» Articles » PMID: 33148654

Liver-expressed and Limit Hepatitis C Virus Cross-species Transmission to Mice

Abstract

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 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.

Citing Articles

TMPRSS2-mediated SARS-CoV-2 uptake boosts innate immune activation, enhances cytopathology, and drives convergent virus evolution.

Qu B, Miskey C, Gomer A, Kleinert R, Ibanez S, Eberle R Proc Natl Acad Sci U S A. 2024; 121(23):e2407437121.

PMID: 38814864 PMC: 11161796. DOI: 10.1073/pnas.2407437121.


Unraveling the dynamics of hepatitis C virus adaptive mutations and their impact on antiviral responses in primary human hepatocytes.

Frericks N, Brown R, Reinecke B, Herrmann M, Bruggemann Y, Todt D J Virol. 2024; 98(3):e0192123.

PMID: 38319104 PMC: 10949430. DOI: 10.1128/jvi.01921-23.


Mouse Liver-Expressed Shiftless Is an Evolutionarily Conserved Antiviral Effector Restricting Human and Murine Hepaciviruses.

Zhang Y, Kinast V, Sheldon J, Frericks N, Todt D, Zimmer M Microbiol Spectr. 2023; 11(4):e0128423.

PMID: 37341610 PMC: 10433982. DOI: 10.1128/spectrum.01284-23.


Vaccine-associated enhanced respiratory pathology in COVID-19 hamsters after T2-biased immunization.

Ebenig A, Muraleedharan S, Kazmierski J, Todt D, Auste A, Anzaghe M Cell Rep. 2022; 40(7):111214.

PMID: 35952673 PMC: 9346010. DOI: 10.1016/j.celrep.2022.111214.


The Human Liver-Expressed Lectin CD302 Restricts Hepatitis C Virus Infection.

Reinecke B, Frericks N, Lauber C, Dinkelborg K, Matthaei A, Vondran F J Virol. 2022; 96(7):e0199521.

PMID: 35297672 PMC: 9006913. DOI: 10.1128/jvi.01995-21.


References
1.
Levin J, Yassour M, Adiconis X, Nusbaum C, Thompson D, Friedman N . Comprehensive comparative analysis of strand-specific RNA sequencing methods. Nat Methods. 2010; 7(9):709-15. PMC: 3005310. DOI: 10.1038/nmeth.1491. View

2.
Coller K, Berger K, Heaton N, Cooper J, Yoon R, Randall G . RNA interference and single particle tracking analysis of hepatitis C virus endocytosis. PLoS Pathog. 2009; 5(12):e1000702. PMC: 2790617. DOI: 10.1371/journal.ppat.1000702. View

3.
Sandhu U, Cebula M, Behme S, Riemer P, Wodarczyk C, Metzger D . Strict control of transgene expression in a mouse model for sensitive biological applications based on RMCE compatible ES cells. Nucleic Acids Res. 2010; 39(1):e1. PMC: 3017619. DOI: 10.1093/nar/gkq868. View

4.
Saeed M, Andreo U, Chung H, Espiritu C, Branch A, Silva J . SEC14L2 enables pan-genotype HCV replication in cell culture. Nature. 2015; 524(7566):471-5. PMC: 4632207. DOI: 10.1038/nature14899. View

5.
Evans M, von Hahn T, Tscherne D, Syder A, Panis M, Wolk B . Claudin-1 is a hepatitis C virus co-receptor required for a late step in entry. Nature. 2007; 446(7137):801-5. DOI: 10.1038/nature05654. View