title: Chikungunya virus emergence is constrained in Asia by lineage-specific adaptive landscapes.
abstract: Adaptation of RNA viruses to a new host or vector species often results in emergence of new viral lineages. However, lineage-specific restrictions on the adaptive processes remain largely unexplored. Recently, a Chikungunya virus (CHIKV) lineage of African origin emerged to cause major epidemics of severe, persistent, debilitating arthralgia in Africa and Asia. Surprisingly, this new lineage is actively replacing endemic strains in Southeast Asia that have been circulating there for 60 y. This replacement process is associated with adaptation of the invasive CHIKV strains to an atypical vector, the Aedes albopictus mosquito that is ubiquitously distributed in the region. Here we demonstrate that lineage-specific epistatic interactions between substitutions at amino acid positions 226 and 98 of the E1 envelope glycoprotein, the latter of which likely resulted from a founder effect, have for 60 y restricted the ability of endemic Asian CHIKV strains to adapt to this new vector. This adaptive constraint appears to be allowing invasion of the unoccupied vector niche by Ae. albopictus-adapted African strains. These results underscore how different adaptive landscapes occupied by closely related viral genotypes can profoundly affect the outcome of viral evolution and disease emergence.
authors.affiliation: Institute for Human Infections and Immunity, Center for Tropical Diseases and Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555, USA.
authors.forename: Konstantin A
authors.initials: KA
authors.lastname: Tsetsarkin
authors.forename: Rubing
authors.initials: R
authors.lastname: Chen
authors.forename: Grace
authors.initials: G
authors.lastname: Leal
authors.forename: Naomi
authors.initials: N
authors.lastname: Forrester
authors.forename: Stephen
authors.initials: S
authors.lastname: Higgs
authors.forename: Jing
authors.initials: J
authors.lastname: Huang
authors.forename: Scott C
authors.initials: SC
authors.lastname: Weaver
mesh_terms: D000222:Adaptation, Physiological; D000330:Aedes / Q000821:virology; D018354:Alphavirus Infections / Q000453:epidemiology / Q000635:transmission / Q000821:virology; D019943:Amino Acid Substitution; D000818:Animals; D001210:Asia, Southeastern; D001483:Base Sequence; D065632:Chikungunya Fever; D002646:Chikungunya virus / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology*; D021821:Communicable Diseases, Emerging / Q000453:epidemiology / Q000635:transmission / Q000821:virology; D004279:DNA, Viral / Q000235:genetics; D004843:Epistasis, Genetic; D019143:Evolution, Molecular; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D007303:Insect Vectors / Q000821:virology; D051379:Mice; D008958:Models, Molecular; D010802:Phylogeny; D011993:Recombinant Fusion Proteins / Q000235:genetics; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000235:genetics
chemical_list: D004279:DNA, Viral; D011993:Recombinant Fusion Proteins; D014759:Viral Envelope Proteins; D049452:Green Fluorescent Proteins