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J Virol, June 1998, p. 5207-5214, Vol. 72, No. 6
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Simian-Human Immunodeficiency Virus (SHIV) Containing the nef/Long Terminal Repeat Region of the Highly Virulent SIVsmmPBj14 Causes PBj-Like Activation of Cultured Resting Peripheral Blood Mononuclear Cells, but the Chimera Showed No Increase in Virulence

Edward B. Stephens,* Sampa Mukherjee, Zhen Qian Liu, Darlene Sheffer, Rebecca Lamb-Wharton, Kevin Leung, Wu Zhuge, Sanjay V. Joag, Zhuang Li, Larry Foresman, Istvan Adany, and Opendra Narayan

Marion Merrell Dow Laboratory for Viral Pathogenesis, Department of Microbiology, Molecular Genetics and Immunology, University of Kansas Medical Center, Kansas City, Kansas 66160-7240

Received 7 October 1997/Accepted 20 March 1998

SIVsmmPBj14 is a highly pathogenic lentivirus which causes acute diarrhea, rash, massive lymphocyte proliferation predominantly in the gastrointestinal tract, and death within 7 to 14 days. In cell culture, the virus has mitogenic effects on resting macaque T lymphocytes. In contrast, SIVmac239 causes AIDS in rhesus macaques, generally within 2 years after inoculation. In a previous study, replacement of amino acid residues 17 and 18 of the Nef protein of SIVmac239 with the corresponding amino acid residues of the Nef protein of SIVsmmPBj14 yielded a PBj-like virus that caused extensive activation of resting T lymphocytes in cultures and acute PBj-like disease when inoculated into pig-tailed macaques. This study suggested that nef played a major role in both processes. In this study, we replaced the nef/long terminal repeat (LTR) region of a nonpathogenic simian-human immunodeficiency virus (SHIV), SHIVPPc, with the corresponding region from SIVsmmPBj14 and examined the biological properties of the resultant virus. Like SIVsmmPBj14, SHIVPPcPBjnef caused massive stimulation of resting peripheral blood mononuclear cells (PBMC), which then produced virus in the absence of extraneous interleukin 2. However, when inoculated into macaques, the virus failed to replicate productively or cause disease. Thus, while these results confirmed that the nef/LTR region of SIVsmmPBj14 played a major role in the activation of resting PBMC, duplication of the cellular activation process in macaques may require a further interaction between nef and the envelope glycoprotein of simian immunodeficiency virus because SHIV, containing the envelope of human immunodeficiency virus type 1, failed to cause activation in vivo.

* Corresponding author. Mailing address: Marion Merrell Dow Laboratory for Viral Pathogenesis, Dept. of Microbiology, Molecular Genetics and Immunology, University of Kansas Medical Center, Kansas City, KS 66160-7240. Phone: (913) 588-5575. Fax: (913) 588-5599. E-mail: estephen{at}kumc.edu.

J Virol, June 1998, p. 5207-5214, Vol. 72, No. 6
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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