FAQs Influenza Archives • Microbe Online

Influenza virus has two ways to change — one slow and one fast. The slow change is called “drift” — the virus gradually accumulates individual mutations until its surface proteins are no longer recognized by our immune system. The fast change is called “shift” — different strains of influenza can exchange genetic material if they infect the same cell at the same time. A new “hybrid” strain can emerge with surface proteins that are completely different from the previous year’s epidemic strain. Antigenic Shift and Drift To picture shift and drift, it helps to know a little bit about influenza virus genetics. ANTIGENIC DRIFT IN INFLUENZA VIRUS Influenza viruses are said to “drift” when their surface proteins change gradually. How do they change their surface proteins? All organisms use enzymes called polymerases to make copies of their genetic material that are passed on to their offspring. These polymerases vary in accuracy and the influenza virus polymerase is especially sloppy. In fact, it is so inaccurate that every single progeny virus is likely to have at least one genetic difference from the parent and many of the new viruses will have so many errors that they will not even be functional. From an evolutionary standpoint, the influenza virus doesn’t mind if most of its offspring do not survive, as long as one of them is able to infect a new host. Mutations in the genes that code for the virus’s surface proteins — the parts of the virus that are exposed to the human immune system may make one of the virus’s progeny unrecognizable to the antibodies generated by the previous infection (Figure 4). Changing even one letter in the genetic code can be enough to mask the virus. Drift is both inevitable and unpredictable. Because the mutational changes are random, it is impossible to predict exactly what the virus will “look” like to the immune system from one year to the next. “Drift” is why influenza epidemics happen every year. ANTIGENIC SHIFT IN INFLUENZA VIRUS The influenza virus has another even more dramatic strategy to evade the immune system. Instead of accumulating mutations that gradually change the appearance of its surface proteins, it can acquire entirely new surface proteins. This is called a genetic “shift. ” “Shift” is made possible because of a process called reassortment (Figure 5). Remember, the influenza genome is comprised of eight individual genetic segments each of which must be replicated and then packaged into a protein shell during the intracellular replication cycle. If two different influenza strains infect the same host cell, the genome segments can get shuffled and packaged in new combinations. Sometimes a hybrid virus can be formed that has acquired surface proteins that are completely unfamiliar to everyone’s immune system. Such hybrids are able to spread explosively, often breaking out over entire continents nearly simultaneously — these global outbreaks are called pandemics. Influenza pandemics do not happen very often, but they cause such dramatic outbreaks that it is possible to look back at the historical record and see evidence of them going back hundreds of years. Some of the pandemics were extraordinarily destructive. In 1918 and 1919, an influenza pandemic killed at least twenty million, and perhaps as many as fifty million, people worldwide. In the United States, the 1918 influenza killed 675,000 people. Many of these deaths were actually caused by bacterial infections; lungs that had been weakened by influenza were easy prey for pathogenic bacteria. But even as recently as 1957, when antibiotics were available to treat victims of another pandemic strain, nearly 70,000 Americans died of influenza. There was simply nothing that could be done to slow down the spread of the virus or lessen the severity of the infection. Shifts in the influenza virus are rare — “shift” strains generally emerge only about every thirty years. Like a ‘perfect storm’, it seems that several unusual events must all occur simultaneously for a shift virus to emerge. The historical record suggests, however, that even though these events are rare, they happen with enough regularity that we must assume that another pandemic will eventually happen. One of the important challenges facing influenza researchers is figuring out enough about the circumstances leading to shifting that they can either be prevented from occurring or detected early enough to limit the huge outbreaks they have historically caused. “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 the American Academy of Microbiology.”