Host factor Rab4b promotes the replication of influenza A virus

Rab proteins are involved in all facets of the vesicular transport process and play significant roles in different steps of the viral life cycle. Rab4b is a pivotal player in the endocytic recycling of proteins, whereas its roles in viral replication are still largely unknown. Our earlier work identified Rab4b as a host factor required to replicate the influenza A virus (IAV). Here, we further validated the impact of Rab4b on viral replication by silencing or overexpressing Rab4b. The results showed that silencing Rab4b significantly decreased IAV and influenza B virus (IBV) production. Overexpression of Rab4b enhanced IAV infection. We provided robust evidence to support the important role of Rab4b in facilitating IAV growth independent of the host innate immunity. Mechanism study revealed the involvement of Rab4b in the early steps of the IAV life cycle, including virus attachment, endocytosis of viral particles, virus-host membrane fusion, and nuclear import of viral nucleoprotein (NP). Furthermore, we found that Rab4b interacts with viral ribonucleoprotein (RNP) complexes, suggesting that Rab4b binds to RNP complex to facilitate viral replication. In summary, this work provided the first evidence to support the involvement of Rab4b in the IAV replication. Understanding the mechanisms underlying IAV and Rab4b interactions helps elucidate viral infection and pathogenesis and leads to the development of antiviral therapeutics.