CD147 stimulates HIV-1 infection in a signal-independent fashion.
CD147 is a type I transmembrane protein previously identified as a signal transducing receptor for extracellular cyclophilins. CD147-expressing cells exhibit a characteristic activation of extracellular-signal regulated kinase 1 and 2 (ERK1/2) in response to stimulation with cyclophilin A (CypA). CD147 was also shown to enhance HIV-1 infection in a CypA-dependent fashion, but the role of signaling in this activity of CD147 has not been investigated. In this report, we demonstrate that neither mutations incapacitating signaling response of CD147 to CypA stimulation, nor inhibitor of ERK activation, reduced susceptibility of cells to HIV-1 infection. Surprisingly, truncation of the cytoplasmic tail of CD147 did not abolish signaling response to CypA, but reduced infection by HIV-1 to the level observed in control cells. These results indicate that CD147 enhances HIV-1 replication in a signaling-independent fashion through specific events mediated by the cytoplasmic domain of the protein.
Pushkarsky
Tatiana
T
Department of Microbiology and Tropical Medicine, George Washington University Medical Center, Ross Hall Room 734, 2300 Eye Street NW, Washington, DC 20037, USA.
Yurchenko
Vyacheslav
V
Laborico
Alicia
A
Bukrinsky
Michael
M
D000818:Animals; D051926:Basigin / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D015153:Blotting, Western; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D021984:Cyclophilin A / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D005419:Flavonoids / Q000494:pharmacology; D005434:Flow Cytometry; D015497:HIV-1 / Q000235:genetics / Q000254:growth & development*; D006801:Humans; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism; D009154:Mutation; D010766:Phosphorylation / Q000187:drug effects; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D014162:Transfection
D005419:Flavonoids; D051926:Basigin; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D021984:Cyclophilin A; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one