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Journal of Virology, February 2004, p. 1843-1850, Vol. 78, No. 4
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.4.1843-1850.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Chimeric Human Immunodeficiency Virus Type 1 (HIV-1) Virions Containing HIV-2 or Simian Immunodeficiency Virus Nef Are Resistant to Cyclosporine Treatment

Mahfuz Khan, Lingling Jin, Ming Bo Huang, Lesa Miles, Vincent C. Bond, and Michael D. Powell*

Department of Microbiology, Biochemistry, and Immunology, Morehouse School of Medicine, Atlanta, Georgia 30310

Received 1 July 2003/ Accepted 20 October 2003

The viral protein Nef and the cellular factor cyclophilin A are both required for full infectivity of human immunodeficiency virus type 1 (HIV-1) virions. In contrast, HIV-2 and simian immunodeficiency virus (SIV) do not incorporate cyclophilin A into virions or need it for full infectivity. Since Nef and cyclophilin A appear to act in similar ways on postentry events, we determined whether chimeric HIV-1 virions that contained either HIV-2 or SIV Nef would have a direct effect on cyclophilin A dependence. Our results show that chimeric HIV-1 virions containing either HIV-2 or SIV Nef are resistant to treatment by cyclosporine and enhance the infectivity of virions with mutations in the cyclophilin A binding loop of Gag. Amino acids at the C terminus of HIV-2 and SIV are necessary for inducing cyclosporine resistance. However, transferring these amino acids to the C terminus of HIV-1 Nef is insufficient to induce cyclosporine resistance in HIV-1. These results suggest that HIV-2 and SIV Nef are able to compensate for the need for cyclophilin A for full infectivity and that amino acids present at the C termini of these proteins are important for this function.


* Corresponding author. Mailing address: Morehouse School of Medicine, Dept. of Microbiology, Biochemistry, Immunology, 720 Westview Dr. SW, Atlanta, GA 30310. Phone: (404) 752-1582. Fax: (404) 752-1179. E-mail: powellm{at}msm.edu.


Journal of Virology, February 2004, p. 1843-1850, Vol. 78, No. 4
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.4.1843-1850.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.




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