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Peer reviewedOpen accessHepatitis CHepatitis EHepatitis BHepatitis D

Completion of the entire hepatitis C virus life cycle in genetically humanized mice

Nature·

Marcus Dorner, Joshua A. Horwitz, Bridget M. Donovan, Rachael N. Labitt, William C. Budell, Tamar Friling, Alexander Vogt, Maria Teresa Catanese, Takashi Satoh, Taro Kawai, Shizuo Akira, Mansun Law, Charles M. Rice, Alexander Ploss

DOI
10.1038/nature12427
PMID
23903655
PMCID
PMC3858853
OpenAlex
W2021668929
Study type
Journal article
Publisher
Springer Science and Business Media LLC
Article type
journal-article
Integrity
current

Why this research matters now

The model provides a preclinical platform for testing antiviral drug candidates and may support vaccine efficacy evaluation for a pathogen affecting over 130 million people globally.

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Structured evidence summary

Research question

The study aimed to develop a genetically humanized mouse model capable of supporting the complete hepatitis C virus life cycle in vivo.

Study design

Experimental animal model using transgenic mice expressing human CD81 and occludin, with immune modulation and cyclophilin A knockout variants to assess viral entry, replication, and production.

Population and setting

Genetically humanized inbred mice with stable expression of human entry factors and modified immune or cellular co-factor status.

Main findings

Transgenic mice expressing human CD81 and occludin supported HCV entry, and when antiviral immunity was reduced, measurable viraemia persisted for several weeks. CypA-deficient mice showed markedly diminished RNA replication, and infected mice produced infectious particles that could be inhibited by antiviral drugs, demonstrating completion of the entire HCV life cycle.

Public-health relevance

The model provides a preclinical platform for testing antiviral drug candidates and may support vaccine efficacy evaluation for a pathogen affecting over 130 million people globally.

Important limitations

This summary is limited to the supplied single-article abstract and metadata. Full interpretation of experimental controls, reproducibility, translatability to human infection, and model-specific constraints requires the original paper.

GIDS interpretation

The article was classified under Hepatitis B, C, D, and E diseases and linked to Treatment, Vaccination, and Vaccine effectiveness topics, reflecting its focus on an animal model for HCV research and preclinical therapeutic testing.

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Related GIDS surveillance

Literature context does not validate, explain, or change a surveillance signal. Exact and contextual relationships are shown separately.

03

Evidence relationships

This article has 13 auditable classifier relationships to diseases, places, topics, and study design.

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