Original Article
Analysis of genomic characteristics of human parainfluenza virus 3 in six provinces and cities of China, 2019-2020
Jiang Jie, Sun Liwei, Zhang Feng, Wang Wenhui, Wang Miao, Xie Hui, Wang Wenyang, Zhu Zhen, Zhang Yan, Cui Aili, Li Hai, Mao Naiying
Published 2023-10-30
Cite as Chinese J Exp Clin Virol, 2023, 37(5): 480-490. DOI: 10.3760/cma.j.cn112866-20230830-00024
Abstract
ObjectiveThis study comprehensively analyzed the genomic characterizations of human parainfluenza virus type 3 (HPIV3) strains circulating in six provinces and cities of China (Beijing, Henan, Jilin, Anhui, Gansu, and Shandong) during the period of 2019-2020. The aim was to elucidate the intricate genetic variations and molecular evolutionary trends within the HPIV3 genome.
MethodsBased on genotypic differentiation, genetic divergence, and spatial and temporal distribution, 12 representative HPIV3 strains (including 7 of C3a subtype, 2 of C3b subtype and 3 of C3f subtype) were selected from the aforementioned provinces, and the complete genome sequence was successfully obtained by overlapping amplification of fragments using nested RT-PCR. Subsequently, a complete genome database of global representative HPIV3 strains was constructed and analyzed using bioinformatics tools.
ResultsThe length of complete genome of the 12 HPIV3 strains in the present study varied between 15 227 bp and 15 370 bp, the G+ C content ranged from 35.1% to 35.3% and the nucleotide identity intermediated from 97.6% to 99.6%. Compared with the prototype strain (GenBank accession number: NC_001796.2), the nucleotide identity of 12 HPIV3 strains ranged from 94.2% to 94.5%. Analysis of the complete genome of HPIV3 available in China and globally showed that the genomic variation of HPIV3 was mainly shaped by substitution mutations, and no base deletions or gene recombination were observed.Only a six-base insertion (ATTAAA) was found in the F gene’s 3′UTR region of a representative strain originating from Jilin province (CHN/Jilin036/2019/C3b) in this study, and its potential pathogenic significance needs to be further investigated. Amino acid analysis of the encoded proteins revealed that the C3a lineage of HPIV3, widely prevalent both in China and worldwide, exhibits lineage-specific mutation sites in the N, P and L proteins. Furthermore, within the Chinese prevalent C3a strains, a distinctive mutation site (N216S) in L protein was also identified. Notably, specific variant sites have not been found in Chinese C3b and C3f branch strains. Based on the complete genome, the comprehensive evolutionary analysis showed that the time to the most recent common ancestor (tMRCA) of global HPIV3 strains was estimated to 1927 (95% HPD: 1901-1945), with an average molecular evolutionary rate of 5.29 × 10-4 substitutions/site/year, while the average molecular evolutionary rate of HPIV3 strains in China is 5.24 × 10-4 substitutions/site/year. In addition, each gene of HPIV3 was subjected to negative selection pressure, with the P, HN and F genes showing the most significant nucleotide variation and higher rates of molecular evolution than the other genes.
ConclusionsThis study reveals that the complete genome of HPIV3 strains circulating in six provinces and cities of China tend to evolve conservatively. Moreover, substitution emerge as the main driving force for molecular evolution of HPIV3.
Key words:
Human parainfluenza virus 3; Whole genome sequences; Genetic variation analysis; Molecular evolutionary analysis
Contributor Information
Jiang Jie
NHC Key Laboratory of Medical Virology and Viral Diseases, WHO WPRO Regional Reference Laboratory of Measles and Rubella, National Measles Laboratory, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China
Sun Liwei
Changchun Children’s Hospital, Changchun 130000, China
Zhang Feng
Qingdao Municipal Center for Disease Control and Prevention, Qingdao Institute of Preventive Medicine, Qingdao 266033, China
Wang Wenhui
Henan Provincial Center for Disease Control and Prevention, Zhengzhou 450016, China
Wang Miao
Gansu Provincial Center for Disease Control and Prevention, Lanzhou 730000, China
Xie Hui
Beijing Center for Disease Control and Prevention, Beijing 100013, China
Wang Wenyang
Anhui University of Science and Technology, Huainan 232001, China
Zhu Zhen
NHC Key Laboratory of Medical Virology and Viral Diseases, WHO WPRO Regional Reference Laboratory of Measles and Rubella, National Measles Laboratory, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China
Zhang Yan
NHC Key Laboratory of Medical Virology and Viral Diseases, WHO WPRO Regional Reference Laboratory of Measles and Rubella, National Measles Laboratory, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China
Cui Aili
NHC Key Laboratory of Medical Virology and Viral Diseases, WHO WPRO Regional Reference Laboratory of Measles and Rubella, National Measles Laboratory, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China
Li Hai
NHC Key Laboratory of Medical Virology and Viral Diseases, WHO WPRO Regional Reference Laboratory of Measles and Rubella, National Measles Laboratory, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China
Mao Naiying
NHC Key Laboratory of Medical Virology and Viral Diseases, WHO WPRO Regional Reference Laboratory of Measles and Rubella, National Measles Laboratory, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China