BIOL 1004 Lecture Notes - Macrophage, Memory T Cell, Dendritic Cell

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30 Jan 2013
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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
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