Target cell cyclophilin A modulates human immunodeficiency virus type 1 infectivity

Area of Science:

• Virology
• Cell Biology
• Immunology

Background:

• Cyclophilin A (CypA) is known to interact with the human immunodeficiency virus type 1 (HIV-1) capsid protein (CA).
• CypA is incorporated into HIV-1 virions and has been implicated in enhancing viral spread in cell culture.
• Previous studies suggested CypA's role in both producer and target cells, but its specific contribution remained unclear.

Purpose of the Study:

• To elucidate the distinct roles of producer cell versus target cell CypA in HIV-1 replication.
• To determine whether CypA's interaction with HIV-1 capsid is essential for its function in the viral life cycle.

Main Methods:

• Utilized multiple inhibitors (cyclosporine, MeIle(4)-CsA, Sanglifehrin) to disrupt the CA-CypA interaction.
• Employed HIV-1 capsid mutants with altered CypA binding affinity or dependence.
• Used RNA interference for CypA knockdown in HeLa cells and gene deletion in Jurkat T cells.

Main Results:

• Target cell CypA is essential for HIV-1 capsid-mediated functions and infectivity.
• Producer cell CypA does not play a significant role in HIV-1 virion infectivity.
• Inhibition of HIV-1 infectivity by cyclosporine during production is independent of the CA-CypA interaction.

Conclusions:

• Target cell CypA is the key mediator of CypA's pro-viral activity in HIV-1 infection.
• The findings differentiate the roles of CypA in viral production versus viral entry/replication.
• This research clarifies the specific cellular compartment where CypA exerts its influence on HIV-1.