NS38 is required for aquareovirus replication via interaction with viral core proteins and host eIF3A.

Aquareoviruses contain an 11-segmented double-stranded RNA genome. Previous studies indicated that NS38, a virus-encoded putative single-stranded RNA binding protein, interacts with NS80 in viral inclusion bodies (VIBs). However, the role of NS38 in aquareovirus infection remained unclear. Here, we found that NS38 interacts with inner-capsid proteins (VP1-VP4 and VP6) and the NS80-RNA complex in both transfected and infected cells. Knockdown of NS38 by siRNAs-115/219 clearly reduced viral infection, with decreased mRNA and protein yields. Moreover, NS38 can interact with host cellular eukaryotic translation initiation factor 3 subunit A (eIF3A) in transfected cells, while no association was detected between eIF3A and NS80. This study is the first to define that the NS38 is essential to viral replication. Together, our findings indicate that NS38 might function as a mediator by interacting with viral and host cellular components in VIBs during replication.