Lack of Heparan Sulfate Expression in B-Cell Lines: Implications for Kaposi's Sarcoma-Associated Herpesvirus and Murine Gammaherpesvirus 68 Infections
Lack of Heparan Sulfate Expression in B-Cell Lines: Implications for Kaposi's Sarcoma-Associated Herpesvirus and Murine Gammaherpesvirus 68 Infections
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DOI：
10.1128/jvi.01167-08
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发表时间：
2008-12-15
影响因子：
5.4
通讯作者：
Coscoy, Laurent
中科院分区：
文献类型：
--
作者：
Jarousse, Nadine;Chandran, Bala;Coscoy, Laurent
卡波西肉瘤相关疱疹病毒(KSHV)及其小鼠同源物小鼠伽马疱疹病毒68(MHV68)是嗜淋巴病毒，可在宿主中建立潜伏感染。令人惊讶的是，虽然B细胞是体内主要的病毒库，但B细胞系对MHV68或KSHV的感染容许性很差。在这里，我们报告了大多数B细胞株几乎不表达细胞表面硫酸乙酰肝素(HS)，这是一种糖胺多糖，是感染这些病毒所必需的。我们发现，HS生物合成的关键酶Ext1在这些细胞中的表达水平很低。将Ext1基因导入B细胞系，可恢复细胞表面高表达HS。在小鼠A20和M12 B细胞系中过表达Ext1可增加MHV68的表面结合力，提高感染效率。最后，尽管这不足以允许有效的感染，但HS在BJAB细胞上的表达促进了KSHV在细胞表面的结合。因此，我们的结果表明，由于缺乏表面HS，MHV68和KSHV周期在B细胞系的结合步骤中被阻断。
Kaposi's sarcoma-associated herpesvirus (KSHV) and its murine homolog, murine gammaherpesvirus 68 (MHV68), are lymphotropic viruses that establish latent infection in their host. Surprisingly, while B cells are the main viral reservoir in vivo, B-cell lines are poorly permissive to infection by either MHV68 or KSHV. Here, we report that most B-cell lines express very little to no cell surface heparan sulfate (HS), a glycosaminoglycan that is essential for infection by these viruses. We found that Ext1, a key enzyme in the biosynthesis of HS, was expressed at a low level in these cells. Transfection of B-cell lines with Ext1 restored high HS expression at the cell surface. Overexpression of Ext1 in murine A20 and M12 B-cell lines increased MHV68 surface binding and enhanced the efficiency of infection. Finally, although it was not sufficient to allow efficient infection, the expression of HS on BJAB cells promoted KSHV binding at the cell surface. Thus, our results indicate that MHV68 and KSHV cycles are blocked in B-cell lines at the binding step due to a lack of surface HS.