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Transmembrane regions of bovine herpesvirus 1-encoded UL49.5 and glycoprotein M regulate complex maturation and ER-Golgi trafficking
- Source :
- Journal of General Virology, 100(3), 497. Society for General Microbiology
- Publication Year :
- 2019
-
Abstract
- Bovine herpesvirus 1 (BoHV-1)-encoded UL49.5 (a homologue of herpesvirus glycoprotein N) can combine different functions, regulated by complex formation with viral glycoprotein M (gM). We aimed to identify the mechanisms governing the immunomodulatory activity of BoHV-1 UL49.5. In this study, we addressed the impact of gM/UL49.5-specific regions on heterodimer formation, folding and trafficking from the endoplasmic reticulum (ER) to the trans-Golgi network (TGN) - events previously found to be responsible for abrogation of the UL49.5-mediated inhibition of the transporter associated with antigen processing (TAP). We first established, using viral mutants, that no other viral protein could efficiently compensate for the chaperone function of UL49.5 within the complex. The cytoplasmic tail of gM, containing putative trafficking signals, was dispensable either for ER retention of gM or for the release of the complex. We constructed cell lines with stable co-expression of BoHV-1 gM with chimeric UL49.5 variants, composed of the BoHV-1 N-terminal domain fused to the transmembrane region (TM) from UL49.5 of varicella-zoster virus or TM and the cytoplasmic tail of influenza virus haemagglutinin. Those membrane-anchored N-terminal domains of UL49.5 were sufficient to form a complex, yet gM/UL49.5 folding and ER-TGN trafficking could be affected by the UL49.5 TM sequence. Finally, we found that leucine substitutions in putative glycine zipper motifs within TM helices of gM resulted in strong reduction of complex formation and decreased ability of gM to interfere with UL49.5-mediated major histocompatibility class I downregulation. These findings highlight the importance of gM/UL49.5 transmembrane domains for the biology of this conserved herpesvirus protein complex.
- Subjects :
- 0301 basic medicine
Viral protein
030106 microbiology
Cattle Diseases
Golgi Apparatus
cytoplasmic domain
Alphaherpesviruses
Endoplasmic Reticulum
medicine.disease_cause
transmembrane region
03 medical and health sciences
Protein Domains
Viral Envelope Proteins
Bovine herpesvirus 1
Virology
medicine
UL49.5/glycoprotein M complex
Animals
glycine zipper
Herpesvirus 1, Bovine
Glycine zipper
chemistry.chemical_classification
Membrane Glycoproteins
biology
Endoplasmic reticulum
ER retention
bovine herpesvirus 1
Cytoplasmic domain
Herpesviridae Infections
Transporter associated with antigen processing
Transmembrane protein
alphaherpesviruses
Cell biology
Protein Transport
Transmembrane domain
030104 developmental biology
Transmembrane region
chemistry
Chaperone (protein)
biology.protein
2406 Virology
570 Life sciences
Cattle
Glycoprotein
Protein Binding
10244 Institute of Virology
Subjects
Details
- Language :
- English
- ISSN :
- 00221317
- Database :
- OpenAIRE
- Journal :
- Journal of General Virology, 100(3), 497. Society for General Microbiology
- Accession number :
- edsair.doi.dedup.....c66ec36169c8f9a3cf97e1159ee9c9d8