Service Learning Questions

HIV Questions – Jess, Aimee, and Phil

Questions 1-5 are based on the BMJ paper entitled “Molecular Investigation into Outbreak of HIV in a Scottish Prison” by Yirrell et al.
Note: Maximum likelihood methods reconstruct phylogenies based on the probability that a specific tree best describes the data.


1) Why is the elevated mutation rate in HIV a positive aspect for this phylogenetic study?

The elevated mutation rate in HIV was a positive aspect for this phylogenetic study because it allowed the researchers to determine the relationship between the men infected with HIV and the likely source of the infection. Each mutated strain is genetically different, so the quick rate of mutation allows for a fairly accurate determination of a source. Because 13 out of 14 men had the same evolved strain, it was possible to link these men to a single source.

2) What do env, pol and gag code for in HIV? Why do they differ in their mutation rates? Why, then, did this study choose to sequence gag and env?

The env gene codes for the viral envelope proteins. The pol gene codes for viral enzymes. The gag gene codes for the capsid and the matrix of the virus. They differ in mutation rates because of what they code for. The env gene mutates rapidly because it codes for a susceptible area of the virus that develps first. The pol gene is relatively protected because it codes for the enzymes inside the viral cell. This study chose to sequence the gag and env genes because it is easier to determine similarities between the gag and env gene mutations than in the pol gene mutations. The pol gene is conserved and therefore can be very similar between a wide variety of HIV strains. The env and gag genes will demonstrate more of the differences between strains than the pol genes. The mutation rates of these genes also directly affects the success of treatment. For example, some treatments have targeted the surface proteins of the virus. This treatment is effective in a strain until its gene that codes for the surface protein mutates and then it will not work. In certain cases, this period of time could be as long as many years of effective treatment to only a few weeks.

3) How can you tell, by looking at the phylogenetic trees, that there is a single source of infection for the Glenochil cohort? Could you accurately describe the HIV genes in these prisoners as orthologous? Why or why not?

All of the cohort branches stem from a single node, which suggests that the Glenochil cohort was infected by a single source. No, the HIV genes in the prisoners could not be accurately identified as orthologous because the phylogeny is the best hypothesis of the connection between the prisoners. It is not the definite answer and the genes are always mutating. So the correlation found between the genes in the prisoners is based on close similarities, not exact replications. Also, they are only testing certain sections of the genes, not the entire virus itself. So the different sections can be the same, but the entire chromosomes could have differences.

4) Why was it important to include unrelated HIV strains in this phylogenetic analysis?

It was important to include unrelated HIV strains in the phylogenetic analysis to demonstrate that the results from the prison were not coincidental. It also shows how the unrelated strains are still related in some basic ways to the strain in the prisoners.

5) This paper is over 10 years old. Have there been other measures taken (besides those listed) to reduce the spread of HIV in prisons? At blood centers like the one your interview described?

Some preventative measures being taken include HIV/AIDS education for the prisoners, providing them with bleach and clean needles and syringes, giving them access to drug treatment programs, and providing them with condoms. Blood banks often ban gay men from donating blood. They thoroughly screen possible donors and they test the blood they receive before it goes to another individual.

6) On the next page you will find a figure from Science entitled “Application and Accuracy of Molecular Phylogenies” (Hillis et al. 1994; Vol. 264: 671-677). In the study referenced, the authors considered the allegations of 7 patients (A-G) that they had contracted HIV from their dentist. Were their allegations correct? Describe how the authors might have generated this tree.

According to the tree, 5 out of seven of the patients contracted HIV from their dentist. Patients D and F did not contract HIV from the dentist. It seems that the authors generated this tree by starting with the dental clade, which they knew was a monophyletic group, and working their way out to the HIVELI strain. They had performed the tests on the areas of the x and y strains to determine whether or not the patients were connected to the dentist's strain, and this provided them with the information necessary to construct the dental clade. From there, they compared the similarities, or lack of, until they ended up with the HIVELI strain.

Resources:

http://www.stanford.edu/group/nolan/tutorials/ret_6_gpedesc.html