Post on 03-Jan-2016
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How Does Antiretroviral Therapy How Does Antiretroviral Therapy Affect HIV Mutation and Vice Affect HIV Mutation and Vice
Versa?Versa?
Arlin ToroArlin Toro
Devin IimotoDevin Iimoto
PurposePurpose
To use a case or scenario to motivate To use a case or scenario to motivate student learning about topics in student learning about topics in biology and biochemistry coursesbiology and biochemistry courses
Courses For Which This is an Courses For Which This is an Appropriate ModuleAppropriate Module
Lower level biology courses such as Lower level biology courses such as Introduction to Biology or a Basic Cell Introduction to Biology or a Basic Cell Biology courseBiology course
Upper level biology courses such as Upper level biology courses such as Biochemistry, Molecular Biology, Biochemistry, Molecular Biology, Microbiology, or VirologyMicrobiology, or Virology
The CaseThe Case
Undergraduate students who are Undergraduate students who are shadowing a physician working with shadowing a physician working with HIV infected patientsHIV infected patients
Physician decides to determine the Physician decides to determine the amino acid and nucleotide sequences amino acid and nucleotide sequences in HIV-1 protease and reverse in HIV-1 protease and reverse transcriptase before proscribing transcriptase before proscribing medicationmedication
Database for ExerciseDatabase for ExerciseThe HIV Reverse Transcriptase and The HIV Reverse Transcriptase and Protease Sequence DatabaseProtease Sequence DatabaseCase study used from the databaseCase study used from the database Cabana, Clotet, and Martinez. Cabana, Clotet, and Martinez. Emergence and genetic evolution of Emergence and genetic evolution of HIV-1 variants with mutations HIV-1 variants with mutations conferring resistance to multiple conferring resistance to multiple reverse transcriptase and protease reverse transcriptase and protease inhibitors. J. Med. Virol. 59: 480-490 inhibitors. J. Med. Virol. 59: 480-490 (1999).(1999).
Topics for Student LearningTopics for Student Learning
DNA and protein: structure and DNA and protein: structure and functionfunction
Enzymes Enzymes
EvolutionEvolution
BioinformaticsBioinformatics
AIDS – HIV structure and replication AIDS – HIV structure and replication and treatments and treatments
Learning ProcessLearning Process
Students will be asked the followingStudents will be asked the following– What do you already know about What do you already know about
antiretroviral therapy and HIV mutation?antiretroviral therapy and HIV mutation?– What questions do you have?What questions do you have?– What do you need to know to What do you need to know to
understand how antiretroviral therapy understand how antiretroviral therapy and HIV are linked together?and HIV are linked together?
Background Information – All Background Information – All course levelscourse levels
General AIDS General AIDS informationinformation
HIV structureHIV structure
HIV replicationHIV replication
Immune system Immune system functionfunction
Topics For Lower Division CoursesTopics For Lower Division Courses
DNA replicationDNA replicationTypes of mutationsTypes of mutationsImpacts of those mutationsImpacts of those mutationsEpidemiologyEpidemiologyAmino acids nomenclature and Amino acids nomenclature and structurestructureDendogram interpretationDendogram interpretationBiology workbenchBiology workbench– Clustal WClustal W
Exercises for Lower Division Exercises for Lower Division CoursesCourses
QuestionsQuestionsAre the sequences different?Are the sequences different?What kind of mutations did you think have occurred?What kind of mutations did you think have occurred?How many nucleotides or regions have changed?How many nucleotides or regions have changed?In the regions where you can see changes, based on In the regions where you can see changes, based on the most common nucleotide observed, which of the the most common nucleotide observed, which of the three sequences changes most? Do this is related to three sequences changes most? Do this is related to the time from which the sample was obtained?the time from which the sample was obtained?What did you observe about the mutation rate in HIV in What did you observe about the mutation rate in HIV in this patient?this patient?From what you learn from your evolution class, what From what you learn from your evolution class, what does this rate compare to the evolution rate for most of does this rate compare to the evolution rate for most of organisms?organisms?
How many amino acids would be different How many amino acids would be different in each sequence?in each sequence?Select a region where you can see a Select a region where you can see a change. Compare the structure of the change. Compare the structure of the most frequent amino acid with the one most frequent amino acid with the one that’s different.that’s different.Based on the side chains of the amino Based on the side chains of the amino acids, did the substitution could lead to a acids, did the substitution could lead to a different protein structure? Check on the different protein structure? Check on the other amino acids substitutions to address other amino acids substitutions to address this question.this question.Do you think the mutations in the virus Do you think the mutations in the virus infecting patient a, are enough to enable infecting patient a, are enough to enable virus resistance to the drug that targets virus resistance to the drug that targets the viral protease. the viral protease.
