Genetics of the Influenza Virus

Although most healthy adults who contract the flu experience relatively minor symptoms, influenza and other respiratory viruses are a serious health threat to the U.S. population at large. Children and the elderly are particularly susceptible to the flu epidemic that sweeps the country each winter. Moreover, pandemics involving influenza strains to which most people do not have immunity occur periodically, attended by high levels of mortality and disastrous consequences to public health. Properly preparing for the influenza threat is thus a constant challenge for public health officials, especially given the fact that the viruses that cause infection can mutate rapidly and reassort to form new strains, and that these viruses also have the ability to reside in multiple animal hosts. Unfortunately, despite intensive research over the course of decades, much remains unknown about why some influenza strains are highly transmissible and why certain flu viruses cause such severe disease.

The name "influenza" is derived from the Latin word for "influence," and the pathogens that cause this disease are RNA viruses from the family Orthomyxoviridae.  The genomes of all influenza viruses are composed of eight single-stranded RNA segments.  These RNAs are negative-sense molecules, meaning that they must be copied into positive-sense molecules in order to direct the production of proteins.

There are three basic types of influenza viruses: A, B, and C.  Influenza B and C viruses only infect humans, so new antigens are not introduced from other species.  Only influenza A viruses infect nonhuman hosts, and a reassortment of genes can occur between those subtypes that typically infect animals and those that infect humans, resulting in antigenic shift and potential pandemics. E pidemics of seasonal influenza occur due to influenza A or B viruses.

As in all viruses, the genome of an influenza virus particle is encased in a capsid that consists of protein. The influenza A capsid contains the antigenic glycoproteins hemagglutinin (HA) and neuraminidase (NA); several hundred molecules of each protein are needed to form the capsid.  These proteins are the parts of the virus that are recognized as foreign by a host's immune system, thus eliciting an immune response.  Because many different subtypes of the influenza A HA and NA proteins exist, the human immune system is frequently challenged with new antigens.  For example, point mutations in the HA and NA genes can lead to changes in antigenicity that allow a virus to infect people who were either infected or vaccinated with a previously circulating virus.  

Due to the segmented nature of the influenza genome, in which coding sequences are located on individual RNA strands, genomes are readily shuffled in host cells that are infected with more than one flu virus. For example, when a cell is infected with influenza viruses from different species, reassortment can result in progeny viruses that contain genes from strains that normally infect birds and genes from strains that normally infect humans, leading to the creation of new strains that have never been seen in most hosts.

Molecular Studies of Influenza B Virus

Fair Flu Viruses Closely Matched