New insights into the functionality of a virion-anchored host cell membrane protein: CD28 versus HIV type 1.
It is now well established that the HIV type 1 (HIV-1) incorporates a vast array of host-encoded molecules in its envelope during the budding process. Interestingly, it was demonstrated that the attachment process is accentuated by supplementary interactions between virion-anchored host molecules and their cognate ligands. Such an enhancement of the viral attachment process was found to result in an increase of infectivity for both T and macrophage-tropic strains of HIV-1. Given that previous work indicates that HIV-1 is budding at the site of cell-to-cell contact, a location rich in the costimulatory CD28 glycoprotein, we investigated whether CD28 could be efficiently acquired by HIV-1. We have been able to generate progeny viruses bearing or not bearing on their surfaces host-derived CD28 using our previously described transient transfection and expression system. The physical presence of CD28 was found to markedly increase virus infectivity in a CD28/B7-dependent manner following infection of two human lymphoid cell lines expressing high levels of surface B7-1/B7-2, two natural ligands of CD28. The physiological significance of CD28 incorporation was provided by the observation that an anti-CD28 Ab decreased replication in primary human mononuclear cells of clinical isolates of HIV-1 propagated in such cells. A virus precipitation assay revealed that M-, T-, and dual-tropic clinical strains of HIV-1 produced in primary human mononuclear cells do indeed incorporate CD28. These results show for the first time that HIV-1 can incorporate CD28 and the acquisition of this specific host surface glycoprotein modulates the virus life cycle.
Centre de Recherche en Infectiologie, Département de Biologie Médicale, Université Laval, Sainte-Foy, Québec, Canada.
Jean-François
JF
Giguère
Jean-Sébastien
JS
Paquette
Salim
S
Bounou
Réjean
R
Cantin
Michel J
MJ
Tremblay
D015703:Antigens, CD / Q000096:biosynthesis / Q000235:genetics; D018122:B7-1 Antigen / Q000096:biosynthesis / Q000235:genetics; D051940:B7-2 Antigen; D001665:Binding Sites / Q000235:genetics / Q000276:immunology; D018106:CD28 Antigens / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002460:Cell Line; D002462:Cell Membrane / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000821:virology; D015658:HIV Infections / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000254:growth & development / Q000302:isolation & purification / Q000472:pathogenicity / Q000502:physiology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism / Q000821:virology; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics; D015728:Receptors, HIV / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured; D014771:Virion / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D014779:Virus Replication / Q000235:genetics / Q000276:immunology
D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D018106:CD28 Antigens; C497964:CD86 protein, human; D008562:Membrane Glycoproteins; D015728:Receptors, HIV