Department of Pathology, University of Texas Medical Branch, Galveston, Texas, United States of America.
PLoS One. 2009 Aug 31;4(8):e6835. doi: 10.1371/journal.pone.0006835.
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.
在 2005 年至 2007 年间，基孔肯雅病毒（CHIKV）引发了有记录以来最大的暴发/流行。该疫情的一个不寻常特征是白纹伊蚊成为主要媒介。此前，我们已经证明，E1-A226V 单点突变显著改变了病毒在 LR2006 OPY1 和 37997 等特征明确的 CHIKV 株系背景下感染和经白纹伊蚊传播的能力。然而，在目前的研究中，我们证明将 E1-A226V 突变引入源自 1982 年乌干达分离株 Ag41855 的感染性克隆的背景中，并不会显著增加对白纹伊蚊的感染力。为了阐明影响 CHIKV 对白纹伊蚊中 E1-A226V 突变敏感性的遗传决定因素，使用 LR2006 OPY1 和 Ag41855 株系的基因组构建嵌合病毒和在选定位置具有特定组合点突变的病毒。基于衍生病毒在白纹伊蚊和埃及伊蚊中的中肠感染率，发现 E2-60 和 E2-211 位置的突变对媒介感染起着关键作用。E2-G60D 突变是 CHIKV 对白纹伊蚊和埃及伊蚊感染性的重要决定因素，但在白纹伊蚊中仅适度调节 E1-A226V 突变的作用。然而，E2-I211T 突变对蚊感染的影响更为特异，强烈改变了 E1-A226V 突变在白纹伊蚊中的作用。相比之下，E2-1211T 突变对埃及伊蚊的 CHIKV 感染性没有影响。分析了 CHIKV 分离株中 E2-60G 和 E2-211I 残基的出现情况，发现 E2-211I 残基在属于东/中/南非（ECSA）谱系的菌株中高度流行。这表明 E2-211I 可能对 CHIKV 适应其在 ECSA 菌株所在地区流行的某些特定条件很重要。这些新描述的白纹伊蚊和埃及伊蚊感染性的 CHIKV 决定因素对于研究 CHIKV 适应其媒介物种的详细机制特别重要。
