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Scientific Reports Jun 2024Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging tick-borne virus with a mortality rate of up to 30%. First identified in China in 2009, it was...
Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging tick-borne virus with a mortality rate of up to 30%. First identified in China in 2009, it was later reported in other Asian countries, including Thailand in 2020. SFTSV has been detected in several tick species, including Rhipicephalus sanguineus, known for infesting dogs. We conducted a seroprevalence study of SFTSV in Bangkok and Nong Khai, Thailand, by analyzing 1162 human samples collected between 2019 and 2023. The testing method relied on IgG detection using ELISA and confirmed though a virus seroneutralization test. The results indicated that out of the participants, 12 (1.1%) tested positive for anti-SFTSV IgG antibodies; however, none exhibited positive results in the seroneutralization assay. Additionally, molecular detection of SFTSV, Crimean-Congo hemorrhagic fever (CCHF), Coxiella spp., Bartonella spp., and Rickettsia spp. was performed on 433 Rh. sanguineus ticks collected from 49 dogs in 2023 in Chachoengsao Province, Thailand. No evidence of these pathogens was found in ticks. These findings highlight the importance of exploring viral cross-reactivity. Furthermore, it is important to conduct additional studies to isolate SFTSV from animals and ticks in order to identify the potential transmission routes contributing to human and animal infections in Thailand.
Topics: Animals; Thailand; Seroepidemiologic Studies; Rhipicephalus sanguineus; Humans; Phlebovirus; Middle Aged; Female; Male; Adult; Severe Fever with Thrombocytopenia Syndrome; Dogs; Aged; Adolescent; Antibodies, Viral; Young Adult; Child; Child, Preschool; Aged, 80 and over; Infant; Immunoglobulin G
PubMed: 38862576
DOI: 10.1038/s41598-024-64242-x -
Applied Microbiology and Biotechnology Apr 2024Severe fever with thrombocytopenia syndrome virus (SFTSV) causes the highly fatal disease in humans. To facilitate diagnosis, the native form of subunit glycoprotein...
Severe fever with thrombocytopenia syndrome virus (SFTSV) causes the highly fatal disease in humans. To facilitate diagnosis, the native form of subunit glycoprotein (Gn), a prime target for potential vaccines and therapies, was produced in Nicotiana benthamiana using a Bamboo mosaic virus-based vector system. By fusion with secretory signal tags, SS, derived from the extension protein, and the (SP) motif, the yield of the recombinant Gn (rGn) was remarkably increased to approximately 7 mg/kg infiltrated leaves. Ultimately, an rGn-based ELISA was successfully established for the detection of SFTSV-specific antibodies in serum samples from naturally infected monkeys. As validated with the reference method, the specificity and sensitivity of rGn-ELISA were 94% and 96%, respectively. In conclusion, utilizing well-suited fusion tags facilitates rGn production and purification in substantial quantities while preserving its antigenic properties. The rGn-ELISA, characterized by its commendable sensitivity and specificity could serve as a viable alternative diagnostic method for assessing SFTSV seroprevalence. KEY POINTS: • SFTSV Gn, fused with secretory signal tags, was expressed by the BaMV-based vector. • The plant fusion tags increased expression levels and eased the purification of rGn. • The rGn-ELISA was established and validated; its specificity and sensitivity > 94%.
Topics: Humans; Severe Fever with Thrombocytopenia Syndrome; Phlebovirus; Seroepidemiologic Studies; Glycoproteins; Antibodies
PubMed: 38639795
DOI: 10.1007/s00253-024-13135-0 -
Viruses Oct 2023Rift Valley fever virus (RVFV) is considered to be a high biodefense priority based on its threat to livestock and its ability to cause human hemorrhagic fever....
