Master of Science in Biomedical Science
Graduate School of Biomedical Sciences
School of Osteopathic Medicine
Dmitriy Markov, PhD
Committee Member 1
Mikhail Anikin, PhD
Committee Member 2
Sergei Borukhov, PhD
Committee Member 3
Susan Muller-Weeks, PhD
Committee Member 4
Jennifer Fischer, PhD
HIV, Endosomal Sorting Complexes Required for Transport, Viral Proteins, Ribonucleases
Cell Biology | Genetic Processes | Immunopathology | Laboratory and Basic Science Research | Life Sciences | Medical Cell Biology | Medicine and Health Sciences | Molecular Biology | Molecular Genetics | Virus Diseases | Viruses
A virus is only as powerful as its ability to spread. Enveloped retroviruses, namely HIV-1, use exocytosis pathways that normal host cells use to release particles from the plasma membrane. The main pathways of interest in this study are the Endosomal Sorting Complex Required for Transport (ESCRT) and adjacent ALIX pathways. The ESCRT pathway is especially important for degradation of receptor/cargo complexes that form Multi-Vesicular Bodies (MVBs). Currently, there is no known therapy that targets this endosomal pathway, which would prevent the spread of the virus to other cells. The virus has adapted to jump from pathway to pathway when it becomes environmentally favorable.
To begin viral release, the virus aggregates on the cell membrane using the ESCRT complex. The viral protein, NC domain of HIV-1 Gag, binds to Bro1 domain of human ALIX, which is an important component of ESCRT 1 by recruiting ESCRT 3 complexes, which further enhances aggregation and maturation of the virus at the membrane. ALIX is vital for viral maturation and eventual scission from the cell, but the mechanism by which NC and ALIX bind and interact with each other is poorly understood, however previous studies have shown that there is very little protein-protein interaction specifically between NC and ALIX. Previous studies have shown a controversial claim that RNAse treatment significantly inhibits the NC-Bro1 interaction and suggests that a basic patch of ALIX, called the Bro1 domain, stabilizes the NC-ALIX interaction. We look to resolve this controversy by determining whether RNA enhances the NC-ALIX interaction.
Gross, Scott, "Structural and Functional Interactions Between Bro1 Domain of Human ALIX Protein And Nucleocapsid Packaging RNA Complex from HIV" (2015). Graduate School of Biomedical Sciences Theses and Dissertations. 41.
Cell Biology Commons, Genetic Processes Commons, Immunopathology Commons, Laboratory and Basic Science Research Commons, Medical Cell Biology Commons, Molecular Biology Commons, Molecular Genetics Commons, Virus Diseases Commons, Viruses Commons