Simian Immunodeficiency Viruses with Defective nef Genes Show Increased Susceptibility to the Noncytotoxic Antiviral Activity of CD8 super(+) Lymphocytes

• Published in: Virology (New York, N.Y.) N.Y.), 2002-03, Vol.294 (1), p.209-221
• Main Authors: Binninger-Schinzel, D, Norley, S, Adler, H S, Oberg, H, Kurth, R
• Format: Article
• Language: English
• Subjects: CD8 antigen; Human immunodeficiency virus; interleukin 2; MIP-1^a; MIP-1^b; MIP-1a protein; MIP-1b protein; nef gene; Simian immunodeficiency virus
• ISSN: 0042-6822; 1096-0341
• DOI: 10.1006/viro.2001.1295

The noncytotoxic soluble factor produced by CD8 super(+) T cells inhibits replication of HIV and SIV in vitro and is thought to play a crucial role in combatting infection in vivo. We determined the effect of human CD8 super(+) lymphocytes on the in vitro replication potential of both wild-type and nef-defective mutants of the simian immunodeficiency virus SIVmac251. Although replication of wild-type SIVmac251 in unstimulated human PBMC supplemented with IL-2 was unaffected by the presence of CD8 super(+) T cells, the nef mutants were susceptible to the inhibitory effects. The effect of exogenous IL-2 depended upon the culture conditions: (i) in nonstimulated human PBMC depleted of CD8 super(+) T cells, addition of IL-2 had a positive effect on the growth of the nef-defective viruses; (ii) in total human PBMC, IL-2 appeared to reinforce the CD8 super(+) T-cell-dependent inhibition of the same mutant viruses. This strongly suggests that IL-2 stimulates the noncytotoxic anti-HIV/SIV response of CD8 super(+) cells present in PBMC cultures. PHA stimulation of unfractionated human PBMC overrode the suppression of viral replication by CD8 super(+) T cells. Depletion of activated T cells expressing the IL-2 receptor alpha -chain (CD25 super(+) T cells), present in small amounts in these primary T cell cultures, dramatically reduced viral replication, indicating that the depleted cell population harbors the target cells permissive for viral replication. Furthermore, using neutralizing antibodies we could show that inhibition by the beta -chemokines MIP-1 alpha , MIP-1 beta , and RANTES and the inhibitory effect of CD8 super(+) lymphocytes on nef mutant SIVmac viruses are harbored on different levels. [copy ]2002 Elsevier Science (USA).