The CD8+ cell noncytotoxic anti-HIV response can be blocked by protease inhibitors

Proc Natl Acad Sci U S A. 2003 Mar 18;100(6):3433-8. doi: 10.1073/pnas.0630379100. Epub 2003 Mar 6.


CD8+ cells from healthy HIV-infected individuals can suppress HIV replication in infected CD4(+) cells without killing the cells. This CD8+ cell noncytotoxic antiviral response (CNAR), observed by coculture of CD8+ cells with infected CD4+ cells, is associated with secretion of a CD8+ cell antiviral factor (CAF). In attempts to identify CAF, we discovered that certain protease inhibitors, particularly leupeptin, can block, by up to 95%, the anti-HIV activity in CD8+ cell culture fluids as well as inhibit CNAR. The effect is dose-dependent and is observed in up to 70% of the CAF and CNAR assays by using fluids and cells from several different subjects. Pretreatment of CD8+ cells with leupeptin reduces CNAR, further supporting an inhibitory effect on a CD8+ cell product. This inhibitory activity of protease inhibitors does not affect cell growth, expression of activation antigens, or viability of either CD8+ cells or the infected CD4+ cells. The results suggest that a part of the CD8+ cell noncytotoxic response involves the activity of a protease or a protein that interacts with protease inhibitors. Proteolysis of a CD8+ cell product(s) may be involved. This observation offers a promising approach for identifying the mechanism of CNARCAF activity.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antiviral Agents / metabolism
  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / drug effects*
  • CD8-Positive T-Lymphocytes / immunology*
  • HIV / immunology*
  • HIV / physiology
  • HIV Infections / immunology
  • HIV Infections / virology
  • Humans
  • In Vitro Techniques
  • Leupeptins / pharmacology
  • Protease Inhibitors / pharmacology*
  • Virus Replication


  • Antiviral Agents
  • Leupeptins
  • Protease Inhibitors
  • leupeptin