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Complete genome sequencing and evolutionary analysis of hepatitis C virus subtype 6a, including strains from Guangdong Province, China.

ABSTRACT: We performed an evolutionary analysis using whole genome sequence isolates of hepatitis C virus (HCV) 6a from Guangdong Province and reference sequences from various countries. Less than 5% of the HCV genome was found to be under positive selection. The E1 and E2 proteins had the highest proportion of positively selected sites both within and outside of CD8 T cell epitopes in all of the strains. Regions corresponding to CD8 T cell epitopes were under negative selection except in the isolates from Guangdong. Furthermore, we found evidence of three introductions of the virus into Guangdong from Vietnam and other Southeast Asian countries. Thus, this study provides information about the transmission of HCV 6a by comparison of full-length sequences, indicating the impact of selective constraints in Guangdong and across China.

SUBMITTER: Xu R

PROVIDER: S-EPMC8771652 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature

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Complete genome sequencing and evolutionary analysis of hepatitis C virus subtype 6a, including strains from Guangdong Province, China.

Xu Ru R Wang Hao H Huang Jieting J Wang Min M Liao Qiao Q Shan Zhengang Z Zhong Huishan H Rong Xia X Fu Yongshui Y Fu Yongshui Y

Archives of virology 20220120 2

We performed an evolutionary analysis using whole genome sequence isolates of hepatitis C virus (HCV) 6a from Guangdong Province and reference sequences from various countries. Less than 5% of the HCV genome was found to be under positive selection. The E1 and E2 proteins had the highest proportion of positively selected sites both within and outside of CD8 T cell epitopes in all of the strains. Regions corresponding to CD8 T cell epitopes were under negative selection except in the isolates fro ...[more]

PMID: 35050401

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Project description:To systematically characterize the prevalence and evolution of human T-cell lymphotropic virus (HTLV) infection among voluntary blood donors (BDs) in Guangdong province, China. A three-year survey for HTLV epidemiology among BDs was performed in Guangdong during 2016-2018. Anti-HTLV-1/2 was screened by ELISA and ECLIA, and subsequently confirmed by western blot (WB) and nucleic acid testing (NAT). The prevalence of HTLV in donors from different cities was calculated. The identified HTLV-positive cases were phylogenetically genotyped and analyzed in a Bayesian phylogenetic framework. Among 3,262,271 BDs, 59 were confirmed positive for HTLV-1 (1.81 per 100,000) and no HTLV-2 infection was found. The prevalence of HTLV-1 varied significantly among 21 cities in Guangdong province, China. The highest prevalence was found in donors from Shanwei (13.94 per 100,000), which is a coastal city in eastern Guangdong. Viral genomic sequences genotyped from 55 HTLV-1 carriers showed that 39 were transcontinental subtype and 16 were Japanese subtype. Specially, 13 out of 39 transcontinental subtype sequences were characterized with L55P mutation and 21 out of 55 sequences were characterized with L19F mutation in viral gp46 protein. The L55P mutation seemed be specific to eastern Asia since it only presented in the sequences from Japan, mainland China, and Taiwan. Phylogenetic analysis of gp46 gene shows that HTLV-1a may have been introduced to Guangdong through four different introduction events and formed major transmission clusters: clades I(13,602 years ago), II(16, 010 years ago), III(15,639 years ago) and IV(16,517 years ago). In general, Guangdong is considered to be a low-prevalence region for HTLV-1 infection, but the prevalence is significantly higher in Shanwei city. Transcontinental and Japanese subtype lineages dominate the prevalence in Guangdong. In terms of blood safety, HTLV antibody screening for first-time blood donors can effectively reduce the risk of HTLV transmission.

