Session 46Poster Presentations DC-SIGN and Related Molecules Session Day and Time: Thursday 1:30 - 3:30 pm Room: Hall D
357 Transmission of Cell-surface Bound Human Immunodeficiency Virus Type 1: Interaction Between Cell-surface LFA-1 and Virus-bound ICAM-1 Take Over Interactions Between Cell-surface DC-SIGN and Virus-anchored gp120/ICAM-3 S Bounou*, J F Giguère, R Cantin, M J Tremblay Infectious Diseases Res Ctr, CHUL, Faculty of Med, Laval Univ, Québec, Canada
Background: HIV-1 acquires several host cell membrane proteins during the budding process. It was demonstrated that the attachment process is accentuated by supplementary interactions between virion-anchored host molecules and their cognate ligands. The primary objective of this study was to define whether the nature of virion-bound cell membrane proteins influenced the process of HIV-1 capture and transmission.
Methods: We pulsed cells of monocytoid lineage (established and primary) and CD4-negative epithelial cells transiently expressing DC-SIGN or LFA-1 with isogenic HIV-1 particles either devoid or bearing host-derived ICAM-1 or ICAM-3.
Results: To our surprise, the ICAM-1-LFA-1 association was a more efficient transmission factor than the combined gp120-DC-SIGN and ICAM-3-DC-SIGN interactions. The in vivo relevance of ICAM-1-LFA-1 interactions in virus binding and carriage was revealed when using histocultures of human lymphoid tissue as targets. These results indicate that interactions between virus-incorporated host ICAM-1 and LFA-1 found either on CD4-negative cells or cells expressing low amounts of surface CD4 play a key role in transmission of HIV-1. The reported incorporation of significant amounts of host ICAM-1 in macrophage-tropic and T-tropic isolates of HIV-1 provides physiological significance to these findings.
Conclusions: We propose that virus-associated host cell surface proteins are important in virus-cell contact and efficient dissemination of HIV-1 to target cells.
