Similar Datasets
Project description:Virus species- and tissue-tropism is governed by host dependency and restriction factors. Hepatitis C virus (HCV) exhibits a narrow species-tropism and murine hepatocytes are refractory to infection. Using murine liver cDNA library screening we identified Cd302, a lectin, and Cr1l, a complement receptor, as pan-genotypic restrictors of HCV infection. Cd302/Cr1l interact to impede virion uptake and co-operatively induce a non-canonical transcriptional program, inhibiting HCV and hepatitis B virus (HBV) infection in vitro. CAS9 disruption of murine hepatocyte Cd302 expression increased HCV permissiveness in-vivo and ex-vivo, and modulated the intrinsic hepatocyte transcriptome dysregulating metabolic process and host defense genes. In contrast, co-operative CD302/CR1L expression was absent and HCV restriction reduced in human hepatocytes. The Cd302/Cr1l axis therefore contributes to limiting hepatotropic virus cross-species transmission to mice, opening new avenues for step-wise development of mouse models for these important human pathogens, which cause substantial disease burden globally.
2020-12-01 | GSE140586 | GEO
Project description:Virus species- and tissue-tropism is governed by host dependency and restriction factors. Hepatitis C virus (HCV) exhibits a narrow species-tropism and murine hepatocytes are refractory to infection. Using murine liver cDNA library screening we identified Cd302, a lectin, and Cr1l, a complement receptor, as pan-genotypic restrictors of HCV infection. Cd302/Cr1l interact to impede virion uptake and co-operatively induce a non-canonical transcriptional program, inhibiting HCV and hepatitis B virus (HBV) infection in vitro. CAS9 disruption of murine hepatocyte Cd302 expression increased HCV permissiveness in-vivo and ex-vivo, and modulated the intrinsic hepatocyte transcriptome dysregulating metabolic process and host defense genes. In contrast, co-operative CD302/CR1L expression was absent and HCV restriction reduced in human hepatocytes. The Cd302/Cr1l axis therefore contributes to limiting hepatotropic virus cross-species transmission to mice, opening new avenues for step-wise development of mouse models for these important human pathogens, which cause substantial disease burden globally.
2020-12-01 | GSE140579 | GEO
Project description:Virus species- and tissue-tropism is governed by host dependency and restriction factors. Hepatitis C virus (HCV) exhibits a narrow species-tropism and murine hepatocytes are refractory to infection. Using murine liver cDNA library screening we identified Cd302, a lectin, and Cr1l, a complement receptor, as pan-genotypic restrictors of HCV infection. Cd302/Cr1l interact to impede virion uptake and co-operatively induce a non-canonical transcriptional program, inhibiting HCV and hepatitis B virus (HBV) infection in vitro. CAS9 disruption of murine hepatocyte Cd302 expression increased HCV permissiveness in-vivo and ex-vivo, and modulated the intrinsic hepatocyte transcriptome dysregulating metabolic process and host defense genes. In contrast, co-operative CD302/CR1L expression was absent and HCV restriction reduced in human hepatocytes. The Cd302/Cr1l axis therefore contributes to limiting hepatotropic virus cross-species transmission to mice, opening new avenues for step-wise development of mouse models for these important human pathogens, which cause substantial disease burden globally.
2020-12-01 | GSE140590 | GEO
Project description:Virus species- and tissue-tropism is governed by host dependency and restriction factors. Hepatitis C virus (HCV) exhibits a narrow species-tropism and murine hepatocytes are refractory to infection. Using murine liver cDNA library screening we identified Cd302, a lectin, and Cr1l, a complement receptor, as pan-genotypic restrictors of HCV infection. Cd302/Cr1l interact to impede virion uptake and co-operatively induce a non-canonical transcriptional program, inhibiting HCV and hepatitis B virus (HBV) infection in vitro. CAS9 disruption of murine hepatocyte Cd302 expression increased HCV permissiveness in-vivo and ex-vivo, and modulated the intrinsic hepatocyte transcriptome dysregulating metabolic process and host defense genes. In contrast, co-operative CD302/CR1L expression was absent and HCV restriction reduced in human hepatocytes. The Cd302/Cr1l axis therefore contributes to limiting hepatotropic virus cross-species transmission to mice, opening new avenues for step-wise development of mouse models for these important human pathogens, which cause substantial disease burden globally.
