Productive simian virus 40 infection of neurons in immunosuppressed rhesus monkeys

Xin Dang, Christian Wüthrich, Michael K. Axthelm, Igor J. Koralnik

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

There currently is no animal model of JC virus-associated progressive multifocal leukoencephalopathy (PML). Reactivation of simian virus 40 (SV40) in immunosuppressed rhesus monkeys, however, rarely causes a PML-like illness. We sought to isolate a neurotropic clone of SV40 and determine its pathogenic potential in monkeys. The clone SV40 CNS1 was amplified by polymerase chain reaction from the brain DNA of a simian/human immunodeficiency virus-infected monkey that had developed PML and meningoencephalitis. Compared with the SV40 prototype 776, SV40 CNS1 had a small number of single-amino-acid mutations and caused a productive infection in monkey fibroblasts. It was inoculated into 2 SV40-negative, simian/human immunodeficiency virus-immunosuppressed monkeys. Both animals developed meningoencephalitis with productive SV40 infection of cerebral cortical neurons and glia in the superficial layers of the cortex and at the gray-white junction. Focal SV40-infected cells were also found in the cerebellar molecular and granule cell layers and white matter. Both animals also developed disseminated SV40 infection with nephritis and pneumonitis. Thus, SV40 CNS1 is infectious and pathogenic in immunosuppressed monkeys, but it induces encephalitis with fulminant productive infection in cortical neurons and systemic disease, rather than PML. These findings shed new light on SV40 neurotropism and expand the host cell range of this virus.

Original languageEnglish (US)
Pages (from-to)784-792
Number of pages9
JournalJournal of neuropathology and experimental neurology
Volume67
Issue number8
DOIs
StatePublished - Aug 2008

Keywords

  • Neuron infection
  • Progressive multifocal leukoencephalopathy
  • Rhesus monkey
  • Simian virus 40

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neurology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

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