Researchers developed a method that allowed them to analyse how hepatitis C virus (HCV) evolved differently in a large number of infected people. They found specific genetic variations related to the immune system that affect how HCV evolves and responds to attack and to therapy. The findings highlight the role that joint analyses of host and viral genomes can play in elucidating host-virus molecular interactions to improve prevention and treatment of viral infection.

Hepatitis C is a chronic viral infection that affects more than 185 million people worldwide. Transmitted by blood-toblood contact during intravenous drug use and transfusions, it can progress to liver disease with potentially serious complications, such as hepatocellular cancer and liver failure.

The team of researchers, led by Chris Spencer and Eleanor Barnes of the University of Oxford in the UK, found that changes in the HCV genome that help it elude immune attack and treatment are controlled by variations in two types of host genes.

Human leukocyte antigen (HLA) is a protein found on the surfaces of most cells. When a cell is infected with HCV, HLA presents amino acids from the virus that are then recognized by killer immune cells. The team demonstrated that some variations in the gene that codes for HLA were associated with viral mutations that allow them to avoid presentation of their amino acids by HLAs and thus evade immune attack.

IFNL4 is a human gene that codes for a protein that is released by infected cells as part of the innate immune response to infection. Variations in this gene were found to significantly impact the ‘viral load’ (or how many viruses are present in the blood stream), and to change the genetic make-up of the virus. This is the first time that the innate immune system has been shown to shape the viral genome.

The results demonstrate that individual differences in genetic make-up have an effect on how HCV evolves. This determines whether the immune system is adequately able to respond to and control infection over time.

These new insights into the biological mechanisms and interactions between host and viral genomes that drive HCV evolution in the human body are relevant for future approaches to individualized treatment and vaccine development, the researchers conclude in their study published in the journal Nature Genetics. Ansari

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