我国柯萨奇病毒A组6型VP1区基因分子流行病学特征

范云燕; 欧嵩凤; 陈敏玫

doi:10.16462/j.cnki.zhjbkz.2020.08.014

我国柯萨奇病毒A组6型VP1区基因分子流行病学特征

doi: 10.16462/j.cnki.zhjbkz.2020.08.014

1.
530023 南宁, 南宁市疾病预防控制中心
2.
530028 南宁, 广西壮族自治区疾病预防控制中心

基金项目:

广西自然科学基金项目 2017GXNSFAA198369

详细信息

通讯作者:
陈敏玫，E-mail:13707719199@163.com

中图分类号: R181
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- 被引次数: 0
出版历程
- 收稿日期: 2020-02-01
- 修回日期: 2020-04-18
- 刊出日期: 2020-08-10

Molecular epidemiological characterization for VP1 region gene of coxsackievirus A6 in China

1.
Nanning Center for Disease Control and Prevention, Nanning 530023, China
2.
Guangxi Center for Disease Control and Prevention, Nanning 530028, China

Funds:

Natural Science Foundation of Guangxi Autonomous Region 2017GXNSFAA198369

More Information

Corresponding author: CHEN Min-mei, E-mail:13707719199@163.com

摘要

摘要: 目的分析我国2010―2018年柯萨奇病毒A组6型（Coxsackievirus A6，CV-A6）毒株VP1区基因流行和进化规律，为手足口病的防治提供科学依据。方法从GenBank获得2010―2018年我国CV-A6病毒全长VP1区核苷酸序列，用MEGA V7.0和Interactive Tree of Life V5（iTOLV5）软件构建进化树，用DNAstar V8.1.3软件对核苷酸同源性进行分析。结果 880条序列来源的CV-A6毒株以D3亚型为主，占毒株总数的95.45%，不同基因型核苷酸同源性为80.8%~86.0%，同基因型内核苷酸同源性为88.1%~100.0%。D2亚型VP1区相对稳定，无整体氨基酸变异情况；而D3毒株VP1区发生多点氨基酸替换，其中A5T、T283A、N137S、V242I、A30V、I174V氨基酸替换循环出现，这种进化模式与越南地区相似，但与日本地区却不同。VP1区5T、30A、137N、242V比例逐年增加，可能与CV-A6引起我国手足口的轻症和重症病例比例上升有关。结论具有VP1区遗传多样性的CV-A6 D3株的出现可能是CV-A6在反复流行的一个重要因素，这有助于解释我国CV-A6的流行情况和流行特点。
- 柯萨奇病毒A组6型 /
- VP1区基因 /
- 分子流行病学
Abstract: Objective To analyze the epidemic and genetic evolution principals of Coxsackievirus group A type 6 (CV-A6) VP1 region from 2010 to 2018 in China so as to provide scientific basis for the prevention and treatment of Hand-foot-mouth disease (HFMD). Methods The full-length VP1 nucleotide sequence of CV-A6 virus from 2010 to 2018 in China was obtained from GenBank. The phylogenetic trees based on VP1 sequences of CV-A6 were constructed by the MEGA V7.0 and Interactive Tree of Life V5 (iTOLV5) software, and the nucleotide homology was analyzed with DNAstar V8.1.3. Results The CV-A6 D3 was the main sub-genotype, accounting for 95.45% of the total 880 strains. The homology of nucleotides sequences in different genotype was between 80.8% and 86.0% while the homology of nucleotides sequences in the same genotype was between 88.1% and 100.0%.The VP1 sequences of D2 was relatively stable without any global amino acid variation. However, the VP1 sequences of D3 had multi-point amino acid substitutions, in which A5T, T283A, N137S, V242I, A30V and I174V amino acid substitution occurred circularly. This evolutionary pattern was similar to that in Vietnam but different from that in Japan. The proportion of 5T, 30A, 137N and 242V in the VP1 region increased year by year, which may be related to the increasing proportion of the mild and severe cases of HFMD caused by CV-A6 in China. Conclusions The emergence of CV-A6 D3 Sub-genotype strains with high genetic diversity in VP1 region could be a factor associated with the repeated epidemics, which helps to explain the epidemics and characteristics of CV-A6 in China.
- Coxsackievirus group A type 6 /
- VP1 region gene /
- Molecular epidemiology

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图 1 2010-2018年我国CV-A6 VP1区基因系统进化树

Figure 1. Phylogenetic tree of CV-A6 VP1 sequences isolated in mainland China from 2010 to 2018

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图 2 CV-A6 D2亚型和D3亚型毒株年度比例分布图

Figure 2. Yearly proportional distribution of CV-A6 sub-genotypes D2 and D3

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图 3 CV-A6 D3亚型VP1区6个氨基酸年度替换比例分布

Figure 3. Yearly proportional distribution of amino acid substitution ratio in 6 sites of VP1 region from CV-A6 D3 strains

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表 1 CV-A6原型毒株及参考株

Table 1. CV-A6 prototype strain and reference strain

序号	GenBank 登录号	菌株名称	来源	年份	基因型 /亚型
1	AY421764	Gdula	美国	1949	A
2	JQ364886	92022/SD/CHN/1992	中国	1992	B1
3	KP143075	AFP262/GD/CHN/2005	中国	2008	B2
4	JQ364887	96188/SD/CHN/1996	中国	1996	C1
5	JN203517	N-313	印度	2008	C2
6	FR797988	ESP08/54698	西班牙	2011	D1
7	KC86690	JB14080448	中国	2008	D2
8	KC86616	JB143090122	中国	2009	D2
9	JQ364889	10032/SD/CHN/2010	中国	2010	D2
10	KM114057	Finland/2008	芬兰	2008	D3
11	AB779618	Kyoto5	日本	2009	D3
12	HE572906	CF140007_FRA10	法国	2010	D3
13	JN582001	TW/1537/2011	中国台湾	2011	D3

