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Viruses
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Severe Fever with Thrombocytopenia Syndrome Virus 3.0
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Severe Fever with Thrombocytopenia Syndrome Virus 3.0

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Human Virology and Viral Diseases".

Deadline for manuscript submissions: closed (31 March 2024) | Viewed by 14826

Special Issue Editor

Dr. Masayuki Saijo

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Guest Editor
1. Medical Affairs Department, Health and Welfare Bureau, Sapporo, Hokkaido, Japan
2. National Institute of Infectious Diseases, Tokyo, Japan
Interests: SFTS; SFTSV
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

We are still facing a global pandemic of COVID-19, originating from a novel coronavirus known as severe acute respiratory syndrome virus coronavirus 2 (SARS-CoV-2). In the period of 2013–2016, there was a huge outbreak of Ebola virus disease (EVD) in West Africa. Over the last 30 years, we have identified many novel infectious diseases with high case fatality rate which are caused by viruses and that spilled over from animals to humans. Severe fever with thrombocytopenia syndrome (SFTS) is one of the major emerging viral infections that must be included in this category.

SFTS was reported to be a novel bunyavirus infection by Chinese scientists as far back as 2011. SFTS is a tick-borne viral infection with high morbidity and mortality. SFTS was discovered to be endemic to Japan and South Korea in 2012. The case fatality rate in patients with SFTS in Japan is reported to be approximately 30%. The vectors which play a role in transmitting the causative agent, SFTS virus (SFTSV), are Haemaphysalis longicornis and others. Furthermore, patients with SFTS have been identified in Taiwan and Vietnam, indicating that the endemic area of SFTS is much wider than previously thought.

SFTSV is circulating in Asian countries including China, Korea, and Japan through the transmission of the virus between some species of ticks and mammals. The evidence indicates that SFTS has occurred in the past and will continue to occur in the future, suggesting we are unlikely to be able to escape from the risk being infected with SFTSV and that we are unable to eradicate this virus.

Ten years have passed since the discovery of SFTS. We have had some achievements in the elucidation of the SFTSV characteristics, clarification of the SFTS epidemiology, pathophysiology of SFTS in patients, mechanisms of SFTSV maintenance in nature, and in the development of specific treatments and vaccines. We aim to compile and present some recent research and achievements in minimizing the mortality and morbidity in patients with SFTS in this Special Issue. We welcome submissions addressing topics including, but not limited to the following:

  1. New topics in SFTSV virology;
  2. Epidemiology of SFTS;
  3. Clinical aspects and pathophysiology of SFTS in patients;
  4. Diagnostics of SFTS in humans and animals;
  5. SFTS as a zoonotic disease;
  6. Mechanisms of SFTSV maintenance in nature;
  7. Development of specific treatments for patients with SFTS;
  8. Development of vaccines against SFTS;
  9. Other topics specific to SFTS.

 

Dr. Masayuki Saijo
Guest Editor

Manuscript Submission Information

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Related Special Issues

Published Papers (7 papers)

