Modulation of PML protein expression regulates JCV infection

Journal Article · Sat Aug 01 04:00:00 EDT 2009 · Virology

DOI:https://doi.org/10.1016/j.virol.2009.05.017· OSTI ID:21357529

Gasparovic, Megan L ^[1]; Maginnis, Melissa S; O'Hara, Bethany A; Dugan, Aisling S ^[2]

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1. Graduate Program in Molecular Biology, Cell Biology and Biochemistry, Brown University, Providence, RI 02912 (United States)
2. Department of Molecular Biology, Cell Biology and Biochemistry, Brown University, Providence, RI 02912 (United States)

JC virus (JCV) is a human polyomavirus that infects the majority of the human population worldwide. It is responsible for the fatal demyelinating disease Progressive Multifocal Leukoencephalopathy. JCV binds to cells using the serotonin receptor 5-HT{sub 2A}R and alpha(2-6)- or alpha(2-3)-linked sialic acid. It enters cells using clathrin-dependent endocytosis and traffics to the early endosome and possibly to the endoplasmic reticulum. Viral DNA is then delivered to the nucleus where transcription, replication, and assembly of progeny occur. We found that the early regulatory protein large T antigen accumulates in microdomains in the nucleus adjacent to ND-10 or PML domains. This observation prompted us to explore the role of these domains in JCV infection. We found that a reduction of nuclear PML enhanced virus infection and that an increase in nuclear PML reduced infection. Infection with JCV did not directly modulate nuclear levels of PML but our data indicate that a host response involving interferon beta is likely to restrict virus infection by increasing nuclear PML.

• OSTI ID: 21357529
• Journal Information: Virology, Journal Name: Virology Journal Issue: 2 Vol. 390; ISSN VIRLAX; ISSN 0042-6822
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
AMINES
ANTIGENS
AROMATICS
AUTONOMIC NERVOUS SYSTEM AGENTS
AZAARENES
AZOLES
CELL CONSTITUENTS
DNA
DRUGS
ENDOPLASMIC RETICULUM
HETEROCYCLIC COMPOUNDS
HUMAN POPULATIONS
HYDROXY COMPOUNDS
INDOLES
MEMBRANE PROTEINS
MICROORGANISMS
MODULATION
NEUROREGULATORS
NUCLEIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PARASITES
POPULATIONS
PROTEINS
PYRROLES
RADIOPROTECTIVE SUBSTANCES
RECEPTORS
RESPONSE MODIFYING FACTORS
SEROTONIN
SIALIC ACID
SYMPATHOMIMETICS
TRYPTAMINES
VIRUSES