Metagenomic analysis of viral genetic diversity in respiratory samples from children with severe acute respiratory infection in China

Abstract

Severe acute respiratory infection (SARI) in children is thought to be mainly caused by infection with various viruses, some of which have been well characterized; however, analyses of respiratory tract viromes among children with SARI versus those without are limited. In this study, nasopharyngeal swabs from children with and without SARI (135 versus 15) were collected in China between 2008 and 2010 and subjected to multiplex metagenomic analyses using a next-generation sequencing platform. The results show that members of the Paramyxoviridae, Coronaviridae, Parvoviridae, Orthomyxoviridae, Picornaviridae, Anelloviridae and Adenoviridae families represented the most abundant species identified (>50% genome coverage) in the respiratory tracts of children with SARI. The viral population found in the respiratory tracts of children without SARI was less diverse and mainly dominated by the Anelloviridae family with only a small proportion of common epidemic respiratory viruses. Several almost complete viral genomes were assembled, and the genetic diversity was determined among several samples based on next-generation sequencing. This research provides comprehensive mapping of the viromes of children with SARI and indicates high heterogeneity of known viruses present in the childhood respiratory tract, which may benefit the detection and prevention of respiratory disease.

Keywords: Children; metagenomics; next-generation sequencing; severe acute respiratory tract infection; virome.

Fig. 1

An overview of class distribution of viral content from children with severe acute respiratory infection (SARI) and control group. There were seven main families in the respiratory tract of children with SARI, including Paramyxoviridae, Coronaviridae, Parvoviridae, Orthomyxoviridae, Picornaviridae, Adenoviridae and Anelloviridae.

Fig. 2

Viral genome coverage and sequencing depth analysis. The three representatives included (a) human respiratory syncytial virus (HRSV), (b) human bocavirus 1 (HBoV1), (c) Torque teno mini virus 8 (TTMV-8), (d) influenza A virus segment 8. The main genes of every virus are indicated in the corresponding figures.