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Hepatitis D Virus Infection of Mice Expressing Human Sodium Taurocholate Co-transporting Polypeptide
Journal article   Open access   Peer reviewed

Hepatitis D Virus Infection of Mice Expressing Human Sodium Taurocholate Co-transporting Polypeptide

Wenhui He, Bijie Ren, Fengfeng Mao, Zhiyi Jing, Yunfei Li, Yang Liu, Bo Peng, Huan Yan, Yonghe Qi, Yinyan Sun, …
PLoS pathogens, v 11(4), e1004840
Apr 2015
DOI: https://doi.org/10.1371/journal.ppat.1004840
PMID: 25902143
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://doi.org/10.1371/journal.ppat.1004840View
Published, Version of Record (VoR)CC BY V4.0,  Open

Abstract

Animals Antibodies, Monoclonal - pharmacology Antibodies, Viral - pharmacology Cells, Cultured Crosses, Genetic Female Hepatitis D - drug therapy Hepatitis D - metabolism Hepatitis D - pathology Hepatitis D - virology Hepatitis Delta Virus - drug effects Hepatitis Delta Virus - immunology Hepatitis Delta Virus - physiology Hepatocytes - drug effects Hepatocytes - metabolism Hepatocytes - pathology Hepatocytes - virology Host-Pathogen Interactions - drug effects Humans Immunity, Innate - drug effects Male Mice, Inbred C57BL Mice, Knockout Mice, Transgenic Organic Anion Transporters, Sodium-Dependent - genetics Organic Anion Transporters, Sodium-Dependent - metabolism Receptor, Interferon alpha-beta - genetics Receptor, Interferon alpha-beta - metabolism Recombinant Fusion Proteins - metabolism Specific Pathogen-Free Organisms Symporters - genetics Symporters - metabolism Viral Envelope Proteins - antagonists & inhibitors Viral Envelope Proteins - metabolism
Hepatitis D virus (HDV) is the smallest virus known to infect human. About 15 million people worldwide are infected by HDV among those 240 million infected by its helper hepatitis B virus (HBV). Viral hepatitis D is considered as one of the most severe forms of human viral hepatitis. No specific antivirals are currently available to treat HDV infection and antivirals against HBV do not ameliorate hepatitis D. Liver sodium taurocholate co-transporting polypeptide (NTCP) was recently identified as a common entry receptor for HDV and HBV in cell cultures. Here we show HDV can infect mice expressing human NTCP (hNTCP-Tg). Antibodies against critical regions of HBV envelope proteins blocked HDV infection in the hNTCP-Tg mice. The infection was acute yet HDV genome replication occurred efficiently, evident by the presence of antigenome RNA and edited RNA species specifying large delta antigen in the livers of infected mice. The resolution of HDV infection appears not dependent on adaptive immune response, but might be facilitated by innate immunity. Liver RNA-seq analyses of HDV infected hNTCP-Tg and type I interferon receptor 1 (IFNα/βR1) null hNTCP-Tg mice indicated that in addition to induction of type I IFN response, HDV infection was also associated with up-regulation of novel cellular genes that may modulate HDV infection. Our work has thus proved the concept that NTCP is a functional receptor for HDV infection in vivo and established a convenient small animal model for investigation of HDV pathogenesis and evaluation of antiviral therapeutics against the early steps of infection for this important human pathogen.

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100 citations in Web of Science
105 citations in Scopus

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UN Sustainable Development Goals (SDGs)

This publication has contributed to the advancement of the following goals:

#3 Good Health and Well-Being

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Collaboration types
Domestic collaboration
International collaboration
Web of Science research areas
Microbiology
Parasitology
Virology
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