Bioscope ‘04

by Dr. Barbara Price

Researching the Reassortment: Planning the antigenic shifts and drifts

           The influenza virus infects all vertebrates and has a history of appearing, reappearing and changing human history. Understanding how these changes occur will help us to devise better strategies for vaccines.
           The negative stranded, single strand RNA influenza virus is composed of eight segments. When the virus invades the host cell, these segments separate and head to the nucleus and replicate; the replicated segments regroup and are surrounded by the proteins that make the membrane and envelope; the resulting virions bud out of the host cell. The separate lives of each segment give the virus a chance to come together with segments from different strains. This mix and match during replication is called reassortment.
           Virologists have distinguished between different influenza viruses by the strong immune response to the virus as articulated by the serologic reactions to the two envelope proteins, hemagglutinin (H) and neuraminidase (N). If the infected host survives the infection, the strong immunity to these envelope proteins means that the host will recognize those H and N proteins the next time it tries to invade. The virus may indeed invade the host several times and perhaps one of those times, the virus mutates a bit and survives long enough to be shed from the host. The immune response to this changed virus may not be as strong; the changed virus is not very different from the original virus. This is immunological or antigenic drift. Each year flu vaccines are designed on the different circulating strains of the flu and types of drifts predicted.
           Different animal species are susceptible to different strains of influenza virus. Birds, humans and swine are commonly infected with influenza. If an influenza virus from a bird infects a pig at the same time a human influenza virus does, the reassortment may produce a shift, rather than a drift. If one of the 8 segments in the bird’s influenza virus combines with 7 of the human’s influenza virus, the resulting virus may be more dangerous than either original virus. This immunological or antigenic shift is a bigger change than a drift and represents more of an opportunity for the virus (or more of a threat to humans). Shifts have been responsible for the more virulent influenzas in human history.
           Our previous infections and vaccines have been with H1N1 and H3N2 strains. Humans will have some immunity to H1N2 or H3N1 based on our previous infections and vaccines. The avian flu strain, which is beginning to spread to humans in Asia, is an H5N1 strain; we have no immunity to H5. Hence the concern that if a natural reassortment produces an H5 based influenza most of the human population may be threatened.
           Current research can easily duplicate what happens in nature, and in controlled laboratory experiments, that can be used to develop vaccines. Indeed laboratories in several countries are researching these reassortments to fight the evolving influenza virus and anticipate drifts and shifts. But such research also has risks and costs. The risks include the accidental escape of the engineered flu vaccine, despite carefully controlled biosafety laboratories. And of even greater concern is the purposeful release of an engineered virus designed to be new to our immune systems or more virulent.