Journal article
Infection of Glia by Human Pegivirus Suppresses Peroxisomal and Antiviral Signaling Pathways
Journal of virology, Vol.95(23), pp.e0107421-e0107421
11/09/2021
DOI: 10.1128/JVI.01074-21
PMCID: PMC8577381
PMID: 34524914
Abstract
Human pegivirus (HPgV) infects peripheral leukocytes but was recently shown to be a neurotropic virus associated with leukoencephalitis in humans. In the present study, we investigated the neural cell tropism of HPgV as well as its effects on host immune responses. HPgV wild type (WT) and a mutant virus with a deletion in the HPgV
gene (ΔNS2) were able to productively infect human astrocytes and microglia but not neurons or an oligodendrocyte-derived cell line. Of note, the ΔNS2 virus replicated better than WT pegivirus in astrocytes, with both viruses being able to subsequently infect and spread in fresh human astrocyte cultures. Infection of human glia by HPgV WT and ΔNS2 viruses resulted in suppression of peroxisome-associated genes, including
,
,
,
,
, and
, during peak viral production, which was accompanied by reduced expression of
,
,
, and
, particularly in ΔNS2-infected cells. These data were consistent with analyses of brain tissue from patients infected with HPgV in which we observed suppression of peroxisome and type I interferon gene transcripts, including
,
,
, and
, with concurrent loss of PMP70 immunoreactivity in glia. Our data indicate that human astrocytes and microglia are permissive to HPgV infection, resulting in peroxisome injury and suppressed antiviral signaling that is influenced by viral diversity.
Human pegiviruses are detected in 1 to 5% of the general population, principally infecting leukocytes, although their effects on human health remain uncertain. Here, we show that human pegivirus infects specific neural cell types in culture and human brain and, like other neurotropic flaviviruses, causes suppression of peroxisome and antiviral signaling pathways, which could favor ongoing viral infection and perhaps confer susceptibility to the development of neurological disease.
Details
- Title: Subtitle
- Infection of Glia by Human Pegivirus Suppresses Peroxisomal and Antiviral Signaling Pathways
- Creators
- M A L Doan - Women and Children’s Health Research InstituteA Roczkowsky - University of AlbertaM Smith - University of AlbertaG Blevins - University of AlbertaF K H van Landeghem - University of AlbertaB B Gelman - The University of Texas Medical Branch at GalvestonW G Branton - University of AlbertaJ T Stapleton - University of IowaT C Hobman - University of AlbertaC Power - Women and Children’s Health Research Institute
- Resource Type
- Journal article
- Publication Details
- Journal of virology, Vol.95(23), pp.e0107421-e0107421
- DOI
- 10.1128/JVI.01074-21
- PMID
- 34524914
- PMCID
- PMC8577381
- ISSN
- 0022-538X
- eISSN
- 1098-5514
- Grant note
- U24 MH100931 / NIMH NIH HHS U24 MH100928 / NIMH NIH HHS U24 MH100925 / NIMH NIH HHS U24 MH100930 / NIMH NIH HHS U24 MH100929 / NIMH NIH HHS
- Language
- English
- Date published
- 11/09/2021
- Academic Unit
- Microbiology and Immunology; Infectious Diseases; Internal Medicine
- Record Identifier
- 9984297429502771
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