1887

Abstract

Herpes simplex virus type 1 (HSV-1) glycoprotein M (gM/UL10) is a 473 aa type III transmembrane protein that resides in various membrane compartments. HSV-1 gM contains several putative trafficking motifs, but their functional relevance remains to be elucidated. We show here that transiently expressed gM 19–343 was sufficient for transport to the -Golgi network (TGN), whilst gM 133–473, where the first two transmembrane domains were deleted, and gM 1–342, which lacked the final residue of the last transmembrane domain, were retained in the endoplasmic reticulum (ER), indicating that all transmembrane domains are required for proper folding and ER exit. A series of bacterial artificial chromosome mutants revealed that in addition to the authentic start codon, translation of gM can be initiated at methionine 19 and 133/135. Whilst a protein lacking the first 18 residues supported WT-like growth, gM 133/135–473 resulted in reduced plaque diameters resembling a UL10 deletion mutant. An HSV-1 mutant encoding gM 1–342 showed similar growth characteristics and accumulated non-enveloped cytoplasmic particles, whilst gM 1–343 resulted in a gain of function, indicating that all transmembrane domains of the protein are important for viral growth. A C-terminal extension further supported viral propagation; however, the C-terminal trafficking motifs (residues 423–473) were completely dispensable. We propose a functional core within gM 19–343 comprised of all transmembrane domains that is sufficient to target the protein to the TGN, a favoured site for envelopment, and to support viral functions.

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2015-11-01
2019-10-18
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