OmniVira

Literature detail

Glycosylation of mouse DPP4 plays a role in inhibiting Middle East respiratory syndrome coronavirus infection.

Kayla M Peck1 Adam S Cockrell2 Boyd L Yount3 Trevor Scobey3 Ralph S Baric4 Mark T Heise5
Affiliations 5 institutions
  1. Department of Biology, University of North Carolina-Chapel Hill, Chapel Hill, North Carolina, USA.
  2. Genetics, University of North Carolina-Chapel Hill, Chapel Hill, North Carolina, USA.
  3. Epidemiology, University of North Carolina-Chapel Hill, Chapel Hill, North Carolina, USA.
  4. Epidemiology, University of North Carolina-Chapel Hill, Chapel Hill, North Carolina, USA Microbiology and Immunology, University of North Carolina-Chapel Hill, Chapel Hill, North Carolina, USA [email protected] [email protected].
  5. Genetics, University of North Carolina-Chapel Hill, Chapel Hill, North Carolina, USA Microbiology and Immunology, University of North Carolina-Chapel Hill, Chapel Hill, North Carolina, USA [email protected] [email protected].
PMID 25653445 2015 J Virol eng ppublish
PubMed DOI Browse context

Article

Publication summary

Middle East respiratory syndrome coronavirus (MERS-CoV) utilizes dipeptidyl peptidase 4 (DPP4) as an entry receptor. Mouse DPP4 (mDPP4) does not support MERS-CoV entry; however, changes at positions 288 and 330 can confer permissivity. Position 330 changes the charge and glycosylation state of mDPP4. We show that glycosylation is a major factor impacting DPP4 receptor function. These results provide insight into DPP4 species-specific differences impacting MERS-CoV host range and may inform MERS-CoV mouse model development.

Models, Molecular Virus Internalization Amino Acid Sequence Animals Coronavirus Infections Dipeptidyl Peptidase 4 Fluorescent Antibody Technique Glycosylation Mice Middle East Respiratory Syndrome Coronavirus Molecular Sequence Data Species Specificity Dpp4 protein, mouse

Structured evidence records

Evidence records

3 total
Host Range Experiment 1 records
Host Range Experiment Extraction confidence 0.80
Key finding

MERS-CoV entry was experimentally tested with mouse DPP4, showing that glycosylation inhibits infection, while specific amino acid changes confer susceptibility.

Virus
MERS-CoV
Location
Not specified
Supporting text

Mouse DPP4 (mDPP4) does not support MERS-CoV entry; however, changes at positions 288 and 330 can confer permissivity. Position 330 changes the charge and glycosylation state of mDPP4.

Method
cell-entry assay
Experimental system
in vitro cell culture
Molecular Adaptation 1 records
Molecular Adaptation Extraction confidence 0.90
Key finding

Alteration of mouse DPP4 glycosylation at positions 288 and 330 enables MERS-CoV entry, showing that DPP4 glycosylation mediates species-specific receptor adaptation affecting host range.

Virus
MERS-CoV
Host
Not specified
Location
Not specified
Supporting text

Middle East respiratory syndrome coronavirus (MERS-CoV) utilizes dipeptidyl peptidase 4 (DPP4) as an entry receptor. Mouse DPP4 (mDPP4) does not support MERS-CoV entry; however, changes at positions 288 and 330 can confer permissivity. Position 330 changes the charge and glycosylation state of mDPP4.

Genes or proteins
DPP4
Receptors
DPP4
Mutations
position 288; position 330
Mechanism types
receptor_binding; cell_entry; host_factor_interaction
Receptor Usage 1 records
Receptor Usage Extraction confidence 0.95
Key finding

Glycosylation and amino acid residues at positions 288 and 330 of mouse DPP4 determine its ability to act as the receptor mediating MERS-CoV entry.

Virus
MERS-CoV
Location
Not specified
Supporting text

Middle East respiratory syndrome coronavirus (MERS-CoV) utilizes dipeptidyl peptidase 4 (DPP4) as an entry receptor. Mouse DPP4 (mDPP4) does not support MERS-CoV entry; however, changes at positions 288 and 330 can confer permissivity. Position 330 changes the charge and glycosylation state of mDPP4.

Method
molecular analysis; functional assay
Receptors
dipeptidyl peptidase 4 (DPP4)
Host factors
glycosylation