The Petri Dish: Worries about the flu
December 4, 2012
The arrival of cold weather here in Summit County hails the new influenza season. While many of us equate the flu with sniffles and a runny nose, it is actually a very serious disease that kills thousands of Americans every year. The illness is caused by a particularly crafty virus, the influenza virus, which infects the moist passages of the nose, throat and lungs. While the virus does a considerable amount of damage to these tissues, it is our body’s own immune response to the virus that is responsible for many of the symptoms we suffer, especially the fever and aching muscles.
Flu arrives like clockwork every winter but varies in severity. In normal years, “seasonal” flu is primarily a concern for those with weakened immune systems, including the very elderly. Once in a while, new variants of the virus emerge (referred to as “pandemic” flus) which can be associated with severe illness and high levels of mortality, even among healthy individuals with strong immune systems. The classic example is the Spanish flu of 1918 that killed upwards of 700,000 in the U.S. and untold millions worldwide. Shockingly, it seems that more U.S. soldiers in World War I died from the Spanish flu than from battle wounds. The ever-present danger of pandemic flus, which arise several times a century, keeps health authorities constantly vigilant. You may recall that the 2009 H1N1 flu was a new variant that caused a worldwide pandemic. Fortunately, although it killed many people, this new variant was less dangerous than some past pandemics.
Why does the flu exhibit this pattern of yearly seasonal epidemics punctuated by occasional severe pandemics? The question has fascinated scientists for decades. Its answer lies in the structure of the virus, which can simply be thought of as an inner core surrounded by an outer protein coat. The inner core contains the virus’s genetic code and proteins essential for reproduction of the virus once it has entered the cells lining the throat, nose and lungs. The outer coat is responsible for mediating entry of the virus into those cells. But fascinatingly, the outer coat is also designed to be highly variable in structure, which allows the virus to essentially disguise itself every year and hide in plain sight from the immune system. This is because one of the immune system’s primary mechanisms for attacking the flu virus is the production of antibodies in the blood, molecules that stick to the outer coat of the virus and essentially gum it up, preventing binding to target cells. However, these yearly gradual changes in the “shape” of the viral coat mean that antibodies produced against prior-year infections only poorly recognize the changed virus, resulting in another bout of flu for that individual. It is this constant drift in shape that allows the virus to return year after year and re-infect individuals who should otherwise be immune. It is also why the flu vaccine has to be regularly re-formulated to ensure a match with the current shape of the circulating virus.
But what about pandemic flus? It turns out that occasionally, the flu virus undergoes a seismic shift in the composition of its outer coat (and internal) proteins. Whole protein components can be replaced, presenting the human immune system with a flu virus that looks fundamentally different from any the immune system has seen before. These dramatic changes happen when strains of flu virus circulating in birds or animals mix with the human form of the virus, producing a mosaic with greatly altered shape and infectivity. These “re-assorted” viruses are often associated with much more severe infections, such as the Spanish flu, and can be highly deadly in the year they emerge. And for reasons not entirely clear, the new virus completely replaces the previously circulating version of flu. The end-result after the initial pandemic is over is that the new flu gradually reduces its lethality and becomes a seasonal flu in subsequent years – until a new pandemic strain emerges.
The relationship between humans and influenza is complex. While scientists are able to produce vaccines against both seasonal and pandemic strains of flu, the process is slow, and there is often a rush to make the vaccine available to the population before the flu season starts. Furthermore, vaccines against pandemic strains tend to be less effective for reasons that are not clear (sometimes requiring multiple administrations to achieve effective immunity). Clearly we still have much to learn about the biology of this fascinating virus.
David L. “Woody” Woodland, Ph.D. is the Chief Scientific Officer of Silverthorne-based Keystone Symposia on Molecular and Cellular Biology, a nonprofit dedicated to accelerating life science discovery by convening internationally renowned research conferences in Summit County and worldwide. Woody can be reached at (970) 262-1230 ext. 131 or firstname.lastname@example.org.