71-kilodalton heat shock cognate protein acts as a cellular receptor for syncytium formation induced by human T-cell lymphotropic virus type 1.
We previously reported that the region corresponding to amino acids 197 to 216 of the gp46 surface glycoprotein (gp46-197) served as a binding domain for the interaction between gp46 and trypsin-sensitive membrane components of the target cell, leading to syncytium formation induced by human T-cell lymphotropic virus type 1 (HTLV-1)-bearing cells. Our new evidence shows that the 71-kDa heat shock cognate protein (HSC70) acts as a cellular receptor for syncytium formation. Using affinity chromatography with the peptide gp46-197, followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, we isolated three components (bands A, B, and C) from MOLT-4 cell lysate which exhibited specific interactions with gp46 and inhibitory activities for syncytium formation induced by HTLV-1-bearing cells. Band A and B components were identified as HSC70 and beta-actin, respectively, through amino acid sequencing by tandem mass spectrometry and immunostaining with specific monoclonal antibodies. Band C is likely to be a nonprotein component, because full activity for syncytium formation was seen after extensive trypsin digestion. Anti-HSC70 monoclonal antibody clearly blocked syncytium formation in a coculture of HTLV-1-bearing cells and indicator cells, whereas no inhibition was seen with anti-beta-actin monoclonal antibody. Furthermore, flow cytometric analysis indicated that anti-HSC70 antibody reacted with MOLT-4 cells. Thus, we propose that HSC70 expressed on the target cell surface acts as a cellular acceptor to gp46 exposed on the HTLV-1-infected cell for syncytium formation, thereby leading to cell-to-cell transmission of HTLV-1.
Sagara
Y
Y
Fukuoka Red Cross Blood Center, Japan.
Ishida
C
C
Inoue
Y
Y
Shiraki
H
H
Maeda
Y
Y
D000595:Amino Acid Sequence; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D003588:Cytopathogenic Effect, Viral / Q000502:physiology; D015726:Giant Cells / Q000821:virology; D050883:HSC70 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000502:physiology*; D015490:HTLV-I Infections / Q000209:etiology / Q000235:genetics / Q000503:physiopathology; D015368:Human T-lymphotropic virus 1 / Q000472:pathogenicity* / Q000502:physiology*; D006801:Humans; D008969:Molecular Sequence Data; D011991:Receptors, Virus / Q000235:genetics / Q000502:physiology*
D002352:Carrier Proteins; D050883:HSC70 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; C494371:HSPA8 protein, human; C080823:HTLV-I receptor; D011991:Receptors, Virus