Current perspectives on alphavirus encapsidation, assembly and budding

Alphaviruses are an escalating global concern due to their considerable clinical impact and expanding geographic distribution. Transmitted primarily through the bites of infected mosquitoes, alphaviruses cause a wide spectrum of arthritogenic and encephalitic diseases in both humans and animals. Their ability to re-emerge with enhanced fitness through adaptive mutations further underscores their public health importance. Despite advances in antiviral discovery and vaccine development, no licensed therapies are available for most of them, and vector control can only be partially effective. These limitations underscore the need for a mechanistic understanding of the virus life cycle to guide rational intervention strategies. Deciphering the molecular mechanisms of alphavirus assembly and budding has been a central research frontier. This perspective brings together the research on viral RNA encapsidation, structural elucidation of virus architecture, and the essential functions of host factors, membranes, and cytoskeletal components. An integrated understanding of the roles of both viral and host factors, along with the spatial and temporal coordination of events throughout the viral life cycle, is crucial for addressing key mechanistic gaps and for guiding the development of next-generation antiviral and vaccine strategies.