-
Viruses Jun 2021Severe fever with thrombocytopenia syndrome (SFTS) is an acute febrile illness characterized by fever, leukopenia, thrombocytopenia, and gastrointestinal symptoms such... (Review)
Review
Severe fever with thrombocytopenia syndrome (SFTS) is an acute febrile illness characterized by fever, leukopenia, thrombocytopenia, and gastrointestinal symptoms such as diarrhea, nausea, and vomiting resulting from infection with the SFTS virus (SFTSV). The SFTSV is transmitted to humans by tick bites, primarily from , , and . Human-to-human transmission has also been reported. Since the first report of an SFTS patient in China, the number of patients has also been increasing. The mortality rate of patients with SFTS remains high because the disease can quickly lead to death through multiple organ failure. In particular, an average fatality rate of approximately 20% has been reported for SFTS patients, and no treatment strategy has been established. Therefore, effective antiviral agents and vaccines are required. Here, we aim to review the epidemiology, clinical manifestations, laboratory diagnosis, and various specific treatments (i.e., antiviral agents, steroids, intravenous immunoglobulin, and plasma exchange) that have been tested to help to cope with the disease.
Topics: Animals; Antiviral Agents; Humans; Phlebovirus; Severe Fever with Thrombocytopenia Syndrome; Ticks
PubMed: 34201811
DOI: 10.3390/v13071213 -
Nature Microbiology Jan 2023Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne disease caused by a phlebovirus in the Bunyaviridae family. Infection can result in systemic...
Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne disease caused by a phlebovirus in the Bunyaviridae family. Infection can result in systemic inflammatory response syndrome with a high fatality rate, and there are currently no treatments or vaccines available. The microbiota has been implicated in host susceptibility to systemic viral infection and disease outcomes, but whether the gut microbiota is implicated in severe fever with thrombocytopenia syndrome virus (SFTSV) infection is unknown. Here, we analysed faecal and serum samples from patients with SFTS using 16S ribosomal RNA-sequencing and untargeted metabolomics, respectively. We found that the gut commensal Akkermansia muciniphila increased in relative abundance over the course of infection and was reduced in samples from deceased patients. Using germ-free or oral antibiotic-treated mice, we found that A. muciniphila produces the β-carboline alkaloid harmaline, which protects against SFTSV infection by suppressing NF-κB-mediated systemic inflammation. Harmaline indirectly modulated the virus-induced inflammatory response by specifically enhancing bile acid-CoA: amino acid N-acyltransferase expression in hepatic cells to increase conjugated primary bile acids, glycochenodeoxycholic acid and taurochenodeoxycholic acid. These bile acids induced transmembrane G-protein coupled receptor-5-dependent anti-inflammatory responses. These results indicate the probiotic potential of A. muciniphila in mitigating SFTSV infection.
Topics: Animals; Mice; Bunyaviridae Infections; Severe Fever with Thrombocytopenia Syndrome; Harmaline; Phlebovirus; Ticks
PubMed: 36604506
DOI: 10.1038/s41564-022-01279-6 -
Critical Reviews in Microbiology Feb 2021Severe fever with thrombocytopenia syndrome virus (SFTSV) is a novel bunyavirus. Since 2007, SFTS disease has been reported in China with high fatality rate up to 30%,... (Review)
Review
Severe fever with thrombocytopenia syndrome virus (SFTSV) is a novel bunyavirus. Since 2007, SFTS disease has been reported in China with high fatality rate up to 30%, which drew high attention from Centre for Disease Control and Prevention and government. SFTSV is endemic in the centra l and eastern China, Korea and Japan. There also have been similar cases reported in Vietnam. The number of SFTSV infection cases has a steady growth in these years. As SFTSV could transmitted from person to person, it will expose the public to infectious risk. In 2018 annual review of the Blueprint list of priority diseases, World Health Organisation has listed SFTSV infection as prioritised diseases for research and development in emergency contexts. However, the pathogenesis of SFTSV remains largely unclear. Currently, there are no specific therapeutics or vaccines to combat infections of SFTSV. This review discusses recent findings of epidemiology, transmission pathway, pathogenesis and treatments of SFTS disease.
Topics: Animals; Asia; Humans; Phlebovirus; Severe Fever with Thrombocytopenia Syndrome; Virulence
PubMed: 33245676
DOI: 10.1080/1040841X.2020.1847037 -
Frontiers in Immunology 2022Severe 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... (Review)
Review
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.
