The role of Ran-binding protein 3 during influenza A virus replication
Influenza A virus (family Orthomyxoviridae) is one of the most important human pathogens, causing annual epidemics with significant worldwide mortality, and sporadic but potentially devastating pandemics. The influenza A viral genome encodes 14 proteins and consists of 8 segments of negative-stranded RNA. During infection, the virus exploits the host cell signaling machinery to ensure efficient replication. The PI3K/Akt and Ras/ERK are two of the signaling cascades that are induced for virus survival. Influenza A virus replicates in the nucleus, hence the newly synthesized RNPs must be exported from the nucleus and exported to the cell membrane. Although the detailed mechanism of vRNP nuclear export is not yet fully elucidated, several studies on this process have begun to emerge. Influenza A virus nucleoprotein nuclear export is CRM1-dependent. Ran-binding protein 3 (RanBP3) is a Ran-interacting protein that is best known for its role as a cofactor of CRM1-mediated cargo nuclear export. In this study, we investigated the role of RanBP3 during the influenza A virus life cycle. We found that RanBP3 was phosphorylated at Ser58 in early and late phases of infection. Knockdown of RanBP3 expression led to a vRNP nuclear retention, suggesting that RanBP3 is involved in vRNP nuclear export. Moreover, we demonstrated that RanBP3’s function during vRNP nuclear export is regulated by phosphorylation at Ser58, and the RanBP3 phosphorylation is modulated by both PI3K/Akt and Ras/ERK/RSK pathways in the late phase of viral infection. In conclusion, this study has shown that RanBP3 is a host factor that has a vital role during the late stage of influenza A virus replication, specifically as a co-factor in CRM1-mediated nuclear export. Identifying this host factor will contribute to the understanding of the mechanism of vRNP transport.
DegreeMaster of Science (M.Sc.)
DepartmentSchool of Public Health
ProgramVaccinology and Immunotherapeutics
Committeevan den Hurk, Sylvia; Tikoo, Suresh; Yang, Jian
Copyright DateApril 2014
influenza A virus