Worldwide, 185 million people have chronic hepatitis C. Since the late 1980s, when scientists discovered the virus that causes the infection, they have struggled to find ways to grow it in human cells in the lab - an essential part of learning how the virus works and developing new effective treatments.
In a study published in Nature, scientists report that when they overexpressed a particular gene in human liver cancer cell lines, the virus could easily replicate. This discovery allows study of naturally occurring forms of hepatitis C virus (HCV) in the lab.
Scientists have long attempted to understand what makes HCV tick, and in 1999 a group of German scientists succeeded in coaxing modified forms of the virus to replicate in cells in the laboratory. However, it was soon discovered that these forms of the virus were able to replicate because they had acquired certain "adaptive" mutations.
This was true for the vast majority of all samples from patients, except one, and left scientists with a puzzling question for more than a decade: What prevents non-mutated HCV from replicating in laboratory-grown cell lines? Rice and colleagues hypothesized that one or more critical elements might be missing in these cell lines.
To test this idea, they screened a library of about 7,000 human genes to look for one whose expression would allow replication of non-mutated HCV. When the scientists expressed the gene SEC14L2, the virus replicated in its wild-type, non-mutated form. Even adding serum samples from HCV-infected patients to these engineered cell lines resulted in virus replication.
It's not entirely clear how the protein expressed by SEC14L2 works, but it appears to inhibit lipids from interacting with dangerous reactive oxygen species, a process that prevents HCV replication.
Recent advances in HCV treatment have made it possible for millions of people to be cured of the virus. "New therapies, however, are extremely expensive and not perfect," the researchers note. "As more patients are treated, drug resistant forms of HCV are emerging. Having a cell culture system where patient isolates can be grown and tested for resistance or susceptibility to alternative antiviral drug combinations should be useful for optimizing re-treatment strategies for those that fail treatment."
Based on material originally posted by Rockefeller University.