Journal
JOURNAL OF EXPERIMENTAL MEDICINE
Volume 218, Issue 10, Pages -Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20210408
Keywords
-
Categories
Funding
- Swiss National Science Foundation [310030B_201271, 310030_185321]
- European Research Council [865026]
- Swiss National Science Foundation (SNF) [310030B_201271, 310030_185321] Funding Source: Swiss National Science Foundation (SNF)
- European Research Council (ERC) [865026] Funding Source: European Research Council (ERC)
Ask authors/readers for more resources
Our study reveals that the systemic persistence of a prototypic noncytolytic RNA virus depends on continuous spread and reinfection. However, undefined cell-intrinsic mechanisms prevent viral persistence at the single-cell level, but lead to profound transcriptomic alterations in virus-cleared cells.
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available