Host cyclophilin A mediates HIV-1 attachment to target cells via heparans.
The present study proposes a novel mode of action for cyclophilin A (CypA) in the HIV-1 life cycle. We demonstrate that CypA-deficient viruses do not replicate because they fail to attach to target cells. We show that CypA is exposed at the viral membrane and mediates HIV-1 attachment. We identify heparan as the exclusive cellular binding partner for CypA. Furthermore, CypA binds directly to heparan via a domain rich in basic residues similar to known heparin-binding motifs. This interaction between exposed CypA and cell surface heparans represents the initial step of HIV-1 attachment and is a necessary precursor to gp120-binding to CD4. In conclusion, HIV-1 attachment to target cells is a multi-step process that requires an initial CypA-heparan interaction followed by the gp120-CD4 interaction.
Saphire
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AC
Department of Immunology IMM-9, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Bobardt
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MD
Gallay
P A
PA
D015704:CD4 Antigens / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000821:virology; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D006025:Glycosaminoglycans / Q000378:metabolism*; D015699:HIV Envelope Protein gp120 / Q000502:physiology*; D015497:HIV-1 / Q000502:physiology*; D006367:HeLa Cells; D006493:Heparin / Q000378:metabolism; D006801:Humans; D008561:Membrane Fusion; D019696:Peptidylprolyl Isomerase / Q000378:metabolism*; D011485:Protein Binding; D020860:Subtilisin / Q000378:metabolism; D014162:Transfection; D014771:Virion / Q000502:physiology; D019065:Virus Assembly; D014779:Virus Replication
D015704:CD4 Antigens; D006025:Glycosaminoglycans; D015699:HIV Envelope Protein gp120; D006493:Heparin; D020860:Subtilisin; D019696:Peptidylprolyl Isomerase