title: Polyomavirus JC infects human brain microvascular endothelial cells independent of serotonin receptor 2A.
abstract: Although human polyomavirus JC (JCV) is known to cause progressive multifocal leukoencephalopathy (PML) in immunocompromised individuals, the mechanism by which JCV crosses the blood-brain barrier (BBB) remains unclear. To test our hypothesis that cell-free JCV gains entry into the brain by infecting endothelial cells, we inoculated human brain microvascular endothelial (HBMVE) cells with 50 HAU (1.33+/-0.27 x 10(7) genome copies) of JCV(Mad1) and analyzed the expression of early and late viral genes and proteins by immunocytochemistry, quantitative real-time PCR (qPCR), quantitative real-time reverse transcriptase PCR (qRT-PCR) and immunoprecipitation followed by Western blotting. JCV infected and replicated efficiently in HBMVE cells and produced infectious virions several hundred fold higher than the infecting inoculum. HBMVE cells in vitro did not express serotonin receptor 2A (5HT(2A)R), and 5HT(2A)R blockers did not prevent JCV infection of HBMVE cells. Collectively, our data indicate that the productive in vitro infection of HBMVE cells by JCV is independent of 5HT(2A)R.
authors.affiliation: Retrovirology Research Laboratory, Department of Tropical Medicine, Medical Microbiology and Pharmacology, Asia-Pacific Institute of Tropical Medicine and Infectious Diseases, University of Hawaii at Manoa, Honolulu, HI 96813, USA.
authors.forename: Moti L
authors.initials: ML
authors.lastname: Chapagain
authors.forename: Saguna
authors.initials: S
authors.lastname: Verma
authors.forename: Frederic
authors.initials: F
authors.lastname: Mercier
authors.forename: Richard
authors.initials: R
authors.lastname: Yanagihara
authors.forename: Vivek R
authors.initials: VR
authors.lastname: Nerurkar
mesh_terms: D001483:Base Sequence; D001812:Blood-Brain Barrier; D001921:Brain / Q000098:blood supply / Q000378:metabolism / Q000821:virology*; D002478:Cells, Cultured; D017931:DNA Primers / Q000235:genetics; D004279:DNA, Viral / Q000235:genetics / Q000378:metabolism; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism* / Q000821:virology*; D006801:Humans; D007577:JC Virus / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology; D007968:Leukoencephalopathy, Progressive Multifocal / Q000209:etiology / Q000378:metabolism / Q000821:virology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism; D044402:Receptor, Serotonin, 5-HT2A / Q000235:genetics / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000494:pharmacology; D014774:Virulence; D014779:Virus Replication
chemical_list: D017931:DNA Primers; D004279:DNA, Viral; D012333:RNA, Messenger; D012367:RNA, Viral; D044402:Receptor, Serotonin, 5-HT2A; D012702:Serotonin Antagonists