Rearrangement of simian virus 40 regulatory region is not required for induction of progressive multifocal leukoencephalopathy in immunosuppressed rhesus monkeys

Xin Dang, Michael Axthelm, Norman L. Letvin, Igor J. Koralnik

    Research output: Contribution to journalArticle

    11 Citations (Scopus)

    Abstract

    Rearrangements of the JC virus (JCV) regulatory region (RR) are consistently found in the brains of patients with progressive multifocal leukoencephalopathy (PML), whereas the archetype RR is present in their kidneys. In addition, the C terminus of the large T antigen (T-Ag) shows greater variability in PML than does the rest of the coding region. To determine whether similar changes in simian virus 40 (SV40) are necessary for disease induction in monkeys, we sequenced the SV40 RR and the C terminus of the T-Ag from the brain of simian/human immunodeficiency virus (SHIV)-infected monkey 18429, which presented spontaneously with an SV40-associated PML-like disease, as well as from the peripheral blood mononuclear cells (PBMC), kidneys, and brains of SV40-seronegative, SHIV-infected monkeys 21289 and 21306, which were inoculated with the 18429 brain SV40 isolate. These animals developed both SV40-associated PML and meningoencephalitis. Thirteen types of SV40 RR were characterized. Compared to the SV40 archetype, we identified RRs with variable deletions in either the origin of replication, the 21-bp repeat elements, or the late promoter, as well as deletions or duplications of the 72-bp enhancer. The archetype was the most prominent RR in the brain of monkey 18429. Shortly after inoculation, a wide range of RRs could be found in the PBMC of monkeys 21289 and 21306. However, the archetype RR became the predominant type in their blood, kidneys, and brains at the time of sacrifice. On the contrary, the T-Ag C termini remained identical in all compartments of the three animals. These results indicate that unlike JCV in humans, rearrangements of SV40 RR are not required for brain disease induction in immunosuppressed monkeys.

    Original languageEnglish (US)
    Pages (from-to)1361-1366
    Number of pages6
    JournalJournal of Virology
    Volume79
    Issue number3
    DOIs
    StatePublished - Feb 2005

    Fingerprint

    Simian virus 40
    Progressive Multifocal Leukoencephalopathy
    Nucleic Acid Regulatory Sequences
    Macaca mulatta
    Haplorhini
    monkeys
    brain
    Viral Tumor Antigens
    Brain
    JC polyomavirus
    JC Virus
    Simian Immunodeficiency Virus
    Human immunodeficiency virus
    kidneys
    mononuclear leukocytes
    antigens
    Kidney
    Blood Cells
    HIV
    replication origin

    ASJC Scopus subject areas

    • Immunology

    Cite this

    Rearrangement of simian virus 40 regulatory region is not required for induction of progressive multifocal leukoencephalopathy in immunosuppressed rhesus monkeys. / Dang, Xin; Axthelm, Michael; Letvin, Norman L.; Koralnik, Igor J.

    In: Journal of Virology, Vol. 79, No. 3, 02.2005, p. 1361-1366.

    Research output: Contribution to journalArticle

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