Immune Response to Chikungunya Virus: Sex as a Biological Variable and Implications for Natural Delivery via the Mosquito

Chikungunya virus (CHIKV) is a mosquito-borne virus with significant public health implications around the world. Climate change, as well as rapid urbanization, threatens to expand the population range of Aedes vector mosquitoes globally, increasing CHIKV cases worldwide in return. Epidemiological data suggests a sex-dependent response to CHIKV infection. In this review, we draw attention to the importance of studying sex as a biological variable by introducing epidemiological studies from previous CHIKV outbreaks. While the female sex appears to be a risk factor for chronic CHIKV disease, the male sex has recently been suggested as a risk factor for CHIKV-associated death; however, the underlying mechanisms for this phenotype are unknown. Additionally, we emphasize the importance of including mosquito salivary components when studying the immune response to CHIKV. As with other vector-transmitted pathogens, CHIKV has evolved to use these salivary components to replicate more extensively in mammalian hosts; however, the response to natural transmission of CHIKV has not been fully elucidated.