Intrinsically disordered region of influenza A NP regulates viral genome packaging via interactions with viral RNA and host PI(4,5)P2.
To be incorporated into progeny virions, the viral genome must be transported to the inner leaflet of the plasma membrane (PM) and accumulate there. Some viruses utilize lipid components to assemble at the PM. For example, simian virus 40 (SV40) targets the ganglioside GM1 and human immunodeficiency virus type 1 (HIV-1) utilizes phosphatidylinositol (4,5) bisphosphate [PI(4,5)P2]. Recent studies clearly indicate that Rab11-mediated recycling endosomes are required for influenza A virus (IAV) trafficking of vRNPs to the PM but it remains unclear how IAV vRNP localized or accumulate underneath the PM for viral genome incorporation into progeny virions. In this study, we found that the second intrinsically disordered region (IDR2) of NP regulates two binding steps involved in viral genome packaging. First, IDR2 facilitates NP oligomer binding to viral RNA to form vRNP. Secondly, vRNP assemble by interacting with PI(4,5)P2 at the PM via IDR2. These findings suggest that PI(4,5)P2 functions as the determinant of vRNP accumulation at the PM.
Viral Infectious Diseases Unit Wako, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
Michinori
M
Kakisaka
Viral Infectious Diseases Unit Wako, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
Kazunori
K
Yamada
Lipid Biology Laboratory, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
Akiko
A
Yamaji-Hasegawa
Lipid Biology Laboratory, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
Toshihide
T
Kobayashi
Viral Infectious Diseases Unit Wako, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan. Electronic address: aida@riken.jp.
Yoko
Y
Aida
D000818:Animals; D002460:Cell Line; D004285:Dogs; D016679:Genome, Viral; D054884:Host-Pathogen Interactions; D006801:Humans; D009980:Influenza A virus / Q000502:physiology*; D007251:Influenza, Human / Q000378:metabolism* / Q000821:virology*; D064267:Intrinsically Disordered Proteins / Q000378:metabolism*; D008958:Models, Molecular; D008968:Molecular Conformation; D019590:Nucleocapsid Proteins; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D055503:Protein Multimerization; D021381:Protein Transport; D012367:RNA, Viral / Q000737:chemistry / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D013329:Structure-Activity Relationship; D014758:Viral Core Proteins / Q000737:chemistry / Q000378:metabolism*; D019065:Virus Assembly; D014779:Virus Replication
D064267:Intrinsically Disordered Proteins; C048842:NP protein, Influenza A virus; D019590:Nucleocapsid Proteins; D019269:Phosphatidylinositol 4,5-Diphosphate; D012367:RNA, Viral; D016601:RNA-Binding Proteins; D014758:Viral Core Proteins
Genome packaging; IAV; IDR; NP; PI(4,5)P2; vRNA