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HCV resistance

Published on May 29, 2025   17 min

A selection of talks on Biochemistry

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0:00
Hello. My name is Professor John Dillon of University of Dundee. I'm a professor of hepatology, and I'm going to talk today about HCV resistance.
0:11
HCV is a virus. It's an enveloped virus. It's a single-stranded, positive-sense RNA virus. It's a part of the Flaviviridae genus, or family rather, and is its own genus. The genome length of approximately 9.6 kilobases.
0:32
There are seven HCV genotypes, although a probable eighth genotype has been described, and within each of those genotypes there are multiple subtypes. There are six main genotypes worldwide. Genotype 7 and genotype 8 don't have much therapeutic implications. Each genotype has a reference nucleotide sequence and, therefore, an amino acid sequence, and a substitution. A difference in amino acid at a defined position of the HCV protein between a patient's HCV and the reference HCV protein is termed a substitution. You'd also think of it as a polymorphism, in more generic terms, and that's the terminology that's still preferred by the FDA. Most experts will use the word "substitution," and in the resistance context, we will refer to them as resistance-associated substitutions. Some older literature will also refer to them as resistant-associated variants, but that term is now not the preferred term.
1:35
On this slide, there is an illustration of the relationships between the different genotypes and subtypes within the genotypes, showing how much variation there is in genetic sequence. This analysis is done as a phylogenetic analysis to illustrate the variation between the viruses, so it's an important takeaway message from this slide, that there is huge variation in the hepatitis C virus.

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