Persistent RNA virus infection is short-lived at the single-cell level but leaves transcriptomic footprints.
Adaptive Immunity
Animals
Arenaviridae Infections
/ genetics
Chlorocebus aethiops
Gene Expression Profiling
HEK293 Cells
Hepatocytes
/ virology
Humans
Interferons
/ metabolism
Lymphocytic choriomeningitis virus
/ genetics
Mice, Transgenic
Reinfection
Single-Cell Analysis
Vero Cells
Viral Load
Viral Proteins
/ metabolism
Journal
The Journal of experimental medicine
ISSN: 1540-9538
Titre abrégé: J Exp Med
Pays: United States
ID NLM: 2985109R
Informations de publication
Date de publication:
04 10 2021
04 10 2021
Historique:
received:
18
02
2021
revised:
14
06
2021
accepted:
28
07
2021
entrez:
16
8
2021
pubmed:
17
8
2021
medline:
15
12
2021
Statut:
ppublish
Résumé
Several RNA viruses can establish life-long persistent infection in mammalian hosts, but the fate of individual virus-infected cells remains undefined. Here we used Cre recombinase-encoding lymphocytic choriomeningitis virus to establish persistent infection in fluorescent cell fate reporter mice. Virus-infected hepatocytes underwent spontaneous noncytolytic viral clearance independently of type I or type II interferon signaling or adaptive immunity. Viral clearance was accompanied by persistent transcriptomic footprints related to proliferation and extracellular matrix remodeling, immune responses, and metabolism. Substantial overlap with persistent epigenetic alterations in HCV-cured patients suggested a universal RNA virus-induced transcriptomic footprint. Cell-intrinsic clearance occurred in cell culture, too, with sequential infection, reinfection cycles separated by a period of relative refractoriness to infection. Our study reveals that systemic persistence of a prototypic noncytolytic RNA virus depends on continuous spread and reinfection. Yet undefined cell-intrinsic mechanisms prevent viral persistence at the single-cell level but give way to profound transcriptomic alterations in virus-cleared cells.
Identifiants
pubmed: 34398180
pii: 212556
doi: 10.1084/jem.20210408
pmc: PMC8493862
pii:
doi:
Substances chimiques
Viral Proteins
0
Interferons
9008-11-1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Swiss National Science Foundation
ID : 310030_173132
Pays : Switzerland
Organisme : Swiss National Science Foundation
ID : 310030B_201271
Pays : Switzerland
Organisme : European Research Council
ID : 865026
Pays : International
Informations de copyright
© 2021 Reuther et al.
Déclaration de conflit d'intérêts
Disclosures: D.D. Pinschewer reported grants, personal fees, non-financial support, and "other" from Hookipa Pharma Inc. outside the submitted work; in addition, D.D. Pinschewer had a patent to PCT/EP14/055144 issued "Hookipa Pharma Inc.," a patent to PCT/EP14/055144 licensed "Hookipa Pharma Inc.," a patent to PCT/EP14/055144 with royalties paid "Hookipa Pharma Inc.," a patent to PCT/EP2015/076458 issued "Hookipa Pharma Inc.," a patent to PCT/EP2015/076458 licensed "Hookipa Pharma Inc.," a patent to PCT/EP2015/076458 with royalties paid "Hookipa Pharma Inc.," a patent to PCT/EP/08/010994 issued "Hookipa Pharma Inc.," a patent to PCT/EP/08/010994 licensed "Hookipa Pharma Inc.," a patent to PCT/EP/08/010994 with royalties paid "Hookipa Pharma Inc.," a patent to PCT/EP2017/061865 issued "Hookipa Pharma Inc.," a patent to PCT/EP2017/061865 licensed "Hookipa Pharma Inc.," and a patent to PCT/EP2017/061865 with royalties paid. D.D. Pinschewer is a founder, consultant, and shareholder of Hookipa Pharma Inc. and holds stock options of Hookipa Pharma Inc. commercializing arenavirus-based vector technology. No other disclosures were reported.
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