Age has a role in driving host immunopathological response to alphavirus infection

Alphaviruses are a group of arthropod-borne pathogens capable of causing a wide spectrum of clinical symptoms, ranging from milder symptoms like rashes, fever and polyarthralgia, to life-threatening encephalitis. This genus of viruses is prevalent globally, and can infect patients across a wide age range. Interestingly, disease severity of virus-infected patients is wide-ranging. Definitions of the pathogenesis of alphaviruses, as well as the host factors influencing disease severity, remain limited. The innate and adaptive immune systems are important host defences against alphavirus infections. Several reports have highlighted the roles of specific immune subsets in contributing to the immune pathogenesis of these viruses. However, immunosenescence, a gradual deterioration of the immune system brought about by the natural advancement of age, affects the functional roles of these immune subsets. This phenomenon compromises the host's ability to defend against alphavirus infection and pathogenesis. In addition, the lack of maturity in the immune system in newborns and infants also results in more severe disease outcomes. In this review, we will summarize the subtle yet diverse physiological changes in the immune system during aging, and how these changes underlie the differences in disease severity for common alphaviruses.