A Disintegrin and Metalloproteinase 9 Domain (ADAM9) Is a Major Susceptibility Factor in the Early Stages of Encephalomyocarditis Virus Infection.
a disintegrin and metalloproteinase 9 domain (ADAM9)
encephalomyocarditis virus
functional genomic screen
Journal
mBio
ISSN: 2150-7511
Titre abrégé: mBio
Pays: United States
ID NLM: 101519231
Informations de publication
Date de publication:
05 02 2019
05 02 2019
Historique:
entrez:
7
2
2019
pubmed:
7
2
2019
medline:
6
4
2019
Statut:
epublish
Résumé
Encephalomyocarditis virus (EMCV) is a picornavirus that produces lytic infections in murine and human cells. Employing a genome-wide CRISPR-Cas9 knockout screen to find host factors required for EMCV infection, we identified a role for ADAM9 in EMCV infection. CRISPR-mediated deletion of ADAM9 in multiple human cell lines rendered the cells highly resistant to EMCV infection and cell death. Primary fibroblasts from ADAM9 KO mice were also strongly resistant to EMCV infection and cell death. In contrast, ADAM9 KO and WT cells were equally susceptible to infection with other viruses, including the picornavirus Coxsackie virus B. ADAM9 KO cells failed to produce viral progeny when incubated with EMCV. However, bypassing EMCV entry into cells through delivery of viral RNA directly to the cytosol yielded infectious EMCV virions from ADAM9 KO cells, suggesting that ADAM9 is not required for EMCV replication post-entry. These findings establish that ADAM9 is required for the early stage of EMCV infection, likely for virus entry or viral genome delivery to the cytosol.
Identifiants
pubmed: 30723129
pii: mBio.02734-18
doi: 10.1128/mBio.02734-18
pmc: PMC6428755
pii:
doi:
Substances chimiques
Membrane Proteins
0
ADAM Proteins
EC 3.4.24.-
ADAM9 protein, human
EC 3.4.24.-
Adam9 protein, mouse
EC 3.4.24.-
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIAID NIH HHS
ID : R01 AI091786
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI111475
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI116920
Pays : United States
Organisme : NIAID NIH HHS
ID : T32 AI095213
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2019 Bazzone et al.
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