Inhibition of human immunodeficiency virus type 1 infection in macrophages by alpha-v integrin blocking antibody

Inhibition of human immunodeficiency virus type 1 infection in macrophages by alpha-v integrin blocking antibody

Online publication: 01/01/2007

Abstract:

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, alfa v-integrins are upregulated concomitantly with the capacity of HIV to generate a productive virus infection. In the present study we
show that an anti-alfa v 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 alfa g/ml in the absence of cytotoxicity. Similarly,
a monoclonal antibody targeting the alfa v alfa 6 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 alfa v alfa 6 integrin, EMD 409849, reduced HIV replication at subtoxic concentrations. Therefore, our results suggest that alfa v-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 alfa v integrins.

Authors: Bosch, B., Clotet-Codina, I., Blanco, J., Pauls, E., Coma, G., Cedeño, S., Mitjans, F., Llano, A., Bofill, M., Clotet, B., Piulats, J., Esté, J.A.
  • Doi Code: Antiviral Res 69, 173-180

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