Presence of host ICAM-1 in laboratory and clinical strains of human immunodeficiency virus type 1 increases virus infectivity and CD4(+)-T-cell depletion in human lymphoid tissue, a major site of replication in vivo.
Human immunodeficiency virus type 1 (HIV-1) incorporates several host proteins. Earlier studies have indicated that such foreign constituents can modulate the virus life cycle, although the potential roles that these proteins might play in the viral pathology in vivo remain unclear. In an attempt to shed light on this issue, we first exposed explants of human lymphoid tissue to isogenic viruses except for the presence or absence of host-derived ICAM-1. Incorporation of ICAM-1 alone increased HIV-1 infectivity for human tonsillar tissue cultured ex vivo. This observation was made for viruses bearing distinct coreceptor utilization profiles. Conversion of LFA-1 to a high-affinity-high-avidity state for ICAM-1 further augmented the susceptibility of human tonsillar histocultures to infection by ICAM-1-bearing virions. A more massive depletion of CD4(+) T lymphocytes was seen with X4 ICAM-1/POS viruses than with isogenic ICAM-1/NEG virions. Exposure of X4 and R5 primary isolates of HIV-1 to a blocking anti-ICAM-1 antibody resulted in a decrease of virus infection. Finally, X4 and R5 virions derived from a natural human lymphoid tissue microenvironment incorporated high levels of ICAM-1. Altogether, these results indicate that the incorporation of host ICAM-1 can significantly modulate the biology of HIV-1 in a cellular milieu recognized as the major site of replication in vivo and suggest that host proteins found in HIV-1 particles may participate in the pathogenesis of this disease.
Bounou
Salim
S
Centre de Recherche en Infectiologie, Centre Hospitalier Universitaire de Québec, Hôpital CHUL, Ste-Foy, Quebec G1V 4G2, Canada.
Leclerc
Jacques E
JE
Tremblay
Michel J
MJ
D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology; D002461:Cell Line, Transformed; D046508:Culture Techniques; D015497:HIV-1 / Q000276:immunology / Q000302:isolation & purification / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D007753:Laboratories; D008212:Lymphocyte Depletion; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism; D008221:Lymphoid Tissue / Q000166:cytology / Q000276:immunology / Q000821:virology; D014066:Palatine Tonsil / Q000166:cytology / Q000276:immunology* / Q000821:virology; D014771:Virion / Q000378:metabolism; D014779:Virus Replication
D016169:Lymphocyte Function-Associated Antigen-1; D018799:Intercellular Adhesion Molecule-1