Topics for Upper Division CoursesTopics for Upper Division Courses
Michaelis-Menten Michaelis-Menten kinetics kinetics
Michaelis-Menten Michaelis-Menten inhibitorsinhibitors
Enzyme Enzyme MechanismMechanism
HIV-1 protease HIV-1 protease structure and structure and functionfunction
Bioinformatics Exercise for Upper Bioinformatics Exercise for Upper Division CoursesDivision Courses
Questions Questions
- Is there greater amino acid sequence - Is there greater amino acid sequence variation in HIV-1 protease between variation in HIV-1 protease between patients or between time visits for an patients or between time visits for an individual patient?individual patient?
- What amino acids are more likely to - What amino acids are more likely to mutate, and what type of amino acids do mutate, and what type of amino acids do they mutate to? What does this tell you they mutate to? What does this tell you about viral mutation and drug resistance?about viral mutation and drug resistance?
- In which protein domains do these - In which protein domains do these mutations cluster? What does that mutations cluster? What does that tell you about viral mutation and tell you about viral mutation and drug resistance?drug resistance?
- What are some possible structural - What are some possible structural impacts of these mutations?impacts of these mutations?
- How much uncertainty is there in - How much uncertainty is there in predicting protein secondary predicting protein secondary structure from primary structure?structure from primary structure?
Cab-b_1990-05
10 20 30 40 50 60....:....x....:....x....:....x....:....x....:....x....:....xPQITLWQRPLVTIRIGGQLKEALLDTGADDTVLEDMDLPGRWKPKMIGGIGRFIKVRQYD Cab-b_1990-05CCCCCCCEEEEEEEEECCCCCCCCCCCCCCCHHHHCCCCCCCCCCCCCCCCCCCCEHHEC BPSCCEEEEHHCEEEEEECCCHHHHHHCCCCCCEEHHHHCCCCCCCCCHECCECEEEEEEHEC D_RCCCCCCCCCEEEEEECCCHHHHHHCCCCCHHHHHHCCCCCCCEEEEECCCCCCEEECCCC DSCCCCCCCCCCEEEEEECCHHHHHHHHCCCCCEEEECCCCCCCCCCCCEEECCEEEEECCCC GGRCHHEEHHCCEEEEEHCCCCHHHHHHHCCCCHHHHHHHCCCCCCCCCCCCCEEEEEECCCC GORCCCEEECCCCCCEECCCCCHHHHHHCCCCCCCCCCCCCCCCCCCCCCCCCCCCHHHHCCC H_KCCCCCCCCCCHHHHHHHHHHCCCCCCHHHHHHHHHCCCCCCHHHHHHHHHHHHHHHHCCC K_SCCCCCCCCCEEEEEECCCHHHHHHCCCCCCCHHHHCCCCCCCCCCCCCCCCCCEEECCCC JOI 70 80 90 100 110 120....:....x....:....x....:....x....:....x....:....x....:....xQIPIEICGHKAIGTVLVGPTPINIIGRNLLTQIGCTLNF Cab-b_1990-05CCCCCCCCCCCEEEEECEEEECCCEEEECCEEEEECCCC BPSCECEEEECCCHEEEEEECCCCEEEECECHEEEEEEEECC D_RCCEEEEECCCCCEEEEECCCCCEEECCCCCCCCCCCCCC DSCEECEEECCCCCCEEEECCCCCCEEECCEEEEEECCEEEC GGRCCCHEEECCCCCEEEEECCCCCEEEECEEEECEEEEECC GORCCCCCCCCCCCCEEEECCCCCCCEECCCCCCCCCCCCCC H_KCHHHHHHHHHHHHHHHHHCCCCHHHHHHHHHHHHHCCCC K_SCCCCEECCCCCCEEEECCCCCCEEECCCCCECECCCCCC JOI
Future directionsFuture directions
EVOLVE EVOLVE – model the mutation ratemodel the mutation rate
STELLA STELLA – Enzyme kineticsEnzyme kinetics– HIV Prevalence ratesHIV Prevalence rates
EPIDEMIOLOGY EPIDEMIOLOGY – Predictions on spread of HIVPredictions on spread of HIV
Biology Workbench Programs Biology Workbench Programs – TACGTACG– Six FrameSix Frame
Traducción de la actividad para Traducción de la actividad para estudiantes y facultad hispano estudiantes y facultad hispano parlantesparlantes