



However, this may now change based on some startling findings by researchers at the University of Florida. A group led by Dr. Stephanie Karst, an associate professor in the College of Medicine’s department of molecular genetics, just published a paper in Science Magazine that will almost certainly revolutionize norovirus research. Their discovery of how the virus replicates should finally lead to the Holy Grail of norovirus research—making the virus able to replicate in vitro (outside the body).





Those not familiar with virology research or drug discovery may not understand the significance of this. For reasons that are not entirely clear, some viruses will simply not replicate in cells that are not within living animals or humans . One example is the hepatitis C virus (HCV). It is still not possible to grow HCV in living cells in

, and this hampered drug development in the area for years. It was not until the

—an artificial, but predictive

consisting of part of the genome of the virus itself— was invented that

of HCV in cells was possible. HCV research exploded after this discovery,

in amazing drugs, such as Sovaldi and Olysio, which have cure rates in the 90-100% range, something unheard of even five years ago.





A cornerstone of antiviral drug

the ability to grow viruses in cells. With many viruses—

Herpes grows quite easily in cultured cells grown from human tissue— this is





The

to do this takes away one of the most important tools in drug discovery—

(HTS) of huge libraries of compounds in living cells. These libraries, which can contain

millions of different chemical compounds, are





To use a baseball analogy, the lack of a cell-based





The reason scientists have been unable to grow norovirus in vitro is complicated, but

they have been using the wrong cells. It is intuitively obvious that the host cells for norovirus should be those from the the lining of

or small intestine, since this is the region where the





As if this infection itself already isn't enough of a pain, its virology is far more complicated than normal. The Karst group found that the virus does not infect the intestine directly. Rather it infects B cells—a type of white blood cell that is a component of the immune system—that grow within the intestinal wall.





It is known that norovirus must bind to carbohydrate receptors in the gut called human blood group antigens (HBGAs) before viral replication can begin. But the HBGA receptors do not reside on the surface of intestinal epithelial cells. They are, in fact, found on the surface of bacteria that infect the B cells deep within the intestinal wall. This is where norovirus begins its nasty "life."





This is a rather odd





This was elegantly demonstrated by

Karst's group

in two mouse experiments. The group found that norovirus replicated poorly in mice that were pretreated with antibiotics before they were infected with the virus. This fits the proposed mechanism—the fewer bacteria, the fewer HBGAs, and fewer binding sites for the virus. An example of antibiotics preventing a viral infection? Wow!





Possibly even more elegant was another experiment in which mice were bred to have no B cells. Since these cells are part of the immune system, one might expect that these mice would be more susceptible to norovirus infection, but the exact opposite was true. These mice were more resistant to viral infection, not less. Very cool.





What's next? The "recipe" of the cells cultures will be quite different. It will probably





Hopefully, as was the case with the discovery of the HCV replicon, norovirus research will now explode. Instead of your stomach.

Named after the location of first documented outbreak (Norwalk Ohio in 1968) norovirus, aka the "Stomach Flu," "Winter Vomiting Bug," or the "Cruise Ship Virus" is an evil little demon that spares no one. There are few, if any of us, who haven't experienced its misery; it infects 21 million people annually in the US every year— second only to the common cold . It is the leading cause (up to 80 percent) of gastroenteritis in the western world.A common saying about the bug — "it doesn't kill you, but you might wish it did" is actually false. Even in the US, it causes about 60,000 hospitalizations and roughly 700 deaths annually. But in countries lacking supportive therapy—mainly rehydration— it takes a fierce toll. Worldwide , there are 276 million cases annually, resulting in 200,000 deaths.Norovirus is one of the most, if not the single most, infectious pathogens known. As few as 10 viral particles may be sufficient to cause infection. Thus, it is not surprising that it spreads like wildfire in schools, camps, nursing homes, and hospitals. The rapid onset of symptoms—nausea, vomiting and diarrhea— further contributes to its infectious prowess. Although fecal to oral transmission (from poor hand washing, often by food handlers) is the most common way that it is spread, it is far from the only way.The vomit itself is highly contagious, and the virus can even be infective airborne, via mist that travels surprising ly far from the person who is vomiting. There is even a case study of a woman who became ill at the table in a restaurant. There was a direct correlation between the distance from her table with the incidence of subsequent illnesses of people at other tables.An individual can be contagious about a day before symptoms arise, and usually 2-3 days (but sometimes up to two weeks) after it subsides. Between this, and the near indestructibility of the virus—it survives conditions that would eliminate most other viruses—it can remain infective on surfaces for 1-2 weeks. It is not surprising that it is so easily transmitted.Worse, unlike measles, chicken pox, or rubella. there is a very limited, short-term immunity against reinfection, so you can catch it repeatedly—even the same strain. There is no vaccine or any antiviral medicine to treat or prevent it.vitroconstructinhibitionresultingdiscovery iseasy, but occasionally it is not.inabilityhundreds of thousands, or eventested using sophisticated robots, and the effect of any given compound or compounds can be detected, usually by insertion of a reporter gene into the cell genome, which provides a surrogate measurement (often fluorescence) that can be rapidly read by the robot.assay (in virtually any type of drug discovery) is like coming to bat blindfolded, and with two strikes against you. HTS is also used to measure the inhibition of an enzyme or receptor outside of a cell, but getting from there to an efficacy model in animals is far more difficult. Many compounds may inhibit an enzyme that is relevant to a particular disease, but not penetrate the cell where the biological process is taking place. In the absence of the ability to penetrate cells, penetration—the chances of that compound being able to work in a living system (and have an impact on the disease in question)— are very low.fascinating;stomachinfection does its damage. But this turns out to be wrong.occurrence, a virus binding to bacteria that infect cells before it begins its life cycle within those cells. If there is another example of this, I sure don't know about it.consist of B cells, the bacteria that infect them and cells from the region of the intestinal wall where this hideous machine gets going.