Alternate receptor usage of neuropilin-1 and glucose transporter protein 1 by the human T cell leukemia virus type 1.
Recent studies have demonstrated that neuropilin 1 (NP-1) is involved in HTLV-1 entry; however, the role NP-1 plays in this process is not understood. We demonstrated that ectopic expression of human NP-1 but not NP-2 cDNA increased susceptibility to HTLV-1. SiRNA-mediated inhibition of NP-1 expression correlated with significant reduction of HTLV-1 Env-mediated fusion. The vascular endothelial growth factor (VEGF(165)) caused downmodulation of surface NP-1 and inhibited HTLV-1 infection of U87 cells. In contrast, VEGF(165) partially inhibited infection of primary astrocytes and had no significant effect on infection of HeLa cells. VEGF(165) and antibodies to the glucose transporter protein 1 (anti-GLUT-1) were both needed to block infection of primary astrocytes, however, only anti-GLUT-1 antibodies were sufficient to block infection of HeLa cells. HTLV-1 Env forms complexes with both NP-1 and GLUT-1 in primary human astrocytes. The alternate usage of these two cellular receptors may have important implications regarding HTLV-1 neuro-tropism.
Jin
Qingwen
Q
Department of Microbiology and Immunology, Indiana University School of Medicine, 635 Barnhill Drive, Rm#420, Indianapolis, IN, USA.
Alkhatib
Bashar
B
Cornetta
Kenneth
K
Alkhatib
Ghalib
G
D000818:Animals; D001253:Astrocytes / Q000821:virology; D016466:CHO Cells; D002460:Cell Line; D002472:Cell Transformation, Viral; D006224:Cricetinae; D003412:Cricetulus; D015536:Down-Regulation; D051272:Glucose Transporter Type 1 / Q000096:biosynthesis / Q000378:metabolism*; D015490:HTLV-I Infections / Q000378:metabolism; D006367:HeLa Cells; D015368:Human T-lymphotropic virus 1 / Q000378:metabolism*; D006801:Humans; D039942:Neuropilin-1 / Q000096:biosynthesis / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D014759:Viral Envelope Proteins / Q000378:metabolism; D053586:Virus Internalization
D051272:Glucose Transporter Type 1; D042461:Vascular Endothelial Growth Factor A; D014759:Viral Envelope Proteins; D039942:Neuropilin-1