Note: this site last updated in 2006
Cyclophilin A is a cellular protein, but it happens also to be one of the cell proteins that gets incorporated into a newly-budding particle of HIV.
What does it do in a normal cell?
It is involved in T cell activation, and it also functions as a "molecular chaperone" - it helps other proteins to fold up correctly.
OK, so what does it do in HIV?
Investigations into cyclophilin A are quite recent, and still going on, but it seems to do at least three things:
- Firstly, it is important in the production of new copies of the viral Vpr protein. The mechanism isn't entirely clear, but it may help Vpr form into the correct shape by helping it isomerise. HIV-infected cells without cyclophilin A have been shown to produce less Vpr.
- Secondly, cyclophilin A is incorporated into the budding virus particle. How does it get incorporated? Simple - it sticks to one of HIV's own proteins, the CA part of the gag protein. Researchers have found that a HIV-1 particle typically incorporates approximately 250 molecules of cyclophilin A.
- Thirdly, it is important in helping HIV-1 attach to a new target cell. After cyclophilin A has been incorporated into a new virus particle, a small part of it pokes out of the viral membrane, meaning it can attach to molecules on the target cell (molecules called heparans, and/or CD147). This happens before the interaction between gp120 and CD4.
- Saphire, A.C.S., Bobardt, M.D., Gallay,P.A. (1999) Host cyclophilin A mediates HIV-1 attachment to target cells via heparans. EMBO Journal 18(23):6771-6785
- Zander K, Sherman MP, Tessmer U, Bruns K, Wray V, Prechtel AT, Schubert E, Henklein P, Luban J, Neidleman J, Greene WC, Schubert U (2003) Cyclophilin A interacts with HIV-1 Vpr and is required for its functional expression Journal of Biological Chemistry 278 (44): 43202-43213