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University of Windsor
Biological Sciences

o Because thousands of generations of HIV replication take place within each patient during the course of an infection, a single strain of HIV can produce hundreds of different reverse transcriptase variants over time  Because of their large numbers, it is a virtual certainty that one or more of these variants contains an amino acid substitution that lessens reverse transcriptase’s affinity for AZT o If the patient takes AZT, replication of unaltered HIV variants is suppressed, but the resistant mutants will still be able to synthesize some DNA and produce new virions o As the resistant virions reproduce and the non-resistant virions fail to propagate, the fraction of the virions in the patient’s body that are resistant to AZT increases over time  Furthermore, each new generation in the viral population is likely to contain virions with additional new mutations  Some of these additional mutations may further enhance the ability of reverse transcriptase to function in the presence of AZT  Because they reproduce faster, the virions that carry these new mutations will also increase in frequency at the expense of their less- resistant contemporaries  Process of change over time in the composition of the viral population is called evolution by natural selection  Changes in the genetic makeup of HIV populations over time have led to increased drug resistance. This is an example of evolution by natural selection.  When AZT therapy has been stopped, proportion of AZT-resistant virions in the viral population has fallen back toward what it was before AZT treatment began.  Back-mutations that restored reverse transcriptase’s amino acid sequence to its original configuration became common because the virons that carried them out-reproduced AZT- resistant forms  The viral strain that increases in frequency is the one that replicates fastest in the current environment o Without AZT present, natural selection favours nonmutant virions; with AZT present, natural selection favours mutant virions o Is evolution by natural selection unidirectional and irreversible? HELL NO!  Heritable traits that lead to survival and reproductive abundance spread in populations; heritable traits that lead to reproductive deficit disappear. This is evolution by natural selection. 1.1-Why is HIV Fatal?  The idea that evolution by natural selection, is an automatic process that simply happens whenever a population shows the necessary heritable variation in survival and reproductive success o Traits conducive to surviving and reproducing spread throughout the population; traits conducive to dying without issue disappear 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
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