HIV-1 infection of human T lymphocytes results in enhanced alpha 5 beta 1 integrin expression.
Altered T cell adherence after human immunodeficiency virus 1 (HIV-1) infection may contribute to viral pathogenesis in the acquired immune deficiency syndrome. To address this hypothesis, we assessed mechanisms of T cell adherence to extracellular matrix proteins in vitro. We found that after HIV-1 infection, both chronically infected H9 CD4+ T cells and acutely infected primary peripheral blood lymphocytes acquired the ability to adhere to the extracellular matrix glycoprotein fibronectin, to a lesser extent to type IV collagen and laminin, but not to type I collagen. H9 cells chronically infected with two of the three HIV-1 strains studied showed approximately a sevenfold increase in attachment to fibronectin, while the same cells infected with the human retrovirus HIV-2 did not. Adhesion was accompanied by changes in morphology, including marked spreading and increased filopodia. These alterations were not blocked by the protein kinase C inhibitor H-7, which did inhibit TPA-induced T cell attachment to fibronectin. Monoclonal antibodies against both the alpha 5 and the beta 1 subunits of the classical fibronectin receptor as well as an Arg-Gly-Asp (RGD) peptide inhibited attachment, whereas anti-alpha 4 monoclonal antibodies and the CS1 peptide did not. Binding to collagen IV was also inhibited by the anti-beta 1 monoclonal antibody, but not the other antibodies. Cells metabolically labeled with [35S]methionine and analyzed by immunoprecipitation with polyclonal anti-beta 1 integrin antibody showed a 2.5-fold increase in integrin synthesis in infected cells compared to uninfected controls. This increase in synthesis was associated with an increase in cell surface expression of both alpha 5 and beta 1 integrins by FACS (registered trademark of Becton Dickinson for a fluorescence-activated cell sorter) analysis. Enhanced expression of integrins such as alpha 5 beta 1 may cause T cell adherence to a variety of tissues, where released viral gene products may induce some of the tissue-specific manifestations of HIV-1 infection.
Weeks
B S
BS
Laboratory of Developmental Biology, National Institute of Dental Research, National Institutes of Health, Bethesda, Maryland 20892.
Klotman
M E
ME
Dhawan
S
S
Kibbey
M
M
Rappaport
J
J
Kleinman
H K
HK
Yamada
K M
KM
Klotman
P E
PE
D000595:Amino Acid Sequence; D015703:Antigens, CD / Q000502:physiology; D002448:Cell Adhesion; D002460:Cell Line; D002472:Cell Transformation, Viral; D002478:Cells, Cultured; D005353:Fibronectins / Q000378:metabolism; D005434:Flow Cytometry; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D016023:Integrins / Q000096:biosynthesis*; D008213:Lymphocyte Activation; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D017469:Receptors, Fibronectin; D011971:Receptors, Immunologic / Q000032:analysis / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000502:physiology*
D015703:Antigens, CD; D005353:Fibronectins; D016023:Integrins; D046911:Macromolecular Substances; D017469:Receptors, Fibronectin; D011971:Receptors, Immunologic