Project description:BackgroundHCV genotype 6 (HCV-6) typically circulates in Southeast Asia and exhibits the highest genetic diversity among the eight HCV genotypes. In our previous work, a group of HCV-6 sequences was not clearly classified. Here, we further characterized this HCV-6 variant and analyzed the evolutionary history of the enlarged HCV-6 family.MethodsBlood samples from eight HCV seropositive samples collected from intravenous drug users (IDUs) in 2014 in Yunnan Province, China. The full-length HCV genome sequences were amplified by using reverse transcription PCR followed by DNA sequencing and phylogenetic analysis. Bayesian evolutionary analysis was performed with the complete coding region sequences of subtype 6a-6xh.ResultsThe eight genomes had the same coding region of 9051 nucleotides. The complete coding region sequences of the eight HCV isolates formed a distinct phylogenetic group from the previously assigned HCV-6 subtypes (6a-6xf), however which clustered with 6xg reference sequences that were found in Kachin State, Myanmar, and recently assigned and released. The p-distances of the eight isolates to subtype 6a-6xf and 6xh ranged from 0.143 to 0.283. Based on the HCV-6 complete coding region sequences, we constructed a timescaled phylogenetic tree to reveal the HCV-6 evolutionary history, in which there were four HCV-6 phylogenetic subsets, whose median tMRCAs were 294.8, 388.5, 348.5 and 197.0 years ago, respectively. Subtype 6xg clustered into Subset I, and had the most recent common ancestor with subtype 6n, which dated back to 101.2 (95% HPD: 78.7, 125.8) years ago. The genetic evolutionary analysis further confirmed that subtype 6xg originated from Myanmar, and transmitted to Dehong through cross-border IDUs.ConclusionThe HCV-6 variant characterized in this study belonged to newly assigned subtype 6xg. Our finding further confirmed the assignment of 6xg. HCV-6 family was highly divers and had a complicated evolutionary history in Southeast Asia. It is necessary to further characterize HCV-6 genetics in this region.

Project description:Carbapenem-resistant Pseudomonas aeruginosa (CRPA) is a bacterial pathogen that may cause serious drug-resistant infections that are potentially fatal. To investigate the genetic characteristics of these organisms, we tested 416 P. aeruginosa strains recovered from 12 types of clinical samples collected in 29 different hospital wards in 10 hospitals in Guangdong Province, China, from 2017 to 2020. These strains were found to belong to 149 known sequence types (STs) and 72 novel STs, indicating that transmission of these strains involved multiple routes. A high rate of resistance to imipenem (89.4%) and meropenem (79.4%) and a high prevalence of pathogenic serotypes (76.4%) were observed among these strains. Six STs of global high-risk clones (HiRiCs) and a novel HiRiC strains, ST1971, which exhibited extensive drug resistance, were identified. Importantly, ST1971 HiRiC, which was unique in China, also exhibited high virulence, which alarmed the further surveillance on this highly virulent and highly resistant clone. Inactivation of the oprD gene and overexpression of efflux systems were found to be mainly responsible for carbapenem resistance in these strains; carriage of metallo-β-lactamase (MBL)-encoding genes was less common. Interestingly, frameshift mutations (49.0%) and introduction of a stop codon (22.4%) into the oprD genes were the major mechanisms of imipenem resistance. On the other hand, expression of the MexAB-OprM efflux pump and MBL-encoding genes were mechanisms of resistance in >70% of meropenem-resistant strains. The findings presented here provide insights into the development of effective strategies for control of worldwide dissemination of CRPA. IMPORTANCE Carbapenem-resistant Pseudomonas aeruginosa (CRPA) is a major concern in clinical settings worldwide, yet few genetic and epidemiological studies on CRPA strains have been performed in China. Here, we sequence and analyze the genomes of 416 P. aeruginosa strains from hospitals in China to elucidate the genetic, phenotypic, and transmission characteristics of CRPA strains and to identify the molecular signatures responsible for the observed increase in the prevalence of CRPA infections in China. These findings may provide new insight into the development of effective strategies for worldwide control of CRPA and minimize the occurrence of untreatable infections in clinical settings.

Dataset Information

Complete genome sequencing and evolutionary analysis of hepatitis C virus subtype 6a, including strains from Guangdong Province, China.

Publications

Complete genome sequencing and evolutionary analysis of hepatitis C virus subtype 6a, including strains from Guangdong Province, China.

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