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Current status of severe fever with thrombocytopenia syndrome in China (Review)

  • Authors:
    • Hao Sun
    • Quanman Hu
    • Saiwei Lu
    • Yanyan Yang
    • Li Zhang
    • Jinzhao Long
    • Yuefei Jin
    • Haiyan Yang
    • Shuaiyin Chen
    • Guangcai Duan
  • View Affiliations / Copyright

    Affiliations: Department of Epidemiology, College of Public Health, Zhengzhou University, Zhengzhou, Henan 450001, P.R. China, Disease Control and Prevention Center, Xinyang, Henan 463600, P.R. China
    Copyright: © Sun et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 169
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    Published online on: August 18, 2025
       https://doi.org/10.3892/ijmm.2025.5610
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Abstract

Severe fever with thrombocytopenia syndrome (SFTS) is a newly emerging tick‑borne infectious disease caused by the novel Bunyavirus/SFTS virus (SFTSV). The clinical manifestations mainly include fever, thrombocytopenia and multi‑organ dysfunction, with a fatality rate as high as 30%. Since its first report in China in 2009, cases have subsequently emerged in multiple countries across East and Southeast Asia. SFTS demonstrates clear seasonal trends from May to November and tends to cluster geographically, mainly in hilly and mountainous areas. The virus is transmitted through tick bites, animal contact and human‑to‑human transmission. Its genetic diversity and frequent genetic recombination exacerbate public health threats. Pathogenic mechanism studies have shown that SFTSV uses glycoproteins Gn/Gc to mediate host cell invasion. In the early stage, the virus uses its non‑structural protein NSs to inhibit innate immune signal transduction. Massive replication of the virus leads to excessive immune activation, triggering cytokine storms and abnormal platelet activation, and eventually resulting in bleeding and multiple organ failure. The clinical management primarily relies on supportive care, while broad‑spectrum antiviral drugs and neutralizing antibodies remain investigational. Although numerous vaccine candidates have been designed and developed, none have progressed to clinical trials. This review systematically integrates current knowledge spanning virology, epidemiology, pathogenic mechanisms, therapeutic interventions and vaccine development, offering actionable insights for public health strategies and clinical practice.
View Figures

Figure 1

Structure and genome of SFTSV. (A)
SFTSV is a spherical RNA virus, with its surface covered by spikes
composed of Gn and Gc glycoproteins. The virus contains three
single-stranded genomes (L, M and S fragments) inside, which are
wrapped by NPs and form ribonucleoprotein complexes with RdRp. (B)
L fragment (6,368bp): Encodes RdRp. M fragment (3,378 bp): Encodes
glycoproteins Gn and Gc. S fragment (1,174 bp): Encodes the
structural protein NP and the non-structural protein NSs. SFTSV,
severe fever with thrombocytopenia syndrome virus; RdRp, RNA
polymerase; NP, nucleoprotein.

Figure 2

Life cycle of SFTSV. The SFTSV life
cycle starts when viral surface glycoproteins interact with host
cell surface receptors (CCR2, DC-SIGN) and adhesion factors (HS,
NMMHCIIA) to bind to target cells. The virus then enters the cell
via clathrin-mediated endocytosis, forming a coated vesicle that
transports the virus sequentially to Rab5-positive early endosomes
and Rab7-positive late endosomes. As the endosomal pH drops to
~5.6, it triggers a conformational change in the viral surface
glycoproteins. In late endosomes, the Gc glycoprotein undergoes
conformational rearrangement to form a trimeric structure, and its
fusion loop inserts into the host membrane, triggering membrane
fusion and releasing the viral ribonucleoprotein complex RNP into
the cytoplasm. The viral glycoproteins Gn and Gc undergo
N-glycosylation and proper folding mediated by molecular chaperones
(PDI/Bip/CNX) in the endoplasmic reticulum, forming a heterodimer
that is transported to the Golgi apparatus for assembly. The virus
uses the host's endomembrane system to establish replication
complexes, completing genome replication and transcription, and is
finally secreted out of the cell through exocytosis. SFTSV, severe
fever with thrombocytopenia syndrome virus. SFTSV, severe fever
with thrombocytopenia syndrome virus; CCR2, C-C motif chemokine
receptor 2; DC-SIGN, dendritic cell-specific intercellular adhesion
molecule 3-grabbing non-integrin; HS, heparan sulfate; NMMHCIIA,
non-muscle myosin heavy chain IIA; Rab5/7, Ras-related proteins
5/7; Gn/Gc, envelope glycoproteins N and C; RNP, ribonucleoprotein
complex; PDI, protein disulfide isomerase; BiP, binding
immunoglobulin protein; CNX, calnexin.

