title: Heparan sulfate proteoglycans mediate attachment and entry of human T-cell leukemia virus type 1 virions into CD4+ T cells.
abstract: Heparan sulfate proteoglycans (HSPGs) are used by a number of viruses to facilitate entry into host cells. For the retrovirus human T-cell leukemia virus type 1 (HTLV-1), it has recently been reported that HSPGs are critical for efficient binding of soluble HTLV-1 SU and the entry of HTLV pseudotyped viruses into non-T cells. However, the primary in vivo targets of HTLV-1, CD4(+) T cells, have been reported to express low or undetectable levels of HSPGs. For this study, we reexamined the expression of HSPGs in CD4(+) T cells and examined their role in HTLV-1 attachment and entry. We observed that while quiescent primary CD4(+) T cells do not express detectable levels of HSPGs, HSPGs are expressed on primary CD4(+) T cells following immune activation. Enzymatic modification of HSPGs on the surfaces of either established CD4(+) T-cell lines or primary CD4(+) T cells dramatically reduced the binding of both soluble HTLV-1 SU and HTLV-1 virions. HSPGs also affected the efficiency of HTLV-1 entry, since blocking the interaction with HSPGs markedly reduced both the internalization of HTLV-1 virions and the titer of HTLV-1 pseudotyped viral infection in CD4(+) T cells. Thus, HSPGs play a critical role in the binding and entry of HTLV-1 into CD4(+) T cells.
authors.affiliation: Basic Research Program, SAIC-Frederick, National Cancer Institute-Frederick, MD 21702-1201, USA. jonesk@ncifcrf.gov
authors.forename: Kathryn S
authors.initials: KS
authors.lastname: Jones
authors.forename: Cari
authors.initials: C
authors.lastname: Petrow-Sadowski
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Bertolette
authors.forename: Ying
authors.initials: Y
authors.lastname: Huang
authors.forename: Francis W
authors.initials: FW
authors.lastname: Ruscetti
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism / Q000821:virology; D002460:Cell Line; D019812:Heparan Sulfate Proteoglycans / Q000378:metabolism / Q000502:physiology*; D015368:Human T-lymphotropic virus 1 / Q000502:physiology*; D006801:Humans; D014771:Virion / Q000502:physiology*; D014779:Virus Replication
chemical_list: D019812:Heparan Sulfate Proteoglycans