The Acyclic Retinoid Peretinoin Inhibits Hepatitis C Virus Replication and Infectious Virus Release in Vitro

Clinical studies suggest that the oral acyclic retinoid Peretinoin may reduce the recurrence of hepatocellular carcinoma (HCC) following surgical ablation of primary tumours. Since hepatitis C virus (HCV) infection is a major cause of HCC, we assessed whether Peretinoin and other retinoids have any effect on HCV infection. For this purpose, we measured the effects of several retinoids on the replication of genotype 1a, 1b, and 2a HCV in vitro. Peretinoin inhibited RNA replication for all genotypes and showed the strongest antiviral effect among the retinoids tested. Furthermore, it reduced infectious virus release by 80–90% without affecting virus assembly. These effects could be due to reduced signalling from lipid droplets, triglyceride abundance, and the expression of mature sterol regulatory element-binding protein 1c and fatty acid synthase. These negative effects of Peretinoin on HCV infection may be beneficial in addition to its potential for HCC chemoprevention in HCV-infected patients

The acyclic retinoid peretinoin inhibits hepatitis C virus replication and infectious virus release in vitro

Clinical studies suggest that the oral acyclic retinoid Peretinoin may reduce the recurrence of hepatocellular carcinoma (HCC) following surgical ablation of primary tumours. Since hepatitis C virus (HCV) infection is a major cause of HCC, we assessed whether Peretinoin and other retinoids have any effect on HCV infection. For this purpose, we measured the effects of several retinoids on the replication of genotype 1a, 1b, and 2a HCV in vitro. Peretinoin inhibited RNA replication for all genotypes and showed the strongest antiviral effect among the retinoids tested. Furthermore, it reduced infectious virus release by 80-90% without affecting virus assembly. These effects could be due to reduced signalling from lipid droplets, triglyceride abundance, and the expression of mature sterol regulatory element-binding protein 1c and fatty acid synthase. These negative effects of Peretinoin on HCV infection may be beneficial in addition to its potential for HCC chemoprevention in HCV-infected patients

Data for: Persistent hepatitis B virus and HIV coinfections in dually humanized mice engrafted with human liver and immune system

Chronic hepatitis B (CHB), caused by hepatitis B virus (HBV), remains a major medical problem. HBV has a high propensity for progressing to chronicity and can result in severe liver disease, including fibrosis, cirrhosis and hepatocellular carcinoma. CHB patients frequently present with viral coinfection, including HIV and hepatitis delta virus. About 10% of chronic HIV carriers are also persistently infected with HBV which can result in more exacerbated liver disease. Mechanistic studies of HBV-induced immune responses and pathogenesis, which could be significantly influenced by HIV infection, have been hampered by the scarcity of immunocompetent animal models. Here, we demonstrate that humanized mice dually engrafted with components of a human immune system and a human liver supported HBV infection, which was partially controlled by human immune cells, as evidenced by lower levels of serum viremia and HBV replication intermediates in the liver. HBV infection resulted in priming and expansion of human HLA-restricted CD8+ T cells, which acquired an activated phenotype. Notably, our dually humanized mice support persistent coinfections with HBV and HIV which opens opportunities for analyzing immune dysregulation during HBV and HIV coinfection and preclinical testing of novel immunotherapeutics.This study was supported by grants from the National Institutes of Health (R01 AI138797 to A.P. and L.S., R01 AI153236, R01 AI146917, R01 AI168048 all to A.P), a Research Scholar Award from the American Cancer Society (RSG-15-048-01-MPC to A.P.), a Burroughs Wellcome Fund Award for Investigators in Pathogenesis (to A.P.) a Graduate fellowship from the Health Grand Challenge from the Global Health Fund of Princeton University (to B.Y.W.). The NYU Experimental Pathology Immunohistochemistry Core Laboratory is supported in part by the Laura and Isaac Perlmutter Cancer Center Support Grant; NIH /NCI P30CA016087” and the National Institutes of Health S10 Grants; NIH/ORIP S10OD01058 and S10OD018338. B.Y.W. was a recipient of F31 NIH/NRSA Ruth L. Kirschstein Predoctoral awarded from the NIAID and a graduate fellowship from the New Jersey Commission on Cancer Research and was supported by an NIH training grant (T32GM007388). J.S. was a recipient of a postdoctoral fellowships from the German Research Foundation.Excel spreadsheets with all the raw data for the main figures 1-7 and supplementary figures 1&2; readme fil

Myasthenia gravis-specific aberrant neuromuscular gene expression by medullary thymic epithelial cells in thymoma

Myasthenia Gravis and thymoma are frequently associated with patients suffering from both diseases. Here the authors perform single cell sequencing of thymoma and find that there are autoimmune antigens such as neuromuscular proteins expressed aberrantly in neuromuscular mTECs in patients with both diseases