In vivo importance of heparan sulfate-binding glycoproteins for murid herpesvirus-4 infection.
In vivo importance of heparan sulfate-binding glycoproteins for murid herpesvirus-4 infection.
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DOI：
10.1099/vir.0.005785-0
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发表时间：
2009-03
期刊：
影响因子：
--
通讯作者：
Stevenson PG
中科院分区：
文献类型：
--
作者：
Gillet L;May JS;Stevenson PG
许多疱疹病毒与硫酸乙酰肝素（HS）结合。鼠疱疹病毒-4（MuHV-4）通过其包膜糖蛋白gp 70和gH/gL这样做。MuHV-4 gp 150进一步调节HS非依赖性相互作用，使其也依赖于HS。因此，MuHV-4病毒粒子的细胞结合是强烈的HS依赖性的。Gp 70和gH/gL显示出一些体外冗余：抗体介导的HS结合的阻断被一个很好地耐受，而两者的阻断严重损害感染。为了了解HS结合MuHV-4在体内的重要性，我们产生了缺乏gL和gp 70的突变体。正如预期的那样，gL− gp 70 − MuHV-4显示出非常差的细胞结合。它在高剂量下感染小鼠，但在低剂量下不感染，表明有缺陷的宿主进入。但一旦进入发生，宿主定植，这对于MuHV-4是相对独立的感染剂量，是非常正常的。gL− gp 70 −进入缺陷比gL−或gp 70 −单一敲除的缺陷大得多。而gp 150的破坏，允许HS非依赖性细胞结合，在很大程度上挽救了gL− gp 70 −细胞结合和宿主进入缺陷。因此，看来MuHV-4 HS结合在体内是重要的，主要是为了有效进入宿主。
Many herpesviruses bind to heparan sulfate (HS). Murid herpesvirus-4 (MuHV-4) does so via its envelope glycoproteins gp70 and gH/gL. MuHV-4 gp150 further regulates an HS-independent interaction to make that HS-dependent too. Cell binding by MuHV-4 virions is consequently strongly HS-dependent. Gp70 and gH/gL show some in vitro redundancy: an antibody-mediated blockade of HS binding by one is well tolerated, whereas a blockade of both severely impairs infection. In order to understand the importance of HS binding for MuHV-4 in vivo, we generated mutants lacking both gL and gp70. As expected, gL−gp70− MuHV-4 showed very poor cell binding. It infected mice at high dose but not at low dose, indicating defective host entry. But once entry occurred, host colonization, which for MuHV-4 is relatively independent of the infection dose, was remarkably normal. The gL−gp70− entry deficit was much greater than that of gL− or gp70− single knockouts. And gp150 disruption, which allows HS-independent cell binding, largely rescued the gL−gp70− cell binding and host entry deficits. Thus, it appeared that MuHV-4 HS binding is important in vivo, principally for efficient host entry.
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