How does antiretroviral therapy affect hiv mutation and vice versa
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How Does Antiretroviral Therapy Affect HIV Mutation and Vice Versa?. Arlin Toro Devin Iimoto. Purpose. To use a case or scenario to motivate student learning about topics in biology and biochemistry courses. Courses For Which This is an Appropriate Module.

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How Does Antiretroviral Therapy Affect HIV Mutation and Vice Versa?

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How does antiretroviral therapy affect hiv mutation and vice versa

How Does Antiretroviral Therapy Affect HIV Mutation and Vice Versa?

Arlin Toro

Devin Iimoto


Purpose

Purpose

  • To use a case or scenario to motivate student learning about topics in biology and biochemistry courses


Courses for which this is an appropriate module

Courses For Which This is an Appropriate Module

  • Lower level biology courses such as Introduction to Biology or a Basic Cell Biology course

  • Upper level biology courses such as Biochemistry, Molecular Biology, Microbiology, or Virology


The case

The Case

  • Undergraduate students are shadowing a physician working with HIV infected patients

  • Physician decides to determine the amino acid and nucleotide sequences in HIV-1 protease and reverse transcriptase before prescribing medication


Database for exercise

Database for Exercise

  • The HIV Reverse Transcriptase and Protease Sequence Database

  • Case study used from the database Cabana, Clotet, and Martinez. Emergence and genetic evolution of HIV-1 variants with mutations conferring resistance to multiple reverse transcriptase and protease inhibitors. J. Med. Virol. 59: 480-490 (1999).


Topics for student learning

Topics for Student Learning

  • DNA and protein: structure and function

  • Enzymes

  • Evolution

  • Bioinformatics

  • AIDS – HIV structure and replication and treatments


Learning process

Learning Process

  • Students will be asked the following

    • What do you already know about antiretroviral therapy and HIV mutation?

    • What questions do you have?

    • What do you need to know to understand how antiretroviral therapy and HIV are linked together?


Background information all course levels

Background Information – All course levels

  • General AIDS information

  • HIV structure

  • HIV replication

  • Immune system function


Topics for lower division courses

Topics For Lower Division Courses

  • DNA replication

  • Types of mutations

  • Impacts of those mutations

  • Epidemiology

  • Amino acids nomenclature and structure

  • Dendogram interpretation

  • Biology workbench

    • Clustal W


Exercises for lower division courses

Exercises for Lower Division Courses

  • Questions

  • Are the sequences different?

  • What mutations occurred?

  • How many nucleotides or regions have changed?

  • In mutated regions of the protein/gene, which sequences changed most?

  • Which patient had the greatest number of mutations in the protein/nucleotide sequences over time? What did you observe about the mutation rate in the patient?

  • From what you have learned from your evolution class, how does this evolution rate compare to most organisms?


How does antiretroviral therapy affect hiv mutation and vice versa

  • How many amino acids are different in each sequence?

  • Select a region where you can see a change. Compare the structure of the most frequently mutated amino acid before and after mutation.

  • Based on the side chains of the amino acids, could the substitution lead to a different protein structure? Check on the other amino acids substitutions to address this question.

  • Do you think the mutations in the virus infecting patient “a” are enough to enable viral resistance to the drug that targets the viral protease.


Topics for upper division courses

Topics for Upper Division Courses

  • Michaelis-Menten kinetics

  • Michaelis-Menten inhibitors

  • Enzyme Mechanism

  • HIV-1 protease structure and function


Bioinformatics exercise for upper division courses

Bioinformatics Exercise for Upper Division Courses

  • Questions

    - Is there greater amino acid sequence variation in HIV-1 protease between patients or between time visits for an individual patient?

    - What amino acids are more likely to mutate, and what type of amino acids do they mutate to? What does this tell you about viral mutation and drug resistance?


How does antiretroviral therapy affect hiv mutation and vice versa

- In which protein domains do these mutations cluster? What does that tell you about viral mutation and drug resistance?

- What are some possible structural impacts of these mutations?

- How much uncertainty is there in predicting protein secondary structure from primary structure?


How does antiretroviral therapy affect hiv mutation and vice versa

10 20 30 40 50 60

....:....x....:....x....:....x....:....x....:....x....:....x

PQITLWQRPLVTIRIGGQLKEALLDTGADDTVLEDMDLPGRWKPKMIGGIGRFIKVRQYD Cab-b_1990-05

CCCCCCCEEEEEEEEECCCCCCCCCCCCCCCHHHHCCCCCCCCCCCCCCCCCCCCEHHEC BPS

CCEEEEHHCEEEEEECCCHHHHHHCCCCCCEEHHHHCCCCCCCCCHECCECEEEEEEHEC D_R

CCCCCCCCCEEEEEECCCHHHHHHCCCCCHHHHHHCCCCCCCEEEEECCCCCCEEECCCC DSC

CCCCCCCCCEEEEEECCHHHHHHHHCCCCCEEEECCCCCCCCCCCCEEECCEEEEECCCC GGR

CHHEEHHCCEEEEEHCCCCHHHHHHHCCCCHHHHHHHCCCCCCCCCCCCCEEEEEECCCC GOR

CCCEEECCCCCCEECCCCCHHHHHHCCCCCCCCCCCCCCCCCCCCCCCCCCCCHHHHCCC H_K

CCCCCCCCCCHHHHHHHHHHCCCCCCHHHHHHHHHCCCCCCHHHHHHHHHHHHHHHHCCC K_S

CCCCCCCCCEEEEEECCCHHHHHHCCCCCCCHHHHCCCCCCCCCCCCCCCCCCEEECCCC JOI

70 80 90 100 110 120

....:....x....:....x....:....x....:....x....:....x....:....x

QIPIEICGHKAIGTVLVGPTPINIIGRNLLTQIGCTLNF Cab-b_1990-05

CCCCCCCCCCCEEEEECEEEECCCEEEECCEEEEECCCC BPS

CECEEEECCCHEEEEEECCCCEEEECECHEEEEEEEECC D_R

CCEEEEECCCCCEEEEECCCCCEEECCCCCCCCCCCCCC DSC

EECEEECCCCCCEEEECCCCCCEEECCEEEEEECCEEEC GGR

CCCHEEECCCCCEEEEECCCCCEEEECEEEECEEEEECC GOR

CCCCCCCCCCCCEEEECCCCCCCEECCCCCCCCCCCCCC H_K

CHHHHHHHHHHHHHHHHHCCCCHHHHHHHHHHHHHCCCC K_S

CCCCEECCCCCCEEEECCCCCCEEECCCCCECECCCCCC JOI


Future directions

Future directions

  • EVOLVE

    • Model the mutation rate

  • STELLA

    • Enzyme kinetics

    • HIV Prevalence rates

  • EPIDEMIOLOGY

    • Predictions on spread of HIV


How does antiretroviral therapy affect hiv mutation and vice versa

  • Biology Workbench Programs

    • TACG

    • Six Frame

  • Traducción de la actividad para estudiantes y facultad de habla hispana


  • Login