1887

Abstract

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 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 , we generated mutants lacking both gL and gp70. As expected, gLgp70 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 gLgp70 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 gLgp70 cell binding and host entry deficits. Thus, it appeared that MuHV-4 HS binding is important , principally for efficient host entry.

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2009-03-01
2020-08-03
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