Abstract

BackgroundInfluenza A(H1N1)pdm09 viruses have undergone rapid evolution, and in recent years the complementary and antagonistic effects of HA and NA have gathered more attentions; however, the effects of co-occurring mutations in HA and NA on the patients’ clinical characteristics are still poorly understood. In this study, we analyzed molecular epidemiology and evolution of A(H1N1) pdm09, explored co-occurring mutations of HA and NA, and investigated effect of co-occurring mutations on patients’ clinical features.MethodsA(H1N1)pdm09 was confirmed by reverse transcription-polymerase chain reaction. HA and NA genes were sequenced and phylogenetically analyzed. Clinical characteristics of the co-occurring mutations were analyzed statistically.ResultsBy analyzing the HA and NA gene sequences of 33 A(H1N1)pdm09 viruses during the 2015–2017 influenza season, we found that all the viruses shared high similarities to each other and the HA genes of these viruses exclusively belonged to subclade 6B.1A. Several unreported substitutions in HA and NA proteins were observed, furthermore, co-occurring mutations of HA-V169T, A278S, E508G, D518E and NA-V67I were detected in 30.3% (10/33) A(H1N1)pdm09 virus strains when comparing with vaccine strains A/California/07/2009 and A/Michigan/45/2015 (H1N1). Sore throat was significantly associated with co-occurring mutations in HA and NA of A(H1N1)pdm09 (χ2, P < 0.05).ConclusionsCo-occurring mutations in HA and NA were detected in A(H1N1)pdm09 isolated during 2015–2017 in Beijing. Symptomatically, sore throat was associated with co-occurring mutations in HA and NA of A(H1N1)pdm09. Therefore, studying the effect and mechanism of co-occurring mutations in HA and NA on patients’ clinical features is of note needed.

Highlights

  • Influenza A(H1N1)pdm09 viruses have undergone rapid evolution, and in recent years the complementary and antagonistic effects of HA and NA have gathered more attentions; the effects of co-occurring mutations in HA and NA on the patients’ clinical characteristics are still poorly understood

  • In order to elucidate the epidemiology of influenza virus in northern China during April 2015 to May 2017, we summarized the weekly data during the influenza epidemic

  • Co‐occurring mutation analysis in both HA and NA proteins Based on above substitution analysis of HA and NA genes, co-occurring mutations of HA-V169T, A278S, E508G, D518E and NA-V67I were detected in 30.3% (10/33) A(H1N1)pdm09 virus strains when comparing with vaccine strains A/California/07/2009 and A/Michigan/45/2015 (H1N1)

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Summary

Introduction

Influenza A(H1N1)pdm viruses have undergone rapid evolution, and in recent years the complementary and antagonistic effects of HA and NA have gathered more attentions; the effects of co-occurring mutations in HA and NA on the patients’ clinical characteristics are still poorly understood. We analyzed molecular epidemiology and evolution of A(H1N1) pdm, explored co-occurring mutations of HA and NA, and investigated effect of co-occurring mutations on patients’ clinical features. Influenza is one of the most important respiratory infections of humans with significant morbidity and mortality each year worldwide. Evolutionary analysis of previous studies showed that influenza A(H1N1) pdm virus was derived from several viruses circulating in swine, and that the initial transmission to humans occurred several months before recognition of the outbreak [6]. Active epidemiological monitoring of influenza virus at molecular level is necessary [7], which is conducive to understand the evolution of influenza virus, in order to better select vaccine strains for effective prevention [8]

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