Do Mutations in the GAG Gene Impact the Ability of HIV-1 to Kill T-Cells?

Overview

Objectives/Goals Human Immunodeficiency Virus (HIV) is the cause of the Acquired Immune Deficiency Syndrome (AIDS). HIV causes disease by killing the T-cells of the host and destroying the host's ability to fight infection. Replication Capactiy (RC) is an approximate measure of the virus' ability to kill T-cells. The purpose of my project is to determine whether or not mutations present in the 3' end of the Gag gene of HIV are reponsible for changes in RC, and may possibly account for differences in the ability of individual viruses to kill T-cells. Methods/Materials Sequenced 12 viruses (plasmid DNA) on an ABI DNA sequencer, that had no drug resistance and had not been sequenced before. In the lab I used primers and a sequencing kit, pipettemen, tubes & 96 well plates. I compared the their Gag sequences with 68 Gag sequences in the database (half had high RC >90th % and low RC <10th %). These sequences were aligned to a reference Gag sequence (NL4-3) to determine if there were mutations present that were responsible for differences in RC in wild-type HIV. Results The amino acid sequences from 80 different patients, 43 with low RC and 37 with high RC, were aligned on Vector NTI and analyzed. I was looking for similar mutations present in one group and not in another. There were slightly more mutations in the low RC viruses than in the high RC viruses, however; there were no obvious mutations that are present in only one of the two groups that would explain the RC differences. Conclusions/Discussion After aligning and comparing the sequences, I concluded that there is no clear evidence that mutations in the 3' region of Gag explain the differences in RC that are seen in wild-type HIV. Other regions of the HIV genome could be responsible for the differences in RC. Another possible explanation is that we do not have a large enough data set to see the differences.

Awards (1)

• Category Award

Competition history

• CSEF 2003 Biochemistry/ Molecular Biology · Entry J0402

Resources

• CSEF project summary ↗

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