Pathogenetic characteristics of the first local case of severe fever with thrombocytopenia syndrome in Beijing
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摘要:
目的 对北京市首例发热伴血小板减少综合征（SFTS）本土病例进行病原学特征研究。 方法 对患者样本进行病毒分离、全基因测序，与不同基因型的发热伴血小板减少综合征病毒（SFTSV）进行同源性比较和遗传进化分析，并且对基因进行重组重配分析和氨基酸突变位点分析。 结果 从患者血液标本中分离到病毒，将其命名为BJ001-2021。 该毒株的L、M片段与河南省的17-China_Henan-72株最为接近，S片段与来自山东省的SD2013-094最为接近，遗传进化分析结果显示BJ001-2021与HB29、SD24等同属于B基因型,无基因重配重组事件，但发现一些氨基酸突变位点。 结论 北京市首例本土SFTS病例由SFTSV的B基因型引起，未发生基因组的重组重配。 -
关键词:
- 发热伴血小板减少综合征 /
- 本土病例 /
- B基因型 /
- 氨基酸突变
Abstract:Objective To investigate the pathogenetic characteristics of the first local case of severe fever with thrombocytopenia syndrome (SFTS) in Beijing. Methods Virus isolation from patient samples and full-genome sequencing were performed, followed by homology comparison and phylogenetic analysis with different genotypes of SFTS virus. Recombination and amino acid mutation site analyses were also conducted. Results The virus was isolated from the patient's blood sample and named as BJ001-2021. The L and M segments of the isolated virus were most closely related to the 17-China_Henan-72 strain from Henan, while the S segment was most closely related to the SD2013-094 strain from Shandong. Phylogenetic tree indicated that BJ001-2021 belongs to genotype B, along with HB29 and SD24, and no gene recombination occurred, however, some amino acid mutation sites were identified. Conclusion The first local case of SFTS in Beijing was caused by SFTS virus genotype B, and no gene recombination or reassortment occurred. -
图 1 发热伴血小板减少综合征病毒L、M、S片段全基因组的遗传进化分析
注：红色圆点表示北京分离株；A、B、C、D、E、F表示不同的基因型别
Figure 1. Phylogenetic analysis based on the complete nucleotide sequences of the L, M and S segments of severe fever with thrombocytopenia syndrome virus
表 1 发热伴血小板减少综合征病毒A～F基因型参考株序列信息
Table 1. Sequnce information for genotype A–F strains of severe fever with thrombocytopenia syndrome virus
毒株 地点 GenBank 序列号 基因型a L M S AHZ/China/2011 中国安徽省 JQ670929 JQ670931 JQ670933 A LN2 中国辽宁省 HQ141607 HQ141608 HQ141609 A 20 中国河南省 JF682773 JF682774 JF682775 A JS2011-034 中国江苏省 KC505132 KC505133 KC505134 A Gangwon/Korea/2012 韩国 KF358691 KF358692 KF358693 A HB2014-04 中国湖北省 KU524075 KR080475 KP984502 A HN-LR/China/05/2012 中国浙江省 KR017842 KR017861 KR017823 A SD24 中国山东省 HM802200 HM802201 HM802205 B JS2011-062 中国江苏省 KC505135 KC505136 KC505137 B 2012YSH9 中国河南省 KF711882 KF711921 KF711890 B KASJH 韩国 KP663731 KP663732 KP663733 B SD2015-094 中国山东省 MT005228 MT005270 MT114318 B HB29 中国湖北省 NC_018136 NC_018138 NC_018137 B LN2012-038 中国辽宁省 MT114207 MT114223 MT114267 B SD4 中国山东省 HM802202 HM802203 HM802204 C JS4 中国省江苏 HQ141604 HQ141605 HQ141606 C SD2012-017 中国山东省 MT005213 MT005255 MT114303 C SD2013-054 中国山东省 MT005218 MT005260 MT114308 C SD2014-157 中国山东省 MT005233 MT005275 MT114323 C SPL087A 日本 AB983515 AB985309 AB985541 D D E AHL/China/2011 中国安徽省 JQ670934 