Heparan sulfate Proteoglycans mediate attachment and entry of human T-cell leukemia virus type 1 virions into CD4+ T cells
Heparan sulfate Proteoglycans mediate attachment and entry of human T-cell leukemia virus type 1 virions into CD4+ T cells
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DOI：
10.1128/jvi.79.20.12692-12702.2005
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发表时间：
2005-10-01
影响因子：
5.4
通讯作者：
Ruscetti, FW
中科院分区：
文献类型：
--
作者：
Jones, KS;Petrow-Sadowski, C;Ruscetti, FW
硫酸乙酰肝素蛋白聚糖（HSPG）被许多病毒用于促进进入宿主细胞。对于逆转录病毒人T细胞白血病病毒1型（HTLV-1），最近报道HSPG对于可溶性HTLV-1 SU的有效结合和HTLV假型病毒进入非T细胞是关键的。然而，据报道，HTLV-1的主要体内靶标CD 4（+）T细胞表达低水平或不可检测水平的HSPG。在这项研究中，我们重新检测了HSPGs在CD 4（+）T细胞中的表达，并检测了它们在HTLV-1附着和进入中的作用。我们观察到，虽然静止的原代CD 4（+）T细胞不表达可检测水平的HSPG，但在免疫激活后，HSPG在原代CD 4（+）T细胞上表达。在已建立的CD 4（+）T细胞系或原代CD 4（+）T细胞表面上的HSPG的酶促修饰显著降低了可溶性HTLV-1 SU和HTLV-1病毒粒子的结合。HSPG也影响HTLV-1进入的效率，因为阻断与HSPG的相互作用显著降低了HTLV-1病毒粒子的内化和CD 4（+）T细胞中HTLV-1假型病毒感染的滴度。因此，HSPG在HTLV-1结合和进入CD 4（+）T细胞中起关键作用。
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.