Why Influenza Changes Every Year
The Influenza viruses are known for their ability to change their antigenic structure. It is changes in this structure that causes new strains of influenza to appear every year. The antigenic structure of the Influenza virus is defined by two different proteins on the protein coat. These proteins are hemagglutinin (H) and neuraminidase (N) changes in either of these will change the antigenic nature of the virus. Sometimes these changes are minor but at other times a major change can occur leading to an Influenza pandemic.
There are three types of Influenza virus which can infect man. Influenza A and Influenza B give rise to classic “flu” like illnesses while Influenza C gives only a mild cold like illness. In addition to being an annual cause of “flu” the Influenza A virus is responsible for major pandemics such as the Spanish “flu” of 1918 and the Hong Kong “flu” of 1968.
These viruses are able to change their antigenic structure so readily because of their nucleic acid structure. Unlike all other living organisms viruses have only one type of nucleic acid either ribonucleic acid (RNA) or deoxyribonucleic acid (DNA) not both. In the case of the Influenza viruses they are RNA viruses. The viral genome of the Influenza virus is segmented consisting of eight separate strands of RNA. For the virus to be infectious all strands must be present in the viral particle.
When the Influenza virus enters a host cell it “hi-jacks” the cells metabolism making it create more virus particles. The eukaryotic cell normally transcribes RNA from a DNA template while the genetic code is maintained in the DNA. Within the cell are a number of enzymes designed to ensure the DNA is correctly transcribed and replicated. These enzymes do not work when RNA being transcribed or replicated from a RNA template. Without these checks small errors in the viral nucleic acid can occur. Some of these errors may have no effect on the viruses structure others may cause a slight change in the amino acid sequence of the viral proteins. Where the amino acid change is within the antigenic proteins of the viral coat a change in the resulting viral antigenic nature occurs. This is known as antigenic drift.
Antigenic drift can occur in all three of the Influenza viruses leading to a gradual change in the circulating viruses that are causing infections at the time. Another method of antigenic change antigenic shift – occurs only in the Influenza A virus. Antigenic shift causes a sudden totally new antigenic structure to the virus rather than the gradual change seen in antigenic drift.
It is possible for a cell to be infected by two different Influenza strains at the same time when the segmented genome is packaged into the protein coat parts on the genome from one virus may become mixed with that of the other. For example if two viruses infecting a cell were defined as H1N1 and H2N3 then any of the following antigenic combinations could arise H1N3, H2N1, H1N1 and H2N3. In this example the H1N3 and H2N1 viral strains would be the result of antigenic shift.
This antigenic shift can lead to new deadly forms of the infection arising as was seen in 1918. It can be a particular problem as Influenza A is also a pathogen of birds and other animals. Avian Influenza has many more H forms than human Influenza and with antigenic shift it is probable that one or more of these strains will jump the species barrier to become highly pathogenic to man leading to another pandemic.
Because of its changeable nature the provision of new “flu” shots every year is required. Close monitoring of circulating influenza strains around the world allow scientists to make an educated guess as to the likely strains to be infecting man during the “flu season”. Even then it is not always possible to provide a suitable vaccine as new strains will not always be covered. It takes time to prepare and quality control each batch of vaccine and during this time the virus is always changing.
By Allison Bowler, Medical Microbiologist, from London, Middlesex, GB