Bobak Seddighzadeh Week 5

Question

The question that my partner and I wanted to tackle for the HIV Evolution project is: what is or are the nucleotide sequences in the env region of the V3 domain that are responsible for the increased genetic diversity, divergence, and rate of CD4 T cell decline amongst rapid, moderate, and non-progressors. The question began with the general desire to know why a disparity exists in the rate of evolution amongst variants.

Prediction

My partner and I predict that the increased rate of CD4 decline, genetic divergence and diversity are directly related to two possible mechanism: A) HIV-1 variants termed rapid progressors selected for a structural mechanism that does not protect the genetic material against mutations as effectively B) or HIV-1 variants termed rapid progressors selected for a mechanism that induces mutations on its own DNA. I also predict that both these mechanism are related to nucleotide differences found in the env region of the V3 domain. As stated in the discussion, Markham concluded in his discussion that "higher levels of both genetic diversity and divergence in the HIV-1 variants present in a given individual were associated with a greater decline in CD4 T cells" (Markham et al., 1998). Therefore, we know that CD4 T cell decline is proportional to genetic diversity and divergence. Intuitively what led me to the prediction is genetic diversity and divergence are affected by the rate of mutations. I modeled my prediction after a possible mechanism that would increase the mutation rate of genetic material.

Plan of Attack

To approach this question properly, we need a set of data from subjects, visits, and clones in the env region of the V3 domain that possesses variable rates of divergence and diversity that can be classified as either a rapid or non progrogressor. For the rapid progressors, we have chosen 10-V4, 10-V5, 10-V6, 4-V5, 4-V6, 4-V7, 11-V7, 11-V8, 11-V9. Subjects 4, 10, and 11 were chosen because they had the highest rates of annual CD4 T cell decline. Having a high annual rate of CD4 T cell decline which is a potential good lead into specific nucleotide sequences that cause increased rates of diversity and divergence. We chose the visit based upon the biggest drop in T cell counts. For the group of non-progressors, we have chosen 2-V3, 2-V4, 2-V5, 12-V3, 12-V5, 12-V6, 13-V5, 13-V6, 13-V10. These subjects were chosen because they were the only recorded nonprogressors in the experiment. These visits were chosen because they had the highest CD4 T cell count among all visits. These clones will be analyzed for each visit to find a difference in the nucleotide sequence.

Journal Articles

The journals that I will be using to aid me in my research are ranked in order of relevance:

1. Hill MD and Hernández W. Nucleotide and amino acid mutations in human immunodeficiency virus corresponding to CD4+ decline. Arch Virol. 2006 Jun;151(6):1149-58. DOI:10.1007/s00705-005-0693-8 |
2. Bozek K, Thielen A, Sierra S, Kaiser R, and Lengauer T. V3 loop sequence space analysis suggests different evolutionary patterns of CCR5- and CXCR4-tropic HIV. PLoS One. 2009 Oct 9;4(10):e7387. DOI:10.1371/journal.pone.0007387 |
3. Borrego P, Marcelino JM, Rocha C, Doroana M, Antunes F, Maltez F, Gomes P, Novo C, Barroso H, and Taveira N. The role of the humoral immune response in the molecular evolution of the envelope C2, V3 and C3 regions in chronically HIV-2 infected patients. Retrovirology. 2008 Sep 8;5:78. DOI:10.1186/1742-4690-5-78 |
4. Templeton AR, Reichert RA, Weisstein AE, Yu XF, and Markham RB. Selection in context: patterns of natural selection in the glycoprotein 120 region of human immunodeficiency virus 1 within infected individuals. Genetics. 2004 Aug;167(4):1547-61. DOI:10.1534/genetics.103.023945 |

• Electronic Journal

1. Bobak Seddighzadeh Week 2
2. Bobak Seddighzadeh Week 3
3. Bobak Seddighzadeh Week 4
4. Bobak Seddighzadeh Week 5
5. Bobak Seddighzadeh Week 6
6. Bobak Seddighzadeh Week 7
7. Bobak Seddighzadeh Week 8
8. Bobak Seddighzadeh Week 9
9. Bobak Seddighzadeh Week 10
10. Bobak Seddighzadeh Week 11
11. Bobak Seddighzadeh Week 12
12. Bobak Seddighzadeh Week 13

• Shared Journal

1. BIOL398-01/S10:Class Journal Week 2
2. BIOL398-01/S10:Class Journal Week 3
3. BIOL398-01/S10:Class Journal Week 4
4. BIOL398-01/S10:Class Journal Week 5
5. BIOL398-01/S10:Class Journal Week 6
6. BIOL398-01/S10:Class Journal Week 7
7. BIOL398-01/S10:Class Journal Week 8
8. BIOL398-01/S10:Class Journal Week 9
9. BIOL398-01/S10:Class Journal Week 10
10. BIOL398-01/S10:Class Journal Week 11
11. BIOL398-01/S10:Class Journal Week 12
12. BIOL398-01/S10:Class Journal Week 13

• Assignments

1. BIOL398-01/S10:Week 2
2. BIOL398-01/S10:Week 3
3. BIOL398-01/S10:Week 4
4. BIOL398-01/S10:Week 5
5. BIOL398-01/S10:Week 6
6. BIOL398-01/S10:Week 7
7. BIOL398-01/S10:Week 8
8. BIOL398-01/S10:Week 9
9. BIOL398-01/S10:Week 10
10. BIOL398-01/S10:Week 11
11. BIOL398-01/S10:Week 12
12. BIOL398-01/S10:Week 13

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