NDSU researchers aim to understand how a virus inhibits natural cell processes
The work of a team of North Dakota State University researchers, led by Sangita Sinha, NDSU Jordan A. Engberg professor of chemistry and biochemistry, has been featured as a cover story of Volume 62, Issue 20 of Biochemistry (an American Chemical Society publication). The research is funded by Sinha’s recent National Institutes of Health (NIH) R15 award and it investigates how a protein from a specific virus can interfere with a natural cellular cleaning process, which might be a key factor in how the virus can cause diseases like cancer.
The research focuses on the Epstein-Barr virus (EBV), which is a widespread human virus that infects a large portion of the global population. EBV has been associated with various health issues including infectious mononucleosis, multiple sclerosis, and several types of cancers.
The study shows that a specific protein produced by EBV called BHRF1 blocks autophagy, a fundamental natural process that helps cells maintain their health by breaking down damaged organelles and proteins or harmful pathogens that have infected the cell. This helps EBV survive in infected human cells. The study reveals that BHRF1 blocks autophagy by binding to a key protein involved in autophagy called BECN1. Additionally, it describes the structural details of the interaction between BHRF1 and BECN1, explaining how BHRF1 blocks autophagy in cells infected by EBV. The study also demonstrates that it is possible to develop cell-permeable inhibitors that prevent BHRF1 from binding to BECN1 in cells, thereby restoring autophagy to normal levels.
Thus, the study shows an important mechanism by which EBV proteins may manipulate a host cell’s processes which in turn contributes to the development of EBV-associated diseases, and provides detailed information that may guide the development of inhibitors that target these EBV proteins, allowing normal cellular immune defenses to destroy the virus.
Other NDSU researchers that contributed to this study include graduate students Samuel Wyatt, Karen Glover and Srinivasalu Dasanna, undergraduate student Monica Lewison, and Christopher Colbert, professor of chemistry and biochemistry.
"This study is a nice example of the potential applications of basic scientific research to solve real world health problems," commented Sinha.
Colleen Fitzgerald, NDSU vice president for research and creative activity noted the importance of the research to NDSU students. "NIH R15 awards are meant to support meritorious research that exposes students to new areas of research," she said. "Dr. Sinha's work is a great example of how an R15 award can drive new discoveries in a field while incorporating student learning directly in the work."
About Biochemistry
The ACS journal is an international forum for publishing exceptional, rigorous, high-impact research across all of biological chemistry. This broad scope includes studies on the chemical, physical, mechanistic, and/or structural basis of biological or cell function, and encompasses the fields of chemical biology, synthetic biology, disease biology, cell biology, nucleic acid biology, neuroscience, structural biology, and biophysics.