| Start Date: | 11/16/2016 | Start Time: | 9:00 AM |
| End Date: | 11/16/2016 | End Time: | 11:00 AM |
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Event Description
BIOMED PhD Research Proposal
Title:
Mechanisms of Viral Resistance to Macrocyclic Env-targeting HIV-1 Inactivators
Speaker:
Shiyu Zhang, PhD Candidate, School of Biomedical Engineering, Science and Health Systems
Advisors:
Kara Spiller, PhD, Assistant Professor, School of Biomedical Engineering, Science and Health Systems
Irwin Chaiken, PhD, Professor of Biochemistry and Molecular Biology, College of Medicine
Abstract:
Antiretroviral therapy (ART) is a current medical treatment for HIV/AIDS. From monotherapy to highly active antiretroviral therapy (HAART), the treatment for HIV-1 infection is becoming much more effective sby combining different customized HIV-targeting drugs to stop high-rate replication of HIV through inhibiting different viral replication processes. However, HIV gains resistance against inhibitors by acquiring mutations which prevent inhibitory functions of drugs, but still maintains viral normal infection and replication. Considering the high rate of replication of HIV-1 and the replication error in viral genome, a large amount of HIV variants can be generated. Under certain drug pressure, some dormant viral variants become active and increase in number even though they were at a low level previously. During HARRT, the possibility of drug resistance is decreased as it is difficult for HIV to escape from different HIV-targeting drugs. In reality, about 10%-17% of ART-native patients possess at least 1 antiretroviral compound-resistance. 5%-8% transmitted viruses are resistant to more than one class of antiretroviral drugs. Therefore, the world urgently requires an effective treatment regimen for HIV/AIDS.
The unknown viral evolution mechanism of drug resistance remains an obstacle for HIV/AIDS treatment. The Chaiken Lab has discovered a group of HIV-1 entry-targeting inhibitors, cyclic peptide triazoles, that inactivate HIV-1 through the shedding of gp120 that makes up a part of HIV-1 envelope. Further, the sulfhydryl-containing peptide triazole, AAR029c, trigger cell-free virolysis in addition to gp120 shedding compared to that of macrocyclic peptide triazole, AAR029N2. By using escape study, we plan to generate evolved HIV-1 resistant variants against macrocyclic and sulfhydryl-containing peptide triaozles, respectively, to explore the underlying mechanisms of viral escape and inactivation. We also plan to Compare the viral escape patterns against two different types of peptide triazoles to identify the possible mechanism of virolysis. These results would be of help for further design of more potent peptide triazole-based compounds. |
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Location:
Bossone Research Center, Room 709, located at 32nd and Market Streets. |
Audience:
Undergraduate StudentsGraduate StudentsFacultyStaff |
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