Interferon Regulatory Factor 7 Attenuates Chronic Gammaherpesvirus Infection.
Adenosine Deaminase
Animals
CD8-Positive T-Lymphocytes
/ immunology
Gammaherpesvirinae
/ immunology
Herpesviridae Infections
/ immunology
Host-Pathogen Interactions
/ immunology
Immunity, Innate
Interferon Regulatory Factor-7
/ drug effects
Interferon Type I
/ genetics
Mice
Mice, Inbred C57BL
Mice, Knockout
Spleen
/ virology
Virus Latency
IRF-7
MHV68
chronic infection
gammaherpesvirus
Journal
Journal of virology
ISSN: 1098-5514
Titre abrégé: J Virol
Pays: United States
ID NLM: 0113724
Informations de publication
Date de publication:
23 11 2020
23 11 2020
Historique:
received:
29
07
2020
accepted:
15
09
2020
pubmed:
25
9
2020
medline:
26
1
2021
entrez:
24
9
2020
Statut:
epublish
Résumé
Gammaherpesviruses are ubiquitous pathogens that establish lifelong infections and are associated with a variety of malignancies, including lymphomas. Interferon regulatory factor 7 (IRF-7) is an innate immune transcription factor that restricts acute replication of diverse viruses, including murine gammaherpesvirus 68 (MHV68). Importantly, very little is known about the role of IRF-7 during chronic virus infections. In this study, we demonstrate that IRF-7 attenuates chronic infection by restricting establishment of gammaherpesvirus latency in the peritoneal cavity and, to a lesser extent, viral reactivation in the spleen. Despite the classical role of IRF-7 as a stimulator of type I interferon (IFN) transcription, there were no global effects on the expression of IFN-induced genes (ISGs) in the absence of IRF-7, with only a few ISGs showing attenuated expression in IRF-7-deficient peritoneal cells. Further, IRF-7 expression was dispensable for the induction of a virus-specific CD8 T cell response. In contrast, IRF-7 expression restricted latent gammaherpesvirus infection in the peritoneal cavity under conditions where the viral latent reservoir is predominantly hosted by peritoneal B cells. This report is the first demonstration of the antiviral role of IRF-7 during the chronic stage of gammaherpesvirus infection.
Identifiants
pubmed: 32967960
pii: JVI.01554-20
doi: 10.1128/JVI.01554-20
pmc: PMC7925175
pii:
doi:
Substances chimiques
Interferon Regulatory Factor-7
0
Interferon Type I
0
Irf7 protein, mouse
0
ADAR1 protein, mouse
EC 3.5.4.4
Adenosine Deaminase
EC 3.5.4.4
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NCI NIH HHS
ID : R01 CA183593
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA203923
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM080202
Pays : United States
Organisme : NCI NIH HHS
ID : F31 CA243364
Pays : United States
Organisme : NCI NIH HHS
ID : F30 CA247000
Pays : United States
Informations de copyright
Copyright © 2020 American Society for Microbiology.
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