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Whitney Krueger

Whitney is an infectious disease epidemiologist.

My posts are presented as opinion and commentary and do not represent the views of LabSpaces Productions, LLC, my employer, or my educational institution.

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I just came to this site from  Kyle Lewis Amoeba Awareness Foundation site where I read about Kyle. I am not involved in Science or . . .Read More
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The information that you provided is very interesting. I researched the H5N1 Virus for a research paper that I did and I found that there have been a few cases where people have only came close to . . .Read More
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Sep 28, 2011, 7:39pm
Thursday, April 7, 2011

If I had to pick any one pathogen to call my "favorite", it would be the influenza virus.  In truth, it picked me.  It's a passion of my boss/mentor, so naturally much of my work and study has revolved around various influenza viruses.  Zoonotic influenza research is the primary focus of his applied laboratory in which I work.  Our "niche" is occupational animal exposures as risk factors for zoonotic influenza infections.  From the countless grant proposals, manuscripts, and undergrad lecturing, to a key component of my dissertation, I've developed quite an interest in this virus and even consider it as a career focus after graduating. 

This first post of the blog series will cover the basics of influenza A viruses and their pandemic potential.  Later I'll go into the epidemiology of influenza viruses, but this first post serves as a starting point.  A word of caution: I'm not a virologist, so I've kept things simple.  Now let's jump right in...

Influenza virus basics.  There are three species, or types, of influenza viruses (A, B, and C).  Humans can be infected with all types, but influenza A is the most virulent.  Wild aquatic birds are the natural reservoirs for most influenza A viruses, but through various modes of transmission and evolution, influenza A viruses can also infect domestic birds, and a wide range of mammals, including humans, pigs, horses, dogs, cats, and marine mammals.  Influenza A viruses are further classified by subtype (serotype), which is based on two main surface glycoproteins: hemagglutinin (HA) and neuraminidase (NA).  Sixteen HA and nine NA glycoproteins are recognized.  Subtypes of influenza A currently circulating among people worldwide are H1N1, H1N2, and H3N2 viruses.  Influenza A subtypes are further classified by strain.

What makes influenza so unique? Influenza is an RNA virus.  In general, RNA viruses are more prone to mutations because of the error-prone RNA synthesis (viral RNA polymerases cannot proof-read).  But what makes influenza even more unique is its segmented ribonucleoprotein (RNP), for which influenza A contains 8 gene segments: PB1, PB2, PA, NP, M, NS, HA, and NA. When a virus infects a living cell, the genome is transported into the nucleus were the 8 segments undergo transcription and translation.  The viral proteins then exit the nucleus and reassemble near the cell membrane.  Influenza A's pathogenesis relies on several virus and host characteristics, with a key virulence factor being the HA glycoprotein.  It mediates virus binding to cell receptors and viral RNP introduction into the cell.  HA also elicits host virus-neutralizing antibodies that may prevent infection. 

Credit: CDC

It's all about the Drift and Shift.  Influenza viruses evolve by three distinctive mechanisms. 

Antigenic Drift

Antigenic drift creates new strains within an influenza subtype due to minor, unpredictable point mutations in the genes that produce the HA and NA surface proteins. 

This continual "drifting" is why seasonal flu vaccines must be updated annually.  New strains may not be recognized by our immune systems (from previous infections or vaccines); therefore, we can be infected with multiple strains of the same influenza subtype.  

Experts meet annually to try to predict which strains will cause the majority of the seasonal influenza infections the following year.  Two influenza A viruses and 1 B virus make up the seasonal vaccine.  And yes, it usually is a shot in the dark. Some years they're right, some they are not.  


The other type of genetic change is called antigenic shift, which can occur by two processes.

