title: The receptor complex associated with human T-cell lymphotropic virus type 3 (HTLV-3) Env-mediated binding and entry is distinct from, but overlaps with, the receptor complexes of HTLV-1 and HTLV-2.
abstract: Little is known about the transmission or tropism of the newly discovered human retrovirus, human T-cell lymphotropic virus type 3 (HTLV-3). Here, we examine the entry requirements of HTLV-3 using independently expressed Env proteins. We observed that HTLV-3 surface glycoprotein (SU) binds efficiently to both activated CD4(+) and CD8(+) T cells. This contrasts with both HTLV-1 SU, which primarily binds to activated CD4(+) T cells, and HTLV-2 SU, which primarily binds to activated CD8(+) T cells. Binding studies with heparan sulfate proteoglycans (HSPGs) and neuropilin-1 (NRP-1), two molecules important for HTLV-1 entry, revealed that these molecules also enhance HTLV-3 SU binding. However, unlike HTLV-1 SU, HTLV-3 SU can bind efficiently in the absence of both HSPGs and NRP-1. Studies of entry performed with HTLV-3 Env-pseudotyped viruses together with SU binding studies revealed that, for HTLV-1, glucose transporter 1 (GLUT-1) functions at a postbinding step during HTLV-3 Env-mediated entry. Further studies revealed that HTLV-3 SU binds efficiently to naive CD4(+) T cells, which do not bind either HTLV-1 or HTLV-2 SU and do not express detectable levels of HSPGs, NRP-1, and GLUT-1. These results indicate that the complex of receptor molecules used by HTLV-3 to bind to primary T lymphocytes differs from that of both HTLV-1 and HTLV-2.
authors.affiliation: Basic Science Program, SAIC-Frederick, National Cancer Institute-Frederick, Frederick, MD 21702-1201, USA. joneska@mail.nih.gov
authors.forename: Kathryn S
authors.initials: KS
authors.lastname: Jones
authors.forename: Ying K
authors.initials: YK
authors.lastname: Huang
authors.forename: Sébastien A
authors.initials: SA
authors.lastname: Chevalier
authors.forename: Philippe V
authors.initials: PV
authors.lastname: Afonso
authors.forename: Cari
authors.initials: C
authors.lastname: Petrow-Sadowski
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Bertolette
authors.forename: Antoine
authors.initials: A
authors.lastname: Gessain
authors.forename: Francis W
authors.initials: FW
authors.lastname: Ruscetti
authors.forename: Renaud
authors.initials: R
authors.lastname: Mahieux
mesh_terms: D000595:Amino Acid Sequence; D015496:CD4-Positive T-Lymphocytes / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000821:virology; D002460:Cell Line; D017977:Deltaretrovirus / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D015485:Deltaretrovirus Antigens / Q000378:metabolism*; D015686:Gene Products, env / Q000378:metabolism*; D051272:Glucose Transporter Type 1 / Q000378:metabolism; D019812:Heparan Sulfate Proteoglycans / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D010802:Phylogeny; D011485:Protein Binding; D011991:Receptors, Virus / Q000378:metabolism*; D016415:Sequence Alignment; D014161:Transduction, Genetic; D053585:Virus Attachment
chemical_list: D015485:Deltaretrovirus Antigens; D015686:Gene Products, env; D051272:Glucose Transporter Type 1; D019812:Heparan Sulfate Proteoglycans; D011991:Receptors, Virus