Yes, you read that correctly. Dr. Mary Estes and her research group at Baylor College of Medicine have successfully cultured the human norovirus in intestinal cells. The article was just published today in Science and additional information is available in a press release from Baylor College of Medicine.
To put this into perspective, scientists have been trying to culture the virus for almost fifty years, ever since the first recorded outbreak of Norwalk virus, or “winter vomiting disease,” back in 1968 in Norwalk, Ohio.
The lack of a cell culture system for the human norovirus has also been long considered the biggest stumbling block to norovirus research. NoroCORE, which is funded by USDA-NIFA, along with the National Institutes of Health, supported this work.
We here at NoroCORE are having a party, and you should join in the fun!
What does it mean to culture a virus?
Viruses need host cells in order to replicate, or make copies of themselves. In some instances, we can keep some of these cells alive outside of the host organism, and under the right conditions, get viruses to infect these cells and replicate in a laboratory. Once this point is reached, it opens up a new realm of possibilities for research.
Up until now, we have had to use other methods to study norovirus, such as molecular techniques like RT-qPCR, electron microscopy, human volunteer studies, and making inferences from related viruses that we can culture, such as murine (mouse) norovirus and feline calicivirus. These other methods have, and will continue to help us make discoveries about the human norovirus, but the game changes now that we can directly produce the virus outside of a human host.
How did they do it?
Here is an infographic we created to explain how this new method works.
Some viruses are harder to propagate in cell culture than others, and sometimes it means having the right type of host cell, and/or the right kind of mixture to help the cells grow or make them able to be infected. In the case of the human norovirus, getting the best results required both.
The Estes group followed new technology developed by Drs. Sato and Clevers from the Netherlands to grow miniature three-dimensional intestines, or “miniguts.” It begins with samples of human intestinal tissue, in this case tissues that were already being removed for medical reasons, and were considered medical waste.
Our intestines are lined with epithelial cells, which are created in intestinal crypts from stem cells. The researchers isolated these crypts from the sample tissues, and gave the cells the proper conditions to grow and multiply, creating the miniguts, also called Human Intestinal Enteroids, or HIE’s. These HIE’s were inoculated with human norovirus, and within a couple of days the researchers were recovering 1000 times more of the genetic material than they initially added, meaning the virus was infecting and replicating in these cells. Success!
Yet the team at Baylor College of Medicine took it a step further, and through careful experimentation, they found that the presence of bile, a substance we produce to aid our digestion of food, significantly improved replication of the virus. It was another important piece of the puzzle!
Why is this so important?
Norovirus is the most common cause of diarrhea in the world and the most common cause of foodborne illness in the United States. Most of us will experience this virus five times over the course of our lives. And with its vomiting and diarrhea, it is miserable.
This research is very important because it will allow us to answer long-standing questions that have remained elusive for decades. This can lead to vaccines, therapeutics, and other measures to control the virus in humans. It will also affect how we manage norovirus transmission. For example, this is the first step towards being able to directly ascertain how effective disinfectants and food processes are in inactivating infectious human norovirus. The result: clearer guidelines for preventing virus spread, and better products to inactivate the virus.
A culture method such as the one released today forms the foundation for future scientific breakthroughs, which will lead to considerable public health improvements in the years to come. Fewer cases of disease, less hospitalization and death, and associated economic benefits will make our lives easier and safer. And it all started with a tiny virus, some special intestinal cells, and the know how of a group of stellar scientists. Thanks to the entire collaborative team for making a contribution that will likely touch many lives into the future.
This is what science is all about!
Written by Lee-Ann Jaykus, Scientific Director of NoroCORE, and Elizabeth Bradshaw, Extension Associate