Multi-peaked adaptive landscape for chikungunya virus evolution predicts continued fitness optimization in Aedes albopictus mosquitoes

Tsetsarkin, Konstantin A.; Chen, Rubing; Yun, Ruimei; Rossi, Shannan L.; Plante, Kenneth S.; Guerbois, Mathilde; Forrester, Naomi; Perng, Guey Chuen; Sreekumar, Easwaran; Leal, Grace; Huang, Jing; Mukhopadhyay, Suchetana; Weaver, Scott C.

Host species-specific fitness landscapes largely determine the outcome of host switching during pathogen emergence. Using chikungunya virus (CHIKV) to study adaptation to a mosquito vector, we evaluated mutations associated with recently evolved sub-lineages. Multiple Aedes albopictus-adaptive fitness peaks became available after CHIKV acquired an initial adaptive (E1-A226V) substitution, permitting rapid lineage diversification observed in nature. All second-step mutations involved replacements by glutamine or glutamic acid of E2 glycoprotein amino acids in the acid-sensitive region, providing a framework to anticipate additional A. albopictus-adaptive mutations. The combination of second-step adaptive mutations into a single, ‘super-adaptive’ fitness peak also predicted the future emergence of CHIKV strains with even greater transmission efficiency in some current regions of endemic circulation, followed by their likely global spread. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/ncomms5084) contains supplementary material, which is available to authorized users.