Host-derived ICAM-1 glycoproteins incorporated on human immunodeficiency virus type 1 are biologically active and enhance viral infectivity

Abstract

Human immunodeficiency virus type 1 (HIV-1) acquires several host cell membrane proteins when it buds from infected cells. To study the effect of virally incorporated host-derived ICAM-1 glycoproteins on the biology of HIV-1, we have developed a transient expression system that has enabled us to produce virus particles differing only in the absence or the presence of virion-bound ICAM-1. By using a single-round infection assay based on an ICAM-1-negative target T-cell line stably transfected with an HIV-1 long terminal repeat driven luciferase gene construct, we have been able to demonstrate that the acquisition of host-derived ICAM-1 by HIV-1 has functional significance, since it leads to a pronounced increase in viral infectivity (4.6-to 9.8-fold) in an ICAM-1/LFA-1-dependent fashion, as shown by blocking with anti-ICAM-1 and-LFA-1 antibodies. The same potentiating effect on viral infectivity was also observed with monocytoid cells. Studies of the kinetics of infection revealed that the positive effect mediated by virally embedded host cell membrane ICAM-1 is due to an increase in the efficiency of early steps in the viral life cycle. These results provide new insights into how incorporation of host proteins can modulate the biological properties of HIV-1. Our findings have direct clinical relevance, considering that ICAM-1 is expressed on the surface of virus-infected cells and, more importantly, that host-derived ICAM-1 has been shown to be acquired by clinical HIV-1 isolates grown on primary mononuclear cells. These data justify a more complete analysis of the other putative role(s) that virally incorporated ICAM-1 may play in the life cycle of HIV-1, for example, at the level of neutralization sensitivity.

Incorporation of podoplanin into HIV released from HEK-293T cells, but not PBMC, is required for efficient binding to the attachment factor CLEC-2

“…Podoplanin therefore joins the list of host factors which can be incorporated into the HIV-1 envelope and impact HIV-1 infection by interacting with their cognate ligands [9,10]. A prominent example for such a factor is ICAM-1 which was found to be incorporated into the viral membrane, and to facilitate HIV-1 infection by binding to its ligand LFA-1 on T-cells [12].…”

“…Incorporation of host cell factors into the HIV envelope can also increase viral infectivity. The augmentation of infectivity is due to the interaction of the virion-incorporated factors with their cognate receptors on HIV target cells, as exemplified by the up to 100-fold increased infectivity of ICAM-1-bearing viruses for LFA-1 positive target cells [12,13]. Finally, attachment of HIV to dendritic cells can also promote HIV infection of adjacent T-cells [14,15], and this property has been associated with the expression of DC-SIGN [16], a calcium-dependent (C-type) lectin which recognizes mannose-rich carbohydrates on the HIV Env protein [17][18][19].…”

Cell Entry of Enveloped Viruses

“…All viruses likely bind at least weakly to multiple cell surface components such as heparan sulfate proteoglycans, DC-SIGN, integrins, or glycolipids (Bounou et al, 2002;Cantin et al, 1997;Fortin et al, 1997;Jinno-Oue et al, 2001;Mondor et al, 1998;Saphire et al, 1999Saphire et al, , 2001. Although such binding substances probably do not induce conformational changes in EnvGP that are necessary for membrane fusion, they can enhance viral adsorption and substantially increase efficiencies of infections, thus contributing to pathogenesis (Alvarez et al, 2002;Bounou et al, 2002;Geijtenbeek et al, 2000;Jinno-Oue et al, 2001;Saphire et al, 2001).…”

Cellular Proteins Associated with the Interior and Exterior of Vesicular Stomatitis Virus Virions

“…This is an especially important consideration for viruses, including VSV, used in therapeutic applications where large numbers of virus particles are administered, as it may influence efficacy as well as the potential for adverse side effects. Incorporation of ICAM-I into the envelope of human immunodeficiency virus type-1 (HIV-1) not only increased infection efficiency [8,9,10,11] but also interfered with virus neutralization by host antibodies [12,13,14,15]. In another example, the presence of host complement control proteins such as CD46, CD55 and CD59 in the viral envelope has been shown to protect against antibody dependent complement mediated virus lysis in several viruses including human T cell leukemia/ lymphoma virus type I [16], human cytomegalovirus [16], hepatitis C virus [17], HIV-1 [18,19], extracellular enveloped vaccinia virus [20], simian virus 5 [21] and mumps virus [21].…”