Development of Ebola VP30 Transgenic Hamsters to Complement a Biologically Contained Ebolavirus
Abstract
Ebola virus is a very lethal pathogen. What makes Ebola virus even more worrisome is that there are no drugs to treat infection. An important step in finding much needed drugs to treat Ebola virus is testing drugs in animal models. But to be useful, animal models should have similar symptoms of disease as humans infected with Ebola virus. Typically, mice and guinea pigs are often used in testing drugs against Ebola virus, but these animals do not share the same disease symptoms seen in infected humans. Monkeys are also used for testing drugs against Ebola virus because they do have symptoms similar to those seen in infected humans, but monkey studies are expensive for the initial stage of drug testing. Recently, golden Syrian hamsters were identified as an ideal small animal model for Ebola virus infection because they have symptoms similar to infected humans, and they are not cost prohibitive like larger animal models. Because Ebola virus is so deadly, testing of drugs against the virus needs to be performed in specialized labs. Since there are not many of these labs in the world, this is a factor that hurts the identification and testing of therapeutics against Ebola virus. To make the virus safe to study, researchers developed a modified Ebola virus that is missing a critical gene called VP30 in its genome. Without this gene, the virus is dead or inert and can be studied safely outside of specialized labs. The virus can be active again if the VP30 gene is genetically introduced into cells or animals, but once outside of these genetically modified systems, the virus is inert again. Here, we will use an established method to genetically modify golden Syrian hamsters to introduce the Ebola virus VP30 gene into the hamster’s DNA. Then, we will infect these genetically modified hamsters with the inert Ebola virus and see if the virus becomes active again. If these hamsters allow for active virus growth, we will determine if these modified hamsters have disease symptoms similar to humans and monkeys infected with Ebola virus. This proposal addresses the Area of Encouragement that focuses on the “research, development, and validation of animals models for the study of infectious diseases that clearly show the pathophysiological mechanism of the disease and provide translational data to advance drug products to human clinical trial” outlined in the Fiscal Year 2019 Peer Reviewed Medical Research Program Topic Area “Emerging Infectious Diseases.” Ultimately, this new animal model will be a safe way to accelerate the identification of drugs to fight Ebola virus without the initial need of specialized and limited lab space. Some of these drugs may eventually be approved for human use to benefit both U.S. Service members and the general public.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 10, 2021
- Source ID
- W81XWH2010051
Entities
People
- Yoshihiro Kawaoka
Organizations
- United States Army
- University of Wisconsin–Madison