Gillet Laurent, May Janet S, Stevenson Philip G
Division of Virology, Department of Pathology, University of Cambridge, UK.
J Gen Virol. 2009 Mar;90(Pt 3):602-613. doi: 10.1099/vir.0.005785-0.
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.
许多疱疹病毒可与硫酸乙酰肝素（HS）结合。鼠疱疹病毒4型（MuHV - 4）通过其包膜糖蛋白gp70和gH/gL实现这种结合。MuHV - 4的gp150进一步调节一种不依赖HS的相互作用，使其也依赖于HS。因此，MuHV - 4病毒粒子与细胞的结合强烈依赖于HS。Gp70和gH/gL在体外表现出一定的冗余性：一种蛋白通过抗体介导的对HS结合的阻断可被很好地耐受，而两种蛋白的阻断则会严重损害感染。为了了解HS结合对MuHV - 4在体内的重要性，我们构建了同时缺失gL和gp70的突变体。正如预期的那样，gL(-)gp70(-) MuHV - 4表现出非常差的细胞结合能力。它在高剂量时可感染小鼠，但在低剂量时则不能，这表明宿主进入存在缺陷。但一旦发生进入，对于MuHV - 4而言相对独立于感染剂量的宿主定植却非常正常。gL(-)gp