JQ670930 JQ670932 D E B AH15 中国安徽省 HQ141592 HQ141593 HQ141594 E LN3 中国辽宁省 HQ141610 HQ141611 HQ141612 E 2010-FQM 中国湖北省 HQ419227 HQ419236 HQ419240 E JS2007-01 中国江苏省 JF837593 JF837594 JF837595 E 2012YXX1 中国河南省 KF711862 KF711929 KF711901 E NB08/CHN/2013 中国浙江省 KR698349 KR698336 KR698323 E SD2013-076 中国山东省 MT005223 MT005265 MT114313 E SPL003A 日本 AB817980 AB817988 AB817996 F SPL129A 日本 AB983533 AB985326 AB985559 F Zhao 中国浙江省 KF374682 KF374683 KF374684 F KACNH3 韩国 KP663743 KP663744 KP663745 F NB24/CHN/2013 中国浙江省 KR698350 KR698337 KR698324 F DS02/CHN/2013 中国浙江省 KR698345 KR698332 KR698319 F _KAGBH6 韩国 KP663740 KP663741 KP663742 F 注：a.3个片段的分型结果，3个基因型为3个片段结果分属不同基因型 
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表 2 发热伴血小板减少综合征病毒RNA依赖的RNA聚合酶氨基酸变异情况
Table 2. Comparison of RNA-dependent RNA polymerase amino acid substitutions among genotypes of severe fever with thrombocytopenia syndrome virus
基因型 毒 株 位 点 449 479 572 1045 1353 1447 1684 1991 B OQ832099 BJ001-2021 T I R S T V K T HM802200 Shandong SD24 · V K · N · · A KC505135 Jiangsu JS2011-062 · V K · N I R A KF711881 Henan 2012YSH9 · V K · N · · A KP663731 South Korea KASJH · V K · N I R A MT005241 Shandong SD2015-101 · V K · N · · A NC 018136 Hubei HB29 · V K · N · · A MT114207 Liaoning LN2012-038 · V K · N I R A A JQ670929 Anhui AHZ-China-2011- · · K · N I R A HQ141607 Liaoning LN2 · · K · N I R A JF682773 Henan 20 · · K · N I R A KC505132 Jiangsu JS2011-034 · · K · N I R A KF358691 South Korea Gangwon Korea 2012 · · K · N I R A KR080475 Hubei HB2014-04 · · K · N I R A KR017842 Zhejiang HN-LR-China-05-2012 · · K · N I R A C HM802202 Shandong SD4 · · K T S I R A HQ141604 Jiangsu JS4 · · K T S I R A MT005213 Shandong SD2012-017 · · K T S I R A MT005218 Shandong SD2013-054 · · K T S I R A MT005233 Shandong SD2014-157 · · K T S I R A E HQ141592 Anhui AH15 A V K · S I R A HQ141610 Liaonin LN3 A V K · S I R A HQ419227 Hubei 2010-FQM A V K · N I R A JF837593 Jiangsu JS2007-01 A V K · N I R A KF711862 Henan 2012YXX1 A V K · N I R A KR698349 Zhejinag NB08-CHN-2013 A V K · N I R A MT005223 Shandong SD2013-076 A V K · N I R A F AB817980 Japan SPL003A · V K · N I R A AB983533 Japan SPL129A · · K · N I R A KF374682 Zhejiang Zhao · V K · N I R A KP6637443 South korea KACNH3 · · K · N · R A KR698350 Zhejiang NB24-CHN-2013 · V K · N I R A KR698345 Zhejiang DS02-CHN-2013 · V K · N I R A KP663740 South korea KAGBH6 · V K · N I R A 注：T. 苏氨酸；A. 丙氨酸； I. 异亮氨酸；V. 缬氨酸；R. 精氨酸；K. 赖氨酸；S. 丝氨酸；N. 天冬酰胺
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表 3 发热伴血小板减少综合征病毒糖蛋白氨基酸变异情况
Table 3. Comparison of glycoprotein amino acid substitutions among genotypes of severe fever with thrombocytopenia syndrome virus
