HIV-1 preferentially binds receptors copatched with cell-surface elastase.
Human leukocyte elastase (HLE) interacts with HIV-1 glycoprotein (gp)41, suggesting a nonenzymatic receptor function for HLE in the context of HIV-1. HLE is found localized to the cell surface, but not granules in HIV permissive clones, and to granules, but not the cell surface of HIV nonpermissive clones. Inducing cell-surface HLE expression on HLE null, HIV nonpermissive clones permits HIV infectivity. HIV binding and infectivity diminish in proportion to HLE RNA subtraction. HIV binding and infectivity show dose dependence for the natural HLE ligand alpha1 proteinase inhibitor (alpha1antitrypsin, alpha1PI). Chemokines prevent, whereas alpha1PI promotes, copatching of HLE with the canonical HIV receptors. Recent demonstration that decreased viral RNA is significantly correlated with decreased circulating alpha1PI in HIV seropositive individuals is consistent with a model in which HLE and alpha1PI can serve as HIV coreceptor and cofactor, respectively, and potentially participate in the pathophysiology of HIV disease progression.
Bristow
Cynthia L
CL
Laboratory of Cellular Physiology and Immunology, The Rockefeller University and Population Council, New York, NY 10021, USA. bristoc@mail.rockefeller.edu
Mercatante
Danielle R
DR
Kole
Ryszard
R
D015704:CD4 Antigens / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism* / Q000821:virology; D018925:Chemokines / Q000494:pharmacology; D002999:Clone Cells / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism / Q000821:virology; D003594:Cytoplasmic Granules / Q000201:enzymology; D018450:Disease Progression; D015700:HIV Envelope Protein gp41 / Q000378:metabolism*; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D019272:Leukocyte Elastase / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D046911:Macromolecular Substances; D008565:Membrane Proteins / Q000378:metabolism*; D008954:Models, Biological; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011940:Receptor Aggregation; D019718:Receptors, CXCR4 / Q000378:metabolism; D020298:U937 Cells / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism* / Q000821:virology; D000515:alpha 1-Antitrypsin / Q000494:pharmacology / Q000502:physiology*
D015704:CD4 Antigens; D018925:Chemokines; D015700:HIV Envelope Protein gp41; D008070:Lipopolysaccharides; D046911:Macromolecular Substances; D008565:Membrane Proteins; D019718:Receptors, CXCR4; D000515:alpha 1-Antitrypsin; D019272:Leukocyte Elastase