Inhibition of human immunodeficiency virus type 1 infection in macrophages by an alpha-v integrin blocking antibody.
Macrophages are key cells for HIV infection and HIV spreading inside the organism. Macrophages cultured in vitro can be successfully infected after differentiation with cytokines such as macrophage colony stimulating factor (M-CSF). In the monocyte to macrophage differentiation process with M-CSF, alphav-integrins are upregulated concomitantly with the capacity of HIV to generate a productive virus infection. In the present study we show that an anti-alphav antibody, 17E6, inhibited HIV-1 infection of primary macrophages. The effect of 17E6 on HIV-1 BaL replication in acutely infected macrophages was dose-dependent, with a 50% effective concentration (EC50) of 17+/-2 microg/ml in the absence of cytotoxicity. Similarly, a monoclonal antibody targeting the alphavbeta6 integrin (14D9.F8) also inhibited HIV-1 BaL infection in this cell type. 17E6 reduced the detection of HIV-1 BaL proviral DNA in acutely infected macrophages, but was completely ineffective against HIV-1 BaL production in chronically infected macrophages, suggesting that 17E6 inhibited HIV infection at an early stage of the virus cycle. Finally, a small molecular weight antagonist of the alphavbeta6 integrin, EMD 409849, reduced HIV replication at subtoxic concentrations. Therefore, our results suggest that alphav-containing integrins could play a role in HIV replication in macrophages and suggest that small-molecular-weight compounds might interfere with HIV replication in macrophages through the interaction with alphav integrins.
Fundació irsiCaixa, Laboratori de Retrovirologia, Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona, Ctra. Del Canyet s/n, 08916 Badalona, Spain.
Berta
B
Bosch
Imma
I
Clotet-Codina
Julià
J
Blanco
Eduardo
E
Pauls
Gemma
G
Coma
Samandhy
S
Cedeño
Francesc
F
Mitjans
Anuska
A
Llano
Margarita
M
Bofill
Bonaventura
B
Clotet
Jaume
J
Piulats
José A
JA
Esté
D000911:Antibodies, Monoclonal / Q000276:immunology*; D000951:Antigens, Neoplasm / Q000276:immunology; D002478:Cells, Cultured; D004279:DNA, Viral / Q000032:analysis; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D039564:Integrin alphaV / Q000276:immunology*; D016023:Integrins / Q000037:antagonists & inhibitors* / Q000276:immunology; D007963:Leukocytes, Mononuclear; D008264:Macrophages / Q000276:immunology / Q000821:virology*; D011533:Proviruses / Q000235:genetics; D015728:Receptors, HIV / Q000378:metabolism; D014779:Virus Replication
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D004279:DNA, Viral; D039564:Integrin alphaV; D016023:Integrins; D015728:Receptors, HIV; C073878:integrin alphavbeta6