Flu Shots- An Introduction to Influenza

Well it’s that time again, the kids are back in school, Shipyard is brewing its Pumpkinhead beer and the flu season is gearing up. According to the experts, the best way to prepare for the flu season is with a flu shot. In my adult years, I have never gotten a flu vaccine. I tell myself that this has been an educated decision from back when I took virology in graduate school. Seeing as that was years ago and I did actually have the flu last year I thought I’d brush up on the educated part of my decision for this year’s influenza season. One thing that is in the negative column for getting the flu vaccination is there are different types, subtypes, and strains of influenza. The efficiency of a flu vaccine is an interplay between how many different strains are represented in the cocktail and how effective the exposure will be. Right now the magic number is three strains, and the Center for Disease Control (CDC) posts the recommendations as to which three strains should be included in a given year’s vaccination. This means that out of all the possible strains that are capable of infecting, the vaccine only protects against three of them in a given flu season.

The World Health Organization (WHO) makes its best guess as to which three strains are going to be the most problematic for the upcoming flu season. Most years this is a successful guess, but there are years when the three in the vaccine do not represent those which most infect people over that particular season. 2003 stands out as a mismatch year for example, where the most prevalent strains were not represented in the cocktail. According to the CDC website, the flu shot for the 2011-2012 season is the same cocktail of three flu viruses which the shot contained for the 2010-2011 season. Even so it is still recommended everyone, including those who got the vaccine last year, get vaccinated. Let’s backtrack a little here in order to look closer at the virus and how the naming of the strains occurs.

Influenza virus is a negative-sense, single strand RNA virus belonging to the Orthomyxovirus family. A negative-sense RNA virus needs to have in its genome coding to make its own RNA polymerase in order to make the copy that passes as mRNA in the host. A positive-sense stranded RNA virus is already oriented in the same way as host mRNA and does not need an RNA polymerase to make the complementary strand. The mutation rate in RNA viruses compared to DNA viruses is higher due to the error rate of RNA polymerase. Another key factor is the organization of the viral genome- for influenza the genome is segmented. This means the RNA is divided into separate sections and it is all contained within a single virus particle. The mutation rate and the segmented nature of the genome are key factors in the effectiveness of the influenza virus, to be touched upon later. Influenza‘s genome is made up of only eight genes. Four genes make up the components necessary for transcription- PA, PB1, and PB2-which work along with the nucleoprotein made by the NP gene. The M gene makes up two matrix proteins and the NS gene codes for two non-structural proteins. These genes are both able to make two different products due to a shift in the reading frame. Lastly, The HA gene codes for the surface protein haemagglutinin (or hemagglutinin), while the NA gene codes for a second surface protein neuraminidase.

There are three types of Influenza A, B, and C this nomenclature goes in order of severity of infection. A is the type that almost all outbreaks are caused by, B causes a milder infection than A, and C doesn’t really cause much infection at all. The nucleoprotein varies for each of the three types. Since the 2009 flu outbreak, most people are familiar with the phrase H1N1. This additional naming of the flu virus is the subtype and it is only used for type A. H refers to the hemagglutinin protein and N refers to neuraminidase protein. Hemagglutinin and neuraminidase are responsible for the virus binding to host cells; this binding is the first step to the virus causing the host harm. The last part of naming is strain, and this is used only for type A and B. Take this year’s recommendations for the vaccine- they are ‘A/California/7/2009 (H1N1)-like virus, ‘A/Perth/16/2009 (H3N2)-like virus’ and ‘B/Brisbane/60/2008-like virus.’ The origin of the virus, the laboratory that identified it, and the year of the outbreak are also included in the full naming along with the type and subtype. Another common feature found in the naming of flu viruses is the organism that particular strain infects.

The hemagglutinin is known to have 16 subtypes, while the neuraminidase has 9 known subtypes. H1, H2, and H3 are those known to infect human while N1 and N2 are the two out of nine neuraminidase subtypes which infect humans. The other subtypes for these proteins are found to infect other species such as birds and pigs. The species specificity boils down to these surface proteins- they are the key to entering the host cells but in order to get in the surface protein must identify and bind to a particular sugar reside on the host cell’s receptor. In theory the lack of a particular sugar residue on a given species’ receptor is the reason why only certain subtypes of the Influenza A are able to infect that particular species. However some of the characteristics of Influenza previously pointed out, namely the mutation tendencies, allow for inter-species infectivity. When two subtypes have the opportunity to intermingle, gene reassortment of the virus’ genes can occur and this creates a genetically novel flu strain. The venue for this gene reassortment is theorized to be a species which can be infected by various subtypes of the flu virus. This theory was looked into in an article in the Journal of Virology in 1999 by Zhou et al. The paper details this idea of two strains of virus, one human and one avian, infecting a third host simultaneously and rearranging to form new genetic variations of the virus. The host in recent years is pig, which is known to be infected by both human and avian strains of the flu. This reassortment allows for new versions of flu which the immune system has no experience fighting and are not represented in any flu vaccines for initial outbreaks.

There is a lot of information that can be learned about the flu virus, this is really just skimming the surface. Even though this brief glimpse makes the negative column stack up, the positives are there as well. Sure there is the realistic view of the cocktail vaccine being a best guess, the knowledge there are lots of other subtypes/strains, and scarily new ones re-assorting themselves in unsuspecting pigs. However, all of this still doesn’t add up to avoiding a vaccination that could very well prevent me from being laid up in bed for several day feeling like I’ve been hit by a Mack truck. Even if the negatives outweigh the positives, the bottom line is there’s really no harm in going to any number of convenient places and getting a quick shot that could prevent the flu.