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Genome-to-genome analysis highlights the impact of the human innate and adaptive immune systems on the hepatitis C virus

Outcomes of hepatitis C virus (HCV) infection and treatment depend on viral and host genetic factors. We use human genome-wide genotyping arrays and new whole-genome HCV viral sequencing technologies to perform a systematic genome-to-genome study of 542 individuals chronically infected with HCV, predominately genotype 3. We show that both HLA alleles and interferon lambda innate immune system genes drive viral genome polymorphism, and that IFNL4 genotypes determine HCV viral load through a mechanism that is dependent on a specific polymorphism in the HCV polyprotein. We highlight the interplay between innate immune responses and the viral genome in HCV control.

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Dataset ID Description Technology Samples
EGAD00010001202 Affymetrix UKBiobank Array 563
Publications Citations
Genome-to-genome analysis highlights the effect of the human innate and adaptive immune systems on the hepatitis C virus.
Nat Genet 49: 2017 666-673
Interferon lambda 4 impacts the genetic diversity of hepatitis C virus.
Elife 8: 2019 e42463
Using host genetics to infer the global spread and evolutionary history of HCV subtype 3a.
Virus Evol 7: 2021 veab065