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Biology 1001A
Tom Haffie

Lecture 2 1 The general mechanisms by which vaccines protect against diseasesVaccines protect against disease by priming the immune system They introduce a harmless version of the disease into the body that allows the immune system to gain memory of the invader for the next time it encounters the diseaseLater due to priming by the vaccine the immune system is able to respond faster and with more intensity with antibodies to the real damaging form of the disease 2Why developing a vaccine against HIV is relatively challenging compared to other diseasesHIV has a high mutation rate so it changes the markers on its surface too often to develop an effective vaccine Each time the markers change the vaccine is useless and the immune system cant recognize the virus 3 Why people are encouraged to get a flu vaccine each year as opposed to one time onlyEvery year the flu virus mutates so the previous years vaccine is rendered useless by the mutation of the virus Lecture 2 lecture 1 General global distribution of HIV infectionHIV is felt globally a pandemicEvery inhabited continent has been stricken with HIV HIV is felt everywhereIn Canada in the US and in Europe HIV is less commonIn SubSaharan Africa Aids and HIV are an incredibly prevalent disease SubSaharan accounts for about 60 of all people infected with the disease and 90 of children living with the disease 2 General temporal trends in HIV infection ratesOver the last 20 years HIV infection rates have increased but may be reaching a plateauDeaths due to AIDS have been on the decline 3 Factors that explain why no cure or universal vaccine has been developed for HIVAIDSThe virus mutates and changes over timeOur immune defenses are crippled by HIV 4 Reasons why viruses are not considered aliveViruses cant self reproduce they need a host obligate parasitesNo metabolic processes not made up of cellsViruses are not cellular 5 Reasons why antiviral drug therapies often have serious side effectsViruses need a host cell to reproduce and use host cell mechanisms for that purposeSevere side effects because viruses are using the host cell almost every step of the way so there is no way to target the virus without targeting the host cellAntiviral drugs can kill the virus but there will be a lot of collateral damage as well 6 Major steps in life cycle of HIVThe glycoproteins on the surface of HIV mediates attachment to the protein receptors on the host cell and fuses with itThe viruses injects RNA and reverse transcriptase into the host cell which splices its genetic code into the host cells DNA with the help of integraseTranscription of the viral DNA results in the production of RNA which can serve as the genome for new viruses and can be translated to produce viral proteinsComplete HIV particles are assembled and in macrophages HIV buds out without rupturing the cell while in T cells HIV exits by rupturing and killing the cell 7 Specific role of integrase and reverse transcriptase in retroviral life cycleIntegrase splices viral DNA into host DNAReverse transcriptase reverse transcribes the viral RNA into double stranded viral DNA It is highly error prone no proofreading enzymes so it causes a lot of mutations 8 Mechanism of action of AZTAntiretroviral therapies inhibit virusspecific enzymesAZT mimics thymidine and inhibits reverse transcriptase 9 Reasons why effectiveness of AZT decreases over timeAZT resistance began to emerge as the virus evolvedIn a population of viruses some will be more resistant to AZT than othersThe presence of AZT selects for individuals with resistance so over time the population of the viruses becomes primarily populated by resistant individuals as they reproduce successfully in the presence of AZT while the other do notEvolution and natural selection in action 10 Rationale for multidrug drug cocktail approach to treating viral infectionsIf multiple points of HIV action are targeted it is much harder for resistance to evolve11 Principles of evolution of HIV variation heritability differential reproduction change in genotype of populationVariation in a large population of HIV particles some virions will have different mutations than others with mutations occurring at a high frequency This creates a large variability in the genotypes of the HIV particlesHeritability mother virions produce daughter virions that are similar so the mutations in a population are passed on from one generation to the next heritabilityDifferential reproduction selection pressure favours reproduction of some virions over otherChange in genotype of population eventually the susceptible virions die off Only the resistant virions are able to reproduce The population thus changes over time
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