Cimakasky LM, Hildreth JE; Conference on Retroviruses and Opportunistic Infections.

Abstr 10th Conf Retrovir Oppor Infect Feb 10 14 2003 Hynes Conv Cent Boston Mass USA Conf Retrovir Oppor Infect 10th 2003 Boston Mass. 2003 Feb 10-14; 10: abstract no. 294.

Johns Hopkins Univ Sch of Med, Baltimore, MD

BACKGROUND: We have shown that an anti-LFA-1 monoclonal antibody (MAb) blocks HIV-1 infection of primary cells through a post-entry mechanism. Investigation of the mechanism by which anti-LFA-1 MAb blocks infection suggested that apoptosis may be involved. We hypothesized that caspase-dependent apoptosis is induced by inhibition of LFA-1 on newly infected cells.METHODS: We used PHA-stimulated peripheral blood mononuclear cells (PBMC) from normal donors and the laboratory strain HIV-IIIB. We examined the effect of anti-LFA-1 MAb on HIV-IIIB infection, attachment, entry, and output. Virus was measured by p24 ELISA. Caspase activity was measured using a conjugated caspase substrate that fluoresces upon cleavage. The pan-caspase inhibitor z-VAD-fmk and the caspase 8 inhibitor z-IETD-fmk, both cell-permeable, were used to block caspase activity.RESULTS: Anti-LFA-1 MAb blocked HIV-IIIB infection in PHA-stimulated PBMC. However, anti-LFA-1 MAb did not block virus attachment, entry, or output. Instead, caspase 8 activity was associated with anti-LFA-1 MAb treatment of infected cultures. The pan-caspase inhibitor z-VAD-fmk and the caspase 8 inhibitor z-IETD-fmk reversed anti-LFA-1 MAb inhibition of infection.CONCLUSIONS: Our data suggest that anti-LFA-1 MAb blocks HIV-1 infection by the induction of caspase-dependent apoptosis.

Publication Types:

• Meeting Abstracts

Keywords:

• Amino Acid Chloromethyl Ketones
• Antibodies, Monoclonal
• Apoptosis
• Apoptosis Regulatory Proteins
• Caspase 8
• Caspases
• HIV Infections
• Lymphocyte Function-Associated Antigen-1
• Oligopeptides
• anti-LFA-1 monoclonal antibody
• benzyloxycarbonyl-isoleucyl-glutamyl-threonyl-aspartic acid fluoromethyl ketone
• benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone
• immunology

Other ID:

• GWAIDS0021253

UI: 102260877

From Meeting Abstracts