Infographic: Norovirus, Cultured

NOROVIRUS, CULTURED.

A 48 YEAR MYSTERY SOLVED Dr. Mary Estes and her Lab at Baylor College of Medicine have successfully cultured human norovirus in intestinal cells. Scientists have been trying to culture the virus since the first norovirus outbreak was described in 1968. The lack of an in vitro culture system has long been considered the single greatest barrier to norovirus research.

HISTORY OF NOROVIRUS RESEARCH READ THE ARTICLE 1929 1972 1992 RUMORED VISUALIZED CREATED Dr. John Zahorsky, a pediatrician, The Norwalk virus is first Empty shells of norovirus K. Ettayebi et al., Science gives the name “winter vomiting seen by Dr. Albert Kapikian proteins (capsids) are artifically disease” to a common childhood and his team at NIH created by the Estes Lab. These 10.1126/science.aaf5211 (2016). illness that causes vomiting, using immune electron virus-like particles are not infectious diarrhea, and a fever. microscopy (IEM). and enable studies of the capsid.

WHAT IS NOROVIRUS?

It is a tiny (≈27nm), spherical virus belonging to the Caliciviridae family.

It is the most common cause of diarrhea in the world and the most common cause of foodborne illness in the United States. 1968 1990 2016 An estimated 1 in 15 Americans DESCRIBED CLONED CULTURED experience the virus each year, Human noroviruses are An elementary school in The Norwalk virus genome is amounting to around 20 million cases. Norwalk, OH experiences cloned, paving the way for successfully cultured an outbreak of “winter an era of molecular studies. by Dr. Mary Estes and vomiting disease.” A her team at Baylor virus is suspected. College of Medicine.

HOW DOES THE CULTURE SYSTEM WORK? A SECRET INGREDIENT

Viruses need host cells to replicate. Human noroviruses replicate in the epithelial cells that line our gut. (This was Through careful experimentation, confirmed by the fact that the culture system works.) the Estes team found a key addition Intestinal crypts, which contain stem cells, create these to the media greatly increased virus epithelial cells in our bodies every day, and are rapidly yields. It was human bile. We dividing. produce bile in our livers and secrete it into our gut to help 1 The researchers followed new technology developed by digest food. They found that Drs. Sato and Clevers in the Netherlands and made new some norovirus types, like GII.3, epithelial cell cultures from crypts from adult human need bile to replicate, while it only enhances intestinal tissue (biopsy samples or samples from gastric replication of other bypass surgeries). These tissues were medical waste and noroviruses, like GII.4. would have been discarded. The bile is affecting the cells, not the virus itself, TISSUE SAMPLES and pig bile works as a substitute for human bile. CELLS FROM ISOLATED CRYPTS

These “miniguts” were 3 inoculated with human norovirus, and after 72 hours, the researchers were CRYPTS IN THE INTESTINE seeing far more viral genetic material than they initially 2 Under the right conditions, the stem cells in the crypts GROWN MINIGUT added (a 1,000-fold multiply and form the surface (epithelial) layer of our gut, READY FOR VIRUS increase), indicating the only in miniature and in a dish, to become Human virus was infecting and Intestinal Enteroids (HIEs) or “miniguts.” They function like multiplying in the cells. the tissue they came from, and can be used indefinitely. A NEW ERA OF NOROVIRUS RESEARCH GENERAL VIROLOGY We can dig deeper into how noroviruses CLINICAL MEDICINE work and what makes them so good at making us sick. This knowledge may Being able to work with the actual virus shine light on other viruses. will be a boon to vaccine research, and we will better understand what the virus does in the body, potentially leading to FOOD AND more targeted treatments. ENVIRONMENTAL VIROLOGY This is the first step towards directly testing EPIDEMIOLOGY inactivation methods against the human norovirus to know if they are effective. This We can better understand how the virus could lead to better disinfectants, prevention evolves, spreads, and how it affects strategies, and safer food and water. populations. This can lead to better risk management strategies that protect public health around the world. This research was performed at Food Virology Baylor College of Medicine with support from USDA-NIFA and NIH. Some icons designed by Freepik.