Severe fever with thrombocytopenia syndrome (SFTS) is an emerging hemorrhagic fever-like disease caused by SFTS virus, a member of the Phlebovirus genus, Phenuiviridae family, Bunyavirales order.

SFTS was listed as one of the top priority diseases for research and development by World Health Organization due to its high case-fatality rate between 12 and 30%, the lack of specific medical countermeasures, the multiple transmission routes, and the trend of wider distribution.

However, there is currently no vaccine or antiviral available and the viral pathogenesis remains largely unknown.

In a recent study, by cooperation with the research team led by Prof. ZHENG Xin from Tongji Medical College, Huazhong University of Science and Technology, the research groups led by Prof. WANG Hualin, Prof. HU Zhihong and Prof. DENG Fei from Wuhan Institute of Virology of the Chinese Academy of Sciences demonstrated that SFTSV infection results in substantial production of serum interferon-γ (IFN-γ) in patients and then that IFN-γ in turn exhibits a robust anti-SFTSV activity in cultured cells, indicating the potential role of IFN-γ in anti-SFTSV immune responses.

In this study, the scientists are the first to explore the effect of type II IFN, IFN-γ, on SFTSV infection. Firstly, they detected the significant induction of IFN-γ expression in SFTS patient sera, indicating the remarkable host IFN-γ responses. Then, they demonstrated that IFN-γ indeed has the anti-SFTSV efficacy, especially when used before the viral infection establishment. There is currently no specific vaccine or antiviral against SFTSV, while the present study indicates some potential of IFN-γ as a prophylactic drug against the lethal viral infection.

Subsequently, the scientists showed that SFTSV has armed with a complex IFN-γ antagonism capacity. SFTSV can abate IFN-γ signaling through the NSs-STAT1 interaction-mediated sequestration of STAT1 in viral IBs and viral infection-induced down-regulation of STAT1 protein abundance.

These findings complement our knowledge of the interactions between SFTSV and IFN system and present an interesting picture of the virus-host arm race, providing new insights into IFN-γ antiviral biology and SFTSV pathogenesis.

The study was published in Frontiers in Immunology entitled “Interferon-γ-directed Inhibition of a Novel High-pathogenic Phlebovirus and Viral Antagonism of the Antiviral Signaling by Targeting STAT1”.

This work was supported by the National Natural Science Foundation of China, the strategic priority research program of the Chinese Academy of Sciences, the National Key Research and Development Program of China, European Union's Horizon 2020 project European Virus Archive goes global, and the One-Three-Five Research Program of Wuhan Institute of Virology.

Model for the interplays between SFTSV infection and IFN-γ-STAT1 signaling. Image by NING Yunjia