1 / 7

Hypervariability of GP-120 and Disease Progression in HIV-1 Infected Patients.

Hypervariability of GP-120 and Disease Progression in HIV-1 Infected Patients. BioQUEST BEDROCK Workshop, Jackson Laboratory, Bar Harbor, Maine Majid Masso, George Mason University Jon Connolly, Husson College Brad Haskell, Husson College/Eastern Maine Community College

shana
Download Presentation

Hypervariability of GP-120 and Disease Progression in HIV-1 Infected Patients.

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Hypervariability of GP-120 and Disease Progression in HIV-1 Infected Patients. BioQUEST BEDROCK Workshop, Jackson Laboratory, Bar Harbor, Maine Majid Masso, George Mason University Jon Connolly, Husson College Brad Haskell, Husson College/Eastern Maine Community College John Chiment, Cornell University Christopher Easton, Eastern Maine Community College

  2. Introduction • Markham's theory stated that the rate of mutation (generation of new clones) should increase in (or be greater in) those patients who show a rapid decline in CD4+ cells. • The outcome of Markham's theory is that the differences between visit 1 and visit 2 of a patient who shows rapid decline should be less [the clones should be more similar] than between visits 3 and 4 or between 1 and 4. • Patients not in rapid decline would be similar (though variable) at all visits.

  3. Results • However, for patient 3 (a rapid decliner) while visit 3 and 4 are more different than visits 1 and 3. Visits 1 and 4 are less different than visits 1 and 3. This suggests that the differences precede the decline.

  4. Our new theory suggests that as HIV buds from the cells GP120 is displayed on the cell surface. Hypervariability helps the virus hide from antibody producing cells. However, this may carry a cost of triggering T8 NK Cell attack on an infected T4 that displays certain changes in sequence. • This suggests that the precipitous drop in T4 is not due to a direct lethal effect of the HIV virus, but rather of a normal immunologic response to its presence (if detected). • Under this theory, after a patient seroconverts and goes through several rounds of viral replication, several clones will possess T8 detectable mutations. These cells carrying the clones are killed leading to a decline in T4 numbers. Only those clones most like the original infection (that did not trigger T8 attack) survive to reproduce.

  5. Further analysis of patients with severe decline demonstrates that the specific number of unique mutations is not predictive, but that the "direction" of mutation seems to be. • Patient 10 shows a distinct variability in one subset of clones (Figure 4) that correlates to decline in CD4+ cells.

More Related