Christopher Basler, Ph.D.
Georgia State University
Chris Basler is a leading expert in emerging viruses, particularly the Ebola virus. Basler’s lab has discovered crucial information about how the Ebola virus evades and manipulates the immune system. The Basler team is using this knowledge to develop drugs that could treat Ebola and viruses like it.
Basler came to Georgia in early 2016 from the Icahn School of Medicine at Mount Sinai in New York to join Georgia State’s Institute for Biomedical Sciences, where he is founding director of the Center for Microbial Pathogenesis. He arrived having secured $20 million in federal grants to advance his work through 2019.
Ebola and similar filoviruses such as Marburg virus are rated by the National Institute of Allergy and Infectious Diseases as Category A priority pathogens because of their high rates of transmission and fatality. These deadly filoviruses are also a concern as potential weapons of bioterrorism.
No approved vaccines or antiviral drugs exist for Ebola and other filoviruses. Physicians can only manage Ebola’s symptoms by providing intravenous fluids, oxygen and blood transfusions, which may allow the patient to recover. But Basler and his lab have made a string of discoveries about how filoviruses evade innate immune defenses, an ability that makes the diseases so deadly. He and his team are now searching for drug compounds to target these mechanisms, potentially offering an effective treatment for Ebola.
In healthy immune response, when a virus invades a cell, the infected cell produces interferons that signal the surrounding cells to develop resistance. Basler and his colleagues discovered that the Ebola virus includes a protein called VP35, which blocks the ability of the virus-infected cell to produce interferons. With VP35 blocking the way, the infected cell can’t send out signals to protect nearby cells.
Basler’s team also discovered another Ebola virus protein that works in tandem with VP35. While VP35 prevents a cell from producing interferons, its sidekick VP24 prevents neighboring cells from responding to interferons. Any interferons that manage to sneak past VP35 are neutralized by VP24.
In further studies on VP35, Basler and his team have discovered they can modify the protein to remove its interferon-blocking function. Working with collaborators, they’ve tested this modified version of the virus in animal models and shown it to be less virulent and less lethal. This finding supports Basler’s idea that a drug compound that inhibits VP35 could treat Ebola.
Basler’s team developed a way to model Ebola’s viral replication machinery in a petri dish, allowing the researchers to conduct high-throughput screening on thousands of potential drug compounds to measure the drugs’ effect. Through these tests, Basler’s team has identified a handful of drug compounds that seem to inhibit the VP35 protein. They’ll focus on these compounds in future studies.
Basler is also investigating how filoviruses affect bats, which battle the disease better than humans or other primates. Because the Ebola virus tends to kill people quickly, humans are not the most effective hosts. Some evidence suggests bats are long-term reservoirs for Ebola, Marburg and other filoviruses, and are typically the cause of new outbreaks. Understanding how bats’ immune systems fight Ebola might lead to another treatment for humans.
Because Ebola and Marburg are such dangerous pathogens, only about a dozen labs across the U.S. are approved to work with live samples of the virus. These labs are rated Biosafety Level 4, and they maintain the strictest level of safety precautions, such as protective suits, required decontamination showers when exiting and entrances with airlocks.
Georgia State is home to one of the few BSL-4 labs in the U.S., providing Basler’s team the safe and secure facilities needed to continue their work. Before the move to Georgia State, Basler and his team were confined to working with viral proteins or other non-active fragments of the virus, or relying on collaborators with access to BSL-4 laboratories. Now, they can expand their capabilities and begin a more intensive phase of research as they continue to develop potential treatments for Ebola and other deadly filoviruses.
- Immune evasion and replication mechanisms of filoviruses and other RNA viruses
- Identification of Ebola virus and Marburg virus interferon antagonist proteins
- Filovirus-bat interactions, including innate immune responses
- Pandemic influenza viruses, especially the 1918 flu pandemic
“Along with the advantage of the BSL-4 lab, Georgia State’s Institute of Biomedical Sciences has two areas of expertise that are particularly appealing for me and my colleagues. Lots of researchers here are experts in inflammatory responses, which is important because Ebola is deadly due to the uncontrolled inflammation it causes. There are also a lot of people here who are developing antiviral drugs, which is synergistic with the therapeutics aspect of our research.”