Recent Molecular Evolution of Human Metapneumovirus (HMPV): Subdivision of HMPV A2b Strains.

Naganori Nao,Tsuyoshi Sekizuka,Nobuko Tanaka,Makoto Takeda,Miwako Saikusa,Hidekazu Nishimura,Shuzo Usuku,Ko Sato

doi:10.3390/microorganisms8091280

Naganori Nao, Tsuyoshi Sekizuka + Show 6 more

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https://doi.org/10.3390/microorganisms8091280

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Abstract

Human metapneumovirus (HMPV) is a major etiological agent of acute respiratory infections in humans. HMPV has been circulating worldwide for more than six decades and is currently divided into five agreed-upon subtypes: A1, A2a, A2b, B1, and B2. Recently, the novel HMPV subtypes A2c, A2b1, and A2b2 have been proposed. However, the phylogenetic and evolutionary relationships between these recently proposed HMPV subtypes are unclear. Here, we report a genome-wide phylogenetic and evolutionary analysis of 161 HMPV strains, including unique HMPV subtype A2b strains with a 180- or 111-nucleotide duplication in the G gene (nt-dup). Our data demonstrate that the HMPV A2b subtype contains two distinct subtypes, A2b1 and A2b2, and that the HMPV subtypes A2c and A2b2 may be different names for the same subtype. HMPV A2b strains with a nt-dup also belong to subtype A2b2. Molecular evolutionary analyses indicate that subtypes A2b1 and A2b2 diverged from subtype A2b around a decade after the subtype A2 was divided into the subtypes A2a and A2b. These data support the A2b1 and A2b2 subtypes proposed in 2012 and are essential for the unified classification of HMPV subtype A2 strains, which is important for future HMPV surveillance and epidemiological studies.

Highlights

Human metapneumovirus (HMPV) was first discovered in 2001, but seroepidemiological studies indicate that HMPV has been a major etiological agent of acute respiratory infections (ARIs) in humans for more than six decades [1]
VeroE6/TMPRSS2 cells were inoculated with the HMPV A2b111nt-dup strains from clinical specimens, incubated with DMEM supplemented with 5% fetal calf serum (FCS) and antibiotics until a cytopathic effect (CPE) was observed
The HMPV A2b111nt-dup strains isolated in Yokohama city belong to subtype A2b2 together with seven other HMPV strains that were isolated in Sendai city, Japan, four of which have a 180nt-dup and three of which have no nt-dup

Summary

Introduction

Human metapneumovirus (HMPV) was first discovered in 2001, but seroepidemiological studies indicate that HMPV has been a major etiological agent of acute respiratory infections (ARIs) in humans for more than six decades [1]. The SH protein may suppress the innate immune response of host cells via suppressing NF-κB activation [11]. This protein has properties consistent with those of a viroporin and can modulate viral fusogenic activity [12]. The G protein of some HMPV lineages binds to glycosaminoglycans on the host cell surface and contributes to HMPV infection [13,14]. The HMPV G protein associates with RIG-I, inhibits RIG-I-dependent gene transcription, and suppresses host innate immune responses [15]

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