Contribution of virion ICAM-1 to human immunodeficiency virus infectivity and sensitivity to neutralization

Abstract

Incorporation of the intercellular adhesion molecule ICAM-1 into human immunodeficiency virus type 1 (HIV-1) particles increased virus infectivity on peripheral blood mononuclear cells (PBMCs) by two-to sevenfold. The degree of ICAM-1-mediated enhancement was greater for viruses bearing envelope glycoproteins derived from primary HIV-1 isolates than for those bearing envelope glycoproteins from laboratoryadapted strains. Treatment of target PBMCs with an antibody against LFA-1, a principal ICAM-1 receptor, was able to nullify the ICAM-1-mediated enhancement. The incorporation of ICAM-1 rendered HIV-1 virions less susceptible to neutralization by a monoclonal antibody directed against the viral envelope glycoproteins. Surprisingly, an antibody against ICAM-1 completely neutralized infection by ICAM-1-containing viruses, reducing the efficiency of virus entry by almost 100-fold. Thus, HIV-1 neutralization by an ICAM-1-directed antibody involves more than an inhibition of the contribution of ICAM-1 to virus entry.

The antiviral activity of antibodies in vitro and in vivo

“…Interestingly, the neutralizing antibody activity observed is comparable in magnitude to that of "classic" neutralization. The neutralizing effect, therefore, is far greater than can be explained by the loss of adhesion provided by virion ICAM-1 in contact with its cognate receptor LFA-1 on the target cell (Rizzuto and Sodroski, 1997).…”

“…This may have important consequences, as macaques immunized with human cells or HLA-DR, for example, can be protected from challenge with SIV grown in human host cells (Arthur et al, 1995;Stott, 1994). It has been suggested that cellular adhesion molecules associated with HIV-1 may have a function in increasing adherence to the target cell and thus enhance virus entry; a particularly well-studied example of which is ICAM-1 (Rizzuto and Sodroski, 1997). Antibodies against such host cell-derived molecules can have neutralizing activity; for example, ICAM-1-expressing HIV-1 virions can be completely neutralized by an antibody against ICAM-1.…”

Neutralization of Virus Infectivity by Antibodies: Old Problems in New Perspectives

“…This is strong support for the coating version of the occupancy theory. Analogously, the theory would explain why antibodies to some cellular passenger antigens such as ICAM-1 and MHC on the surface of HIV or SIV virions do neutralize, albeit in a largely complement-dependent manner [118][119][120]: the antigen is so abundant that its coating partly impedes access to the few envelope glycoprotein trimers.…”

Vaccine-induced enhancement of viral infections

“…In addition, augmented TNF␣ production may be implicated in increased viral loads [74]. Infection of leukocyte adhesion molecule leukocyte function-associated antigen (LFA)-1 expressing cells may be further increased by incorporation of intercellular adhesion molecule (ICAM)-1 into the virus particles that bud from activated T-cells [78][79][80].…”