Intrinsic Viral Factors Are the Dominant Determinants of the Hepatitis C Virus Response to Interferon Alpha Treatment in Chimeric Mice

PloS One
Ran ChenD Lorne Tyrrell

Abstract

Hepatitis C virus infection is a global health problem. New direct-acting antiviral agents have been recently approved. However, due to their high cost and some genotypes remaining difficult to treat, interferon-based therapy with pegylated interferon and ribavirin likely may remain a component of hepatitis C virus treatment for some patients. Unfortunately, pegylated interferon / ribavirin treatment achieved favorable outcomes in less than 50% of patients. Factors determining the outcome to pegylated interferon/ribavirin include both host and viral factors. It has been a major challenge to separate the host and viral factors in most in vivo systems. We used two hepatitis C virus strains from patients with different interferon-sensitivities and three hepatocyte donors, each with distinct interleukin 28B and interferon lambda 4 single nucleotide polymorphisms to investigate the contributions of viral and host factors to the response of hepatitis C virus to interferon treatment in chimeric mice. We found that viral factors were the dominant factors in determining the interferon treatment outcomes in chimeric mice. Host factors, such as pre-treatment liver interferon-stimulated gene expression and single nucleotide polymorphisms n...Continue Reading

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Citations

Jan 22, 2021·Molecular Therapy. Methods & Clinical Development·Daniel StoneKeith R Jerome

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Methods Mentioned

BETA
ELISA
Assay
PCR
Genotyping
enzyme-linked immunosorbent assay
cDNA library construction
biopsies
biopsy

Software Mentioned

Applied
samtools
Prism X
Primer Express
bowtie
SOAPdenovo
Biosystems SDS

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