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22 pages, 12152 KiB  
Article
Time-Course Transcriptome Analysis Reveals Distinct Phases and Identifies Two Key Genes during Severe Fever with Thrombocytopenia Syndrome Virus Infection in PMA-Induced THP-1 Cells
by Tao Huang, Xueqi Wang, Yuqian Mi, Wei Wu, Xiao Xu, Chuan Li, Yanhan Wen, Boyang Li, Yang Li, Lina Sun, Jiandong Li, Mengxuan Wang, Tiezhu Liu, Shiwen Wang and Mifang Liang
Viruses 2024, 16(1), 59; https://doi.org/10.3390/v16010059 - 29 Dec 2023
Viewed by 1675
Abstract
In recent years, there have been significant advancements in the research of Severe Fever with Thrombocytopenia Syndrome Virus (SFTSV). However, several limitations and challenges still exist. For instance, researchers face constraints regarding experimental conditions and the feasibility of sample acquisition for studying SFTSV. [...] Read more.
In recent years, there have been significant advancements in the research of Severe Fever with Thrombocytopenia Syndrome Virus (SFTSV). However, several limitations and challenges still exist. For instance, researchers face constraints regarding experimental conditions and the feasibility of sample acquisition for studying SFTSV. To enhance the quality and comprehensiveness of SFTSV research, we opted to employ PMA-induced THP-1 cells as a model for SFTSV infection. Multiple time points of SFTSV infection were designed to capture the dynamic nature of the virus–host interaction. Through a comprehensive analysis utilizing various bioinformatics approaches, including diverse clustering methods, MUfzz analysis, and LASSO/Cox machine learning, we performed dynamic analysis and identified key genes associated with SFTSV infection at the host cell transcriptomic level. Notably, successful clustering was achieved for samples infected at different time points, leading to the identification of two important genes, PHGDH and NLRP12. And these findings may provide valuable insights into the pathogenesis of SFTSV and contribute to our understanding of host–virus interactions. Full article
(This article belongs to the Special Issue Severe Fever with Thrombocytopenia Syndrome Virus 3.0)
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11 pages, 1068 KiB  
Article
Epidemiology of Severe Fever with Thrombocytopenia Syndrome in Dogs and Cats in Taiwan
by Chih-Ying Kuan, Shan-Chia Ou, Chao-Chin Chang, Pei-Ling Kao, Ruei-Sheng Tsai, Porjai Rattanapanadda, Tsai-Lu Lin, Ken Maeda, Tsun-Li Cheng, Ya-Jane Lee, Shih-Te Chuang, Shiun-Long Lin, Hsien-Yueh Liu, Fong-Yuan Lin, Jen-Wei Lin, Wei-Li Hsu and Chi-Chung Chou
Viruses 2023, 15(12), 2338; https://doi.org/10.3390/v15122338 - 28 Nov 2023
Viewed by 3024
Abstract
Severe Fever with Thrombocytopenia Syndrome (SFTS), caused by the SFTS Virus (SFTSV), is a global health threat. SFTSV in Taiwan has only been reported in ruminants and wild animals. Thus, we aimed to investigate the infection statuses of dogs and cats, the animals [...] Read more.
Severe Fever with Thrombocytopenia Syndrome (SFTS), caused by the SFTS Virus (SFTSV), is a global health threat. SFTSV in Taiwan has only been reported in ruminants and wild animals. Thus, we aimed to investigate the infection statuses of dogs and cats, the animals with closer human interactions. Overall, the SFTSV RNA prevalence was 23% (170/735), with dogs showing a 25.9% (111/429) prevalence and cats at 19.3% (59/306) prevalence. Noticeably, the prevalence in stray animals (39.8% 77/193) was significantly higher than in domesticated ones (17.2%, 93/542). Among the four categories analyzed, the highest SFTSV prevalence was found in the stray dogs at 53.9% (120/193), significantly higher than the 24.2% prevalence noted in stray cats. In contrast, domesticated animals exhibited similar prevalence rates, with 17.1% for dogs and 17.2% for cats. It is noteworthy that in the domesticated animal groups, a significantly elevated prevalence (45%, 9/20) was observed among cats exhibiting thrombocytopenia compared to those platelet counts in the reference range (4.8%, 1/21). The high infection rate in stray animals, especially stray dogs, indicated that exposure to various outdoor environments influences the prevalence of infections. Given the higher human interaction with dogs and cats, there is a need for proactive measures to reduce the risk associated with the infection of SFTSV in both animals and humans. Full article
