Investigation on the functional roles of interaction between human karyopherin isoforms and nucleoprotein of influenza B virus

Abstract

Influenza B viruses are capable of causing disease with severity similar to that of influenza A. Yet, unlike influenza A viruses, which naturally exit in waterfowl, the animal reservoir of influenza B virus has not been identified and endemics are mainly restricted to humans. Factors determining the host specificity of influenza B virus have not been well studied. To establish interspecies transmission, a virus must be able to propagate efficiently in host cells of both species. The nuclear translocation of viral proteins of the ribonucleoprotein complex (vRNP) is a crucial step during virus replication, which relies on a group of cellular protein called karyopherin subunit α (KPNAs). These KPNA isoforms recognize the nuclear localization sequences (NLS) on cargo proteins including the vRNP components and facilitate their transportation across nuclear pore complexes (NPC).

In this study, we showed that the nucleoprotein (NP) of influenza B virus interacted with human KPNA 1, 2, 3, 4, and 6. KPNA silenced human cells were employed to determine the roles of each KPNA on viral polymerase activity, transcription efficiency and virus replication. We showed that absence of KPNA2 decreased the polymerase activity of influenza B for 60%. However, KPNA2 silencing did not affect viral transcription and replication in our infection model. From our transcriptomic analysis, distinctive cellular responses were triggered between the cells infected by influenza A and B viruses suggesting that the two viruses may adapt to different strategies upon infection.

Given that studies on influenza B viruses are relatively limited compared to those on influenza A, our study gained a better understanding on the interplay between the host factors and NP of influenza B virus.