Influenza

May 4th, 2009 | By | Category: Medicine

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As a pathogen, influenza is the cat’s pajamas; influenza puts the ortho in orthomyxovirus, the segments in its RNA genome and the misery in sneeze droplets everywhere.

Let’s unpack H1N1 and H5N1. The ‘N’ in both stands for neuraminidase, a fancy way for saying “snot eating enzyme.” The virus needs to get to the juicy cells at the back of the throat. Our bodies pour out copious amounts of snot in defense, forming a sticky wall of doom for all manner of pathogens. Stuck on the outside of every flu virus is a sea of this neuraminidase enzyme. The enzyme gobbles up the snot, allowing the virus to reach the cells lining our throat. In comes the ‘H’ or hemagglutinin protein, also located on the outside of the virus. Hemagglutinin binds the salicylate receptors located on the outside of almost all cells (salicylate is a special way of saying aspirin), dragging the virus into the cells. Once inside, you’re infected. Huzzah for our little virus. Go team!

Influenza has been around for a while–co-evolving with many other species beyond man. As a result, different versions of the H and N enzymes have split off over time. The numbers after H and N in a flu virus name indicate the rough genetic heritage of a given flu’s enzymes. H1 and H5 are like Montagues and Capulets–alike in kind if not kin. A given H (or N) is accomplishing the same task, but in slightly different ways.

In comes the home team. If the B-cells in our immune system can make antibodies against the neuraminidase and hemagglutinin, blocking their function, we can stop the virus. Making antibodies takes time. While we’re waiting, CD8 T-cells (cytotoxic T-cells) come in and kill any of our own cells that are infected with virus, a sort of controlled Kamikaze mission in defense of the Home Islands. (Dead cells can’t make more copies of the virus; once you’re infected, brother cell, it’s too late to save you.) With each kill, the CD8 cells release a little bit of activating cytokine and become a bit more bold. This self-death is a large part of the misery of the flu. You are sore because your body is literally killing itself in battle. It takes a week or two for the B-cells to start pumping out antibodies to a new(-ish) virus, at which point the CD8 cells are told to lay off, and take a break.

What we have here is the co-evolution of a host and parasite. My favorite! This sort of host-pathogen interaction is an evolutionary saddle-point, with two possible resolutions:
1. All out battle to the death! Host and pathogen strike fast and hard, in an all-out effort against the other. This is true misery for both, with the eventual true end to this situation the extinction of the pathogen, or host and pathogen together.

2. A detente. The pathogen tries to go out its business in the least offensive way possible, with the host ignoring the pathogen (due to the lack of mayhem perhaps making the pathogen invisible to the host). The eventual end of this evolutionary path is the pathogen becoming commensal, completely harmless. Tons of viruses end up this way, including Kaposi Sarcoma virus. Eventually, a once-pathogen can actually become symbiotic, helping its host out in life, and benefiting as a result. Consider this the environmentalist bug gameplan.

Which path a host and pathogen take is dependent upon a bit of other environmental factors, and also pure random chance. A typical year’s influenza tends towards plan #2, thanks to antigenic drift. Even within a given family of the viral enzymes, thanks to mutation, the surface proteins of the virus are constantly drifting. For example, the 2007-2008 and 2006-2007 flu seaons both had H1N1 influenzas in circulation. In a year’s time, the viral proteins had mutated enough to ensure that people infected with the 2006-7 version of H1N1 could be reinfected with the 2007-8 version. The antibodies we developed in the 2006-7 were good enough to slow down the 2007-08 virus, but not stop it entirely. The CD8 cells still needed to be activated, but not as much as they would for a totally new virus. This is the start of a detente, with the full-scale war held back by the similarity between the 2006-7 virus to the 2007-8 H1N1 virus allowing the older antibodies to work a little and hold the infection in check. So long as a given influenza virus has been around humans for a while, it’ll trend to a detente-style interaction with the human host, holding back the carnage.

What makes this new swine H1N1 virus so concerning is that it’s never been seen by humans before. As a result, none of our existing memory B-cells have an antibody that even wings these H1N1 proteins. We cannot hold back the initial infection at all. The initial defense against the virus is completely reliant upon those destructive CD8 T-cells. This can select for viruses employing strategy #1 (all-out battle) this Spring, Summer and Fall until the next flu season starts; this H1N1 might have a detente with swine, but has no such arrangement with the human immune system.

If the CD8 cells get excited enough by the unusually aggressive virus (a cytokine storm), the lungs of the young and healthy get trashed during these early stages of meeting. People in their twenties and thirties will die in numbers not seen during the more typical detente-style human-flu interaction.

We honestly have no clue how this virus will re-emerge in the Fall. It could be just like a regular-old flu, or it could be a monster that has undergone extensive selection for virulence. The furious-paced efforts to develop and manufacture a vaccine are our safety net.

18 comments
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  1. Pesky little bastards! So what does Tamiflu or the other drug do to help us?

  2. H1N1 are very deadly, right now many people are affected around the world, and WHO now has vaccines for that, but takes about weeks to release. TamiFlu might be also helpful. Thanks for this great information.

  3. I am not 100% sure if Tamiflu will help the swine flu. I know that is what they gave my husband when it came back he had the seasonal flu about 2 weeks ago. He took and he is doing much better now. I know that the swine flu is going around and they did test him for that but it came back negative. He is all better now and back to himself again.

  4. Thanks.
    Very good informations.
    Autumn comes and I am not 100% sure if Tamiflu will help with flu.
    I know it because I am doctor.

  5. Influenza is and will be part of this world and our lives. No need to fight it with brute force, you will just make it more resistant. Good article bytheway.

  6. my uncle got stomach ulcers because he took a lot of Aspirin to take care of his high blood pressure.,;,

  7. aspirin is a good anti-inflammatory still in use today. -;,

  8. aspirin is one of the safest anti-inflammatories that you can use for lots of things—

  9. aspirin has been time tested to relieve minor pains and inflammation and it is cheap too ,–

  10. i enjoy your article. great job. keep it simple

  11. very true but every country is the same now.
    it is the need to be payed for the time/ to find a bug.
    in view of the steps to acheive a credited apinion.
    is proveing in play a time delay.
    so then in turn confusing/ then in in turn a look around at the problem oragen/ leeds to more money and use of the machines, that are not going to give the end result as it is a tool/ not the mind.
    so if the medical system is to work then the mind of each doctor /should look at where it comes from as larger the population the more places it could come from/ travel /were will it come from and how would you asume this in this town its not common.
    medical feuld is harder then thinking is there day job a process factury worker from istan bull.
    thay have common problem over there but we do not have it here. also we could be all sick from the release by sadame hussan test to the 16 thousand iran tested in 1991/ max volume of thet of I presume the bug called Jahova. very smart worm. treat as a worm but be care full, if it is and it detects the reversul it will kill the host!

  12. the jahova big has symtoms: bed persperation, adult or children pimple like red mountains/ puss filled then dry lumps. chicken pox/ nuewphonia/ same as q fever symtoms gut pains with persperation, typhoad mental confusion, all brought by the smart little bug.
    commonly contracted by selmanella.
    or intreduced by a infected person by persperation.
    end result un treated death. by suffication/ lungs die off to cause death.
    the persperation is cause by lack of ozygen to the blood.

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