Nucleoporin 85 interacts with influenza A virus PB1 and PB2 to promote its replication by facilitating nuclear import of ribonucleoprotein

Abstract

Transcription and replication of the influenza A virus (IAV) genome take place in the nucleus of infected cells, which rely on host factors to aid viral ribonucleoprotein (vRNP) to cross the nuclear pore complex (NPC) and complete the bidirectional nucleocytoplasmic trafficking. Here, we showed that nucleoporin 85 (NUP85), a component of NPC, interacted with RNP subunits polymerase basic 1 (PB1) and polymerase basic 2 (PB2) in an RNA-dependent manner during IAV infection. Knockdown of NUP85 delayed the nuclear import of vRNP, PB1 and PB2, inhibiting polymerase activity and ultimately suppressing viral replication. Further analysis revealed that NUP85 assisted the binding of PB1 to nuclear transport factor Ran-binding protein 5 (RanBP5) and the binding of PB2 to nuclear transport factor importin α1 and importin α7. We also found that NUP85 expression was downregulated upon IAV infection. Together, our study demonstrated that NUP85 positively regulated IAV infection by interacting with viral PB1 and PB2, which may provide new insight into the process of vRNP nuclear import and a novel target for effective antivirals.

Predicting Functional Consequences of Recent Natural Selection in Britain

“…S4, Supplementary Material online). NUP85 encodes a part of the nucleoporin complex, which controls transport between the cytoplasm and the nucleus ( Ling et al 2022 ). It is involved in the recruitment and migration of immune cells through chemokine signaling ( Toda et al 2009 ), as well as the control of viral replication ( Brass et al 2008 ; Ling et al 2022 ), suggesting pathogen-induced selective pressures.…”

Predicting functional consequences of recent natural selection in Britain

“…Of these three, NUP85 is upregulated in GBR LCLs compared to the other European 1kG populations, as would be expected under our inferred scenario of selection for increased expression on this gene in Britain (Supplementary Figure 4). NUP85 encodes a part of the nucleoporin complex, which controls transport between the cytoplasm and the nucleus (Ling et al, 2022). It is involved in the recruitment and migration of immune cells through chemokine signaling (Toda et al, 2009), as well as the control of viral replication (Brass et al, 2008; Ling et al, 2022), suggesting pathogen-induced selective pressures.…”

“…NUP85 encodes a part of the nucleoporin complex, which controls transport between the cytoplasm and the nucleus (Ling et al, 2022). It is involved in the recruitment and migration of immune cells through chemokine signaling (Toda et al, 2009), as well as the control of viral replication (Brass et al, 2008; Ling et al, 2022), suggesting pathogen-induced selective pressures.…”

Virulence and transmission characteristics of clade 2.3.4.4b H5N6 subtype avian influenza viruses possessing different internal gene constellations

“…The RNA polymerase complex of the influenza virus is a heterotrimeric structure composed of PB2, PB1, and PA proteins, which mainly participate in the replication and transcription process after virus infection and entry into host cells [ 41 ]. The PB1 protein is located in the centre of the complex, with its N-terminal and C-terminal interacting with PA and PB2 proteins, respectively [ 42 ].…”