Phylogenetic analysis and clinical characteristics of the co-occurring mutations in HA and NA genes of influenza A(H1N1)
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RESEARCH
Phylogenetic analysis and clinical characteristics of the co‑occurring mutations in HA and NA genes of influenza A(H1N1) pdm09 viruses during 2015–2017 in Beijing, China Yafen Liu1†, Yue Wang1†, Baiyi Liu1, Xu Cong2, Ying Ji2, Xiaolin Guo1 and Yan Gao1*
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
Fever hours
30.0 ± 17.2
37.2 ± 24.3
> 0.05
Max temperature (°C)
39.1 ± 0.5
39.1 ± 0.4
> 0.05
Headache (%)
5 (50.0)
6 (60.0)
> 0.05
Joint and muscular soreness (%)
7 (70.0)
9 (90.0)
> 0.05
Nasal congestion and rhinorrhea (%)
5 (50.0)
6 (60.0)
> 0.05
Sore throat (%)
10 (100.0)
5 (50.0)
0.05
Expectoration (%)
3 (30.0)
7 (70.0)
> 0.05
Chestpain (%)
2 (20.0)
0 (0.0)
> 0.05
White blood cell counts (× 109/L)
7.6 ± 3.2
6.5 ± 1.2
> 0.05
Neutrophil (%)
71.5 ± 10.7
73.0 ± 8.2
> 0.05
Neutrophil (× 109/L)
5.5 ± 2.6
4.7 ± 1.2
> 0.05
Lymphocyte (%)
17.0 ± 6.3
15.4 ± 5.6
> 0.05
Lymphocyte (× 109/L)
1.2 ± 0.6
1.0 ± 0.4
> 0.05
Monocyte (%)
10.3 ± 5.0
10.9 ± 3.2
> 0.05
Monocyte (× 109/L)
0.8 ± 0.6
0.7 ± 0.2
> 0.05
Hemoglobin(g/L)
136.1 ± 22.9
139.7 ± 12.7
> 0.05
Platelets (× 109/L)
209.5 ± 53.0
205.3 ± 34.7
> 0.05
C-reactive protein (mg/L)
15.7 ± 9.9
21.2 ± 33.2
> 0.05
Pneumonia (%)
0 (0.0)
1 (10.0)
> 0.05
Liu et al. Virol J
(2020) 17:182
Conclusions In this study, we analyzed molecular evolution and amino acid variation characteristics of HA and NA of A(H1N1) pdm09 during the 2015–2017 influenza seasons in Beijing, founding these viruses shared common evolutionary lineages to the vaccine strain A/Michigan/45/2015 (H1N1). However, through our team’s monitoring on molecular
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