Role of the leukocyte function antigen-1 conformational state in the process of human immunodeficiency virus type 1-mediated syncytium formation and virus infection

Human immunodeficiency virus type 1 (HIV-1)-mediated syncytium formation is recognized as being highly dependent on intercellular adhesion molecule (I CAM)-1-leukocyte function-associated molecule 1 (LFA)-1 interaction, wherea s the process of infection with cell-free virions is independent of such co mplementary interaction. Our group has recently demonstrated that an antibo dy-mediated induction of the high affinity state of LFA-1 for ICAM-1 render s target T cells more prone to HIV-1-dependent syncytium formation and infe ction by ICAM-1-bearing virions. To further substantiate these results, we made use of mutant cell lines expressing LFA-I in either a low (parental HP B-ALL and HAmut) or a high affinity slate for ICAM-1 (HAP4) and compared sy ncytium formation and virus infection. Cells expressing the activated form of LFA-1 were found to be more susceptible to HIV-1-induced syncytium forma tion and to infection by ICAM-1-bearing HIV-1 particles. The observed incre ase was solely due to the LFA-1 activation state because it was abrogated b y anti-LFA-1 or anti-ICAM-1 antibodies and not due to variations in surface expression of LFA-1, CD4, or the chemokine coreceptor CXCR4. However, a li near relation was seen between the level of CXCR4 surface expression and su sceptibility to syncytium formation/virus infection when ICAM-1-LFA-1 inter action was either absent (i.e., infection with ICAM-1-negative virions) or abrogated (treatment with anti-LFA-1 or anti-ICAM-1 antibodies). These resu lts emphasize the important role of the LFA-1 activation stale with respect to virus-induced syncytium formation and HIV-1 infection. (C) 1999 Academi c Press.