Biological Sciences Division
Published November 4, 2020 | Version v1
Journal article Open

Liver-expressed Cd302 and Cr1l limit hepatitis C virus cross-species transmission to mice

Creators

  • 1. Paul Ehrlich Institute
  • 2. Twincore
  • 3. University of Veterinary Medicine Hannover
  • 4. Hannover Medical School
  • 5. University of Chicago

Description

Hepatitis C virus (HCV) has no animal reservoir, infecting only humans. To investigate species barrier determinants limiting infection of rodents, murine liver complementary DNA library screening was performed, identifying transmembrane proteins Cd302 and Cr1l as potent restrictors of HCV propagation. Combined ectopic expression in human hepatoma cells impeded HCV uptake and cooperatively mediated transcriptional dysregulation of a noncanonical program of immunity genes. Murine hepatocyte expression of both factors was constitutive and not interferon inducible, while differences in liver expression and the ability to restrict HCV were observed between the murine orthologs and their human counterparts. Genetic ablation of endogenous Cd302 expression in human HCV entry factor transgenic mice increased hepatocyte permissiveness for an adapted HCV strain and dysregulated expression of metabolic process and host defense genes. These findings highlight human-mouse differences in liver-intrinsic antiviral immunity and facilitate the development of next-generation murine models for preclinical testing of HCV vaccine candidates.

Notes

Due to the large number of authors, only the first 20 and the University of Chicago authors are included on the above author list. Please download the article for the complete list of authors.

Data availability

All data needed to evaluate the conclusions in the paper are present in the paper and/or the Supplementary Materials. Additional data related to this paper may be requested from the authors. Raw and processed RNA-seq data generated in this study are submitted to the NCBI GEO database (GEO accession number GSE140591). RNA-seq data from Huh-7.5 cells transduced with a control EMTPY lentivirus are reported in Tegtmeyer and Vieyres (manuscript in revision: accession number GSE132548). Transgenic knockout mice generated in this study are available from the authors under a material transfer agreement.

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Additional details

Identifiers

DOI
10.1126/SCIADV.ABD3233
Other
oai:uchicago.tind.io:10999

Funding

H2020 European Research Council
VIRAFRONT
Bundesministerium für Gesundheit
1-2516-FSB-416

UChicago Information

Division(s)
Biological Sciences Division
Department(s)
Microbiology