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The immunosuppressant cyclosporin A (CsA) forms a trimolecular complex with cyclophilin and calcineurins to inhibit calcineurin phosphatase activity. Cyclophilins are conserved, ubiquitous and abundant cytosolic peptidyl-prolyl cis-trans isomerases that accelerate the isomerization of XaaPro peptide bonds and the refolding of proteins. Human cyclophilin A (CyPA), an intracellular protein of 165 amino acids, is the target of the CsA and is encoded by a single unique gene conserved from yeast to humans. CyPA is involved in T cell differentiation and proliferation and is highly expressed in brain. CyPA is incorporated into the virion of the type 1 human immunodeficiency virus (HIV-1) via a direct interaction with the capsid domain of the viral Gag polyprotein and is crucial for efficient viral replication.
