Induction of human T cell leukemia virus type I receptors on quiescent naive T lymphocytes by TGF-beta.
The retrovirus human T cell leukemia virus (HTLV) type I (HTLV-I) is primarily transmitted by breast-feeding or sexual contact, by cell-to-cell contact between T cells. TGF-beta, which has been shown to enhance transmission of HTLV-I in vitro, is found at high levels in breast milk and semen. In this study, the ability of TGF-beta to regulate expression of molecules involved in HTLV-I binding and entry was examined. Previous studies using a soluble form of the HTLV-I envelope protein SU have shown that quiescent human T cells do not express cell surface molecules that specifically bind SU. After T cell activation, HTLV SU binding proteins are rapidly induced. In this study, we report that TGF-beta induces expression of proteins that bind soluble HTLV SU and HTLV virions on naive CD4(+) T lymphocytes. The induction of these proteins occurred without cell cycle entry or expression of activation markers, involved TGF-beta-induced intracellular signaling, and required de novo transcription and translation. Treatment of naive CD4(+) T lymphocytes with TGF-beta induced expression of GLUT-1, which has recently been reported to function as a receptor for HTLV. Treatment of a TGF-beta-sensitive human myeloid cell line increased the titer of both HTLV-I- and HTLV-II-pseudotyped viruses. Although earlier studies suggested that HTLV SU binding proteins might be an early marker of T cell activation and/or cell proliferation, we report in this study that TGF-beta induces binding of HTLV virions and expression of glucose transporter type 1 in primary CD4(+) T lymphocytes that remain quiescent.
Jones
Kathryn S
KS
Basic Research Program, Science Applications International Corporation-Frederick, Inc., National Cancer Institute-Frederick, Frederick, MD 21702-1201, USA. jonesk@ncifcrf.gov <jonesk@ncifcrf.gov>
Akel
Salem
S
Petrow-Sadowski
Cari
C
Huang
Ying
Y
Bertolette
Daniel C
DC
Ruscetti
Francis W
FW
D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism / Q000821:virology*; D005312:Fetal Blood; D005786:Gene Expression Regulation / Q000187:drug effects*; D015686:Gene Products, env / Q000378:metabolism; D051272:Glucose Transporter Type 1; D015368:Human T-lymphotropic virus 1; D006801:Humans; D008213:Lymphocyte Activation; D009004:Monosaccharide Transport Proteins / Q000235:genetics*; D011485:Protein Binding; D011991:Receptors, Virus / Q000235:genetics*; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D015854:Up-Regulation
D015686:Gene Products, env; D051272:Glucose Transporter Type 1; D009004:Monosaccharide Transport Proteins; D011991:Receptors, Virus; C495677:SLC2A1 protein, human; D016212:Transforming Growth Factor beta