Beyond The Bench

One hundred and forty-nine people are dead in Mexico, with 2,000 more believed to be infected. At least 40 cases have cropped up in “our own backyard”: in California, Kansas, New York, and Texas. Swine flu might be spreading, but what is spreading even more rapidly is paranoia.

The flu is scary because it is so easily transmitted; a mere cough or a sneeze from a nearby carrier is enough to pass along the virus. What’s even scarier is that the virus has such a variety of symptoms (an abbreviated list includes fever, headache, tiredness, cough, sore throat, runny/stuffy nose, bodily aches, diarrhea, and vomiting), and they manifest themselves so variably among individuals, it is nearly impossible to differentiate between strains without testing every single individual person. Moreover, these symptoms are often dismissed as evidence of a mere common cold (HPIV)—except when we are reminded to look for influenza, as is occurring presently.

So we know it came from pigs (hence the obvious name “swine flu”), but why is this significant? Ask Joe Shmoe on the street, and his answer would most likely be something along the lines of, “Because the media says it could spread. People died!” In that case, we should all stay in quarantine—all the time. Cancer-causing second-hand smoke “spreads.” People die from bee stings!

In order to understand the significance of the swine flu, the nature of the virus must first be understood. When the influenza virus enters a host (through the nose, throat, etc.), it uses a spike-shaped protein called hemagglutinin to search for specific sugar chains that protrude from proteins located on surface of body cells. When hemagglutinin finds the target cell, it binds to the sugar chains and “injects” the virus inside. Although the cell’s endoplasm is acidic in order to ward off “intruders,” the acidic environment is actually beneficial to the virus and assists it in reconfiguring the shape of the hemagglutinin, which leads to the next step of infection where the viral and cellular membranes fuse. Then, the viral RNA flows into the cell, and the process of transcription—which will consequently cause the infection—begins.

Obviously the body makes antibodies to fight against influenza. Therefore, to “survive,” the virus has to “evolve.” Influenza can do this in two ways. One way is via antigenic drift. This happens when RNA polymerase (the transcribing agent in the cell’s nucleus) makes a mistake. Typically, RNA polymerase makes a single nucleotide insertion error roughly every 10 thousand nucleotides. This is the average length of the influenza’s RNA, so a majority of the reproduced influenza viruses are mutants.

Antigenic drift happens when mutations which occur at the anti-body bonding sites on the virus accumulate; consequently, old antibodies that worked against previous stains are no longer effective against these newly created viruses, leaving once-immune populations susceptible to infection. For instance, in 1918 the Spanish Flu pandemic arose as the result of an avian H1N1 strain “morphing” to become capable of quickly and efficiently infecting humans.

The other way—and the one that is presently causing concern—in which influenza can mutate is by antigenic shift, also termed genetic reassortment. This involves two viral genomes recombining, usually in such a way that the hemagglutinin in the human strain is replaced with a new subtype that had not been present before in human influenza viruses. Outbreaks that have occurred in the past as the result of antigenic shift include the Asian Flu pandemic of 1957 and the Hong Kong Flu pandemic of 1968.

What makes swine flu particularly worrisome is its likelihood to be a result of the latter mutation method (antigenic shift), and therefore its likelihood to turn into a pandemic. Pigs are ideal “mixing vessels” for viruses: they are susceptible to infection by viruses from all varieties of birds and mammals and therefore provide prime opportunity for genetic reassortments (i.e. antigenic shifts). For instance, a pig could become simultaneously infected with a human influenza virus and an avian virus. Then, if an antigenic shift were to create a virus containing mostly human genes but hemagglutinins from the avian virus, the new virus would be capable of infecting and spreading between humans, but resistant to most (if not all) antibodies.

Mexico has closed its schools and is considering shutting down public transportation, as well. China and Japan have set up quarantines. Airplane passengers all over the world are now having their temperatures taken as part of the de-boarding process. The U.S. overreacted to the 1976 outbreak at Fort Dix and over-immunized people with a risky vaccine. Alternatively, early detection and early action enabled Asia to contain SARS. Let us hope that history has been an effective teacher and that we are armed and prepared for what is to come.

This entry was posted on Tuesday, April 28th, 2009 at 9:21 am and is filed under Uncategorized. You can follow any responses to this entry through the RSS 2.0 feed. You can leave a response, or trackback from your own site.