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

Autor: Andrew C. S. Saphire, Michael Bobardt, Philippe Gallay
Rok vydání: 1999
Předmět:
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