Interferon-alpha treatment rapidly clears Hepatitis E virus infection in humanized mice.

ABSTRACT: Antiviral treatment options for chronic Hepatitis E Virus (HEV) infections are limited and immunological determinants of viral persistence remain largely unexplored. We studied the antiviral potency of pegylated interferon-? (pegIFN?) against HEV infections in humanized mice and modelled intrahepatic interferon stimulated gene (ISG) responses. Human gene expression levels in humanized mouse livers were analyzed by qPCR and Nanostring. Human CXCL10 was measured in mouse serum. HEV genotype 3 (gt3) infections were cleared from liver and feces within 8 pegIFN? doses in all mice and relapsed after a single pegIFN? injection in only half of treated animals. Rapid viral clearance by pegIFN? was confirmed in HEV gt1, but not in Hepatitis B Virus infected animals. No ISG induction was observed in untreated HEV gt3 and gt1 infected humanized livers compared to control chimeric mice, irrespective of the human hepatocyte donor, viral isolate or HEV infection duration. Human specific ISG transcript levels in mouse liver increased significantly after pegIFN? treatment and induced high circulating human CXCL10 in mouse serum. In conclusion, HEV gt1 and gt3 infections do not elicit innate intrahepatic immune responses and remain highly sensitive to pegIFN? in immunocompromised humanized mice.

SUBMITTER: van de Garde MDB 

PROVIDER: S-EPMC5557905 | biostudies-other | 2017 Aug

REPOSITORIES: biostudies-other