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J Virol, March 1998, p. 2105-2112, Vol. 72, No. 3
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
T Cells Expressing Activated LFA-1 Are More Susceptible to
Infection with Human Immunodeficiency Virus Type 1 Particles
Bearing Host-Encoded ICAM-1
Jean-François
Fortin,
Réjean
Cantin, and
Michel J.
Tremblay*
Centre de Recherche en Infectiologie, Centre
Hospitalier Universitaire de Québec, Pavillon CHUL, and
Département de Microbiologie, Faculté de Médecine,
Université Laval, Ste-Foy, Québec, Canada G1V 4G2
Received 13 October 1997/Accepted 6 December 1997
The incorporation of host-derived proteins in nascent human
immunodeficiency virus type 1 (HIV-1) particles is a
well-established phenomenon. We recently demonstrated that the physical
presence of host-encoded ICAM-1 glycoproteins on HIV-1 leads to a
significant increase in virus infectivity in an ICAM-1/LFA-1-dependent
fashion (J.-F. Fortin, R. Cantin, G. Lamontagne, and M. Tremblay,
J. Virol. 71:3588-3596, 1997). We show here that conversion of
LFA-1 to high affinity for ICAM-1 with the use of anti-LFA-1 antibodies (clones NKI-L16 and MEM83) markedly enhances the susceptibility of
different target T-lymphoid cell lines, as well as of primary peripheral blood mononuclear cells, to infection by ICAM-1-bearing HIV-1 particles (6- to 95-fold). It is known that T-cell receptor (TCR)
cross-linking induces a transient increase in LFA-1 affinity for
ICAM-1. Treatment of peripheral blood mononuclear cells with anti-TCR
antibodies (clone OKT3) resulted in a transient increase in
susceptibility to infection by ICAM-1-positive virions that parallels
the previously reported kinetics of the LFA-1/ICAM-1 adhesion
mechanism. Our results led us to postulate that the strong interaction
taking place between virally incorporated ICAM-1 and cell
surface-activated LFA-1 markedly enhances the efficiency of virus
binding and entry, thus favoring greater infection by ICAM-1-bearing
HIV-1 particles. In view of the knowledge that primary HIV-1 isolates
harbor host-derived ICAM-1 on their surfaces, these results provide new
information about the role of host-derived ICAM-1 in the life cycle of
HIV-1 and how it could positively modulate the dynamics of the viral
infection, mainly in cellular compartments, such as the lymphoid
tissues, where the level of cellular activation is high and where the
probability of encountering a T cell expressing the activated LFA-1
form is also elevated.
*
Corresponding author. Mailing address: Centre de
Recherche en Infectiologie, RC709, Centre Hospitalier Universitaire de
Québec, Pavillon CHUL, 2705 boul. Laurier, Ste-Foy, Québec,
Canada G1V 4G2. Phone: (418) 654-2705. Fax: (418) 654-2715. E-mail: Michel.J.Tremblay{at}crchul.ulaval.ca.
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