Researchers can now study replication of Hepatitis C virus genotypes 3 and 4 in cultured cells, described in 2 articles in the January issue of Gastroenterology. These new tools will improve our understanding of how they cause liver disease, and could lead to new treatments.
HCV leads to chronic infection and advanced liver diseases in most infected adults. It is a positive-strand RNA virus that replicates its genome with the help of an RNA-dependent RNA polymerase.
There are 6 major HCV genotypes. Genotypes 1 and 2 are the most prevalent in North America, Europe, and Japan, and are the most highly studied. However, other genotypes have specific characteristics. Genotype 3a infection can cause hepatic steatosis, and is more resistant to treatment with telaprevir and boceprevir. Genotype 4 is prevalent in the Middle East and many African countries, and is becoming more common in central and northern Europe; it accounts for 93% of HCV infections in Egypt, and 5%–15% of infections in several European countries.
HCV replicons—almost-complete viral RNA sequences that can replicate autonomously in cells—are important for studying viral replication and were essential for the development of many current drugs against the infection. However, only replicons for HCV genotypes 1a, 1b, and 2a have been developed. The first efficient HCV cell culture system was based on genotype 1b-derived subgenomic replicons (see below figure).