The novel human astrovirus VA1 requires the proteasome during cell entry

Astroviruses are important aetiological agents of gastroenteritis. Recently, two novel human astrovirus (HAstV) clades, VA and MLB, have been identified. However, the replication cycle of these viruses remains poorly characterized. Among these, the novel astrovirus VA1 has been of particular interest due to its reported association with neurological disease in immunocompromised patients. Previous studies have demonstrated that a functional proteasome is essential for the efficient replication of classic HAstVs. In this study, we investigated the role of the proteasome in the replication of HAstV-VA1. We assessed the impact of two proteasome inhibitors, MG132 and bortezomib, on viral replication. Both inhibitors significantly reduced viral protein and infectious progeny production in a dose-dependent manner. Our findings indicate that the inhibitory effects of these compounds are mediated through a mechanism affecting virus entry and a post-entry step in the viral replication cycle during the virus replication cycle.