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表 2 2010-2018年不同省/自治区/直辖市CV-A6 VP1区序列分布情况

Table 2. CV-A6 VP1 sequences in different province from 2010 to 2018

地区	序列数量(条)									合计(%)
地区	2010年	2011年	2012年	2013年	2014年	2015年	2016年	2017年	2018年	合计(%)
上海	2	30	66	87	19	17				221(25.11)
云南				9	50	8	42	63	43	215(24.43)
广西	1	2	7	5	10	17	8	51		101(11.48)
北京	2	3		17	19	29	19			89(10.11)
河南		3	9	30	13	24				79(8.98)
江西			23	20	5	3				51(5.80)
江苏				28						28(3.18)
山东	1			4		5			14	24(2.73)
河北		1	1	4		7				13(1.48)
新疆			2	4	3	1				10(1.14)
甘肃		1		1	2	5				9(1.02)
吉林				6		1				7(0.80)
辽宁				1	1	5				7(0.80)
山西		2		4						6(0.68)
广东				3	2					5(0.57)
湖南					3	2				5(0.57)
四川				2	1	1				4(0.45)
浙江				4						4(0.45)
重庆						2				2(0.23)
合计	6	42	108	229	128	127	69	114	57	880(100.00)

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表 3 CV-A10病毒VP1区核苷酸序列同源性比对分析

Table 3. The homology analysis of CV-A6 VP1 nucleotide acid sequences

参考株/各年度毒株	基因型/亚型	核苷酸同源性(%)
参考株/各年度毒株	基因型/亚型	2010年	2011年	2012年	2013年	2014年	2015年	2016年	2017年	2018年
Gdula	A	81.4~83.7	80.8~83.7	81.5~83.5	81.3~83.6	81.7~84.2	81.9~84.2	82.0~83.7	81.5~83.9	82.0~83.8
92022/SD/CHN/1992	B1	82.5~83.6	82.2~83.7	82.7~84.0	82.3~84.4	82.2~84.5	82.2~84.5	82.6~84.2	82.4~84.5	82.7~84.2
AFP262/GD/CHN/2005	B2	83.6~84.6	83.1~84.6	82.8~84.8	83.0~85.0	83.1~85.1	83.1~85.1	83.4~84.7	83.1~85.0	83.6~85.2
96188/SD/CHN/1996	C1	84.6~85.7	84.5~85.6	84.3~85.6	83.5~86.0	83.4~85.9	83.7~85.9	84.2~85.8	84.0~85.7	83.9~86.0
N~313	C2	84.3~85.4	84.5~85.6	83.9~85.8	83.5~85.8	83.6~86.0	83.6~86.0	83.3~85.7	83.3~85.4	83.1~84.7
ESP08/54698	D1	90.4~100.0	90.6~91.7	90.6~92.3	89.0~92.3	89.0~92.3	90.5~92.3	89.8~91.9	89.5~91.7	90.2~91.8
JB14080448	D2	91.0~98.0	90.2~97.2	89.9~97.7	89.9~97.0	89.6~95.5	89.6~91.5	88.9~91.3	88.6~90.5	88.3~90.8
JB143090122	D2	91.1~98.3	90.3~98.1	90.1~98.3	89.7~96.7	89.8~94.5	89.6~91.6	89.0~91.6	88.7~91.6	88.9~91.3
10032/SD/CHN/2010	D2	90.3~100.0	89.6~97.2	89.5~97.0	89.3~98.1	89.2~94.6	89.8~90.8	88.2~90.7	88.0~90.5	88.2~90.5
Finland/2008	D3	90.6~96.8	90.7~97.0	90.7~96.8	89.3~96.8	89.3~96.4	94.6~96.4	94.2~95.7	93.7~95.4	92.8~95.3
Kyoto5	D3	90.3~96.9	89.9~97.2	90.2~96.9	88.1~96.7	88.3~96.5	94.6~96.5	93.6~96.2	93.7~95.6	93.7~95.4
CF140007_FRA10	D3	90.8~96.2	91.1~96.0	90.9~96.5	89.5~96.4	89.5~96.2	94.2~96.2	93.6~95.5	93.2~95.2	92.8~95.3
TW/1537/2011	D3	90.8~99.6	90.6~97.8	90.7~98.8	89.0~99.1	89.1~98.9	95.2~98.9	94.1~98.8	94.5~98.0	95.5~97.9
2010年	D2/D3	90.3~98.3	89.6~99.7	89.5~99.2	88.5~99.1	88.5~98.7	88.7~98.4	88.2~97.7	88.0~96.3	88.2~96.3
2011年	D2/D3		89.0~99.9	88.8~99.6	88.0~99.6	88.0~99.1	88.2~98.9	87.8~98.1	87.4~96.6	87.1~96.5
2012年	D2/D3			89.7~100.0	87.5~100.0	89.4~99.8	89.3~99.6	89.1~99.5	89.0~99.5	88.1~99.6
2013年	D2/D3				88.0~100.0	87.8~99.6	87.1~99.6	87.2~99.5	86.1~99.1	86.1~98.6
2014年	D2/D3					88.0~100.0	87.5~99.9	92.3~99.6	86.9~99.5	86.1~98.3
2015年	D3						92.0~100.0	91.5~99.8	91.8~99.5	91.1~98.5
2016年	D3							91.5~100.0	90.9~99.9	91.1~99.0
2017年	D3								92.2~100.0	91.1~99.7
2018年	D3									93.9~100.0

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