Adenoviral protein V promotes a process of viral assembly through nucleophosmin 1.
Adenoviral infection induces nucleoplasmic redistribution of a nucleolar nucleophosmin 1/NPM1/B23.1. NPM1 is preferentially localized in the nucleoli of normal cells, whereas it is also present at the nuclear matrix in cancer cells. However, the biological roles of NPM1 during infection are unknown. Here, by analyzing a pV-deletion mutant, Ad5-dV/TSB, we demonstrate that pV promotes the NPM1 translocation from the nucleoli to the nucleoplasm in normal cells, and the NPM1 translocation is correlated with adenoviral replication. Lack of pV causes a dramatic reduction of adenoviral replication in normal cells, but not cancer cells, and Ad5-dV/TSB was defective in viral assembly in normal cells. NPM1 knockdown inhibits adenoviral replication, suggesting an involvement of NPM1 in adenoviral biology. Further, we show that NPM1 interacts with empty adenovirus particles which are an intermediate during virion maturation by immunoelectron microscopy. Collectively, these data implicate that pV participates in a process of viral assembly through NPM1.
Division of Human Gene Therapy, Departments of Medicine, Obstetrics and Gynecology, Pathology, and Surgery, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Hideyo
H
Ugai
George C
GC
Dobbins
Minghui
M
Wang
Long P
LP
Le
David A
DA
Matthews
David T
DT
Curiel
D000256:Adenoviridae / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002466:Cell Nucleolus / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D000090243:Nucleophosmin; D014758:Viral Core Proteins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D019065:Virus Assembly / Q000187:drug effects*; D014779:Virus Replication
C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D014758:Viral Core Proteins; D000090243:Nucleophosmin