into one of the lesser studied HCV genotypes and compares the diversity seen in a large pre-treatment cohort with other subtypes. KeywordsHepatitis C, genotype 5, interferon, mutations, therapy Highlights  We examined mutational changes of hepatitis C in the core/E1 and NS5B genes. Phylogenetic analyses were performed using Bayesian inferences. Diversity within known CD4+ and CD8+ T-cell epitopes was also explored. Mutations, associated with interferon resistance, were present in genotype 5a samples at baseline. 2

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“…Although six genotypes (genotypes 1 to 6), 18 subtypes (subtypes 1a, 1b, 1c, 2a, 2b, 2f, 3a, 3b, 4d, 5a, 6a, 6e, 6g, 6k, 6n, 6u, 6v, and 6w), and a number of unassigned variants have been detected in China, over 95% of these isolates belong to five major subtypes: 1b, 2a, 3a, 3b, and 6a (12)(13)(14)(15)(16)(17)(18)(19). Among them, subtype 1b is predominant nationwide, accounting for approximately 75% of all HCV infections, and this is followed by 2a.…”

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confidence: 99%

Migration Patterns of Hepatitis C Virus in China Characterized for Five Major Subtypes Based on Samples from 411 Volunteer Blood Donors from 17 Provinces and Municipalities

Lü

Wang

Xia

et al. 2014

J Virol

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We investigated the migration patterns of hepatitis C virus (HCV) in China. Partial E1 and/or NS5B sequences from 411 volunteer blood donors sampled in 17 provinces and municipalities located in five large regions, the north-northeast, northwest, southwest, central south, and southeast, were characterized. The sequences were classified into eight subtypes (1a, n ‫؍‬ 3; 1b, n ‫؍‬ 183; 2a, n ‫؍‬ 83; 3a, n ‫؍‬ 30; 3b, n ‫؍‬ 44; 6a, n ‫؍‬ 55; 6n, n ‫؍‬ 10; 6v, n ‫؍‬ 1) and a new subtype candidate. Bayesian evolutionary analysis by sampling trees of the E1 sequences of the five major subtypes revealed distinct migration patterns. Subtype 1b showed four groups: one is prevalent nationwide with possible origins in the north-northeast; two are locally epidemic in the central south and northwest, respectively, and have spread sporadically to other regions; and the fourth one is likely linked to the long-distance dispersion among intravenous drug users from the northwest. Subtype 2a showed two groups: the larger one was mainly restricted to the northwest and seemed to show a trend toward migration via the Silk Road; the smaller one was geographically mixed and may represent descendants of those that spread widely during the contaminated plasma campaign in the 1990s. Subtype 3a exhibited three well-separated geographic groups that may be epidemically unrelated: one showed origins in the northwest, one showed origins in the southwest, and the other showed origins in the central south. In contrast, subtype 3b had a mixture of geographic origins, suggesting migrations from the southwest to the northwest and sporadically to other regions. Structurally resembling the tree for subtype 3a, the tree for subtype 6a showed four groups that may indicate migrations from the central south to southeast, southwest, and northwest. Strikingly, no subtype 6a strain was identified in the north-northeast. IMPORTANCEWith a population of greater than 1.3 billion and a territory of >9.6 million square kilometers, China has a total of 34 provinces and municipalities. In such a vast country, the epidemic history and migration trends of HCV are thought to be unique and complex but variable among regions and are unlikely to be represented by those observed in only one or at best a few provinces and municipalities. However, due to the difficulties in recruiting patients, all previous studies for this purpose have been based only on data from limited regions, and therefore, geographical biases were unavoidable. In this study, such biases were greatly reduced because we utilized samples collected from volunteer blood donors in 17 provinces and municipalities. To our knowledge, this is the first study in which the HCV isolates represented such a large portion of the country, and thus, the results should shed light on the current understanding of HCV molecular epidemiology.

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A panel of 16 full-length HCV genomes was characterized in China belonging to genotypes 1–6 including subtype 2f and two novel genotype 6 variants

Cited by 14 publications

References 21 publications

A Unique Pattern of HCV Genotype Distribution on Hainan Island in China Revealed by Evolutionary Analysis

A Unique Pattern of HCV Genotype Distribution on Hainan Island in China Revealed by Evolutionary Analysis

Naturally occurring resistance mutations within the core and NS5B regions in hepatitis C genotypes, particularly genotype 5a, in South Africa

Migration Patterns of Hepatitis C Virus in China Characterized for Five Major Subtypes Based on Samples from 411 Volunteer Blood Donors from 17 Provinces and Municipalities

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