Topics: Bunyaviridae Infections; Humans; Immunity, Innate; Phlebovirus; Severe Fever with Thrombocytopenia Syndrome
PubMed: 35967309
DOI: 10.3389/fimmu.2022.937684 -
Experimental & Molecular Medicine May 2021An emerging infectious disease first identified in central China in 2009, severe fever with thrombocytopenia syndrome (SFTS) was found to be caused by a novel... (Review)
Review
An emerging infectious disease first identified in central China in 2009, severe fever with thrombocytopenia syndrome (SFTS) was found to be caused by a novel phlebovirus. Since SFTSV was first identified, epidemics have occurred in several East Asian countries. With the escalating incidence of SFTS and the rapid, worldwide spread of SFTSV vector, it is clear this virus has pandemic potential and presents an impending global public health threat. In this review, we concisely summarize the latest findings regarding SFTSV, including vector and virus transmission, genotype diversity and epidemiology, probable pathogenic mechanism, and clinical presentation of human SFTS. Ticks most likely transmit SFTSV to animals including humans; however, human-to-human transmission has been reported. The majority of arbovirus transmission cycle includes vertebrate hosts, and potential reservoirs include a variety of both domestic and wild animals. Reports of the seroprevalence of SFTSV in both wild and domestic animals raises the probability that domestic animals act as amplifying hosts for the virus. Major clinical manifestation of human SFTS infection is high fever, thrombocytopenia, leukocytopenia, gastrointestinal symptoms, and a high case-fatality rate. Several animal models were developed to further understand the pathogenesis of the virus and aid in the discovery of therapeutics and preventive measures.
Topics: Animals; Communicable Disease Control; Communicable Diseases, Emerging; Disease Management; Disease Models, Animal; Disease Susceptibility; Genetic Variation; Host-Pathogen Interactions; Humans; Phlebovirus; Reassortant Viruses; Seroepidemiologic Studies; Severe Fever with Thrombocytopenia Syndrome; Symptom Assessment; Viral Zoonoses
PubMed: 33953322
DOI: 10.1038/s12276-021-00610-1 -
Science Advances Aug 2023Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging tick-borne bunyavirus causing a high fatality rate of up to 30%. To date, the receptor mediating...
Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging tick-borne bunyavirus causing a high fatality rate of up to 30%. To date, the receptor mediating SFTSV entry remained uncharacterized, hindering the understanding of disease pathogenesis. Here, C-C motif chemokine receptor 2 (CCR2) was identified as a host receptor for SFTSV based on a genome-wide CRISPR-Cas9 screen. Knockout of CCR2 substantially reduced viral binding and infection. CCR2 enhanced SFTSV binding through direct binding to SFTSV glycoprotein N (Gn), which is mediated by its N-terminal extracellular domain. Depletion of CCR2 in C57BL/6J mouse model attenuated SFTSV replication and pathogenesis. The peripheral blood primary monocytes from elderly individuals or subjects with underlying diabetes mellitus showed higher CCR2 surface expression and supported stronger binding and replication of SFTSV. Together, these data indicate that CCR2 is a host entry receptor for SFTSV infection and a novel target for developing anti-SFTSV therapeutics.
Topics: Animals; Mice; Mice, Inbred C57BL; Mice, Knockout; Phlebovirus; Severe Fever with Thrombocytopenia Syndrome; Receptors, CCR2
PubMed: 37531422
DOI: 10.1126/sciadv.adg6856 -
International Journal of Molecular... Sep 2022Severe fever with thrombocytopenia syndrome (SFTS) has been acknowledged as an emerging infectious disease that is caused by the SFTS virus (SFTSV). The main clinical... (Review)
Review
Severe fever with thrombocytopenia syndrome (SFTS) has been acknowledged as an emerging infectious disease that is caused by the SFTS virus (SFTSV). The main clinical features of SFTS on presentation include fever, thrombocytopenia, leukocytopenia and gastrointestinal symptoms. The mortality rate is estimated to range between 5‑30% in East Asia. However, SFTSV infection is increasing on an annual basis globally and is becoming a public health problem. The transmission cycle of SFTSV remains poorly understood, which is compounded by the pathogenesis of SFTS not being fully elucidated. Since the mechanism underlying the host immune response towards SFTSV is also unclear, there are no effective vaccines or specific therapeutic agents against SFTS, with supportive care being the only realistic option. Therefore, it is now crucial to understand all aspects of the host‑virus interaction following SFTSV infection, including the antiviral states and viral evasion mechanisms. In the present review, recent research progress into the possible host immune responses against SFTSV was summarized, which may be useful in designing novel therapeutics against SFTS.
