The Severe Fever with Thrombocytopenia Syndrome Virus NSs Protein Interacts with CDK1 To Induce G 2 Cell Cycle Arrest and Positively Regulate Viral Replication

Abstract

Severe fever with thrombocytopenia syndrome virus (SFTSV) is a tick-borne pathogen that causes severe hemorrhagic fever. Although SFTSV poses a serious threat to public health and was recently isolated, its pathogenesis remains unclear. In particular, the relationship between SFTSV infection and the host cell cycle has not been described. Here, we show for the first time that both asynchronized and synchronized SFTSV-susceptible cells arrest at the G 2 /M checkpoint following SFTSV infection and that the accumulation of cells at this checkpoint facilitates viral replication. We also identify a key mechanism underlying SFTSV-induced G 2 /M arrest, in which SFTSV NSs interacts with CDK1 to inhibit formation and nuclear import of the cyclin B1-CDK1 complex, thus preventing it from regulating cell cycle progression. Our study highlights the key role that NSs plays in SFTSV-induced G 2 /M arrest.