Last updated on July 4th, 2021
After an epidemic, shouldn’t everyone be immune to the virus? Why is influenza able to come back again and again? The answer lies in the virus’s genetic structure and high mutation rate. The truth of the matter is that an individual’s immune system rarely sees the same influenza virus twice and that means it cannot provide the permanent protection it offers against more stable infectious agents.
Whenever you are infected by a pathogen, your immune system generates compounds called antibodies that bind to the infectious agent and target it for destruction. After the infection is cured, a few of the white blood cells that make those specific antibodies continue to circulate in your blood. Called “memory cells”, these cells are quickly activated. if the same infectious agent attacks you again, preventing the infectious agent from establishing itself and preventing you from getting sick. That is why vaccination works: a vaccine presents the immune system with a harmless form of an infectious agent so that if you are infected by the real thing, your immune system will be primed to destroy it quickly.
Unfortunately for humans, the influenza virus has evolved several strategies to outwit the immune system. Like all other organisms, the influenza virus changes every time it reproduces, generating progeny that are ever so slightly different from the parent.
Influenza viruses practice an extreme form of this lifestyle — they can change in several ways, some of them gradual and subtle, and some of them rapid and dramatic, but all of them allowing influenza to appear like a brand-new virus to the immune system. As a result, influenza strains change enough from year to year to allow them to repeatedly cause new epidemics.
The situation is made more complicated because there are at least four different influenza viruses circulating at any one time in the human population. The influenza virus family includes three main groups, called influenza A, B and C.
Only influenza A and B cause epidemics. Of these two types, there are generally two distinct strains in circulation, and the strains are different enough that immunity to one of them does not confer immunity to the others. The variety of influenza viruses in circulation guarantees that there will be “flu season” every year because last year’s flu victims will not have immunity if they encounter a different subtype or strain this year. It also greatly complicates the process of producing the annual influenza vaccine.
Influenza A strains are named according to which versions of two main proteins they carry on their surfaces, hemagglutinin and neuraminidase. So far, 16 varieties of hemagglutinin and 9 neuraminidases have been identified . So a strain called “H3N2” has hemagglutinin #3 and neuraminidase #2. Only strains carrying hemagglutinins #1 ,2, and 3 and neuraminidases 1 and 2 have caused epidemics in human. At present, both H3N2 and H1N1 viruses circulate widely in humans. All of the other varieties are found in wild birds, but some of those have caused serious zoonotics (outbreaks in an animal population) in domestic poultry.
Where do new pandemic influenza strains come from?
The influenza virus family is very large. Almost all vertebrates, including birds, seals, pigs, horses and humans, can be infected by at least one influenza strain. Wild birds, especially waterfowl like ducks and geese, carry dozens of different influenza strains. These wild bird influenza viruses are highly adapted to their hosts.
Occasionally, and unpredictably, new influenza strains containing genes from wild bird viruses begin infecting humans. Exactly where and how these hybrid viruses form is not known. There are many obstacles to overcome for a bird virus to infect a human. That it ever succeeds is testimony to the tremendous genetic flexibility of the influenza virus family.
Viruses are highly specialized. Most of them only infect a single kind of cell in a specific host. Why is this? Host specificity is the result of millions of years of evolutionary battle in which the host evolves methods to avoid the virus and the virus evolves counterattacks to overcome host defenses.
To survive, a virus must be able to infiltrate a host cell’s defenses and co-opt a variety of internal proteins, while preventing the cell from alerting the immune system to its intrusion for as long as possible. Like an undercover agent, a virus must, if you will, speak the language of its target cell fluently, fit in seamlessly to its culture, and be able to fool its watchdogs — in other words, the virus must be a specialist, not a generalist.
Influenza viruses are somewhat unusual in that very closely related viruses are found in a number of host species and some interspecies infection is possible. For example, humans can be infected by swine-adapted viruses and vice versa. Domestic birds, especially ducks, but also chickens and turkeys, can be infected by wild bird viruses. Generally, bird viruses do not infect mammals and mammalian viruses do not infect birds. There are a number of special adaptations that restrict bird and flu viruses to their particular hosts. For example, in wild birds, influenza is an intestinal virus that spreads via fecal matter.
Bird influenza viruses also prefer to grow at the higher temperatures found in the bird gut. Human influenza viruses, by contrast, infect epithelial cells lining the nasal passage. So they spread through the air and prefer to grow at the cooler temperatures found in the upper respiratory tract. Also, as mentioned above, bird and human adapted influenza viruses bind to very specific chemical compounds on the surface of their target host cells. Mammalian adapted influenza viruses bind to compounds that are found more readily on mammalian cells, and less so on bird cells. Bird viruses bind to compounds found predominantly on bird cells. All of these specializations mean that bird viruses cannot spread directly to humans.
There are a few critical exceptions to this general rule, however. The H5N1 avian influenza can infect humans, although it does not spread easily between them. Also, swine respiratory cells display both kinds of chemical compounds on their surfaces, so they can be infected by both avian and mammalian viruses. Therefore, it has long been thought that pigs act as a ‘mixing bowl’ where reassortment between human and bird viruses can take place and create a “shift” pandemic strain.
“Source: This excerpt is taken from FAQ: Influenza, a report from the American Academy of Microbiology published in April 2013. The original, entire report can be downloaded free here, and this excerpt is published with permission from American Academy of Microbiology.”