To know a norovirus
In the aftermath of Hurricane Katrina’s devastating assault on the Gulf Coast in 2005, some 24,000 evacuees took refuge in Houston’s Reliant Park Complex. Unfortunately, so did a nasty virus.
During a period of 11 days, a wave of illness swept through the complex, ultimately afflicting more than 1,000 residents with diarrhea, vomiting or both. The culprit was a norovirus, a bug renowned for its ability to cause explosive outbreaks of gastroenteritis (inflammation of the stomach and small intestine) in settings where large groups of people come together: daycare centers, nursing homes, cruise ships and military barracks, for instance.
While the infections usually aren’t deadly, they can take a heavy toll by thinning the ranks of caretakers, soldiers and other essential personnel. In one outbreak among British troops and field hospital workers in Afghanistan, for example, some troops with particularly severe symptoms had to be medically evacuated, and medical attendants who treated the soldiers in flight also got sick.
With new strains on the rise, norovirus is a significant public health concern. But until recently, scientists lacked key tools for studying it: a small animal model of the infection and a system for probing its reproduction in the lab. As a result, “little or no information is available in many areas of norovirus biology, and no directed disease prevention and control strategies exist for these viruses,” says Christiane Wobus, whose research centers on understanding the earliest steps in norovirus infection.
As a postdoctoral fellow at Washington University, Wobus was involved in the discovery of the first mouse norovirus (MNV11) in 2003, making a small animal model finally available. Soon after, she devised the first laboratory culture system for a norovirus. With additional genetic tools she developed in collaboration with researchers from the UK and New Zealand, “we have a unique system for detailed analysis of different aspects of norovirus biology,” says Wobus.
Already, her research group has learned that MNV-1 infects only certain kinds of cells, namely immune system cells known as macrophages and dendritic cells, and experiments suggest that some early event, such as binding to receptors on cell surfaces, is the password that admits the virus into those cells.
Now, the Wobus lab is focused on finding answers to three main questions:
- What are the receptors on the surfaces of macrophages and dendritic cells to which the virus binds?
- What cellular mechanisms does the virus exploit to get into the cell? All viruses hijack some aspect of normal cell function and use it for their own purposes, so which one does norovirus subvert?
- How does the virus move across the cells that line the intestinal tract to reach the macrophages and dendritic cells?
“If we can understand these early events,” says Wobus, “we can learn what determines which cells can be infected and perhaps find ways to block those initial steps, preventing infection.” That could make for smoother sailing on vacation cruises and undiminished military might.
