Abstract
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.
Highlights
The recent massive epidemics of Chikungunya virus (CHIKV) in Africa, the Indian Ocean islands, India, and the small outbreak in Europe have elevated this arthropod-borne virus to the status of a major global health problem [1]
To further investigate the effect of this mutation on infectivity of different strains of CHIKV for Ae. albopictus, the E1-A226V mutation was introduced into an enhanced green fluorescent protein expressing infectious clones (i.c.) of the Ag41855 strain of CHIKV
Individual expression of the E2-G60D or E2-I211T mutation in the 41855-GFP-226V virus has an identical effect on the Oral Infectious Dose 50% values (OID50) for Ae. albopictus, and their combined expression increases infectivity of strain Ag41855, into which the E1-A226V mutation was introduced, to the level characteristic for strains LR2006 OPY1 and 37997
Summary
The recent massive epidemics of Chikungunya virus (CHIKV) in Africa, the Indian Ocean islands, India, and the small outbreak in Europe have elevated this arthropod-borne virus (arbovirus) to the status of a major global health problem [1]. CHIKV isolates from Reunion Island possessing valine at position E1-226 disseminate significantly more efficiently to the salivary glands of Ae. albopictus mosquitoes collected from La Reunion Island and Mayotte, as compared with CHIKV isolates bearing alanine at this position [10]. Taken together, these findings provide compelling evidence that the E1-A226V mutation is a major genetic determinant of adaptation of CHIKV to a new vector species, Ae. albopictus, and provides a plausible explanation for how this mutant CHIKV caused an epidemic in a region lacking the more typical urban vector, Ae. aegypti
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