Antigenic Shift
  1. An abrupt, major change of an influenza virus can lead to direct species-to-species transmission (such as avian-to-pig transmission, or pig-to-human transmission).  This is a notably rare event for any influenza virus. 
  2. Two or more influenza viruses can mix in an intermediate host to create a new influenza subtype (new HA or NA).  For example, a human virus and an avian virus mixing in a pig. Because the genome is segmented, if two  influenza viruses infect the same cell, then each of their 8 segments can intermix during the assembly stage and produce a new progeny virus with components of both parent viruses.  This exchange of genetic material between multiple influenza viruses is called reassortment

In both instances of antigenic shift, people and animals will have no immunity to this new virus. The virus is able to spread rapidly through a community and potentially lead to a pandemic.

Cross-species transmission and the swine "mixing bowl" theory.  It has been suggested that some of influenza's host specificity relies on specific cell receptors in the host's respiratory tract.  (Although, currently this theory is beginning to get debunked, or at least no longer considered the driving factor...but for now, it's the most researched.)  To compare avian, swine, and human influenza viruses:  The HA and NA surface glycoproteins of avian influenza viruses bind to α2,3-linked sialic acid receptors in the host's respiratory tract.  Swine and human influenza viruses bind to α2,6-linked sialic acid receptors in the host.  Generally, birds predominantly express α2,3-linked receptors and humans predominantly express α2,6Gal receptors.  Pigs' respiratory tracts express both α2,3-linked and α2,6-linked receptors. 

Therefore, when considering cross-species transmission, humans are more readily infected with swine influenzas than avian influenzas because the swine viruses also bind to the α2,6-linked receptor.  Human infections with avian influenza, (and avian infections with swine and human influenzas), do still occur but are less common.  Because swine have cell receptors appropriate for both avian and mammalian HA subtypes, they can serve as an effective “mixing bowl” for reassortment of viruses from different species.  Avian and human influenza viruses that co-infect the  same cell in one pig could lead to reassortment of viral genes and potentially novel progeny viruses.

Until recently, the swine “mixing bowl” theory was the central theory regarding the emergence of pandemic strains.  However, beginning in 1997, the increasing number of direct avian-to-human influenza infections reported have shaken that popular theory.  While it is still a valid means in which reassortment can occur, the recent events illustrate that influenza viruses have other means in which to cross the species barrier.  Fortunately, thus far the human infections have been relatively few and incidental compared to large high-pathogenicity avian influenza outbreaks.  

Credit: eMJA. Hampson, 2006 Nov 20;185, Suppl):S39-43.


Influenza's pandemic potential.  Influenza pandemics occur when 1) a novel virus subtype emerges that 2) causes serious illness in humans who have little or no immunity against the virus and 3) spreads easily from person to person.  Often the human immune system is naive and susceptible because the novel viruses present with antigens of animal virus origin. Whereas the pandemics of 1918, 1957, and 1968 had genetic components from avian viruses, pandemic viruses may arise from any number of animal influenza viruses, such as the case with the recent pandemic H1N1 (2009) virus.  This novel H1N1 pandemic virus had a lineage of human, swine, and avian origins. 

What's next.  My next 4 blogs in the series will individually examine the epidemiology of avian, human, swine, and other often neglected influenza viruses (equine, canine, marine mammal, etc).  The last of the series will be a more in depth discussion of influenza virus evolution and its pandemic potential - a look into the past to predict the future.

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Blog Comments

Brian Krueger, PhD
Columbia University Medical Center
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Marine Mammal??  I'm so glad I don't have any dolphins in my fish tank.

Dub C Med School
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Bookmarked, and I'm so pointing people at this post later this year. You do a much better job of explaining pandemic potential in a succinct manner.

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Great post!

27 and a PhD
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Sweet post! Thanks Whitney.

Whitney Krueger
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Thanks guys! Much appreciated! :)

Erika Villanueba

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The information that you provided is very interesting. I researched the H5N1 Virus for a research paper that I did and I found that there have been a few cases where people have only came close to an infected bird and still caught the virus. I also learned that researchers believe that the world is due for a pandemic around the world, and it could be with the bird flu. Do you think this is possible? I thought Doctor's were taking percaution about the flu this year because it is worse today then it has ever been before?  

Whitney Kruegersaid:

Thanks guys! Much appreciated! :)

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