As the infection by one specific strain of a pathogenic microorganism moves through a population, more and more individuals develop immunity to that strain, and the virus starts to disappear due to the lack of potential hosts.
However, pathogenic microorganisms often have various means for varying the antigenic molecules on their surfaces. Should a new strain develop with new antigens on its surface, this strain of the same microorganism likely will be able cause infection, and once again the virus will begin to spread through the population.
Influenza A, which commonly causes "flu" in humans, illustrates a number of the mechanisms that vary surface antigens.
Often infectious microorganisms have many subtypes, each with different antigenic molecules on their surfaces. Influenza A has two important surface molecules: hemagglutinin and neuraminidase. Hemagglutinin is the molecule that binds to the surface of cells in the body, following which the cell takes up the virus and become infected. Neuraminidase is a nearby enzyme that cleaves the molecule on the host cell that binds hemagglutinin. This is important after the cell makes new virus particles because the new viruses adhere to the cell. Once the hemagglutinin causing the adhesion is no longer attached to the cell, the viruses are free to move on and infect other cells.
There are 16 different hemagglutinin types and 9 different neuraminidase types. For example, one specific subtype of the virus is designated "influenza A (H3N2)". This means this subtype of the virus has the third hemagglutinin type and the second neuraminidase type. Antibodies directed against these specific molecules can be quite effective in preventing the spread of this subtype, but would be unlikely to work against, for example, influenza A (H1N1).
Influenza A is basically a bird virus and all of the subtypes are found in birds. The subtypes that are specifically human are H1N1, H1N2 and H3N2. The other subtypes usually don't infect humans.
However, there are exceptions, including the influenza A (H5N1) that has been causing serious poultry epidemics in Southeast Asia and elsewhere. This subtype is normally a bird virus that does not infect humans. But, while not common, there are well established cases in which this H5N1 strain has infected humans, and the present strain have proved to be quite virulent, often causing death. To date, this subtype has only rarely moved from humans to humans. Thus most cases are scattered and in individuals exposed to poultry.
A typical cause of variation results from antigenic drift. As mentioned, after one strain of influenza A has moved through the population and died out due to developing immunological resistance, another strain typically arises that again moves through the population. This usually occurs because the hemagglutinin and/or neuraminidase molecules have acquired point mutations. Often this will change one or both of these molecules enough to allow them to infect the same individuals that had become resistant to the earlier strain. This new variation is now able to spread through the same people that had developed immunity to the previous strain. Thus influenza tends to appear regularly despite the immunity we developed in previous years. And a new vaccine is required that includes the new strain.
Usually the point mutations in the antigenic drift cause small changes that do not present the immune system with an entirely new situation. As a result they usually just cause the usual, frequent epidemics of influenza. By itself, antigenic drift does not tend to cause more serious, extensive global epidemics, which are termed pandemics.
Occasionally, a serious pandemic of influenza A sweeps through the world. Typically they occur only at intervals of several decades. These result from a substantial change in the genes of influenza A often caused by antigenic shift.
Antigenic shift can occur in influenza A because its genome is encoded in eight segments of RNA. If two different subtypes of influenza A infect the same individual, it is possible for new viruses to wind up with segments of RNA from both sources.
The place where the antigenic shift occurs depends on the subtype. For example, often human influenza A can infect a pig. Likewise, some bird influenza A can infect a pig, but not a human. Thus, simultaneous infection of a pig with both types of virus could lead to antigenic shift. Then if this new type in the pig can infect a human, it could cause a new outbreak in humans.
In other cases, perhaps the antigenic shift could occur in birds. Also note that influenza A (H5N1) can infect humans and thus potentially a human could be infected with this virus and with a human influenza A virus.
Should antigenic shift occur in H5N1, the result might be a virus that could be passed from human to human easily. If this happens, the result would be a pandemic. Since the H5N1 subtype is not normally a human virus, our immune systems would be much less prepared to deal with it than normal epidemics of influenza. Potentially, too, an emerging strain could retain a virulence for humans similar to the current strain causing the poultry epidemic. The ease with which this might happen with influenza A (H5N1) is why health authorities are so worried. The H5N1 influenza has been steadily changing and no one knows how many changes might be required to become strongly infectious among humans. Nor is it known if such an infectious virus would retain the same virility as it now has in birds.
In class we covered some points related to influenza A (H5N1). What differences did we note between the pattern of infection of ordinary influenza and influenza A (H5N1)? What is pneumonia? What are some differences between bacterial and viral pneumonia? Also, discuss our use of the term "cytokine storm", and indicate some of the serious repercussions of this.
Influenza B, which is the other form of influenza, cannot undergo antigenic shift and thus only causes epidemics.
The current influenza vaccines that are injected are from killed viruses and contain the three subtypes that the experts feel are most important for that year to be included. There are also vaccines that are sprayed intranasally. These are attenuated, live viruses, which usually work by causing mucosal immunity.
The antivirals that are effective against influenza A (H5N1) are neuraminidase inhibitors. Oseltamivir (Tamiflu) is taken orally, while zanamivir (Relenza) is a powder that is inhaled.
SEE IF YOU REMEMBER: Which one of the two mechanisms typically causes pandemics?
a. antigenic drift
b. antigenic shift.
BY ANY CHANCE, can you name the molecule that causes influenza A viruses to adhere to cells?
Investigators sequenced the genome of influenza virus taken from an individual who died in the severe influenza pandemic in 1918 and who has been frozen in the permafrost of Alaska since then. Comparisions with H5N1 have found, for example, that the specific types of RNA polymerases may be important in the virulence. Also, the current avian influenza seems to have a hemagglutinin that splits easily. The virulence seems to be due to a combination of all these factors. But all this is part of current, ongoing investigation.