Epistatic roles of E2 glycoprotein mutations in adaption of chikungunya virus to Aedes albopictus and Ae. aegypti mosquitoes.

Epistatic roles of E2 glycoprotein mutations in adaption of chikungunya virus to Aedes albopictus and Ae. aegypti mosquitoes.
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DOI:
10.1371/journal.pone.0006835
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发表时间:
2009-08-31
期刊:
影响因子:
3.7
通讯作者:
Higgs S
Higgs S
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Tsetsarkin KA;McGee CE;Volk SM;Vanlandingham DL;Weaver SC;Higgs S

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在2005年至2007年期间,基孔肯雅病毒(CHIKV)引起了有史以来最大的爆发/流行。这种流行病的一个不寻常的特点是涉及的AE。白纹伊蚊为主要传播媒介。先前我们已经证明,当在充分表征的CHIKV毒株LR 2006 OPY 1和37997的背景中表达时,单一突变E1-A226 V显著改变了病毒感染和通过该载体传播的能力。然而,在目前的研究中,我们证明,引入E1-A226 V突变的感染性克隆来源于Ag 41855株(1982年在乌干达分离)的背景并没有显着增加感染性。白纹伊蚊为了阐明影响CHIKV对Ae.在白纹伊蚊中,LR 2006 OPY 1和Ag 41855毒株的基因组用于构建嵌合病毒和在选定位置具有点突变的特定组合的病毒。根据Ae. albopictus和Ae.埃及蚊中,E2-60和E2-211位突变对媒介感染的关键作用被揭示。E2-G60 D突变是CHIKV对Ae. albopictus和Ae.埃及伊蚊,但只有适度调制的E1-A226 V突变的影响,在埃及伊蚊。白纹伊蚊然而,E2-I211 T突变对蚊子感染的影响更具特异性,强烈改变了Ae中E1-A226 V突变的影响。白纹伊蚊相比之下,CHIKV对Ae. E2- 1211 T突变对埃及伊蚊无影响。分析了CHIKV分离株中E2- 60 G和E2- 211 I残基的出现,揭示了属于东部/中部/南非(ECSA)进化枝的菌株中E2- 211 I的高流行率。这表明E2- 211 I对于CHIKV适应ECSA染色占据的区域中普遍存在的一些特定条件可能是重要的。这些新描述的CHIKV蚊子对Ae. albopictus和Ae.埃及伊蚊对于旨在调查CHIKV适应其载体物种的详细机制的研究特别重要。
Between 2005 and 2007 Chikungunya virus (CHIKV) caused its largest outbreak/epidemic in documented history. An unusual feature of this epidemic is the involvement of Ae. albopictus as a principal vector. Previously we have demonstrated that a single mutation E1-A226V significantly changed the ability of the virus to infect and be transmitted by this vector when expressed in the background of well characterized CHIKV strains LR2006 OPY1 and 37997. However, in the current study we demonstrate that introduction of the E1-A226V mutation into the background of an infectious clone derived from the Ag41855 strain (isolated in Uganda in 1982) does not significantly increase infectivity for Ae. albopictus. In order to elucidate the genetic determinants that affect CHIKV sensitivity to the E1-A226V mutation in Ae. albopictus, the genomes of the LR2006 OPY1 and Ag41855 strains were used for construction of chimeric viruses and viruses with a specific combination of point mutations at selected positions. Based upon the midgut infection rates of the derived viruses in Ae. albopictus and Ae. aegypti mosquitoes, a critical role of the mutations at positions E2-60 and E2-211 on vector infection was revealed. The E2-G60D mutation was an important determinant of CHIKV infectivity for both Ae. albopictus and Ae. aegypti, but only moderately modulated the effect of the E1-A226V mutation in Ae. albopictus. However, the effect of the E2-I211T mutation with respect to mosquito infections was much more specific, strongly modifying the effect of the E1-A226V mutation in Ae. albopictus. In contrast, CHIKV infectivity for Ae. aegypti was not influenced by the E2-1211T mutation. The occurrence of the E2-60G and E2-211I residues among CHIKV isolates was analyzed, revealing a high prevalence of E2-211I among strains belonging to the Eastern/Central/South African (ECSA) clade. This suggests that the E2-211I might be important for adaptation of CHIKV to some particular conditions prevalent in areas occupied by ECSA stains. These newly described determinants of CHIKV mosquito infectivity for Ae. albopictus and Ae. aegypti are of particular importance for studies aimed at the investigation of the detailed mechanisms of CHIKV adaptations to its vector species.
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