J'aime C. Moehlman's Week 6
HIV Research Project
Continued from Week 5
- We ran two multiple sequence alignment (one for each grouping).
- The first group included subjects 10,11 and 15.
- The second group included subjects 6,12 and 13.
- Each of the subjects clones were chosen from visit 4 in order to keep the amount of time passed a constant in our experiment.
- When running the multiple sequence alignments we discovered that the two groups were similar.
- We then tried a clustalW(distance matrix) to see if the differences were significant between the two groups; again the amount difference was not significant enough to prove our hypothesis.
- We decided to approach our hypothesis and question with two experiments: comparing the similarities of each group, and the second was to compare the differences from each group(the minimum and maximums).
Env Gene Article
Adaptation in the env Gene of HIV-1 and Evolutionary Theories of Disease Progression - S. Williamson
- HIV symptoms- after initial infection, long period of no symptoms follows during which CD4 T-cells decline.
- After the immune system can't contain viral replication, HIV progresses to AIDS.
- Many hypotheses suggest adaptation leads to pathogenicity.
- Characterizing rate and pattern of adaptation, removing misleading neutral mutations.
- "Env" gene codes for envelope glycoprotein gp160, which is precursor for gp41 and gp120.
- Focuses on region of "env" that gives rise to gp120--embedded in lipid membrane, responsible for host cell receptor binding site; divided into 5 regions (V1-V5).
- Contains sites for antibodies, and two T lymphocytes.
- V1-V2 region has highest adaptation rates- once every 2.5 months- but are only from perinatally infected children.
- V3 region- one adaptive event per 5.9 months.
- V4-V5- every 12.2 months.
- Adaptive event occurs every 45 days in whole gene.
- Generation time of HIV-1: 1.2-2.6 days.
- Therefore, 1 adaptive event every 25 generations-- fastest rate in single protein-coding gene.
- Slow progressors= progression time to AIDS over 7 years; Moderate progressors= between 5-7 years
- Adaptive events in slow progressors significantly higher than moderate.
- Viral adaptation in C2-V5 region is related to disease duration.