Rift Valley fever virus (RVFV) is considered to be a high biodefense priority based on its threat to livestock and its ability to cause human hemorrhagic fever. RVFV-infected livestock are also a significant risk factor for human infection by direct contact with contaminated blood, tissues, and aborted fetal materials. Therefore, livestock vaccination in the affected regions has the direct dual benefit and one-health approach of protecting the lives of millions of animals and eliminating the risk of severe and sometimes lethal human Rift Valley fever (RVF) disease. Recently, we have developed a bovine herpesvirus type 1 (BoHV-1) quadruple gene mutant virus (BoHV-1qmv) vector that lacks virulence and immunosuppressive properties due to the deletion of envelope proteins UL49.5, glycoprotein G (gG), gE cytoplasmic tail, and US9 coding sequences. In the current study, we engineered the BoHV-1qmv further by incorporating a chimeric gene sequence to express a proteolytically cleavable polyprotein: RVFV envelope proteins Gn ectodomain sequence fused with bovine granulocyte-macrophage colony-stimulating factor (GMCSF) and Gc, resulting in a live BoHV-1qmv-vectored subunit vaccine against RVFV for livestock. In vitro, the resulting recombinant virus, BoHV-1qmv Sub-RVFV, was replicated in cell culture with high titers. The chimeric Gn-GMCSF and Gc proteins expressed by the vaccine virus formed the Gn-Gc complex. In calves, the BoHV-1qmv Sub-RVFV vaccination was safe and induced moderate levels of the RVFV vaccine strain, MP12-specific neutralizing antibody titers. Additionally, the peripheral blood mononuclear cells from the vaccinated calves had six-fold increased levels of interferon-gamma transcription compared with that of the BoHV-1qmv (vector)-vaccinated calves when stimulated with heat-inactivated MP12 antigen in vitro. Based on these findings, we believe that a single dose of BoHV-1qmv Sub-RVFV vaccine generated a protective RVFV-MP12-specific humoral and cellular immune response. Therefore, the BoHV-1qmv sub-RVFV can potentially be a protective subunit vaccine for cattle against RVFV.
Topics: Animals; Cattle; Humans; Rift Valley fever virus; Rift Valley Fever; Antibodies, Neutralizing; Antibodies, Viral; Leukocytes, Mononuclear; Viral Vaccines; Immunity, Cellular; Vaccines, Attenuated; Vaccines, Subunit
PubMed: 38005861
DOI: 10.3390/v15112183 -
Virologica Sinica Oct 2023• Hedgehogs and ticks can maintain the natural circulation of SFTSV in the city ecosystem. • Hedgehogs and ticks are becoming common in Beijing. •...
• Hedgehogs and ticks can maintain the natural circulation of SFTSV in the city ecosystem. • Hedgehogs and ticks are becoming common in Beijing. • Parthenogenetic ticks are discovered in Beijing.
Topics: Animals; Humans; Ticks; Severe Fever with Thrombocytopenia Syndrome; Ecosystem; Phlebovirus; China; Bunyaviridae Infections
PubMed: 37634660
DOI: 10.1016/j.virs.2023.08.004 -
Microbiology Spectrum Jun 2024Cyclic GMP-AMP synthase (cGAS) is an important DNA pattern recognition receptor that senses double-stranded DNA derived from invading pathogens or self DNA in cytoplasm,...
UNLABELLED
Cyclic GMP-AMP synthase (cGAS) is an important DNA pattern recognition receptor that senses double-stranded DNA derived from invading pathogens or self DNA in cytoplasm, leading to an antiviral interferon response. A tick-borne Bunyavirus, severe fever with thrombocytopenia syndrome virus (SFTSV), is an RNA virus that causes a severe emerging viral hemorrhagic fever in Asia with a high case fatality rate of up to 30%. However, it is unclear whether cGAS interacts with SFTSV infection. In this study, we found that SFTSV infection upregulated cGAS RNA transcription and protein expression, indicating that cGAS is an important innate immune response against SFTSV infection. The mechanism of cGAS recognizing SFTSV is by cGAS interacting with misplaced mitochondrial DNA in the cytoplasm. Depletion of mitochondrial DNA significantly inhibited cGAS activation under SFTSV infection. Strikingly, we found that SFTSV nucleoprotein (N) induced cGAS degradation in a dose-dependent manner. Mechanically, N interacted with the 161-382 domain of cGAS and linked the cGAS to LC3. The cGAS-N-LC3 trimer was targeted to N-induced autophagy, and the cGAS was degraded in autolysosome. Taken together, our study discovered a novel antagonistic mechanism of RNA viruses, SFTSV is able to suppress the cGAS-dependent antiviral innate immune responses through N-hijacking cGAS into N-induced autophagy. Our results indicated that SFTSV N is an important virulence factor of SFTSV in mediating host antiviral immune responses.
