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lecture 24.docx

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BIOL 4503

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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 o Lethal strains of HIV become predominant in the host because they enjoy a short-term advantage in survival and reproduction A Correlation between Lethality and Transmission?  Short-sighted evolution is not the only reason HIV infection is fatal o There is evidence that there are rare strains of HIV exist that kill their hosts more slowly than common strains  Important point is that, alterations to HIV’s genome can render the virus less damaging to
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