Host cyclophilin A mediates HIV-1 attachment to target cells via heparans. NLM AIDSLINE Important note: Information in this article was accurate in 2000. The state of the art may have changed since the publication date.

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Host cyclophilin A mediates HIV-1 attachment to target cells via heparans.

EMBO J. 1999 Dec 1;18(23):6771-85. Unique Identifier : AIDSLINE MED/20050571
Saphire AC; Bobardt MD; Gallay PA; Department of Immunology IMM-9, The Scripps Research Institute,; 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.

Abstract: 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.

Keywords: JOURNAL ARTICLE Antigens, CD4/METABOLISM Cell Line Cell Membrane/METABOLISM CD4-Positive T-Lymphocytes/VIROLOGY Glycosaminoglycans/*METABOLISM Hela Cells Heparin/METABOLISM Human HIV Envelope Protein gp120/*PHYSIOLOGY HIV-1/*PHYSIOLOGY Membrane Fusion Peptidylprolyl Isomerase/*METABOLISM Protein Binding Subtilisin/METABOLISM Support, Non-U.S. Gov't Transfection Virion/PHYSIOLOGY *Virus Assembly Virus Replication

KWDjournalarticleantigens,cd4/metabolismcelllinecellmembrane/metabolismcd4-positivet-lymphocytes/virologyglycosaminoglycans/KWDmetabolismhelacellsheparin/metabolismhumanhivenvelopeproteingp120/KWDphysiologyhiv-1/KWDphysiologymembranefusionpeptidylprolylisomerase/KWDmetabolismproteinbindingsubtilisin/metabolismsupport,non-uKWDsKWDgov'ttransfectionvirion/physiologyKWDvirusassemblyvirusreplication
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