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Nat Commun. 2014 Jun 16;5:4084. doi: 10.1038/ncomms5084.

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

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Department of Pathology, Center for Tropical Diseases, Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, Texas, 77555-0609 USA.
1] Department of Pathology and Laboratory Medicine, Emory Vaccine Center, Emory University School of Medicine, Atlanta, Georgia, 30322 USA [2] Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan, Taiwan [3] Center of Infectious Disease and Signaling Research, National Cheng Kung University, Tainan City 701, Taiwan.
Viral Disease Biology Program, Rajiv Gandhi Centre for Biotechnology (RGCB), Thiruvananthapuram, Kerala 695012, India.
Department of Biology, Indiana University, Bloomington, 47405-7000 Indiana, USA.


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.

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