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

by Izzati Kausar Azman, Yoke Fun Chan, Chong Long Chua, Zainal Abidin Abd Mutalib, Sarat Chandra Dass, Balvinder Singh Gill, Nor Hayati Ismail, Jenarun Jelip, Ming Keong Wan, Wenn-Chyau Lee, Indra Vythilingam, Luke Alphey, I-Ching Sam

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.