IMPORTANCE
Severe fever with thrombocytopenia syndrome virus (SFTSV) is a tick-borne RNA virus that is widespread in East and Southeast Asian countries with a high fatality rate of up to 30%. Up to now, many cytoplasmic pattern recognition receptors, such as RIG-I, MDA5, and SAFA, have been reported to recognize SFTSV genomic RNA and trigger interferon-dependent antiviral responses. However, current knowledge is not clear whether SFTSV can be recognized by DNA sensor cyclic GMP-AMP synthase (cGAS). Our study demonstrated that cGAS could recognize SFTSV infection via ectopic mitochondrial DNA, and the activated cGAS-stimulator of interferon genes signaling pathway could significantly inhibit SFTSV replication. Importantly, we further uncovered a novel mechanism of SFTSV to inhibit innate immune responses by the degradation of cGAS. cGAS was degraded in N-induced autophagy. Collectively, this study illustrated a novel virulence factor of SFTSV to suppress innate immune responses through autophagy-dependent cGAS degradation.
Topics: Phlebovirus; Nucleotidyltransferases; Humans; Immunity, Innate; Nucleoproteins; HEK293 Cells; Severe Fever with Thrombocytopenia Syndrome; Autophagy; Animals; DNA, Mitochondrial; Interferons; Viral Proteins
PubMed: 38712963
DOI: 10.1128/spectrum.03796-23 -
Viruses Nov 2023Rift Valley fever virus (RVFV) is a mosquito-borne zoonotic pathogen causing disease in livestock and humans. Whilst initially restricted to the African continent,...
Rift Valley fever virus (RVFV) is a mosquito-borne zoonotic pathogen causing disease in livestock and humans. Whilst initially restricted to the African continent, recent spread to the Arabian Peninsula has highlighted the likelihood of entry into new regions. Due to the absence of a regulatory-approved human vaccine, work is ongoing to develop and assess countermeasures. As such, small animal models play a pivotal role in providing information on disease pathogenesis and elucidating which intervention strategies confer protection. To develop and establish the BALB/c mouse model, we challenged mice with RVFV grown from two separate cell lines: one derived from mosquitoes (C6/36) and the other mammalian derived (Vero E6). Following infection, we assessed the clinical course of disease progression at days 1 and 3 post-challenge and evaluated viral tropism and immune analytes. The results demonstrated that RVFV infection was affected by the cell line used to propagate the challenge virus, with those grown in insect cells resulting in a more rapid disease progression. The lowest dose that caused uniform severe disease remained the same across both virus preparations. In addition, to demonstrate reproducibility, the lowest dose was used for a subsequent infection study using male and female animals. The results further demonstrated that male mice succumbed to infection more rapidly than their female counterparts. Our results establish an RVFV mouse model and key parameters that affect the course of disease progression in BALB/c mice.
Topics: Male; Female; Humans; Animals; Mice; Rift Valley fever virus; Rift Valley Fever; Mice, Inbred BALB C; Reproducibility of Results; Disease Progression; Mammals
PubMed: 38140610
DOI: 10.3390/v15122369 -
Internal Medicine (Tokyo, Japan) Mar 2024We herein report a case of severe fever with thrombocytopenia syndrome (SFTS) with Pasteurella multilocida bacteremia in a 65-year-old man with alcoholic cirrhosis who...
We herein report a case of severe fever with thrombocytopenia syndrome (SFTS) with Pasteurella multilocida bacteremia in a 65-year-old man with alcoholic cirrhosis who was admitted to our hospital with anorexia and severe fatigue. Laboratory tests revealed pancytopenia and liver and kidney dysfunction. After admission, he developed impaired consciousness, mucosal hemorrhaging, and septic shock. SFTS virus was detected on polymerase chain reaction testing of blood and throat swabs, and Pasteurella multocida was detected on blood culture. Despite being treated with invasive mechanical ventilation, vasopressors, and antibiotics, the patient's condition progressively deteriorated, and he died four days after admission.
