Requirements for lymphocyte activation by unusual strains of simian immunodeficiency virus

D. U. Zhenjian, Petr O. Ilyinskii, Vito G. Sasseville, Michael Newstein, Andrew A. Lackner, Ronald C. Desrosiers

Research output: Contribution to journalArticle

45 Scopus citations

Abstract

When residues 17 and 18 in nef of simian immunodeficiency virus strain SIVmac239 were changed from RQ to YE, the resultant virus was able to replicate in peripheral blood mononuclear cell cultures without prior lymphocyte activation and without the addition of exogenous interleukin-2, caused extensive lymphocyte activation in these cultures, and produced an acute disease in rhesus and pigtail macaques (Z. Du, S. M. Lang, V. G. Sasseville, A. A. Lackner, P. O. Ilyinskii, M. D. Daniel, J. U. Jung, and R. C. Desrosiers, Cell 82:665-674, 1995). These properties are similar to those of the acutely lethal pathogen SIVpbj14 but dissimilar to those of the parental SIVmac239. We show here that the single change of R to Y at position 17 in nef of SIVmac239 is sufficient to confer the full, unusual phenotype. Conversely, the lymphocyte-activating properties of SIVpbj14 were lost by the single change of Y to R at position 17 of nef. The change of R17F or Q18E in SIVmac239 nef did not confer the unusual in vitro properties. Since SIVpbj14 has a duplication of the NF-κB binding sequence in the transcriptional control region, we also constructed and tested strains of SIVmac239/R17Y with zero, one, and two NF-κB binding elements. We found no difference in the properties of SIVmac239/R17Y, either in cell culture or in vivo, whether zero, one, or two NF-κB binding sites were present. Thus, tyrosine at position 17 of nef is absolutely necessary for the unusual phenotype of SIVpbj14 and is sufficient to convert SIVmac239 to a virus with a phenotype like that of SIVpbj14. Multiple NF-κB binding sites are not required for the in vitro properties or for acute disease.

Original languageEnglish (US)
Pages (from-to)4157-4161
Number of pages5
JournalJournal of virology
Volume70
Issue number6
StatePublished - Jun 3 1996
Externally publishedYes

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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  • Cite this

    Zhenjian, D. U., Ilyinskii, P. O., Sasseville, V. G., Newstein, M., Lackner, A. A., & Desrosiers, R. C. (1996). Requirements for lymphocyte activation by unusual strains of simian immunodeficiency virus. Journal of virology, 70(6), 4157-4161.