Evasion of the Hosts Immune Response

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Evasion of the Hosts Immune Response

• Melissa Quinn and Jessica Castleberry

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Pathogens and their hosts are in conflict!
PATHOGENS AND THEIR HOSTS ARE IN CONFLICT!
Pathogens are attempting to convert the host
cells into more pathogens Hosts are trying
to kill the pathogens, which requires
the ability to both recognize
and physically destroy the invader.
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Result? The hosts immune system selects for
pathogens that can evade detection!

• Pathogens can evolve quickly, because most have
• Large population size
• Short generation times
• High mutation rates

Fitch and colleagues estimated that flu viruses
evolve a million times faster than mammals, so 5
years for a flu virus is roughly equal to the
time separating humans from chimpanzees.
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1991 - Walter Fitch and colleagues study location
of mutations in flu genome

• Hypothesis- Flu strains with novel antigenic
  sites would enjoy
• selective advantage.
• From 20 years of frozen influenza A samples, they
  constructed a phylogeny based on the molecular
  evolution of hemogglutinin, a coat protein which
  is the primary protein recognized and attacked by
  the hosts immune system.
• They found that
• Flu samples accumulated
• mutations at a steady rate.
• Most were closely related, not diverging
• widely, and many were extinct side branches.

An antigenic site is the specific part of a
protein that the immune system recognizes and
remembers.
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Results They found that in surviving
lineages, there was a much higher mutation rate
in the antigenic sites than in nonantigenic sites,
but in lineages that had gone extinct the
mutation rate for antigenic and nonantigenic
sites were about the same. Amino acid
replacements Surviving Extinct In antigenic
sites 33 31 In nonantigenic sites
10 35 This supported their hypothesis - more
than 75 of the surviving lineages replacements
in the hemagglutinin gene were in
antigenic sites, while fewer than half of the
extinct lineages replacements were in antigenic
sites.
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• In a follow-up study, Fitch and colleagues
  studied the hemagglutinin genes in a different
  group of influenza A strains.
• Overall silent substitutions outnumbered
  replacement
• substitutions (191 to 140), which was consistent
  with neutral theory.
• However, there were 18 codons where there were
  significantly more replacement substitutions,
  ranging from 4 replacement substitutions and 0
  silent substitutions to 20 replacement
  substitutions and 1 silent substitution.
• This was not consistent with the neutral
  theory.
• They found that these 18 codons were all for
  amino acids in theantigenic sites of the
  hemagglutinin protein, and concluded thatthey
  were being selected by the hosts immune system.

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The Origin of Pandemic Flu Strains
A pandemic is an epidemic that covers a wide
geographical areaand affects a large proportion
of the population.
If a flu strain could somehow alter the
structure of itshemagglutinin so that it was
different than any that had ever been seen by any
humans immune system, then it could sweep the
world and potentially infect everyone alive.
Bio
Evo
How could this happen? Should we be worried?
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Yes.
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If two flu strains infect the same host cell
simultaneously,their genomes can recombine,
creating new genecombinations.
Evidence for this was found via phylogenetic
analysis of flu strains. In 1991, Owen Gorman
and colleagues created a phylogeny of influenza
strains based on nucleoprotein genes.
Nucleoproteinsare thought to be the viral
protein most responsible for host specificity,
so they enable the strain to infect particular
species,but also can confine them to only those
species.
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Hemagglutinin and neuraminidaseare coat proteins
which are definedby the hosts ability to
recognizethem.
Gorman and colleagues cladogram (Fig.
13.5) groups flu strains according
tonucleoproteins, and classifies
hemagglutinin and neuraminidase
into groups based on similarity.
Figure 13.3
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They found that in several places, strains that
were found to bevery similar in the
nucleoprotein gene were very different in
thehemagglutinin and/or neuraminides genes. It
is very unlikely that this big jump was caused by
evolution bymutation, and the new genes already
existed in strains that affecteddifferent
animals. This, therefore, is evidence that gene
swapping betweenstrains has occurred.
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Flu strains that infect people and birds can
sometimes moveto pigs, and pig strains can move
back to people. For this reason,researchers
keep close tabs on circulation of strains in all
thesegroups in order to spot possible pandemic
strains in time to geta vaccination available.