Topics: Male; Humans; Aged; Pasteurella multocida; Severe Fever with Thrombocytopenia Syndrome; Coinfection; Phlebovirus; Anti-Bacterial Agents; Liver
PubMed: 37468245
DOI: 10.2169/internalmedicine.2027-23 -
EBioMedicine Feb 2024
Topics: Humans; Biology; Phlebovirus
PubMed: 38194743
DOI: 10.1016/j.ebiom.2024.104968 -
Scientific Reports May 2024Hard ticks are known vectors of various pathogens, including the severe fever with thrombocytopenia syndrome virus, Rickettsia spp., Coxiella burnetii, Borrelia spp.,...
Hard ticks are known vectors of various pathogens, including the severe fever with thrombocytopenia syndrome virus, Rickettsia spp., Coxiella burnetii, Borrelia spp., Anaplasma phagocytophilum, and Ehrlichia spp. This study aims to investigate the distribution and prevalence of tick-borne pathogens in southwestern Korea from 2019 to 2022. A total of 13,280 ticks were collected during the study period, with H. longicornis accounting for 86.1% of the collected ticks. H. flava, I. nipponensis and A. testudinarium comprised 9.4%, 3.6%, and 0.8% of the ticks, respectively. Among 983 pools tested, Rickettsia spp. (216 pools, 1.6% MIR) were the most prevalent pathogens across all tick species, with R. japonica and R. monacensis frequently detected in I. nipponensis and Haemaphysalis spp., respectively. Borrelia spp. (28 pools, 0.2% MIR) were predominantly detected in I. nipponensis (27 pools, 13.8% MIR, P < 0.001). Co-infections, mainly involving Rickettsia monacensis and Borrelia afzelii, were detected in I. nipponensis. Notably, this study identified R. monacensis for the first time in A. testudinarium in South Korea. These findings offer valuable insights into the tick population and associated pathogens in the region, underscoring the importance of tick-borne disease surveillance and prevention measures.
Topics: Animals; Republic of Korea; Rickettsia; Ticks; Tick-Borne Diseases; Prevalence; Borrelia; Anaplasma phagocytophilum; Ehrlichia; Coxiella burnetii; Phlebovirus
PubMed: 38811622
DOI: 10.1038/s41598-024-61126-y -
Pathogens (Basel, Switzerland) Apr 2024The aim of this study was to determine the prevalence of six viruses, from two families of the order , in the general population of central Tunisia. Sera collected from...
The aim of this study was to determine the prevalence of six viruses, from two families of the order , in the general population of central Tunisia. Sera collected from 377 asymptomatic blood donors were serologically assayed for Rift Valley fever virus (RVFV), Crimean-Congo hemorrhagic fever virus (CCHFV), and four sandfly-borne phleboviruses: Toscana virus (TOSV), sandfly fever Naples virus (SFNV), sandfly fever Sicilian virus (SFSV), and sandfly fever Cyprus virus (SFCV). Of the 377 subjects enrolled in this study, 17.3% were IgG positive for at least one of the viruses tested. The most frequently detected antibodies were against TOSV (13.3%), followed by SFCV (2.9%), RVFV (1.9%), SFSV (1.3%), and SFNV (1.1%). Only one sample was IgG positive for CCHFV. Dual reactivity was observed in nine cases: SFSV + SFCV in three cases (0.8%) and TOSV + SFNV, TOSV + SFCV, and TOSV + RVFV in two cases (0.5%) each. 15.9% of donors were IgG positive against sandfly-borne phleboviruses. Among the 65 donors IgG positive for phleboviruses, 50.8% were from rural areas compared to 12.3% from urban areas ( < 0.001); 92.3% had animals in their living quarters ( = 0.009); and 70.8% lived in the vicinity of stagnant water ( = 0.062). Seroprevalence was significantly higher among donors living with chronic diseases ( = 0.039). Furthermore, the seroprevalence of phleboviruses was higher in Kairouan, the central governorate, than in the two coastal governorates: Monastir and Sousse, with 33.4%, 24.2%, and 14.9%, respectively. The presence of antibodies in the general population needs further investigation to better assess the extent of these viruses. Only TOSV was known to have an extensive circulation in Tunisia and in North Africa. Continued surveillance and interventions are necessary to detect the emergence of all arboviruses and to prevent further transmission.
PubMed: 38668303
DOI: 10.3390/pathogens13040348