(This article belongs to the Special Issue Severe Fever with Thrombocytopenia Syndrome Virus 3.0)
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14 pages, 1795 KiB  
Article
Long-Term Detection and Isolation of Severe Fever with Thrombocytopenia Syndrome (SFTS) Virus in Dog Urine
by Yumiko Saga, Toshikazu Yoshida, Rieko Yoshida, Shunsuke Yazawa, Takahisa Shimada, Noriko Inasaki, Masae Itamochi, Emiko Yamazaki, Kazunori Oishi and Hideki Tani
Viruses 2023, 15(11), 2228; https://doi.org/10.3390/v15112228 - 8 Nov 2023
Viewed by 1824
Abstract
Severe fever with thrombocytopenia syndrome (SFTS) is a tick-borne infection caused by the SFTS virus (SFTSV), with a high fatality rate of approximately 30% in humans. In recent years, cases of contact infection with SFTSV via bodily fluids of infected dogs and cats [...] Read more.
Severe fever with thrombocytopenia syndrome (SFTS) is a tick-borne infection caused by the SFTS virus (SFTSV), with a high fatality rate of approximately 30% in humans. In recent years, cases of contact infection with SFTSV via bodily fluids of infected dogs and cats have been reported. In this study, clinical and virological analyses were performed in two dogs in which SFTSV infection was confirmed for the first time in the Toyama prefecture. Both dogs recovered; however, one was severely ill and the other mildly ill. The amount of the SFTSV gene was reduced to almost similar levels in both dogs. In the dogs’ sera, the SFTSV gene was detected at a low level but fell below the detection limit approximately 2 weeks after onset. Notably, the SFTSV gene was detected at levels several thousand times higher in urine than in other specimens from both dogs. Furthermore, the gene was detected in the urine for a long period of >2 months. The clinical signs disappeared on days 1 or 6 after onset, but infectious SFTSV was detected in the urine up to 3 weeks later. Therefore, it is necessary to be careful about contact with bodily fluids, especially urine, even after symptoms have disappeared. Full article
(This article belongs to the Special Issue Severe Fever with Thrombocytopenia Syndrome Virus 3.0)
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20 pages, 6112 KiB  
Article
Identification and Analysis of a Four-Gene Set for Diagnosing SFTS Virus Infection Based on Machine Learning Methods and Its Association with Immune Cell Infiltration
by Tao Huang, Xueqi Wang, Yuqian Mi, Tiezhu Liu, Yang Li, Ruixue Zhang, Zhen Qian, Yanhan Wen, Boyang Li, Lina Sun, Wei Wu, Jiandong Li, Shiwen Wang and Mifang Liang
Viruses 2023, 15(10), 2126; https://doi.org/10.3390/v15102126 - 20 Oct 2023
Cited by 1 | Viewed by 1865
Abstract
Severe Fever with thrombocytopenia syndrome (SFTS) is a highly fatal viral infectious disease that poses a significant threat to public health. Currently, the phase and pathogenesis of SFTS are not well understood, and there are no specific vaccines or effective treatment available. Therefore, [...] Read more.
Severe Fever with thrombocytopenia syndrome (SFTS) is a highly fatal viral infectious disease that poses a significant threat to public health. Currently, the phase and pathogenesis of SFTS are not well understood, and there are no specific vaccines or effective treatment available. Therefore, it is crucial to identify biomarkers for diagnosing acute SFTS, which has a high mortality rate. In this study, we conducted differentially expressed genes (DEGs) analysis and WGCNA module analysis on the GSE144358 dataset, comparing the acute phase of SFTSV-infected patients with healthy individuals. Through the LASSO–Cox and random forest algorithms, a total of 2128 genes were analyzed, leading to the identification of four genes: ADIPOR1, CENPO, E2F2, and H2AC17. The GSEA analysis of these four genes demonstrated a significant correlation with immune cell function and cell cycle, aligning with the functional enrichment findings of DEGs. Furthermore, we also utilized CIBERSORT to analyze the immune cell infiltration and its correlation with characteristic genes. The results indicate that the combination of ADIPOR1, CENPO, E2F2, and H2AC17 genes has the potential as characteristic genes for diagnosing and studying the acute phase of SFTS virus (SFTSV) infection. Full article
