BIOL 4503 Lecture Notes - Genetic Drift, Epitope, Cytotoxic T Cell

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2 Feb 2013
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Short-Sighted Evolution
If there is a resistant to HIV and Aids, then we can expect that resistance will spread throughout the
human population as generations pass
Antibodies and killer T cells recognize HIV and HIV-infected cells by binding to epitopes- short pieces of
viral protein displayed on the surface of the virion or the infected cell
o These epitopes are encoded in HIV’s genes
Mutations in the genes can change the epitopes and may enable the mutant virion to evade detection by
the host’s current arsenal of antibodies and killer T cells
As the infection progresses from the acute phase to the chronic phase, the HIV population has already
evolved
Variants easily recognized by the first wave of the immune attack have disappeared; variants less easily
recognized persist
Because the immune system never completely curtails HIV’s replication, the HIV population inside a host
evolves throughout the chronic phase of infection
The evolution of the HIV population appears to contribute to the collapse of the immune system in at
least three ways
o First- it is the continuous evolution toward novel epitopes that enables the viral population to
stay far enough ahead of the immune response to keep replicating in high numbers---these novel
epitopes will enable the viral population to be undetected by the immune cells of the host’s body
Eventually, the continuously replicating viral population burns through the host’s supply
of naive and memory T cells and destroys the body’s ability to replace them
o Second- the viral population within most hosts evolves toward ever more aggressive replication
The longer a patient harbours an HIV population, the more damaging the virions in the
population become
o Third- in at least half of all hosts- and possibly many more- strains of HIV evolve that can infect
naive T cells
An HIV virion’s ability to infect a given cell type is determined by the coreceptor the
virion uses
The coreceptor is the second of two proteins the HIV latches onto to infiltrate a
host cell
Early in most HIV infections, most virions in the HIV population use as their
coreceptor a protein called CCR5
o CCR5 is found on dendritic cells, macrophages, and regulatory, resting,
and effector T cells
As the infection progresses and the HIV populations evolves, virions often
emerge that exploit a different coreceptor, a protein called CXCR4
CXCR4 is found on naive T cells
Because naive T cells are the progenitors of memory and effector T cells, the emergence of virions that
can infect and kill naive T cells is typically bad news for the host
The rapid evolution of the HIV population inside a host hastens the collapse of the host’s immune system.
This evolution is short-sighted because it also hastens the extinction of the HIV population.
The evolution of the HIV population within a host is short-sighted
The virions do not look to the future and anticipate that as their population evolves it will ultimately kill its
host and thereby cause its own extinction
The virions cant look to the future, they are just tiny, thoughtless molecular machines
Evolution by natural selection does not look to the future either
o It can’t; it is just a mathematical process that happens automatically
Therefore, the HIV population in any particular host ultimately evolves itself right out of
existence
HIV infection is fatal, because of the short-sighted evolution of the HIV population inside the host
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