Host cyclophilin A mediates HIV-1 attachment to target cells via heparans
Autor: | Andrew C. S. Saphire, Michael Bobardt, Philippe Gallay |
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Rok vydání: | 1999 |
Předmět: |
CD4-Positive T-Lymphocytes
Cypa Plasma protein binding HIV Envelope Protein gp120 Transfection Virus Replication Membrane Fusion General Biochemistry Genetics and Molecular Biology Cell Line Cell membrane Cyclophilin A medicine Humans Molecular Biology Glycosaminoglycans Peptidylprolyl isomerase General Immunology and Microbiology biology Heparin Virus Assembly General Neuroscience Cell Membrane Subtilisin Virion Peptidylprolyl Isomerase Viral membrane biology.organism_classification Molecular biology Cell biology medicine.anatomical_structure Viral replication CD4 Antigens HIV-1 HeLa Cells Protein Binding Research Article |
Zdroj: | The EMBO Journal. 18:6771-6785 |
ISSN: | 1460-2075 |
DOI: | 10.1093/emboj/18.23.6771 |
Popis: | 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. |
Databáze: | OpenAIRE |
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