Alphavirus-induced membrane rearrangements during replication, assembly, and budding

Alphaviruses are arthropod-borne viruses mainly transmitted by hematophagous insects that cause moderate to fatal disease in humans and other animals. Currently, there are no approved vaccines or antivirals to mitigate alphavirus infections. In this review, we summarize the current knowledge of alphavirus-induced structures and their functions in infected cells. Throughout their lifecycle, alphaviruses induce several structural modifications, including replication spherules, type I and type II cytopathic vacuoles, and filopodial extensions. Type I cytopathic vacuoles are replication-induced structures containing replication spherules that are sites of RNA replication on the endosomal and lysosomal limiting membrane. Type II cytopathic vacuoles are assembly induced structures that originate from the Golgi apparatus. Filopodial extensions are induced at the plasma membrane and are involved in budding and cell-to-cell transport of virions. This review provides an overview of the viral and host factors involved in the biogenesis and function of these virus-induced structures. Understanding virus–host interactions in infected cells will lead to the identification of new targets for antiviral discovery.