Involvement of integrin alphavbeta3 in the pathogenesis of human immunodeficiency virus type 1 infection in monocytes.
Attachment of HIV to macrophages is a critical early event in the establishment of infection. In the present study, we demonstrate the involvement of integrin alphavbeta3 (vitronectin receptor) in HIV infection of peripheral blood monocyte-derived macrophages. Culturing monocytes in the presence of M-CSF for 3 days upregulated expression of the alphav-containing integrins, alphavbeta3 and alphavbeta5. The increase in alphavbeta3 expression was accompanied by increased HIV-1 replication by monocytes. Immunoblot analysis showed that purified HIV-gp120 protein interacted with CD4 and alphavbeta3 in immunoprecipitation experiments. Neutralizing antibodies against the alphavbeta3 integrin interfered with the coprecipitation of alphavbeta3 with an anti-gp120 antibody and substantially inhibited HIV infection of monocytes. Neutralizing antibodies against alphavbeta5 or beta1 integrins did not significantly affect HIV infection. These results indicate that HIV infection of primary monocytes requires differentiation of these cells and may involve alphavbeta3 interaction with the HIV-1 envelope protein gp120 for productive infection.
Lafrenie
Robert M
RM
Northeastern Ontario Regional Cancer Centre, Sudbury, Ontario, Canada P3E 5J1. rlafrenie@neorcc.on.ca
Lee
Sherwin F
SF
Hewlett
Indira K
IK
Yamada
Kenneth M
KM
Dhawan
Subhash
S
D000906:Antibodies / Q000276:immunology; D015704:CD4 Antigens / Q000378:metabolism; D002462:Cell Membrane / Q000821:virology; D002478:Cells, Cultured; D015699:HIV Envelope Protein gp120 / Q000302:isolation & purification / Q000378:metabolism; D015497:HIV-1 / Q000472:pathogenicity*; D006801:Humans; D009000:Monocytes / Q000821:virology*; D011233:Precipitin Tests; D011485:Protein Binding; D019030:Receptors, Vitronectin / Q000096:biosynthesis / Q000276:immunology / Q000378:metabolism*; D014779:Virus Replication
D000906:Antibodies; D015704:CD4 Antigens; D015699:HIV Envelope Protein gp120; D019030:Receptors, Vitronectin