Influenza continues to occupy our attention at the beginning of the 2011-2012 flu season. While we are awaiting the appearance of our first influenza cases, there has been continued activity across the globe. As I mentioned in a previous post, avian influenza has been smoldering in the East. Now authorities in India have reported a mutant H5N1 strain of influenza has infected chickens in West Bengal. Avian influenza has been contagious for poultry and other birds but rather difficult to transmit from person to person. Given that the human case fatality rate is well over 50%, it is a good thing that the virus is not easier spread amongst humans. Officials in West Bengal have begun culling chickens and destroying eggs in an attempt to abort the continued activity. Avian flu continues to infect birds in Viet Nam and China.
Now for a little biology.
There are 3 types of influenza viruses: A, B, and C. Epidemics are caused by types A and B. Type C viruses usually cause mild respiratory tract infections and not epidemics. Type A influenza viruses are divided into subtypes based on 2 of the surface proteins: the hemaglutinin (H) and neuraminidase (N). There are 16 H subtypes and 9 different N subtypes and the viruses found circulating during the flu season can be described by this system. So, H1N1, indicates subtype 1 H and subtype 1 N proteins whereas H3N2 depicts the subtype 3 H and subtype 2 N protein.
Type A viruses are the ones we worry about the most each year.
Types B and C viruses are not further subtyped.
The 2009 pandemic made popular the designation of influenza viruses, e.g., H1N1, H3N2. The “H” stands for the hemagglutinin and the “N”, neuraminidase, 2 molecules on the surface of the virus that easily mutate and therefore, are responsible for our need for annual immunization for influenza. Major changes in these are called “antigenic shift”, and minor changes are called antigenic drifts. Epidemics and pandemics are caused by viruses that have undergone the major change, the antigenic shift, while, more minor changes in these proteins, i.e., antigenic drift is responsible for more localized outbreaks. The ability of influenza viruses to infect various species of animals, including humans, depends on the specific H and N proteins present on the virus surface. Most bird influenza viruses (avian flu) prefer to infect only birds and find it very difficult to bind to the human respiratory tract, making this virus relatively hard for humans to contract. The one animal though that is a host for both bird and human influenza viruses is the pig. In areas of the world where humans, birds, and pigs are in close proximity to each other, it is easy for the viruses that prefer each of these species to mix together, as will be discussed below.
Here is a link to click on to see a depiction of the surface of the influenza virus:
(I need to figure out how to embed pictures into the blog. My apologies.)
The viral surface has been simplified to show only the H and N proteins. The genetic material consists of 8 strands of RNA. When the virus reproduces, the RNA floats freely in the mammalian host cell. New viruses form a coat (the envelope) around 8 strands of RNA to form new virus particles. You can imagine that if there are 2 different viruses present in the infected animal (or person), the 8 strands of RNA from one virus can mix with the 8 strands from the second virus, giving rise to new viruses containing different numbers of RNA strands from each virus; for example, 1 strand from virus 1 and 7 strands from virus 2; or 5 strands from virus 1 and 3 strands from virus 2. If one of the viruses is the highly lethal but not infectious avian flu (H5N1) and the other is a regular seasonal flu strain that is very contagious but not very lethal (e.g., H3N2), we could see the formation of a very contagious and very lethal new virus with different characteristics of either parent virus.
Now, what do the H and N proteins do? Both of them mediate the attachment of the virus to respiratory tract epithelium. The hemaglutinin binds to sialic acid residues on the lining cells of the respiratory tract. Different animals have different sialic acid configurations on the surfaces of the respiratory tract lining cells. For example, bird and human sialic acids differ in capablility to bind to H proteins on the influenza virus. That is what makes some viruses more easily infect one species of animal than another. The sialic acid in pigs easily binds H subtypes that are present on viruses that are spread both from person to person and from bird to bird. Once in the pig, reassortment of the RNA strands encoding the H proteins from birds and humans, can result in viruses now capable of easily infecting the other species. Thus, when escaping from the pig host, the new influenza virus might now more easily infect humans, yet possess the same virulence of the avian influenza virus. This is how epidemics and pandemics are born.
Neuraminidase, the N protein, cleaves sialic acid residues, thereby releasing the bound virus particle (via the H protein), allowing the virus to penetrate into the host cell. Thus both H and N proteins are responsible for the binding of influenza virus to the host cell, mediating the fusion with the host cell membrane and releasing the virus to the inside of the host cell so that the virus can reproduce.
You can see an animated video of this here: http://www.hhmi.org/biointeractive/animations/subunit/sub_middle_frames.htm
You will need to keep hitting the play button to get through the short video. A Google search of animation of influenza virus reproduction will get you to other animations of this process.
There is much more that is known about the influenza virus. This very, very short primer will make you aware of the significance of H and N proteins in the nomenclature of this pathogen.
Posted by DrSugar on 10/06/2011 at 11:08 AM