Career Development and Training Program
Individual Project CD006
Collaborating Institution: University of Texas Medical Branch (UTMB), Galveston, TX
Principal Investigator: Patricia Aguilar, PhD
Title of the Project: Evasion of Host Innate Immunity by Severe Fever with Thrombocytopenia Syndrome Virus
- Xuejie Yu, MD, PhD – UTMB, Galveston, TX
- Robert Tesh, MD – UTMB, Galveston, TX
- Adolfo Garcia-Sastre, PhD – Mount Sinai School of Medicine, New York, NY
- Shinji Makino, DVM, PhD – UTMB, Galveston, TX
Expected Product: This study aims to provide critical information that can be used to develop a reverse genetic system that could aid in the development of live-attenuated vaccines for SFTSV.
Description: Interferons (IFNs) have long been recognized as essential components of the innate immune response to viral infection, and therefore many pathogens have developed strategies to interrupt the IFN response by blocking production of IFN or blocking IFN signaling. Importantly, studies with positive- and negative-strand RNA viruses have shown that abrogation of the IFN response attenuates viruses, suggesting that evasion of the interferon response is an important event for viral pathogenesis. These studies have opened new avenues for the development and optimization of live-attenuated vaccines.
The novel bunyavirus, severe fever with thrombocytopenia syndrome virus (SFTSV), was recently isolated from patients presenting with fever, thrombocytopenia and hemorrhagic manifestations. An initial case-fatality rate of 12-30% has been reported and evidence of person-to-person transmission has also been recently documented. The exact mechanism by which this virus causes disease is still unknown. We have identified two viral proteins with the ability to block IFN responses. This proposal is intended to further elucidate the role of these viral proteins in the evasion of host responses by SFTSV and determine their contribution to viral pathogenesis.