Details

Autor(en) / Beteiligte

• Cocchi, Francesca
• Fusco, Daniela
• Menotti, Laura
• Gianni, Tatiana
• Eisenberg, Roselyn J.
• Cohen, Gary H.
• Campadelli-Fiume, Gabriella
• Roizman, Bernard

Titel

The Soluble Ectodomain of Herpes Simplex Virus gD Contains a Membrane-Proximal Pro-Fusion Domain and Suffices to Mediate Virus Entry

Ist Teil von

• Proceedings of the National Academy of Sciences - PNAS, 2004-05, Vol.101 (19), p.7445-7450

Ort / Verlag

United States: National Academy of Sciences

Erscheinungsjahr

2004

Quelle

MEDLINE

Beschreibungen/Notizen

• Entry of herpes simplex virus (HSV) 1 into cells requires the interaction of HSV gD with herpesvirus entry mediator or nectin 1 receptors, and fusion with cell membrane mediated by the fusion glycoproteins gB, gH, and gL. We report that the gD ectodomain in soluble form (amino acids 1-305) was sufficient to rescue the infectivity of a gD-null HSV mutant, indicating that gD does not need to be anchored to the virion envelope to mediate entry. Entry mediated by soluble gD required, in addition to the receptor-binding sites contained within residues 1-250, a discrete downstream portion (amino acids 261-305), located proximal to the transmembrane segment in full-length gD. We named it as profusion domain. The pro-fusion domain was required for entry mediated by virion-bound gD, because its substitution with the corresponding region of CD8 failed to complement the infectivity of gD-/+ HSV. Furthermore, a receptor-negative gD ( gDΔ 6-259) inhibited virus infectivity when coexpressed with wild-type gD; i.e., it acted as a dominant-negative gD mutant. The pro-fusion domain is proline-rich, which is characteristic of regions involved in protein-protein interactions. P291L-P292A substitutions diminished the gD capacity to complement gD-/+ HSV infectivity. We propose that gD forms a tripartite complex with its receptor and, by way of the proline-rich pro-fusion domain, with the fusion glycoproteins, or with one of them. The tripartite complex would serve to recruit/activate the fusion glycoproteins and bring them from a fusion-inactive to a fusion-active state, such that they execute fusion of the virion envelope with cell membrane.