By: Ada Chong
September 2023
Greg Melikian is a biophysicist by training and studied the lipid membrane fusion during his PhD. After his PhD, he fell in love with studying viruses and has been focusing on it ever since. His research interests extend to several enveloped viruses including HIV, arenaviruses and SARS-CoV-2. Dr. Melikian investigates the mechanistic aspects of virus entry into host cells. Dr. Melikian and his team are looking for answers to the following questions: “How do these enveloped viruses attach and fuse with target cells, releasing their genetic material into the cytoplasm and initiate infection? What host factors are involved in promoting virus entry into cells and, ultimately, productive infection?” Dr. Melikian also hopes to further his knowledge in understanding proteins, processes and interactions that are parts of the host innate responses that prevent viral infections. He hopes to learn how these factors/processes can prevent viral fusion and thereby block infection.
Dr. Melikian’s research involves generating viruses from DNA clones in cell culture instead of patients. The techniques used in Dr. Melikian’s research include advanced microscopy applications. Dr. Melikian’s team labels the viruses, so individual viral particles can be visualized and tracked in real time as they enter the cell. This allows him to identify rare productive viral fusion events that culminates in infection. The application of correlative fluorescence-electron microcopy techniques provides important ultrastructural insights into virus entry, cellular structures supporting this process, and the mechanisms of virus restriction by host factors.
Broadly stated, the top goals for his research include understanding early pathogen-host cell interactions and learning about critical downstream processes after viruses attach to cells. Where in the cell does the virus entry occur and what host factors are required for infection? How does the virus hijack the cell’s machinery? On the HIV side, he hopes to figure out the mechanisms of virus import to the nucleus, capsid uncoating and sites of integration into the host genome. Dr. Melikian says it’s important to get a bigger picture of virus-host interaction network and how viruses evolve to coopt cellular factors and processes to ensure efficient infection.