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Abstract
CD147 FACILITATES HIV-1 INFECTION BY INTERACTING WITH VIRUS ASSOCIATED CYCLOPHILIN A
BUKRINSKY M, PUSHKARSKY T, YURCHENKO V, ZYBARTH G, SHERRY B
Cyclophilin A (CypA) is a ubiquitously distributed protein with both intracellular (protein folding) and extracellular (chemotactic) activities. In addition, CyPA is specifically incorporated into the virions of HIV-1 and has been shown to enhance significantly (approximately, 6-8 fold in one replication cycle) an early step of cellular HIV-1 infection. However, the mechanism of this activity of CyPA remains unknown. Here, using yeast two-hybrid screen, we identified CD147 as a cell-surface receptor for CyPA. Expression of CD147 on CHO cells initiated a series of CyPA-dependent signaling events culminating in MAP kinase activation and chemotaxis. Expression of human CD147 on CHO cells also provided a 6-fold increase of infection by HIV-1 pseudotyped with the envelope of amphotropic MuLV. However, susceptibility to infection by viruses lacking CyPA (pseudotyped SIV or HIV-1 produced in the presence of cyclosporin A) was unaffected by CD147. Virus-associated CyPA co-immunoprecipitated with CD147 from infected cells, indicating that these proteins interact during infection. Antibody to CD147 inhibited HIV-1 entry as evidenced by the delay in translocation of the HIV-1 core proteins from the membrane and by 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. This interaction may represent a novel target for anti-HIV interventions.
The 1st. IAS Conference on HIV Pathogenesis and Treatment
Abstract no.
120
Suggested Citation
"BUKRINSKYM, et al.
CD147 FACILITATES HIV-1 INFECTION BY INTERACTING WITH VIRUS ASSOCIATED CYCLOPHILIN A.
Oral Presentation:
The 1st. IAS Conference on HIV Pathogenesis and Treatment
:
Abstract no.
120"
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