Questions – Influenza
Questions 1-6 are based on the Wildlife Research article entitled “Sialic acid profiles in the
respiratory tracts of selected species of raptors: evidence for potential
binding sites for human and avian influenza A viruses” by Han et. al (2011).
- When
the “bird flu” broke out in the early 2000s, it was referred to as
H1N1. In a molecular context, what
does this mean?
The
Influenza A viruses are classfied according to the presence of two kinds of glycoprotein
antigens found on the viral capsid: Hemagglutin (HA) and Neuraminidase (NA)
(McGraw-Hill, 2007) . These two antigens are critical to the variability of new
strains and host immunity. This nomenclature describes the order in which each
varient was found. To this date, sixteen variances of the Hemagglutin antigen
(H1-H16) and nine, Neuraminidase (N1-N9) have been identified. The HA antigen
comprises almost 25% of the virus’ protein and is therefore, the main target of
the antibodies produced in response to infection. Because it is so large, it is
also the cause of variability in the evolution of new strains. It derives its
name from the agglutination reaction that it produces with erythrocytes. The NA
antigen makes up about 5% of viral protein and functions as an enzyme to remove
sialic acid and aids the virus in release from the infected cell. It is
therefore directly related to the infectious ability of the viral strain.
- In
an evolutionary sense, why is it informative to study human influenza and
its implications in birds (or
horses or pigs, etc)?
Because influenza viral strains mutate so rapidly and can
infect a variety of hosts, the infectious, evolutionary path a strain takes can
be an interesting one. Avian species serve as the natural reservoirs for all
identified Influenza A HA and NA strains (Han et al., 2011), while hosts such
as pigs are believed to be “mixing vessels” for influenza strains because they
can be infected by both avian strains as well as mammal strains (Ma, Kahn,
Richt, 2008). In a pig, strains that originate from different hosts can undergo
genetic reassortment to produce a new, possibly more virulent strain. So while
avian strains may not directly infect humans, when such a strain first infects
a pig, it may recombine so that it is able to then infect other mammalian hosts
such as humans. According to Han et al. (2011), this host crossover can be
ecologically and epidemiologically applicable as wild animal, domestic animal,
and human species are increasingly forced to cohabitate in the same areas due to
habitat encroachment.
- Apply
Darwin’s four postulates to within-host influenza anti-viral resistance.
Charles Darwin had
four postulates: 1) there is variation among individuals of the same species;
2) at least some of these variations are hereditary; 3) in every generation,
there are more offspring produced than can survive; and 4) natural selection
operates on populations. The first
postulate says there is variation among individuals and this can be seen in
influenza because there is variation in the different strains of influenza
along with the difference in sialic acid receptors seen in the birds. In the second postulate, it says that at
least some of these variations are hereditary, and this can apply to influenza
because certain strains will continue to be passed from generation to
generation. In the study, it helps
support this postulate because both avian and human influenza virus receptors
were expressed in six different species of raptors. The third postulate states
that in every generation there are more offspring produced than can
survive. This can be applied because
there are some types of influenza that maybe produced that do not survive in a
population. An example of this would be
the reisolation of the avian influenza virus in the pigeon population. The last postulate is Natural Selection
operates on populations. This can be
applied to influenza because in certain species different types of influenza
will not be an affect on the given population.
- On
page 650, the authors assert that “No correlation between phylogeny of
birds and their sialic acid receptor distributions was observed.” Why wouldn’t a phylogeny of this
character reflect the phylogeny of the group? If the authors added more characters to
their dataset, would it be more likely to reflect the true species
phylogeny?
The evolutionary history of the raptors can be attributed to
the selection for or against specific traits throughout the course of the
species’ history. Phylogenetic trees that illustrate this evolutionary history
were based historically upon morphological traits, and only more recently on
DNA genomics and molecular traits. However, the sialic acid receptors to which
the Influenza A virus binds would not follow the phylogenetic history of raptor
species for several reasons. These receptors are found within the epithelial
lining of the respiratory tract of the raptors. It would be difficult to
determine the type of sialic acid receptors found in ancestral species from
fossil evidence, especially since such evidence is sparse, in variable
conditions, and incomplete. Moreover, according to the article, the
distribution of these receptors differs even within species (Han et al., 2011).
As such, the sialic acid profile of an individual raptor could not be
generalized to apply to an entire species. Other contributing factors than
genetics, could contribute to the distribution of these receptors for each
bird.
If the researchers added more characters to determine
phylogeny of the raptors, they would risk trading the more parsimonious
phylogeny for one that is more complex. Phylogeny aims to determine the
simplest explanation as it is considered the most correct.
5. Explain why avian
flu viruses are not directly transmissible from human to human.
According
to Han et al. (2011), a possible reason has to do with the type of receptors
found in the human upper respiratory tract versus the lower respiratory tract
and the type of receptor that the virus binds to in each host (p. 648). Avian
strains usually bind to sialic acid receptors linked to galactose by a2, 3
linkages (SAa2,3-gal)
while human strains usually bind to sialic acid with a2, 6 linkages (SAa2,6-gal). The upper respiratory tract of humans mostly
expresses the SAa2,
6-gal type of receptors which makes it unlikely that the SAaPLP2,3-gal
preferring avian strains can bind to such receptors.
- Why is it important to study protein folding/misfolding in
influenza, even though we know its cause?
In order for the influenza virus to enter into the cell it
must first undergo protein folding.
Hemagglutinin is a viral protein in influenza that controls entry into
the cell. Hemagglutinin interacts with
cell membrane in two specific ways. One
portion of hemagglutinin inserts into the membrane, refolds, and alters its
structure which promotes viral entry.
Another portion of the hemagglutinin protein links the viral and cell
membrane and refolds to bring the two together.
Therefore influenza is using protein folding in order to enter into the
host’s cells and infect them. If the influenza virus is unable to perform this
protein folding then it will not be able to infect the cells. Thus, it is important to examine protein
folding/misfolding in influenza because this can lead to possible new solutions
for hindering the virus from infecting the host.
Sources:
Han
et. al 2011 article:
http://www.publish.csiro.au/paper/WR11003.htm
Ma,
Khan, Richt 2008 article:
McGraw-Hill
Microbiology: http://www.drugswell.com/winow/Medical%20Microbiology/Jawetz/39.htm
Protein Folding Sources:
