A change in circulating chikungunya virus variant impacts Aedes aegypti vector competence and spatiotemporal distribution of disease in Malaysia

Background In 2008–2010, Malaysia experienced a nationwide chikungunya virus (CHIKV) outbreak caused by the Indian Ocean lineage E1-226V (valine) variant, adapted to Aedes albopictus. In 2017–2022, transition to an E1-226A (alanine) variant occurred. Ae. albopictus prevails in rural areas, where most cases occurred during the E1-226V outbreak, while Ae. aegypti dominates urban areas. The shift in circulating CHIKV variants from E1-226V to E1-226A (2009–2022) was hypothesized to result in a transition from rural to urban CHIKV distribution, driven by differences in Ae. aegypti vector competence for the two variants. This study aimed to: (1) map the spatiotemporal spread of CHIKV cases in Malaysia between 2009– 2022; and (2) compare replication of E1-226A and E1-226V variants in the midguts and head/thoraxes of Ae. aegypti. Methodology/Principal findings Spatiotemporal analysis of national notified CHIKV case addresses was performed. Between 2009–2022, 12,446 CHIKV cases were reported, with peaks in 2009 and 2020, and a significant shift from predominantly rural cases in 2009–2011 (85.1% rural), to urban areas in 2017–2022 (86.1% urban; p<0.0001). Two Ae. aegypti strains, field-collected MC1 and laboratory Kuala Lumpur (KL) strains, were fed infectious blood containing constructed CHIKV clones, pCMV-p2020A (E1-226A) and pCMV-p2020V (E1-226V) to measure CHIKV replication by real-time PCR and/or virus titration. The pCMV-p2020A clone replicated better in Ae. aegypti cell line Aag2 and showed higher replication, infection and dissemination efficiency in both Ae. aegypti strains, compared to pCMV-p2020V. Conclusions/Significance This study revealed that a change in circulating CHIKV variants can be associated with changes in vector competence and outbreak epidemiology. Continued genomic surveillance of arboviruses is important.