Role of cellular adhesion molecules in HIV type 1 infection and their impact on virus neutralization

While CD4 and several chemokine receptors are the principal receptors for human immunodeficiency virus type 1 (HIV-1) viruses, other cell membrane proteins also play a role in HIV-1 infection. A large array of host cell- derived membrane proteins, including adhesion molecules, are incorporated into the envelope of HIV-1 virions, and the profile of host cell proteins acquired by the virus depends on the cells used to propagate the virus. The major leukocyte adhesion molecules, such as leukocyte-function associated antigen-1 (LFA-1), intercellular adhesion molecule-1 (ICAM-1), and CD44, retain their biological functions when expressed on the virion surface, and have been shown to increase virus-cell interaction, enhance virus infectivity, and extend the host cell range of the virus. LFA-1 and its ICAM ligands are also necessary for syncytium formation and cell-to-cell transmission of HIV-1. Furthermore, several studies demonstrate that the presence and level of cell-derived adhesion molecules on the surface of HIV- 1 virions affect the process by which antibody-mediated virus neutralization occurs and is measured: the level of virus neutralization is influenced by the host cell-derived adhesion molecules present on the virus, and thus, by the type of host cells in which the virus was produced. Adhesion molecules expressed on the target cells used in neutralization assays similarly affect HIV-1 neutralization by virus-specific antibodies. Consistent with these observations is the finding that neutralizing activities of both HIV + plasma and human anti-gp120 monoclonal antibodies (Mabs) are enhanced by an anti- LFA-1 Mab capable of blocking LFA-1 functions. Hence, LFA-1, ICAM-1, and other cellular adhesion molecules are involved in different stages of HIV-1 infection and profoundly affect HIV-1 neutralization by virus-specific antibodies. These findings illuminate the biology of virus-cell interactions and have significant implications for evaluating candidate HIV vaccines.