The sticky business of Alphavirus capsid–host interactions

Alphaviruses are a serious threat to global health, and specific antiviral therapies are urgently needed. Improved understanding of alphavirus–host interactions will inform new targets and strategies for the development of antivirals.The alphavirus capsid protein is essential for selectively packaging the viral genome. Additional functions in the virus infection cycle are not as well-understood, in part due to the intrinsic biochemical properties of capsid that complicate identification of specific protein interactors.Several new capsid interactor candidates were recently identified, adding to the complexity of capsid–host biology. Functional characterisation of a subset of these candidates, including IRAK1 and UPF1, highlights an emerging role for capsid in host immune evasion.Identification of specific protein interactors of the alphavirus capsid is technically challenging, necessitating extensive functional validation. Alphaviruses are a serious threat to global health and can cause lethal encephalitic or arthritogenic disease in humans and animals. As there are no licensed antivirals, it is critical to improve our understanding of alphavirus interactions with the host cell. Here, we focus on the essential alphavirus protein capsid. While its roles in genome packaging and virus assembly have been well-studied, much less is known about capsid’s interactions with host proteins and their functional relevance for infection. Recently, several new capsid interactor candidates were identified, collectively emphasising the complexity of capsid–host biology. In this review we summarise these novel interactor candidates, highlight capsid’s emerging role in immune evasion, and discuss the challenges and opportunities arising from capsid–host interactions. Alphaviruses are a serious threat to global health and can cause lethal encephalitic or arthritogenic disease in humans and animals. As there are no licensed antivirals, it is critical to improve our understanding of alphavirus interactions with the host cell. Here, we focus on the essential alphavirus protein capsid. While its roles in genome packaging and virus assembly have been wellstudied, much less is known about capsid’s interactions with host proteins and their functional relevance for infection. Recently, several new capsid interactor candidates were identified, collectively emphasising the complexity of capsid–host biology. In this review we summarise these novel interactor candidates, highlight capsid’