Genetic Characteristics of Human Parainfluenza Virus Types 1-4 From Patients With Clinical Respiratory Tract Infection in China.

Nan Shao,Xinming Wang,Lilian Sun,Fan Yang,Bo Liu,Yan Xiao,Jie Dong,Ting Zhang,Yafang Zhu,Lili Ren

doi:10.3389/fmicb.2021.679246

Abstract

Human parainfluenza viruses (HPIV1–4) cause acute respiratory tract infections, thereby impacting human health worldwide. However, there are no current effective antivirals or licensed vaccines for infection prevention. Moreover, sequence information for human parainfluenza viruses (HPIVs) circulating in China is inadequate. Therefore, to shed light on viral genetic diversity and evolution, we collected samples from patients infected with HPIV1–4 in China from 2012 to 2018 to sequence the viruses. We obtained 24 consensus sequences, comprising 1 for HPIV1, 2 for HPIV2, 19 for HPIV3, and 2 for HPIV4A. Phylogenetic analyses classified the 1 HPIV1 into clade 2, and the 2 HPIV4 sequences into cluster 4A. Based on the hemagglutinin-neuraminidase (HN) gene, a new sub-cluster was identified in one of the HPIV2, namely G1c, and the 19 HPIV3 sequences were classified into the genetic lineages of C3f and C3a. The results indicated that HPIV1–4 were co-circulated in China. Further, the lineages of sub-cluster C3 of HPIV3 were co-circulated in China. A recombination analysis indicated that a putative recombination event may have occurred in the HN gene of HPIV3. In the obtained sequences of HPIV3, we found that two amino acid substitution sites (R73K in the F protein of PUMCH14028/2014 and A281V in the HN protein of PUMCH13961/2014) and a negative selection site (amino acid position 398 in the F protein) corresponded to the previously reported neutralization-related sites. Moreover, amino acid substitution site (K108E) corresponded to the negative selection site (amino acid position 108) in the 10 F proteins of HPIV3. However, no amino acid substitution site corresponded to the glycosylation site in the obtained HPIV3 sequences. These results might help in studying virus evolution, developing vaccines, and monitoring HPIV-related respiratory diseases.

Highlights

Human parainfluenza viruses (HPIVs) belong to the family Paramyxoviridae
HPIVs have been grouped into four serotypes according to genetic and antigenic variation (HPIV1–4), among which HPIV1 and HPIV3 are classified into the genus Respirovirus, whereas HPIV2 and HPIV4 are classified into the genus Rubulavirus (Canchola et al, 1964; Henrickson, 2003)
One HPIV1, two HPIV2, 19 HPIV3, and two HPIV4 sequences were obtained from the clinical samples that collected in 2012, 2014, 2017, and 2018

Summary

Introduction

Human parainfluenza viruses (HPIVs) belong to the family Paramyxoviridae. Human parainfluenza viruses are important causative agents of acute respiratory infections (ARIs) and commonly cause upper and lower respiratory tract infections (Schomacker et al, 2012). Lower respiratory tract infections are considered the principal cause of hospitalization and death in certain groups of people (Marx et al, 1999; Mao et al, 2012; Seo et al, 2014). The clinical symptoms of respiratory tract infections include croup, bronchitis, bronchiolitis, and pneumonia; some clinical manifestations are more related to individual HPIVs. HPIV1 and HPIV2 are most likely cause croup, whereas HPIV3 and HPIV4 are more associated with bronchiolitis and pneumonia (Fathima et al, 2016; Linster et al, 2018). HPIVs can co-infect with other viruses or bacteria, such as influenza viruses A and B, human respiratory syncytial virus (RSV), human rhinovirus, adenovirus, human coronavirus, human metapneumovirus, Mycoplasma pneumoniae, and Chlamydia (Liu et al, 2013; Zhong et al, 2019)

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