2020-12-01 | GSE140589 | GEO
Project description:Virus species- and tissue-tropism is governed by host dependency and restriction factors. Hepatitis C virus (HCV) exhibits a narrow species-tropism and murine hepatocytes are refractory to infection. Using murine liver cDNA library screening we identified Cd302, a lectin, and Cr1l, a complement receptor, as pan-genotypic restrictors of HCV infection. Cd302/Cr1l interact to impede virion uptake and co-operatively induce a non-canonical transcriptional program, inhibiting HCV and hepatitis B virus (HBV) infection in vitro. CAS9 disruption of murine hepatocyte Cd302 expression increased HCV permissiveness in-vivo and ex-vivo, and modulated the intrinsic hepatocyte transcriptome dysregulating metabolic process and host defense genes. In contrast, co-operative CD302/CR1L expression was absent and HCV restriction reduced in human hepatocytes. The Cd302/Cr1l axis therefore contributes to limiting hepatotropic virus cross-species transmission to mice, opening new avenues for step-wise development of mouse models for these important human pathogens, which cause substantial disease burden globally.
2020-12-01 | GSE140582 | GEO
Project description:Virus species- and tissue-tropism is governed by host dependency and restriction factors. Hepatitis C virus (HCV) exhibits a narrow species-tropism and murine hepatocytes are refractory to infection. Using murine liver cDNA library screening we identified Cd302, a lectin, and Cr1l, a complement receptor, as pan-genotypic restrictors of HCV infection. Cd302/Cr1l interact to impede virion uptake and co-operatively induce a non-canonical transcriptional program, inhibiting HCV and hepatitis B virus (HBV) infection in vitro. CAS9 disruption of murine hepatocyte Cd302 expression increased HCV permissiveness in-vivo and ex-vivo, and modulated the intrinsic hepatocyte transcriptome dysregulating metabolic process and host defense genes. In contrast, co-operative CD302/CR1L expression was absent and HCV restriction reduced in human hepatocytes. The Cd302/Cr1l axis therefore contributes to limiting hepatotropic virus cross-species transmission to mice, opening new avenues for step-wise development of mouse models for these important human pathogens, which cause substantial disease burden globally.
2020-12-01 | GSE140578 | GEO
Project description:Virus species- and tissue-tropism is governed by host dependency and restriction factors. Hepatitis C virus (HCV) exhibits a narrow species-tropism and murine hepatocytes are refractory to infection. Using murine liver cDNA library screening we identified Cd302, a lectin, and Cr1l, a complement receptor, as pan-genotypic restrictors of HCV infection. Cd302/Cr1l interact to impede virion uptake and co-operatively induce a non-canonical transcriptional program, inhibiting HCV and hepatitis B virus (HBV) infection in vitro. CAS9 disruption of murine hepatocyte Cd302 expression increased HCV permissiveness in-vivo and ex-vivo, and modulated the intrinsic hepatocyte transcriptome dysregulating metabolic process and host defense genes. In contrast, co-operative CD302/CR1L expression was absent and HCV restriction reduced in human hepatocytes. The Cd302/Cr1l axis therefore contributes to limiting hepatotropic virus cross-species transmission to mice, opening new avenues for step-wise development of mouse models for these important human pathogens, which cause substantial disease burden globally.
2020-12-01 | GSE140577 | GEO
Project description:Cd302 and Cr1l restrict human hepatotropic virus cross-species transmission to mice
| PRJNA590215 | ENA
Project 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.
| S-EPMC7673688 | biostudies-literature
Project description:Cd302 and Cr1l restrict human hepatotropic virus cross-species transmission to mice [5PHH]
| PRJNA590220 | ENA