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Association of simian immunodeficiency virus Nef with cellular serine/threonine kinases is dispensable for the development of AIDS in rhesus macaques

Nature Medicine volume 3, pages 860–865 (1997)Cite this article

Abstract

The nef gene of simian immunodeficiency virus (SIV) is essential for high viral load and induction of AIDS in rhesus monkeys. A mutant form of the SIVmac239 Net which contains changes in a putative SH3-binding domain (amino acids 104 and 107 have been changed from PxxP to AxxA), does not associate with cellular serine/threonine kinases, but is fully active in CD4 downregulation and associates with the cellular tyrosine kinase Src. Infection of two rhesus macaques with SIVmac239 containing the mutant AxxA-Nef caused AIDS and rapid death in both animals. No reversions were observed in the majority of nef sequences analyzed from different time points during infection and from lymphatic tissues at the time of death. Our findings indicate that the putative SH3-ligand domain in SIVmac Nef and the association with cellular serine/threonine kinases are not important for efficient replication and pathogenicity of SIVmac in rhesus macaques.

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Author information

Authors and Affiliations

  1. Institute for Clinical and Molecular Virology, University of Erlangen-Nuernberg, Schlossgarten 4, 91054, Erlangen, Germany

    Sabine M. Lang, Marianne Haupt & Frank Kirchhoff

  2. Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, NY, 11724

    A. John Lafrate & Jacek Skowronski

  3. German Primate Center, Kellnerweg 4, 37077, Göttingen, Germany

    Christiane Stahl-Hennig, Eva M. Kuhn, Thomas Nisslein, Franz-Josef Kaup & Gerhard Hunsmann

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Lang, S., Lafrate, A., Stahl-Hennig, C. et al. Association of simian immunodeficiency virus Nef with cellular serine/threonine kinases is dispensable for the development of AIDS in rhesus macaques. Nat Med 3, 860–865 (1997). https://doi.org/10.1038/nm0897-860

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