Chronic viral hepatitis caused by the hepatitis B, C or D viruses (hepatitis D can only infect those with hepatitis B) remains a huge global health problem. particles. Even though these viruses replicate differently, they all have a common factor in that each of them relies on the endoplasmic reticulum-Golgi pathway to multiply within the body. In simple terms, this means that all three viruses require the same set of “replicating machinery” inside a host cell to make more copies of themselves. And this machinery relies on a gene known as the TM5SF2 gene.
Professor Mark Douglas from the Storr Liver Centre at the Westmead Institute for Medical Research (WIMR) helped run a study into this mechanism and gene that made promising findings. As he explained, “Our research team knew that the TM6SF2 gene is associated with fatty liver disease. It is involved in the transportation of fat out of the liver and into the bloodstream. This made us wonder if the gene might also play a similar role in the transportation of virus particles out of the liver.
“We thought that, if it is involved in the spread of virus particles, particularly hepatitis B, C and D, then targeting the gene could potentially stop the spread and might essentially provide a cure for these diseases.”
Professor Douglas’s team team conducted an initial study of people living with hepatitis B and found that when the TM6SF2 gene becomes less effective, the amount of a particular hepatitis B virus protein (HBsAg) in the blood is also reduced.
In the lab, we knocked down the TM6SF2 gene and again found that fewer hepatitis B, C and D virus particles were leaving the liver.
Associate Professor Thomas Tu (also from the Storr Liver Centre) is lead author of the study, now published in The Journal of Infectious Diseases. He explained that “this finding led us to the next step, examining hepatitis B, C and D cells to see if reducing the effectiveness of TM6SF2 had the same effect on all three viruses.
“In the lab, we knocked down the TM6SF2 gene and again found that fewer hepatitis B, C and D virus particles were leaving the liver.”
Gene “knockdown” refers to various laboratory methods which temporarily stop or decrease the expression of one or more targeted genes, meaning that they no longer produce the proteins and other chemicals that they normally create. Associate Professor Tu said that the next step for this research is to discover ways to safely knock down the TM6SF2 gene, and then to develop this into a treatment that is safe and effective in humans.
“While there is still a long way to go, this finding holds a lot of promise. Ultimately, one drug that targets all three viruses at the same time would be life-changing for the millions of people globally who are living with chronic viral hepatitis.”
Last updated 2 December 2024
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