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Herpes simplex virus (HSV) entry into cells requires binding of the envelope glycoprotein D (gD) to one of several cell surface receptors. The 50 C-terminal residues of the gD ectodomain are essential for virus entry, but not for receptor binding. We have determined the structure of an unliganded gD molecule that includes these C-terminal residues. The(More)
Nonliving antiviral vaccines traditionally target proteins expressed at the surface of the virion with the hope of inducing neutralizing antibodies. Orthopoxviruses (OPVs), such as the human smallpox virus and the mouse-equivalent ectromelia virus (ECTV; an agent of mousepox), encode immune response modifiers (IRMs) that can increase virulence by decreasing(More)
Partially purified fractions of rat liver arylhydroxamic acid acyltransferase were used as the external metabolic activation system for N-hydroxy-N-2-fluorenylacetamide in a Salmonella typhimurium mutagenicity assay system. Salmonella strain TA 1538, which is sensitive to arylamine derivatives, was utilized as the indicator strain. Acyltrans ferase,(More)
The analogs of benzidine were assay for mutagenicity using Salmonella typhimurium TA-98 and TA-100 and a mouse liver enzyme preparation. Only 4-aminobiphenyl produced both frameshift and base pair substitution mutations and 3,3'-dichlorobenzidine was the only compound which was mutagenic without the mammalian enzyme factor. When hydrochloride salts of the(More)
Glycoprotein D (gD) is the receptor binding protein of herpes simplex virus (HSV) and binds to at least two distinct protein receptors, herpesvirus entry mediator (HVEM) and nectin-1. While both receptor binding regions are found within the first 234 amino acids, a crystal structure shows that the C terminus of the gD ectodomain normally occludes the(More)
As the receptor-binding protein of herpes simplex virus (HSV), gD plays an essential role in virus entry. In its native state, the last 56 amino acids of the ectodomain C terminus (C-term) occlude binding to its receptors, herpesvirus entry mediator (HVEM) and nectin-1. Although it is clear that movement of the C-term must occur to permit receptor binding,(More)
Herpes simplex virus entry is initiated by glycoprotein D (gD) binding to a cellular receptor, such as HVEM or nectin-1. gD is activated by receptor-induced displacement of the C-terminus from the core of the glycoprotein. Binding of HVEM requires the formation of an N-terminal hairpin loop of gD; once formed this loop masks the nectin-1 binding site on the(More)
32 As the receptor-binding protein of HSV, gD plays an essential role in virus entry. In its 33 native state, the last 56 amino acids of the ectodomain C-terminus (C-term) occlude 34 binding to its receptors, HVEM and nectin-1. Although it is clear that movement of the C35 term must occur to permit receptor binding, we believe that this conformational(More)
The NKG2D receptor is expressed on the surface of NK, T, and macrophage lineage cells and plays an important role in antiviral and antitumor immunity. To evade NKG2D recognition, herpesviruses block the expression of NKG2D ligands on the surface of infected cells using a diverse repertoire of sabotage methods. Cowpox and monkeypox viruses have taken an(More)