Background:  Mammalian cells express factors that inhibit retrovirus replication. HIV-1 is thought to exploit the cis/trans prolyl isomerase cyclophilin A (CypA) as a countermeasure against restriction factors. Here we report that another cis/trans prolyl isomerase, Pin1, has the opposite effect, inhibiting HIV-1 infectivity at a post-entry step.

Methods:  We used co-transfection experiments with FLAG-tagged Pin1 constructs in conjunction with HIV-1 proviral constructs.

Results:  Our research reveals that Pin1 incorporation into HIV-1 is required for inhibition, as are both functional Pin1 isomerase and WW-domain binding domains. Conversely, inhibition of Pin1 isomerase activity using specific drugs within producer cells including patient-derived peripheral blood leukocytes markedly enhances HIV-1 infectivity.  

Conclusions:  Pin1 is the first example of a host molecular chaperone whose activity restricts HIV-1 infectivity, suggesting that the fate of HIV-1 infection may be balanced on the morphological influence of particular chaperones.