Pathogenesis of simian immunodeficiency virus encephalitis: Viral determinants of neurovirulence

Joseph L Mankowski, M. T. Flaherty, J. P. Spelman, D. A. Hauer, P. J. Didier, A. Martin Amedee, M. Murphey-Corb, L. M. Kirstein, Alvaro Munoz, Janice E Clements, Mary Christine Zink

Research output: Contribution to journalArticle

Abstract

To examine the relationship between macrophage tropism and neurovirulence, macaques were inoculated with two recombinant hybrid viruses derived from the parent viruses SIVmac239, a lymphocyte-tropic, non- neurovirulent clone, and SIV/I7E-Br, a macrophage-tropic, neurovirulent virus strain. The first recombinant, SIV/17E-Cl, contained the portion of the env gene that encodes the surface glycoprotein and a short segment of the transmembrane glycoprotein of SIV/17E-Br in the backbone of SIVmac239. Unlike SIVmac239, SIV/17E-Cl replicated productively in macrophages, demonstrating that sequences in the surface portion of env determine macrophage tropism. None of five macaques inoculated with SIV/17E-Cl developed simian immunodeficiency virus (SIV) encephalitis. The second recombinant, SIV/17E- Fr, which contained the entire env and nef genes and the 3' long terminal repeat of SIV/17E-Br in the SIVmac239 backbone, was also macrophage tropic. Six of nine macaques inoculated with SIV/17E-Fr developed SIV encephalitis ranging from mild to moderate in severity, indicating a significant (P = 0.031) difference in the neurovirulence of the two recombinants. In both groups of macaques, CD4+ cell counts declined gradually during infection and there was no significant difference in the rate of the decline between the two groups of macaques. This study demonstrated that macrophage tropism alone is not sufficient for the development of neurological disease. In addition, it showed that while sequences in the surface portion of the envelope gene determine macrophage tropism, additional sequences derived from the transmembrane portion of envelope and/or nef confer neurovirulence.

Original languageEnglish (US)
Pages (from-to)6055-6060
Number of pages6
JournalJournal of Virology
Volume71
Issue number8
StatePublished - Aug 1997

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viral encephalitis
Viral Encephalitis
Simian immunodeficiency virus
Simian Immunodeficiency Virus
pathogenesis
macrophages
Macaca
Macrophages
tropisms
Tropism
env Genes
tropics
Encephalitis
encephalitis
Viruses
viruses
glycoproteins
nef Genes
terminal repeat sequences
neurodevelopment

ASJC Scopus subject areas

  • Immunology

Cite this

Mankowski, J. L., Flaherty, M. T., Spelman, J. P., Hauer, D. A., Didier, P. J., Martin Amedee, A., ... Zink, M. C. (1997). Pathogenesis of simian immunodeficiency virus encephalitis: Viral determinants of neurovirulence. Journal of Virology, 71(8), 6055-6060.

Pathogenesis of simian immunodeficiency virus encephalitis : Viral determinants of neurovirulence. / Mankowski, Joseph L; Flaherty, M. T.; Spelman, J. P.; Hauer, D. A.; Didier, P. J.; Martin Amedee, A.; Murphey-Corb, M.; Kirstein, L. M.; Munoz, Alvaro; Clements, Janice E; Zink, Mary Christine.

In: Journal of Virology, Vol. 71, No. 8, 08.1997, p. 6055-6060.

Research output: Contribution to journalArticle

Mankowski, JL, Flaherty, MT, Spelman, JP, Hauer, DA, Didier, PJ, Martin Amedee, A, Murphey-Corb, M, Kirstein, LM, Munoz, A, Clements, JE & Zink, MC 1997, 'Pathogenesis of simian immunodeficiency virus encephalitis: Viral determinants of neurovirulence', Journal of Virology, vol. 71, no. 8, pp. 6055-6060.
Mankowski JL, Flaherty MT, Spelman JP, Hauer DA, Didier PJ, Martin Amedee A et al. Pathogenesis of simian immunodeficiency virus encephalitis: Viral determinants of neurovirulence. Journal of Virology. 1997 Aug;71(8):6055-6060.
Mankowski, Joseph L ; Flaherty, M. T. ; Spelman, J. P. ; Hauer, D. A. ; Didier, P. J. ; Martin Amedee, A. ; Murphey-Corb, M. ; Kirstein, L. M. ; Munoz, Alvaro ; Clements, Janice E ; Zink, Mary Christine. / Pathogenesis of simian immunodeficiency virus encephalitis : Viral determinants of neurovirulence. In: Journal of Virology. 1997 ; Vol. 71, No. 8. pp. 6055-6060.
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