Identification of adipocyte plasma membrane-associated protein as a novel modulator of human cytomegalovirus infection.
Adipocytes
/ metabolism
Animals
Cell Membrane
/ metabolism
Cytomegalovirus
/ genetics
Cytomegalovirus Infections
/ etiology
Dogs
Epithelial Cells
/ metabolism
Fibroblasts
/ metabolism
Gene Knockout Techniques
Host Microbial Interactions
Humans
Madin Darby Canine Kidney Cells
Membrane Glycoproteins
/ antagonists & inhibitors
Mice
NIH 3T3 Cells
Recombinant Proteins
/ genetics
Viral Structural Proteins
/ metabolism
Virulence
Virus Internalization
Journal
PLoS pathogens
ISSN: 1553-7374
Titre abrégé: PLoS Pathog
Pays: United States
ID NLM: 101238921
Informations de publication
Date de publication:
07 2019
07 2019
Historique:
received:
25
02
2019
accepted:
13
06
2019
revised:
08
08
2019
pubmed:
30
7
2019
medline:
3
1
2020
entrez:
30
7
2019
Statut:
epublish
Résumé
Human cytomegalovirus (HCMV) is a ubiquitous pathogen that can cause disability in newborns and serious clinical diseases in immunocompromised patients. HCMV has a large genome with enormous coding potential; its viral particles are equipped with complicated glycoprotein complexes and can infect a wide range of human cells. Although multiple host cellular receptors interacting with viral glycoproteins have been reported, the mechanism of HCMV infection remains a mystery. Here we report identification of adipocyte plasma membrane-associated protein (APMAP) as a novel modulator active in the early stage of HCMV infection. APMAP is necessary for HCMV infection in both epithelial cells and fibroblasts; knockdown of APMAP expression significantly reduced HCMV infection of these cells. Interestingly, ectopic expression of human APMAP in cells refractory to HCMV infection, such as canine MDCK and murine NIH/3T3 cells, promoted HCMV infection. Furthermore, reduction in viral immediate early (IE) gene transcription at 6 h post infection and delayed nucleus translocation of tegument delivered pp65 at 4 h post infection were detected in APMAP-deficient cells but not in the wildtype cells. These results suggest that APMAP plays a role in the early stage of HCMV infection. Results from biochemical studies of APMAP and HCMV proteins suggest that APMAP could participate in HCMV infection through interaction with gH/gL containing glycoprotein complexes at low pH and mediate nucleus translocation of tegument pp65. Taken together, our results suggest that APMAP functions as a modulator promoting HCMV infection in multiple cell types and is an important player in the complex HCMV infection mechanism.
Identifiants
pubmed: 31356650
doi: 10.1371/journal.ppat.1007914
pii: PPATHOGENS-D-19-00382
pmc: PMC6687193
doi:
Substances chimiques
APMAP protein, human
0
Membrane Glycoproteins
0
Recombinant Proteins
0
Viral Structural Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1007914Déclaration de conflit d'intérêts
Some authors are full time employee of Merck and Co., Inc. However, their employment has not impact on the outcome of this study. There is no patent or product directly associated with this study. Thus, the authors have declared that no competing interests exist.
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