Research progress on the role of host factors in Chikungunya virus infection and intervention strategies.

Chikungunya virus (CHIKV) is a mosquito-borne alphavirus causing acute fever, rashes, and even acute or chronic arthralgia/arthritis. With its expanding global distribution, CHIKV represents a significant public health threat, yet no specific antivirals are approved. The lifecycle of CHIKV is highly dependent on interactions with host factors that mediate viral entry, genome replication, protein translation, assembly, and release. A deeper understanding of these host factors provides new insights into CHIKV pathogenesis and offers strategies to overcome drug resistance associated with high viral mutation rates. This review summarizes and updates current knowledge on the roles of host factors in CHIKV infection, systematically dissects the interaction network and cell-type specificity of key host factors, critically evaluates the druggability of host-directed therapeutic targets, and outlines recent progress in anti-CHIKV drug development, with a focus on strategies targeting both viral proteins and host dependencies, placing a particular emphasis on host-directed antiviral therapies.