Phylogenetic analysis of HA and NA genes and clinical characteristics of the co-occurring mutations in HA and NA of influenza A(H1N1)pdm09 viruses during 2015-2017 in Beijing, China

Abstract

Background: 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; 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.Methods: A(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.Results: By 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).Conclusions: Co-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.

Consortium of “consistent amino acid substitutions” on Influenza A (H1N1) viral proteome emerged at specific stages of viral infection: A big data analysis

“…and c) 234 to 244 (220-loop). As sialic acid binding to HA protein is an important step to viral entry, a significant substitution, reported earlier, D239N (numbering according to H1 strain), impacted glycan binding specificity (3,16,17); however, that was not observed in our present "consistent substitutions." There are four "consistent substitutions" in RBS, i) 130-loop: N146D, ii) 130-loop: K147N, iii) 190-helix: Q206E, and iv) 220-loop: E241A [Table 1b].…”

Phylogenetic analysis of HA and NA genes of influenza A viruses in immunosuppressed inpatients in Beijing during the 2018-2020 influenza seasons

“…1). The genetic evolution of in uenza virus is gradual, and our team conducted active monitoring of in uenza at the molecular level since 2012 [25,26,27,28]. In this study, we analysed molecular epidemiology and evolution of HA and NA of in uenza A viruses in immunosuppressed population, and immunocompetent population were used as controls.…”