Figure 3

Innate immune evasion by SFTSV.
During replication and translation, SFTSV's ssRNA, dsRNA and
proteins activate and evade innate immunity through various
pathways. i) Viral RNA is sensed by TLR3 and TLR7, activating
MyD88, TRAF and TRIF. This leads to IRF3, IRF7 and NF-κB
phosphorylation and nuclear translocation, driving IFN and
pro-inflammatory cytokine secretion. ii) Viral RNA is detected by
RIG-I, MDA5 and SAFA, which interact with MAVS to activate TRAF3
and phosphorylate IRF3 and IRF7. However, NSs sequesters MAVS, IRF3
and IRF7 into viral IBs, blocking their activation and suppressing
IFN production. iii) IFNAR on the cell membrane recognizes secreted
IFN, activating the JAK-STAT pathway. This forms ISRE with IRF9 to
induce ISG expression. NSs counteracts this by sequestering STAT1
and STAT2 into IBs, reducing IFN synthesis. iv) BAK/BAX disrupt
mitochondria, releasing oxidized mtDNA. This activates the NLRP3
inflammasome, releasing IL-1β and IL-18, and is sensed by cGAS,
which activates IRF pathways to boost IFN production. v) NSs
interacts with autophagy proteins like mTOR and Beclin1 to promote
viral autophagy. vi) NP inhibits the BECN1-BCL2 interaction,
inducing BECN1-dependent autophagy. Solid arrows indicate
activation, dashed arrows with a line at the end indicate
inhibition and scissors indicate cleavage. SFTSV, severe fever with
thrombocytopenia syndrome virus; IB, inclusion body. SFTSV, severe
fever with thrombocytopenia syndrome virus; ssRNA, single-stranded
RNA; dsRNA, double-stranded RNA; TLR3/7, toll-like receptor 3/7;
MyD88, myeloid differentiation primary response 88; TRAF, TNF
receptor-associated factor; TRIF, TIR-domain-containing
adapter-inducing IFN-β; IRF3/7/9, IFN regulatory factor 3/7/9;
NF-κB, nuclear factor κ-light-chain-enhancer of activated B cells;
IFN, interferon; RIG-I, retinoic acid-inducible gene I; MDA5,
melanoma differentiation-associated protein 5; SAFA, scaffold
attachment factor A; MAVS, mitochondrial antiviral signaling
protein; NSs, nonstructural protein of SFTSV; IB, inclusion body;
IFNAR, IFN-α/β receptor; JAK, Janus kinase; STAT1/2, signal
transducer and activator of transcription 1/2; ISRE, IFN-stimulated
response element; ISG, IFN-stimulated gene; BAK/BAX, Bcl-2
homologous antagonist/killer/Bcl-2-associated X protein; mtDNA,
mitochondrial DNA; NLRP3, NOD-like receptor family pyrin
domain-containing 3; IL-1β/IL-18, interleukin 1β/18; cGAS, cyclic
GMP-AMP synthase; mTOR, mammalian target of rapamycin; BECN1,
Beclin-1; BCL2, B-cell lymphoma 2; NP, nucleoprotein.

Figure 4

Tissue and organ damage caused by
severe fever with thrombocytopenia syndrome virus. The virus enters
the bloodstream, forming viremia. At this point, macrophages and
dendritic cells carry the virus and cytokines into various tissues
and organs, leading to immune cell infiltration and cytokine
storms, which cause damage to these tissues and organs. In the
early stage (<14 days): The virus infects splenic red pulp
macrophages and adheres to platelet surfaces, forming
virus-platelet complexes that trigger macrophage phagocytosis and
clearance, resulting in a decrease in peripheral blood platelets
and leukocytes; compensatory proliferation of megakaryocytes in the
bone marrow occurs. In the later stage (≥14 days): The liver shows
hepatocyte ballooning degeneration and focal necrosis, while the
kidneys exhibit glomerular cell proliferation and Bowman's capsule
congestion. Neurological complications: The virus crosses the
blood-brain barrier, infecting neurons and activating microglia and
reactive astrocytes, releasing pro-inflammatory factors and
inducing neurotoxicity; some damage may be indirectly mediated by
cytokine storms. Created with BioGDP.com.
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Copy and paste a formatted citation
Spandidos Publications style
Sun H, Hu Q, Lu S, Yang Y, Zhang L, Long J, Jin Y, Yang H, Chen S, Duan G, Duan G, et al: Current status of severe fever with thrombocytopenia syndrome in China (Review). Int J Mol Med 56: 169, 2025.
APA
Sun, H., Hu, Q., Lu, S., Yang, Y., Zhang, L., Long, J. ... Duan, G. (2025). Current status of severe fever with thrombocytopenia syndrome in China (Review). International Journal of Molecular Medicine, 56, 169. https://doi.org/10.3892/ijmm.2025.5610
MLA
Sun, H., Hu, Q., Lu, S., Yang, Y., Zhang, L., Long, J., Jin, Y., Yang, H., Chen, S., Duan, G."Current status of severe fever with thrombocytopenia syndrome in China (Review)". International Journal of Molecular Medicine 56.5 (2025): 169.
Chicago
Sun, H., Hu, Q., Lu, S., Yang, Y., Zhang, L., Long, J., Jin, Y., Yang, H., Chen, S., Duan, G."Current status of severe fever with thrombocytopenia syndrome in China (Review)". International Journal of Molecular Medicine 56, no. 5 (2025): 169. https://doi.org/10.3892/ijmm.2025.5610
Copy and paste a formatted citation
x
Spandidos Publications style
Sun H, Hu Q, Lu S, Yang Y, Zhang L, Long J, Jin Y, Yang H, Chen S, Duan G, Duan G, et al: Current status of severe fever with thrombocytopenia syndrome in China (Review). Int J Mol Med 56: 169, 2025.
APA
Sun, H., Hu, Q., Lu, S., Yang, Y., Zhang, L., Long, J. ... Duan, G. (2025). Current status of severe fever with thrombocytopenia syndrome in China (Review). International Journal of Molecular Medicine, 56, 169. https://doi.org/10.3892/ijmm.2025.5610
MLA
Sun, H., Hu, Q., Lu, S., Yang, Y., Zhang, L., Long, J., Jin, Y., Yang, H., Chen, S., Duan, G."Current status of severe fever with thrombocytopenia syndrome in China (Review)". International Journal of Molecular Medicine 56.5 (2025): 169.
Chicago
Sun, H., Hu, Q., Lu, S., Yang, Y., Zhang, L., Long, J., Jin, Y., Yang, H., Chen, S., Duan, G."Current status of severe fever with thrombocytopenia syndrome in China (Review)". International Journal of Molecular Medicine 56, no. 5 (2025): 169. https://doi.org/10.3892/ijmm.2025.5610
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