CD8 T Cells and STAT1 Signaling Are Essential Codeterminants in Protection from Polyomavirus Encephalopathy.
Adaptive Immunity
Animals
Brain
/ pathology
Brain Diseases
/ pathology
CD8-Positive T-Lymphocytes
/ immunology
Choroid Plexus
Disease Models, Animal
Female
Humans
Immunity, Innate
JC Virus
/ immunology
Leukoencephalopathy, Progressive Multifocal
/ virology
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Polyomavirus
/ immunology
Polyomavirus Infections
/ immunology
STAT1 Transcription Factor
/ genetics
Signal Transduction
Spleen
/ pathology
Viral Load
CD8 T cell
CNS
STAT1
ependyma
polyomavirus
Journal
Journal of virology
ISSN: 1098-5514
Titre abrégé: J Virol
Pays: United States
ID NLM: 0113724
Informations de publication
Date de publication:
31 03 2020
31 03 2020
Historique:
received:
03
12
2019
accepted:
21
01
2020
pubmed:
31
1
2020
medline:
29
9
2020
entrez:
31
1
2020
Statut:
epublish
Résumé
JC polyomavirus (JCPyV), a human-specific virus, causes the aggressive brain-demyelinating disease progressive multifocal leukoencephalopathy (PML) in individuals with depressed immune status. The increasing incidence of PML in patients receiving immunotherapeutic and chemotherapeutic agents creates a pressing clinical need to define biomarkers to stratify PML risk and develop anti-JCPyV interventions. Mouse polyomavirus (MuPyV) CNS infection causes encephalopathology and may provide insight into JCPyV-PML pathogenesis. Type I, II, and III interferons (IFNs), which all signal via the STAT1 transcription factor, mediate innate and adaptive immune defense against a variety of viral infections. We previously reported that type I and II IFNs control MuPyV infection in non-central nervous system (CNS) organs, but their relative contributions to MuPyV control in the brain remain unknown. To this end, mice deficient in type I, II, or III IFN receptors or STAT1 were infected intracerebrally with MuPyV. We found that STAT1, but not type I, II, or III IFNs, mediated viral control during acute and persistent MuPyV encephalitis. Mice deficient in STAT1 also developed severe hydrocephalus, blood-brain barrier permeability, and increased brain infiltration by myeloid cells. CD8 T cell deficiency alone did not increase MuPyV infection and pathology in the brain. In the absence of STAT1 signaling, however, depletion of CD8 T cells resulted in lytic infection of the choroid plexus and ependymal lining, marked meningitis, and 100% mortality within 2 weeks postinfection. Collectively, these findings indicate that STAT1 signaling and CD8 T cells cocontribute to controlling MuPyV infection in the brain and CNS injury.
Identifiants
pubmed: 31996425
pii: JVI.02038-19
doi: 10.1128/JVI.02038-19
pmc: PMC7108847
pii:
doi:
Substances chimiques
STAT1 Transcription Factor
0
Stat1 protein, mouse
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIAID NIH HHS
ID : F31 AI142997
Pays : United States
Organisme : NINDS NIH HHS
ID : F32 NS106730
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS088367
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS092662
Pays : United States
Informations de copyright
Copyright © 2020 American Society for Microbiology.
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