CD147 facilitates HIV-1 infection by interacting with virus-associated cyclophilin A

^*The Picower Institute for Medical Research, 350 Community Drive, Manhasset, NY 11030; and ^‡Tufts University Medical School, Boston, MA 02111

Edited by Anthony Cerami, The Kenneth S. Warren Laboratories, Tarrytown, NY, and approved March 23, 2001 (received for review December 8, 2000)

Abstract

Cyclophilin A (CyPA) is specifically incorporated into the virions of HIV-1 and has been shown to enhance significantly an early step of cellular HIV-1 infection. Our preliminary studies implicated CD147 as a receptor for extracellular CyPA. Here, we demonstrate a role for CyPA–CD147 interaction during the early steps of HIV-1 infection. Expression of human CD147 increased infection by HIV-1 under one-cycle conditions. However, susceptibility to infection by viruses lacking CyPA (simian immunodeficiency virus or HIV-1 produced in the presence of cyclosporin A) was unaffected by CD147. Virus-associated CyPA coimmunoprecipitated with CD147 from infected cells. Antibody to CD147 inhibited HIV-1 entry as evidenced by the delay in translocation of the HIV-1 core proteins from the membrane and inhibition of viral reverse transcription. Viruses whose replication did not require CyPA (SIV or mutant HIV-1) were resistant to the inhibitory effect of anti-CD147 antibody. These results suggest that HIV-1 entry depends on an interaction between virus-associated CyPA and CD147 on a target cell.

Footnotes

↵ † Present address: Biodiscovery, Central Research Division, Pfizer Inc., Groton, CT 06340.
↵ § To whom reprint requests should be addressed. E-mail: mbukrinsky{at}picower.edu.
This paper was submitted directly (Track II) to the PNAS office.
Abbreviations:

CyPA,

cyclophilin A;

CsA,

cyclosporin A;

A-MLV,

amphotropic murine leukemia virus;

PBMCs,

peripheral blood mononuclear cells;

MA,

matrix;

CA,

capsid;

RT,

reverse transcriptase;

CHO,

Chinese hamster ovary;

SIV,

simian immunodeficiency virus;

LAV,

lymphadenopathy-associated virus