[Development of intranuclear inclusions of human polyomavirus JC. Capsid proteins are assembled into virions at the PML nuclear bodies].
Human polyomavirus JC (JCV) is a causative agent for progressive multifocal leukoencephalopathy, a fatal demyelinating disorder. The viruses form intranuclear viral inclusions in infected oligodendrocytes. The outer capsid of JCV is thought to be composed of 360 molecules of major capsid protein VP1, and minor capsid proteins VP2 and VP3 in an appropriate ratio. However, the regulatory mechanisms of gene expression for the capsid proteins, their nuclear transport, and formation of viral inclusions are not well understood. We have recently clarified the following regarding the mechanism underlying JCV virion assembly; (i) major and minor capsid proteins are synthesized from messenger RNAs, the expression ratio of which is determined by alternative splicing, (ii) messenger RNAs for the major and minor capsid proteins are polycistronic, and their translation occurs downstream of the regulatory protein, agnoprotein, (iii) major and minor capsid proteins are translocated to the nucleus in a cooperative manner and accumulate at the dot-shaped intranuclear structures called promyelocytic leukemia nuclear bodies (PML-NBs), (iv) efficient viral replication can occur at the PML-NBs, where capsid assembly is likely to be associated with viral DNA replication. PML-NBs are the sites for expression of important nuclear functions for the host cells. The finding that the target of JCV infection is the PML-NB may contribute greatly to our understanding of the mechanism underlying cellular degeneration, which occurs after the formation of intranuclear viral inclusions.
Shishido-Hara
Yukiko
Y
Department of Pathology, Kyorin University School of Medicine, 6-20-2, Shinkawa, Mitaka, Tokyo, 181-18611, Japan. yhara@kyorin-u.ac.jp
D036022:Capsid Proteins / Q000235:genetics / Q000378:metabolism*; D004261:DNA Replication; D004279:DNA, Viral; D006801:Humans; D045586:Intranuclear Inclusion Bodies / Q000378:metabolism*; D007577:JC Virus / Q000378:metabolism / Q000472:pathogenicity* / Q000502:physiology / Q000648:ultrastructure; D007968:Leukoencephalopathy, Progressive Multifocal / Q000821:virology; D021381:Protein Transport; D012333:RNA, Messenger / Q000378:metabolism; D012367:RNA, Viral / Q000378:metabolism; D014771:Virion / Q000378:metabolism; D014779:Virus Replication
D036022:Capsid Proteins; D004279:DNA, Viral; D012333:RNA, Messenger; D012367:RNA, Viral