Department of Infectious Diseases, Peking University Hepatology Institute, Peking University People's Hospital, No. 11, Xizhimen South Street, Xicheng District, Beijing, 100044, People's Republic of China.
Peking University Hepatology Institute, Peking University People's Hospital, No. 11, Xizhimen South Street, Xicheng District, Beijing, 100044, People's Republic of China.
Virol J. 2020 Nov 19;17(1):182. doi: 10.1186/s12985-020-01446-3.
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.
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.
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 (χ, P < 0.05).
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.
甲型 H1N1 流感病毒经历了快速进化，近年来 HA 和 NA 的互补和拮抗作用受到了更多关注；然而，HA 和 NA 中的共发生突变对患者临床特征的影响仍知之甚少。在本研究中，我们分析了 A（H1N1）pdm09 的分子流行病学和进化，探讨了 HA 和 NA 中的共发生突变，并研究了共发生突变对患者临床特征的影响。
通过逆转录-聚合酶链反应（RT-PCR）确认 A（H1N1）pdm09。对 HA 和 NA 基因进行测序和系统发育分析。对共发生突变的临床特征进行统计学分析。
通过分析 2015-2017 年流感季节 33 株 A（H1N1）pdm09 的 HA 和 NA 基因序列，发现所有病毒彼此之间高度相似，这些病毒的 HA 基因均属于 6B.1A 亚组。还观察到 HA 和 NA 蛋白中的几个未报告的取代，此外，在 30.3%（10/33）的 A（H1N1）pdm09 病毒株中检测到 HA-V169T、A278S、E508G、D518E 和 NA-V67I 的共发生突变，与疫苗株 A/加利福尼亚/07/2009 和 A/密歇根/45/2015（H1N1）相比。与 A（H1N1）pdm09 的 HA 和 NA 共发生突变相比，喉咙痛与 A（H1N1）pdm09 显著相关（χ，P < 0.05）。
在北京 2015-2017 年分离的 A（H1N1）pdm09 中检测到 HA 和 NA 中的共发生突变。症状上，喉咙痛与 A（H1N1）pdm09 的 HA 和 NA 中的共发生突变有关。因此，研究 HA 和 NA 中的共发生突变对患者临床特征的影响和机制值得注意。
