title: Entry of human T-cell leukemia virus type 1 is augmented by heparin sulfate proteoglycans bearing short heparin-like structures.
abstract: Three molecules have been identified as the main cellular factors required for binding and entry of human T-cell leukemia virus type 1 (HTLV-1): glucose transporter 1 (GLUT1), heparan sulfate (HS), and neuropilin 1 (NRP-1). However, the precise mechanism of HTLV-1 cell tropism has yet to be elucidated. Here, we examined the susceptibilities of various human cell lines to HTLV-1 by using vesicular stomatitis virus pseudotypes bearing HTLV-1 envelope proteins. We found that the cellular susceptibility to HTLV-1 infection did not correlate with the expression of GLUT1, HS, or NRP-1 alone. To investigate whether other cellular factors were responsible for HTLV-1 susceptibility, we conducted expression cloning. We identified two HS proteoglycan core proteins, syndecan 1 and syndecan 2, as molecules responsible for susceptibility to HTLV-1. We found that treatment of syndecan 1-transduced cells (expressing increased HS) with heparinase, a heparin-degradative enzyme, reduced HTLV-1 susceptibility without affecting the expression levels of HS chains. To further elucidate these results, we characterized the expression of HS chains in terms of the mass, number, and length of HS in several syndecan 1-transduced cell clones as well as human cell lines. We found a significant correlation between HTLV-1 susceptibility and the number of HS chains with short chain lengths. Our findings suggest that a combination of the number and the length of HS chains containing heparin-like regions is a critical factor which affects the cell tropism of HTLV-1.
authors.affiliation: Department of Virology and Preventive Medicine, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan. atsushit@med.gunma-u.ac.jp
authors.forename: Atsushi
authors.initials: A
authors.lastname: Tanaka
authors.forename: Atsushi
authors.initials: A
authors.lastname: Jinno-Oue
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Shimizu
authors.forename: Ariful
authors.initials: A
authors.lastname: Hoque
authors.forename: Takahisa
authors.initials: T
authors.lastname: Mori
authors.forename: Salequl
authors.initials: S
authors.lastname: Islam
authors.forename: Youko
authors.initials: Y
authors.lastname: Nakatani
authors.forename: Masahiko
authors.initials: M
authors.lastname: Shinagawa
authors.forename: Hiroo
authors.initials: H
authors.lastname: Hoshino
mesh_terms: D045744:Cell Line, Tumor; D015490:HTLV-I Infections / Q000235:genetics / Q000378:metabolism / Q000821:virology*; D015368:Human T-lymphotropic virus 1 / Q000235:genetics / Q000502:physiology*; D006801:Humans; D039942:Neuropilin-1 / Q000235:genetics / Q000378:metabolism; D011991:Receptors, Virus / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D053668:Syndecan-1 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D053669:Syndecan-2 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D053586:Virus Internalization
chemical_list: D011991:Receptors, Virus; D053668:Syndecan-1; D039942:Neuropilin-1; D053669:Syndecan-2