Project description:What happens in cells infected with HEV is largely unknown. We used a recently established genotype 3 HEV cell culture system and profiled the host responses by RNA-seq.
Project description:This Series contains data from 845 participants (188 men and 657 women) in the EPIC-Italy cohort that was produced at the Human Genetics Foundation (HuGeF) in Turin, Italy. At the last follow-up (2010), 424 participants remained cancer-free, 235 had developed primary breast cancer, 166 had developed primary colorectal cancer, and 20 had developed other primary cancers. Anthropometric measurements, and dietary and lifestyle information obtained by questionnaire are also available.
Project description:Hepatitis E virus (HEV) is a globally prevalent pathogen that causes 20 million infections and 60,000 fatalities annually, endangering particularly pregnant women and immunosuppressed individuals. Liver cirrhosis, which results from advanced fibrosis, is the primary symptom and leading mortality cause in chronic hepatitis E patients. However, the causation and process of liver fibrosis triggered by chronic HEV infection remain poorly understood. Here, we unexpectedly discovered that the viral multiple-domain replicase (ORF1) undergoes unique ubiquitin-proteasomal processing in HEV replicon hepatocytes, HEV-infected gerbil livers, and HEV-infected patient livers, which follows a CHIP-mediated K48 ubiquitination and produces the HEV-Derived Smad Activator (HDSA). Lacking putative helicase and RNA polymerase domains, this enriched viral polypeptide in hepatocytes and gerbil livers is non-HSP90-bound, stable, and exhibits exclusively nuclear localization. Surprisingly, HDSA markedly potentiates the fibrogenic TGF-β/Smad pathway in livers by facilitating promoter binding and coactivator recruitment of SMAD3, leading to profound liver fibrotic symptoms and damage. Thus, we have identified the first viral protein derived from the unique proteasomal processing of the host, defined its notable role in liver fibrosis, and highlighted the nature of complex host-HEV interactions that drives HEV pathogenesis.
Project description:This Series contains data from 845 participants (188 men and 657 women) in the EPIC-Italy cohort that was produced at the Human Genetics Foundation (HuGeF) in Turin, Italy. At the last follow-up (2010), 424 participants remained cancer-free, 235 had developed primary breast cancer, 166 had developed primary colorectal cancer, and 20 had developed other primary cancers. Anthropometric measurements, and dietary and lifestyle information obtained by questionnaire are also available. A total of 845 samples from the EPIC-Italy cohort were analyzed.