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 (ICAM)-1-leukocyte function-associated molecule 1 (LFA)-1 interaction, whereas the process of infection with cell-free virions is independent of such complementary interaction. Our group has recently demonstrated that an antibody-mediated induction of the high affinity state of LFA-1 for ICAM-1 renders target T cells more prone to HIV-1-dependent syncytium formation and infection by ICAM-1-bearing virions. To further substantiate these results, we made use of mutant cell lines expressing LFA-1 in either a low (parental HPB-ALL and HAmut) or a high affinity state for ICAM-1 (HAP4) and compared syncytium formation and virus infection. Cells expressing the activated form of LFA-1 were found to be more susceptible to HIV-1-induced syncytium formation and to infection by ICAM-1-bearing HIV-1 particles. The observed increase was solely due to the LFA-1 activation state because it was abrogated by 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 linear relation was seen between the level of CXCR4 surface expression and susceptibility to syncytium formation/virus infection when ICAM-1-LFA-1 interaction was either absent (i.e., infection with ICAM-1-negative virions) or abrogated (treatment with anti-LFA-1 or anti-ICAM-1 antibodies). These results emphasize the important role of the LFA-1 activation state with respect to virus-induced syncytium formation and HIV-1 infection.
Fortin
J F
JF
Faculté de Médecine, Centre Hospitalier Universitaire de Québec, Pavillon CHUL, Ste-Foy, Québec, G1V 4G2, Canada.
Barbeau
B
B
Hedman
H
H
Lundgren
E
E
Tremblay
M J
MJ
D002460:Cell Line; D002472:Cell Transformation, Viral; D015726:Giant Cells / Q000821:virology*; D015658:HIV Infections / Q000821:virology*; D015497:HIV-1 / Q000472:pathogenicity*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D016169:Lymphocyte Function-Associated Antigen-1 / Q000502:physiology*; D011487:Protein Conformation; D019718:Receptors, CXCR4 / Q000096:biosynthesis / Q000378:metabolism; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
D016169:Lymphocyte Function-Associated Antigen-1; D019718:Receptors, CXCR4; D018799:Intercellular Adhesion Molecule-1