GSE140589 Cd302 and Cr1l restrict human hepatotropic virus cross-species transmission to mice  [6PMH siRNA]

Contributors : Richard Brown ; Birthe Tegtmeyer ; Thomas PietschmannSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusVirus 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.
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Mus musculus Source Type: research