Role of JC virus agnoprotein in virion formation.
JC virus (JCV) belongs to the polyomavirus family of double-stranded DNA viruses and causes progressive multifocal leukoencephalopathy in humans. JCV encodes early proteins (large T antigen, small T antigen, and T' antigen) and four late proteins (agnoprotein, and three viral capsid proteins, VP1, VP2, and VP3). In the current study, a novel function for JCV agnoprotein in the morphogenesis of JC virion particles was identified. It was found that mature virions of agnoprotein-negative JCV are irregularly shaped. Sucrose gradient sedimentation and cesium chloride gradient ultracentrifugation analyses revealed that the particles of virus lacking agnoprotein assemble into irregularly sized virions, and that agnoprotein alters the efficiency of formation of VP1 virus-like particles. An in vitro binding assay and immunocytochemistry revealed that agnoprotein binds to glutathione S-transferase fusion proteins of VP1 and that some fractions of agnoprotein colocalize with VP1 in the nucleus. In addition, gel filtration analysis of formation of VP1-pentamers revealed that agnoprotein enhances formation of these pentamers by interacting with VP1. The present findings suggest that JCV agnoprotein plays a role, similar to that of SV40 agnoprotein, in facilitating virion assembly.
Division of Molecular Pathobiology, Hokkaido University, Research Center for Zoonosis Control, N20, W10, Kita-ku, Sapporo, 001-0020, Japan.
Tadaki
T
Suzuki
Shingo
S
Semba
Yuji
Y
Sunden
Yasuko
Y
Orba
Shintaro
S
Kobayashi
Kazuo
K
Nagashima
Takashi
T
Kimura
Hideki
H
Hasegawa
Hirofumi
H
Sawa
D000818:Animals; D036022:Capsid Proteins / Q000737:chemistry; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000737:chemistry / Q000821:virology; D002499:Centrifugation, Density Gradient; D002850:Chromatography, Gel; D005982:Glutathione Transferase / Q000737:chemistry; D006801:Humans; D007150:Immunohistochemistry; D007577:JC Virus / Q000737:chemistry / Q000502:physiology*; D061987:Sf9 Cells; D018411:Spodoptera; D014760:Viral Fusion Proteins / Q000737:chemistry; D054334:Viral Regulatory and Accessory Proteins / Q000737:chemistry*; D014771:Virion / Q000737:chemistry / Q000502:physiology*; D019065:Virus Assembly; D053585:Virus Attachment; D000086082:Viroporin Proteins
D036022:Capsid Proteins; D005982:Glutathione Transferase; D014760:Viral Fusion Proteins; D054334:Viral Regulatory and Accessory Proteins; C062481:VP1 protein, polyomavirus; C042559:agnoprotein, polyomavirus; D000086082:Viroporin Proteins