Revisiting Alphavirus RNA packaging and assembly—A complex story with multiple angles

Alphavirus is a genus of enveloped, single-stranded positive-sense RNA viruses with an icosahedral virion consisting of two T = 4 layers. These viruses are transmitted by invertebrates, are present in almost every ecosystem, and infect a wide range of vertebrates. The assembly and budding of these viruses are highly coordinated processes that involve capsid protein-RNA, capsid protein-capsid protein, capsid protein-glycoprotein, and glycoprotein-glycoprotein interactions. Assembly and budding have been studied for more than 40 years, and in the past decade, key, sometimes paradigm-shifting results have changed our understanding of their structure and assembly. However, there are fundamental aspects of RNA selective packaging, core and virion assembly, budding, and the interactions that control these processes that remain to be fully understood. Here, I provide an updated overview of these processes and highlight areas to further improve our understanding of alphaviruses.