基因型 毒 株 位 点 13 18 273 466 479 491 525 662 787 962 1053 B OQ832098 Beijing BJ001-2021 L S A S V M G P R S L HM802201 Shandong SD24 · · · G · · · · K R · KC505136 Jiangsu JS2011-062 · · · G · · · · K · · KF711919 Henan 2012YSH9 · · · G · · · · K · · KP663732 South Korea KASJH · · · G · · · · K · · MT005270 Shandng SD2013-094 · · · G · · · · K · · NC018138 Hubei HB29 · · · G · · · · K · · MT114223 Liaoning LN2012-038 · · · G · I · · K · · A JQ670931 Anhui AHZ/China/2011 H · T G I I R · K · M HQ141608 Liaoning LN2 H · T G I I R · K · M JF682774 Henan 20 H · T G I I R · K · M KC505133 Jiangsu JS2011-034 H · T G I · R · K · M KF358692 South Korea Gangwon/Korea/2012 H · T G I I R · K · M KR080475 Hubei HB2014-04 H · T G I I R · K · M KR017861 Zhejiang HN-LR/China/05/2012 H · T G I I R · K · M C HM802203 Shandong SD4 H · T G · L R · K · · HQ141605 Jiangsu JS4 H · T G · L R · K · · MT005255 Shandong SD2012-017 H · T G · L R · K · · MT005260 Shandong SD2013-054 H · T G · L R · K · · MT005275 Shandong SD2014-157 H · T G · L R · K · · E HQ141593 Anhui AH15 · G T G · V R · K · · HQ141611 Liaonin LN3 · G T G · V R · K · · HQ419236 Hubei 2010-FQM · G · G · V R · K · · JF837594 Jiangsu JS2007-01 · G T G · V R · K · · KF711929 Henan 2012YXX1 · G T G · V R · K · · KR698336 Zhejinag NB08/CHN/2013 · G T G · V R · K · · MT005265 Shandong SD2013-076 · G T G · · R · K · · F AB817988 Japan SPL003A · · T G · · R S K · · AB985326 Japan SPL129A · · T G · · R S K · · KF374684 Zhejiang Zhao · · T G · · R S K · · KP663744 South korea KACNH3 · · T G · · R S K · · KR698337 Zhejiang NB24/CHN/2013 · · T G · · R S K · · KR698332 Zhejiang DS02/CHN/2013 · · T G · · R S K · · KP663741 South korea KAGBH6 · · T G · R S K · · 注：L. 亮氨酸；F. 苯丙氨酸；S. 丝氨酸；G. 甘氨酸；V. 缬氨酸； I. 异亮氨酸；M. 甲硫氨酸； L. 亮氨酸；R. 精氨酸；P. 脯氨酸；K. 赖氨酸
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表 4 非结构蛋白氨基酸变异情况
Table 4. Comparison of nonstructural protein amino acid substitutions among genotypes
基因型 毒 株 位点 85 272 B OQ832099 BJ001-2021 C S HM802200 Shandong SD24 Y T KC505135 Jiangsu JS2011-062 Y T KF711881 Henan 2012YSH9 Y T KP663731 South Korea KASJH Y T MT005241 Shandong SD2015-101 Y T NC 018136 Hubei HB29 Y T MT114207 Liaoning LN2012-038 Y T A JQ670929 Anhui AHZ-China-2011 Y T HQ141607 Liaoning LN2 Y T JF682773 Henan 20 Y T KC505132 Jiangsu JS2011-034 Y T KF358691 South Korea Gangwon Korea 2012 Y T KR080475 Hubei HB2014-04 Y T KR017842 Zhejiang HN-LR-China-05-2012 Y T C HM802202 Shandong SD4 Y T HQ141604 Jiangsu JS4 Y T MT005213 Shandong SD2012-017 Y T MT005218 Shandong SD2013-054 Y T MT005233 Shandong SD2014-157 Y T E HQ141592 Anhui AH15 Y T HQ141610 Liaonin LN3 Y T HQ419227 Hubei 2010-FQM Y T JF837593 Jiangsu JS2007-01 Y T KF711862 Henan 2012YXX1 Y T KR698349 Zhejinag NB08-CHN-2013 Y T MT005223 Shandong SD2013-076 Y T F AB817980 Japan SPL003A Y T AB983533 Japan SPL129A Y T KF374682 Zhejiang Zhao Y T KP6637443 South korea KACNH3 Y T KR698350 Zhejiang NB24-CHN-2013 Y T KR698345 Zhejiang DS02-CHN-2013 Y T KP663740 South korea KAGBH6 Y T 注：C. 半胱氨酸；Y. 酪氨酸； S. 丝氨酸；T. 苏氨酸
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