Cellular takeover: How new world alphaviruses impact host organelle function

Abstract

Alphavirus replication is dependent on host cell organelles to facilitate multiple steps of the viral life cycle. New world alphaviruses (NWA) consisting of eastern, western and Venezuelan equine encephalitis viruses are a subgroup of alphaviruses associated with central nervous system disease. Despite differing morbidity and mortality amongst these viruses, all are important human pathogens due to their transmission through viral aerosolization and mosquito transmission. In this review, we summarize the utilization of host organelles for NWA replication and the subversion of the host innate immune responses. The impact of viral proteins and replication processes on organelle function is also discussed. Literature involving old world alphaviruses (OWA), such as chikungunya virus and Sindbis virus, is included to compare and contrast between OWA and NWA and highlight gaps in knowledge for NWA. Finally, potential targets for therapeutics or vaccine candidates are highlighted with a focus on host-directed therapeutics.

Keywords: EEEV; Host-trafficking; Organelles; Therapeutic strategies; VEEV; WEEV.