The Hsf1-sHsp cascade has pan-antiviral activity in mosquito cells

Abstract

Aedes mosquitoes transmit pathogenic arthropod-borne (arbo) viruses, putting nearly half the world's population at risk. Blocking virus replication in mosquitoes is a promising approach to prevent arbovirus transmission, the development of which requires in-depth knowledge of virus-host interactions and mosquito immunity. By integrating multi-omics data, we find that heat shock factor 1 (Hsf1) regulates eight small heat shock protein (sHsp) genes within one topologically associated domain in the mosquito genome. This Hsf1-sHsp cascade acts as an early response against chikungunya virus (CHIKV) infection and shows pan-antiviral activity in three vector mosquitoes, Aedes aegypti, Aedes albopictus, and Anopheles gambiae. Importantly, activation of Hsf1 leads to a reduced CHIKV infection rate in adult Ae. aegypti mosquitoes, establishing Hsf1 as a promising target for the development of novel intervention strategies to limit arbovirus transmission by mosquitoes.