Effects of HIV-1 on the surface expression of LFA-1 on cultured monocytes.
CD11a, the alpha chain of LFA-1, which is a member of the LeuCAM family of integrins, has been implicated in the formation of HIV-induced syncytia and may contribute to the depletion of CD4-positive lymphocytes seen in patients with HIV infection. In this study, we examined the effects of HIV-1 infection on the expression of CD11a on cultured monocyte-derived macrophages (MDMs). Monocytes isolated from peripheral blood and maintained in suspension culture were infected in vitro with a monocytotropic variant of HIV-1 (Ba-L). Surface expression of CD11a, measured by indirect immunofluorescence and flow cytometry, was significantly higher on HIV-infected cells than on mock-infected cells from the same donor. Upregulation of CD11a expression was unaffected by the HIV reverse transcriptase inhibitor, zidovudine, indicating that it did not depend on reverse transcription. A step before reverse transcription, such as viral binding, appears sufficient to trigger an increase in CD11a expression. This hypothesis is supported by our findings of soluble recombinant CD4 inhibition of HIV-induced CD11a upregulation. It is possible that induction of a cytokine network by HIV underlies this effect, given our findings that exposure of uninfected MDMs to granulocyte-macrophage colony-stimulating factor (GM-CSF) specifically increased CD11a expression and that HIV-infected MDMs secreted more GM-CSF than mock-infected cells.
Stent
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AIDS Pathogenesis Research Unit, National Centre for HIV Virology Research, Macfarlane Burnet Centre for Medical Research, Fairfield, Victoria, Australia.
Crowe
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D015704:CD4 Antigens / Q000235:genetics / Q000494:pharmacology; D002478:Cells, Cultured; D005434:Flow Cytometry; D019084:Fluorescent Antibody Technique, Indirect; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism / Q000494:pharmacology; D015699:HIV Envelope Protein gp120 / Q000235:genetics / Q000494:pharmacology; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1; D006801:Humans; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism*; D009000:Monocytes / Q000821:virology; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology; D015854:Up-Regulation; D015215:Zidovudine / Q000494:pharmacology
D015704:CD4 Antigens; D015699:HIV Envelope Protein gp120; D016169:Lymphocyte Function-Associated Antigen-1; D012333:RNA, Messenger; D011994:Recombinant Proteins; D018894:Reverse Transcriptase Inhibitors; D015215:Zidovudine; D016178:Granulocyte-Macrophage Colony-Stimulating Factor