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

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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.