title: Agnogene deletion in a novel pathogenic JC virus isolate impairs VP1 expression and virion production.
abstract: Infection of glial cells by the human polyomavirus JC (JCV) causes progressive multifocal leukoencephalopathy (PML). JCV Encephalopathy (JCVE) is a newly identified disease characterized by JCV infection of cortical pyramidal neurons. The virus JCVCPN associated with JCVE contains a unique 143 base pair deletion in the agnogene. Contrary to most JCV brain isolates, JCVCPN has an archetype-like regulatory region (RR) usually found in kidney strains. This provided us with the unique opportunity to determine for the first time how each of these regions contributed to the phenotype of JCVCPN. We characterized the replication of JCVCPN compared to the prototype virus JCVMad-1 in kidney, glial and neuronal cell lines. We found that JCVCPN is capable of replicating viral DNA in all cell lines tested, but is unable to establish persistent infection seen with JCVMad-1. JCVCPN does not have an increased ability to replicate in the neuronal cell line tested. To determine whether this phenotype results from the archetype-like RR or the agnogene deletion, we generated chimeric viruses between JCVCPN of JCVMad-1. We found that the deletion in the agnogene is the predominant cause of the inability of the virus to maintain a persistent infection, with the introduction of a full length agnogene, either with or without agnoprotein expression, rescues the replication of JCVCPN. Studying this naturally occurring pathogenic variant of JCV provides a valuable tool for understanding the functions of the agnogene and RR form in JCV replication.
authors.affiliation: Division of Neurovirology, Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States of America ; Center for Virology and Vaccine Research, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States of America ; Harvard Program in Virology, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Laura C
authors.initials: LC
authors.lastname: Ellis
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Norton
authors.forename: Xin
authors.initials: X
authors.lastname: Dang
authors.forename: Igor J
authors.initials: IJ
authors.lastname: Koralnik
mesh_terms: D000818:Animals; D019556:COS Cells; D036022:Capsid Proteins / Q000235:genetics* / Q000378:metabolism; D002460:Cell Line; D002522:Chlorocebus aethiops; D017353:Gene Deletion; D015967:Gene Expression Regulation, Viral; D023061:Gene Order; D006801:Humans; D007577:JC Virus / Q000502:physiology*; D009457:Neuroglia / Q000378:metabolism / Q000821:virology; D010641:Phenotype; D011995:Recombination, Genetic; D014158:Transcription, Genetic; D054334:Viral Regulatory and Accessory Proteins / Q000235:genetics* / Q000378:metabolism; D014771:Virion / Q000502:physiology*; D019065:Virus Assembly; D014779:Virus Replication; D000086082:Viroporin Proteins
chemical_list: D036022:Capsid Proteins; D054334:Viral Regulatory and Accessory Proteins; C062481:VP1 protein, polyomavirus; C042559:agnoprotein, polyomavirus; D000086082:Viroporin Proteins