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Journal of Virology, October 2005, p. 12692-12702, Vol. 79, No. 20
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.20.12692-12702.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Heparan Sulfate Proteoglycans Mediate Attachment and Entry of Human T-Cell Leukemia Virus Type 1 Virions into CD4+ T Cells

Kathryn S. Jones,1* Cari Petrow-Sadowski,1 Daniel C. Bertolette,2 Ying Huang,2 and Francis W. Ruscetti2

Basic Research Program, SAIC-Frederick, Frederick, Maryland,1 Laboratory of Experimental Immunology, Center for Cancer Research, National Cancer Institute-Frederick, Frederick, Maryland 217022

Received 27 April 2005/ Accepted 17 July 2005

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.

* Corresponding author. Mailing address: Basic Research Program, SAIC-Frederick, National Cancer Institute-Frederick, Frederick, MD 21702-1201. Phone: (301) 846-5262. Fax: (301) 846-7034. E-mail: jonesk{at}ncifcrf.gov.

Journal of Virology, October 2005, p. 12692-12702, Vol. 79, No. 20
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.20.12692-12702.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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