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Resistance is Futile - Or Is It?

The Immunity System and HIV Infection


Annie Prud’homme-Genereux
Continuing Studies and Executive Education
Capilano University


While the majority of people are prone to HIV infection, some individuals remain uninfected despite repeated exposure. This case study is based on the landmark paper by Paxton et al. (1996) that uncovered some of the mechanisms of protection against HIV infection.  Using a progressive disclosure format, students are guided to suggest hypotheses, predict the outcomes of experiments, and compare their predictions with the paper’s results. Developed for a first-year non-majors biology course, the case is appropriate for introducing students to the immune system and the human immunodeficiency virus.


  • Formulate testable hypotheses given preliminary data.
  • Suggest tests to evaluate hypotheses.
  • Predict results of experiments that would confirm each hypothesis.
  • Interpret data and compare to predicted outcomes.
  • Describe cellular and humoral immunity.
  • Draw the HIV virus structure and describe the function of each component.
  • Describe the interaction of the HIV virus with the immune system.
  • Differentiate between resistance and immunity as mechanisms of protection against a foreign particle.
  • Debate the pros and cons of personal knowledge of HIV resistance and immunity.


HIV; human immunodeficiency virus; retrovirus; reverse transcriptase; T cell; immune system; immunity; AIDS; acquired immunodeficiency syndrome; infectious disease; experimental design; data interpretation

Topical Areas

Scientific method, Social issues

Educational Level

Undergraduate lower division



Type / Methods

Interrupted, Journal Article



Subject Headings

Biology (General)  |   Medicine (General)  |   Public Health  |   Cell Biology  |   Molecular Biology  |   Physiology  |   Microbiology  |  

Date Posted


Teaching Notes

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Teaching notes are intended to help teachers select and adopt a case. They typically include a summary of the case, teaching objectives, information about the intended audience, details about how the case may be taught, and a list of references and resources.

Supplemental Materials

The supplemental material below may be used with this case study:

  Click and Learn: Cells of the Immune System hhmi/

Answer Key

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The following video(s) are recommended for use in association with this case study.

  • HIV Life Cycle hhmi/
    A short video clip explaining how HIV infects a cell and replicates itself using reverse transcriptase and the host's cellular machinery. Running time: 4:52 min. Produced by HHMI BioInteractive.


Katayoun Chamany
Natural Sciences and Math
Eugene Lang College, The New School for Liberal Arts
New York, NY
This case is excellent for teaching students how to read and understand data in primary research articles. The approach of the progressive disclosure format emphasizes the epistemology of science and encourages students to consider different hypotheses and to make predictions concerning data that would be consistent with each hypothesis. The worksheet approach of asking students to predict the results in the graphs with respect to amount of virus produced is stellar. No passive learning here! Though the case is designed for non-majors, the biology is rather sophisticated, requiring a fair amount of immunology background to address the different hypotheses for HIV resistance in this context.

Annie Prud'homme Généreux
Life Sciences
Quest University Canada
Squamish, BC V8B 0N8 Canada

The case study "Resistance is Futile" explores the discovery that some people have an apparent resistance to HIV infection. Students are given information about HIV replication and asked to hypothesize about potential mechanisms that could lead to a cell's protection against HIV infection. The mechanism that is explored in the case is a mutation in the protein CCR5, which is used by HIV-1 strains to gain entry into human cells. Without this protein, HIV-1 is unable to attach to cells, thereby protecting the host.

There are, of course, many other mutations that could afford the host some protection. The case alludes to the discovery that some people with repeated low dose exposure to HIV appear to develop immunity, perhaps because they have particularly efficient killer T cells or B cells.

An article published in February 2012 provides yet another possible mechanism of intrinsic HIV-1 resistance. It has been found that the protein SAMHD1 protects macrophages and dendritic cells from HIV-1 infection. The way in which this is achieved is by this protein’s hydrolysis and depletion of the cell's dNTP pool. Without nucleotides, the HIV's reverse transcriptase cannot convert the virus's RNA into DNA, resulting in a failed infection. The concentration of dNTPs in activated CD4 T cells is much higher than in macrophages and dendritic cells, and HIV-1 is therefore not limited for dNTPs in these cells. This is therefore a mechanism of protection that works only in macrophages and dendritic cells. What these findings suggest is a strategy in the development of treatments for HIV-1. Note that HIV-2 strains express a protein which counteracts the activity of SAMHD1 and allows the virus to proliferate in macrophages and dendritic cells.

Instructors using this case might wish to incorporate this recent discovery into the discussion during this case study. It would be a notable addition in Part 1, Question 4, which asks students to hypothesize about the mechanisms that could be used by the cell to resist HIV infection.

A summary of this recent finding is available at the following links:

How a Protein Protects Cells from HIV Infection ( Starve a Virus, Feed a Cure? (

The original article is: Lahouassa H, Daddacha W, Hofmann H, Ayinde D, Logue EC, Dragin L, et al (2012). SAMHD1 restricts the replication of human immunodeficiency virus type 1 by depleting the intracellular pool of deoxynucleoside triphosphates. Nature Immunology [Epub ahead of print] DOI: 10.1038/ni.2236 PMID: 22327569