Heparan sulfate Proteoglycans mediate attachment and entry of human T-cell leukemia virus type 1 virions into CD4+ T cells

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.