Subviral Dense Bodies of Human Cytomegalovirus Induce an Antiviral Type I Interferon Response.
IRGs
dense bodies
human cytomegalovirus
interferon-regulated genes
interferon-β
subviral particles
Journal
Cells
ISSN: 2073-4409
Titre abrégé: Cells
Pays: Switzerland
ID NLM: 101600052
Informations de publication
Date de publication:
13 12 2022
13 12 2022
Historique:
received:
27
10
2022
revised:
07
12
2022
accepted:
09
12
2022
entrez:
23
12
2022
pubmed:
24
12
2022
medline:
27
12
2022
Statut:
epublish
Résumé
(1) Background: Cells infected with the human cytomegalovirus (HCMV) produce subviral particles, termed dense bodies (DBs), both in-vitro and in-vivo. They are released from cells, comparable to infectious virions, and are enclosed by a membrane that resembles the viral envelope and mediates the entry into cells. To date, little is known about how the DB uptake influences the gene expression in target cells. The purpose of this study was to investigate the impact of DBs on cells, in the absence of a viral infection. (2) Methods: Mass spectrometry, immunoblot analyses, siRNA knockdown, and a CRISPR-CAS9 knockout, were used to investigate the changes in cellular gene expression following a DB exposure; (3) Results: A number of interferon-regulated genes (IRGs) were upregulated after the fibroblasts and endothelial cells were exposed to DBs. This upregulation was dependent on the DB entry and mediated by the type I interferon signaling through the JAK-STAT pathway. The induction of IRGs was mediated by the sensing of the DB-introduced DNA by the pattern recognition receptor cGAS. (4) Conclusions: The induction of a strong type I IFN response by DBs is a unique feature of the HCMV infection. The release of DBs may serve as a danger signal and concomitantly contribute to the induction of a strong, antiviral immune response.
Identifiants
pubmed: 36552792
pii: cells11244028
doi: 10.3390/cells11244028
pmc: PMC9777239
pii:
doi:
Substances chimiques
Interferon Type I
0
Janus Kinases
EC 2.7.10.2
STAT Transcription Factors
0
Antiviral Agents
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
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