Topics: Bunyaviridae Infections; Humans; Phlebovirus; Severe Fever with Thrombocytopenia Syndrome; Thrombocytopenia
PubMed: 35856413
DOI: 10.3892/ijmm.2022.5174 -
Annals of the New York Academy of... Dec 2023Phleboviruses are zoonotic pathogens found in parts of Africa, Asia, Europe, and North America and cause disease symptoms ranging from self-limiting febrile illness to... (Review)
Review
Phleboviruses are zoonotic pathogens found in parts of Africa, Asia, Europe, and North America and cause disease symptoms ranging from self-limiting febrile illness to severe disease, including hemorrhagic diathesis, encephalitis, and ocular pathologies. There are currently no approved preventative vaccines against phlebovirus infection or antivirals for the treatment of the disease. Here, we discuss the roles of neutralizing antibodies in phlebovirus infection, the antigenic targets present on the mature polyproteins Gn and Gc, progress in vaccine development, and the prospects of identifying conserved neutralizing epitopes across multiple phleboviruses. Further research in this area will pave the way for the rational design of pan-phlebovirus vaccines that will protect against both known phleboviruses but also newly emerging phleboviruses that may have pandemic potential.
Topics: Humans; Phlebovirus; Immunity, Humoral; Asia; Vaccines; North America
PubMed: 37936483
DOI: 10.1111/nyas.15080 -
Emerging Microbes & Infections Dec 2022Severe fever with thrombocytopenia syndrome virus (SFTSV), an emerging tick-borne bunyavirus, causes mild-to-moderate infection to critical illness or even death in...
Severe fever with thrombocytopenia syndrome virus (SFTSV), an emerging tick-borne bunyavirus, causes mild-to-moderate infection to critical illness or even death in human patients. The effect of virus variations on virulence and related clinical significance is unclear. We prospectively recruited SFTSV-infected patients in a hotspot region of SFTS endemic in China from 2011 to 2020, sequenced whole genome of SFTSV, and assessed the association of virus genomic variants with clinical data, viremia, and inflammatory response. We identified seven viral clades (I-VII) based on phylogenetic characterization of 805 SFTSV genome sequences. A significantly increased case fatality rate (32.9%) was revealed in one unique clade (IV) that possesses a specific co-mutation pattern, compared to other three common clades (I, 16.7%; II, 13.8%; and III, 11.8%). The phenotype-genotype association (hazard ratios ranged 1.327-2.916) was confirmed by multivariate regression adjusting age, sex, and hospitalization delay. We revealed a pronounced inflammation response featured by more production of CXCL9, IL-10, IL-6, IP-10, M-CSF, and IL-1β, in clade IV, which was also related to severe complications. We observed enhanced cytokine expression from clade IV inoculated PBMCs and infected mice. Moreover, the neutralization activity of convalescent serum from patients infected with one specified clade was remarkably reduced to other viral clades. Together, our findings revealed a significant association between one specific viral clade and SFTS fatality, highlighting the need for molecular surveillance for highly lethal strains in endemic regions and unravelled the importance of evaluating cross-clade effect in development of vaccines and therapeutics.
Topics: Animals; Bunyaviridae Infections; Genomics; Humans; Mice; Phlebovirus; Phylogeny; Severe Fever with Thrombocytopenia Syndrome
PubMed: 35603493
DOI: 10.1080/22221751.2022.2081617 -
Autophagy Jul 2022Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging negatively stranded enveloped RNA bunyavirus that causes SFTS with a high case fatality rate of...
Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging negatively stranded enveloped RNA bunyavirus that causes SFTS with a high case fatality rate of up to 30%. Macroautophagy/autophagy is an evolutionarily conserved process involved in the maintenance of host homeostasis, which exhibits anti-viral or pro-viral responses in reaction to different viral challenges. However, the interaction between the bunyavirus SFTSV and the autophagic process is still largely unclear. By establishing various autophagy-deficient cell lines, we found that SFTSV triggered RB1CC1/FIP200-BECN1-ATG5-dependent classical autophagy flux. SFTSV nucleoprotein induced BECN1-dependent autophagy by disrupting the BECN1-BCL2 association. Importantly, SFTSV utilized autophagy for the viral life cycle, which not only assembled in autophagosomes derived from the ERGIC and Golgi complex, but also utilized autophagic vesicles for exocytosis. Taken together, our results suggest a novel virus-autophagy interaction model in which bunyavirus SFTSV induces classical autophagy flux for viral assembly and egress processes, suggesting that autophagy inhibition may be a novel therapy for treating or releasing SFTS.
Topics: Autophagy; Humans; Orthobunyavirus; Phlebovirus; Severe Fever with Thrombocytopenia Syndrome; Virus Assembly
PubMed: 34747299
DOI: 10.1080/15548627.2021.1994296