Background
The Severe Fever with Thrombocytopenia Syndrome Virus (SFTSV) is a new virus discovered in China in 2009. It is a member of the Bunyaviridae, the biggest known RNA virus family, and its single-stranded negative-sense RNA is separated into three segments: large (L), medium (M), and small (S). The virus spreads mostly through tick bites and can infect animals and people. Following infection, the virus has a 5 to 14-day incubation period and a high morbidity and fatality rate (up to 30%). SFTSV affects the immune system, causing clinical symptoms such as high fever and thrombocytopenia, as well as digestive dysfunction, cardiac damage, multiple organ failure, severe cognitive impairment, and, in severe cases, death.
SFTS virus employs various strategies to evade the immune system, such as infecting monocytes, macrophages, and dendritic cells, leading to their depletion or dysfunction, inhibiting the interferon (IFN) signaling pathway, releasing progeny viruses through autophagy, regulating transcription factors to promote its replication, inducing T cell apoptosis, and inhibiting B cell maturation. Recent studies have increasingly suggested that the envelope glycoprotein Gn of SFTSV may play a critical role in the virus's entry and infection processes. Gn can strongly inhibit the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway-induced antiviral innate immune response, mediating immune evasion by SFTS virus. However, detailed mechanisms still require further evidence. Neutralizing antibodies targeting viral glycoproteins (Gn and Gc) are potential clinical treatments. Attaching a histidine tag [His] to the G2 glycoprotein enables researchers to conveniently purify and detect the protein using nickel affinity chromatography (Ni-NTA) and understand the infection mechanism of the SFTS virus, aiding in the development of specific drugs.
Figure 1. Model of the mechanism by which SFTSV Gn inhibits the cGAS-STING signaling pathway (Source: Jia Y, et al., 2024 )
In recent years, the incidence and fatality rate for SFTS has increased. In 2017, the World Health Organization (WHO) designated SFTS as a priority disease requiring urgent research. The virus's genotype is complex and ever-changing, making study challenging. There are no particular drugs or immunizations available for its therapy. Recently, the transmission cycle of SFTSV, host-specific immune responses, and the creation of successful specialized therapeutics have all been investigated. We hope that the research findings address these urgent challenges.
Alternative Names
Glycoprotein G2 of the SFTS virus
G2 protein of the SFTS virus
SFTS virus G2 protein
Severe Fever with Thrombocytopenia Syndrome Bunyavirus Glycoprotein G2
Severe Fever with Thrombocytopenia Syndrome virus Glycoprotein G2
References
- 1. Jia Y, et al., Interaction between the SFTSV envelope glycoprotein Gn and STING inhibits the formation of the STING-TBK1 complex and suppresses the NF-κB signaling pathway.Journal of Virology 2024; 98:e01815-23.
References
Identification and characterization of three monoclonal antibodies targeting the SFTSV glycoprotein and displaying a broad spectrum recognition of SFTSV-related viruses
PLoS Neglected Tropical Diseases
Authors: Wu, X. Moming, A. Zhang, Y. Wang, Z. Zhang, T. Fu, L. Qian, J. Ni, J. Hu, S. Tang, S. Zheng, X. Wang, H. Shen, S. Deng, F.
Abstract
Severe fever with thrombocytopenia syndrome virus (SFTSV) is a novel tick-borne viral pathogen that causes severe fever with thrombocytopenia syndrome (SFTS). The disease was initially reported in central and eastern China, then later in Japan and South Korea, with a mortality rate of 13–30%. Currently, no vaccines or effective therapeutics are available for SFTS treatment. In this study, three monoclonal antibodies (mAbs) targeting the SFTSV envelope glycoprotein Gn were obtained using the hybridoma technique. Two mAbs recognized linear epitopes and did not neutralize SFTSV, while the mAb 40C10 can effectively neutralized SFTSV of different genotypes and also the SFTSV-related Guertu virus (GTV) and Heartland virus (HRTV) by targeting a spatial epitope of Gn. Additionally, the mAb 40C10 showed therapeutic effect in mice infected with different genotypes of SFTSV strains against death by preventing the development of lesions and by promoting virus clearance in tissues. The therapeutic effect could still be observed in mice infected with SFTSV which were administered with mAb 40C10 after infection even up to 4 days. These findings enhance our understanding of SFTSV immunogenicity and provide valuable information for designing detection methods and strategies targeting SFTSV antigens. The neutralizing mAb 40C10 possesses the potential to be further developed as a therapeutic monoclonal antibody against SFTSV and SFTSV-related viruses.
Immune escape mechanisms of severe fever with thrombocytopenia syndrome virus
Frontiers in Immunology
Authors: Wang, T. Xu, L. Zhu, B. Wang, J. Zheng, X.
Abstract
Severe fever with thrombocytopenia syndrome (SFTS), which is caused by SFTS virus (SFTSV), poses a serious threat to global public health, with high fatalities and an increasing prevalence. As effective therapies and prevention strategies are limited, there is an urgent need to elucidate the pathogenesis of SFTS. SFTSV has evolved several mechanisms to escape from host immunity. In this review, we summarize the mechanisms through which SFTSV escapes host immune responses, including the inhibition of innate immunity and evasion of adaptive immunity. Understanding the pathogenesis of SFTS will aid in the development of new strategies for the treatment of this disease.
COA
Publication 
Loading ......
