Active simian immunodeficiency virus (strain smmPGm) infection in macaque central nervous system correlates with neurologic disease

Marilyn S. Smith, Yafen Niu, Shilpa Buch, Zhuang Li, Istvan Adany, David M. Pinson, Raghava Potula, Francis J. Novembre, Opendra Narayan

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

Simian immunodeficiency virus strain smmPGm can induce neuropathology in macaques and is a model for the development of human HIV-related brain injury. For quantitative studies of proviral presence and expression in the central nervous system (CNS), we inoculated 8 macaques intravenously with the virus. Three animals were necropsied 2 to 4 weeks after development of infection, and we obtained lymphoid tissue biopsies from 5 animals before 5 weeks after infection. Peak plasma viral loads averaged 106.76 viral RNA Eq/mL at week 2, whereas cerebrospinal fluid viral loads peaked at 104.4 viral RNA Eq/mL. The proviral DNA loads and viral gag mRNA expression in tissues were quantified by real-time polymerase chain reaction. Two animals developed neurologic disease characterized by meningoencephalitis and meningitis. Proviral DNA levels in CNS tissues of these animals at necropsy revealed 10 5.1 and 103.4 copies/μg of DNA, respectively, whereas viral RNA expression in the CNS reached 100 to 1000 times higher levels than those seen in early necropsies. In sharp contrast, in 2 animals necropsied at later times without CNS disease, virus mRNA expression was not detected in any CNS tissue. Our results are consistent with the hypothesis that active virus expression in the CNS is strongly correlated with neurologic disease and that the event occurs at variable periods after infection.

Original languageEnglish (US)
Pages (from-to)518-530
Number of pages13
JournalJournal of Acquired Immune Deficiency Syndromes
Volume38
Issue number5
DOIs
StatePublished - Apr 15 2005

Keywords

  • Central nervous system infections
  • Encephalitis
  • HIV
  • Meningitis
  • Neuropathogenesis
  • Simian immunodeficiency virus

ASJC Scopus subject areas

  • Infectious Diseases
  • Pharmacology (medical)

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