Role of Cyclophilin A in HIV Replication

Abstract

More than a decade has passed since the discovery that the peptidyl prolyl isomerase cyclophilin A (CypA) specifically binds to a proline-rich sequence in HIV-1 capsid (CA) and is thereby incorporated into viral particles. Since then, a variety of possible functions of CypA in the HIV-1 replication cycle have been intensively investigated, but the biological function of this interaction remains to be determined. The binding of CypA to CA increases HIV-1 infectivity in human cells, but promotes an anti-HIV-1 restriction activity in cells from nonhuman primates. Numerous studies have been undertaken to understand the paradoxical effects of CypA and, along with the parallel discovery of the restriction factor tripartite motif 5α, our understanding of how CypA modulates HIV-1 infectivity has now been changed completely. However, 13 years after its discovery, the biological function of the specific interaction between HIV-1 CA and CypA is still not fully understood. Even though much insight has been provided to date, many questions remain unanswered.

Keywords: :

• antiretroviral therapy
• cyclophilin A
• cyclosporin A
• restriction factor
• tripartite motif 5
• Vpr

Acknowledgements

The work in the laboratory of US related to CypA and HIV-1 was supported by a grant from research network FORINGEN, funded by the State of Bavaria, Germany, by the grant IE-S08T06 from the German Human Genome Research Project, and by grants SFB 466-A11, SFB 643-A1 and GRKK 1071 from the German Research Council. We thank David Mitzner, Liane Neumann, Lisa Sprague and Evelyn Schubert for helpful comments to the manuscript.

Additional information

Funding

The work in the laboratory of US related to CypA and HIV-1 was supported by a grant from research network FORINGEN, funded by the State of Bavaria, Germany, by the grant IE-S08T06 from the German Human Genome Research Project, and by grants SFB 466-A11, SFB 643-A1 and GRKK 1071 from the German Research Council. We thank David Mitzner, Liane Neumann, Lisa Sprague and Evelyn Schubert for helpful comments to the manuscript.