(This article belongs to the Special Issue Severe Fever with Thrombocytopenia Syndrome Virus 3.0)
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12 pages, 3269 KiB  
Article
Non-Structural Protein-W61 as a Novel Target in Severe Fever with Thrombocytopenia Syndrome Virus (SFTSV): An In-Vitro and In-Silico Study on Protein-Protein Interactions with Nucleoprotein and Viral Replication
by Ji-Young Park, Chandran Sivasankar, Perumalraja Kirthika, Dhamodharan Prabhu and John Hwa Lee
Viruses 2023, 15(9), 1963; https://doi.org/10.3390/v15091963 - 20 Sep 2023
Cited by 2 | Viewed by 1924
Abstract
The non-structural protein (NSs) and nucleoprotein (NP) of the severe fever with thrombocytopenia syndrome virus (SFTSV) encoded by the S segment are crucial for viral pathogenesis. They reside in viroplasm-like structures (VLS), but their interaction and their significance in viral propagation remain unclear. [...] Read more.
The non-structural protein (NSs) and nucleoprotein (NP) of the severe fever with thrombocytopenia syndrome virus (SFTSV) encoded by the S segment are crucial for viral pathogenesis. They reside in viroplasm-like structures (VLS), but their interaction and their significance in viral propagation remain unclear. Here, we investigated the significance of the association between NSs and NP during viral infection through in-silico and in-vitro analyses. Through in-silico analysis, three possible binding sites were predicted, at positions C6S (Cystein at 6th position to Serine), W61Y (Tryptophan 61st to Tyrosine), and S207T (Serine 207th to Threonine), three mutants of NSs were developed by site-directed mutagenesis and tested for NP interaction by co-immunoprecipitation. NSsW61Y failed to interact with the nucleoprotein, which was substantiated by the conformational changes observed in the structural analyses. Additionally, molecular docking analysis corroborated that the NSW61Y mutant protein does not interact well compared to wild-type NSs. Over-expression of wild-type NSs in HeLa cells increased the SFTSV replication by five folds, but NSsW61Y exhibited 1.9-folds less viral replication than wild-type. We demonstrated that the W61Y alteration was implicated in the reduction of NSs-NP interaction and viral replication. Thus, the present study identified a critical NSs site, which could be targeted for development of therapeutic regimens against SFTSV. Full article
(This article belongs to the Special Issue Severe Fever with Thrombocytopenia Syndrome Virus 3.0)
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7 pages, 1328 KiB  
Brief Report
Correlation between the Cycle Threshold Values in Detection of Severe Fever with Thrombocytopenia Syndrome Virus Using PowerChekTM SFTSV Real-Time PCR Kit and Viral Load: Prognostic Implications
by Misun Kim, Sang Taek Heo, Hee Cheol Kim, Myeong Jin Kang, Sora Kim, Keun Hwa Lee and Jeong Rae Yoo
Viruses 2024, 16(5), 700; https://doi.org/10.3390/v16050700 - 29 Apr 2024
Viewed by 1320
Abstract
Background: This study aimed to analyze the correlation between the cycle threshold (Ct) values of severe fever with thrombocytopenia syndrome (SFTS) virus small (S) and middle (M) segments and the SFTS viral load, aiming to estimate the initial viral load and predict prognosis [...] Read more.
Background: This study aimed to analyze the correlation between the cycle threshold (Ct) values of severe fever with thrombocytopenia syndrome (SFTS) virus small (S) and middle (M) segments and the SFTS viral load, aiming to estimate the initial viral load and predict prognosis in the early clinical course. Method: A retrospective study was conducted with confirmed SFTS patients at Jeju National University Hospital (2016–2022). Patients were categorized into non-fatal and fatal groups. Results: This study included 49 patients with confirmed SFTS (non-fatal group, n = 42; fatal group, n = 7). A significant negative correlation (−0.783) was observed between the log SFTS viral load and Ct values (p < 0.001). This negative correlation was notably stronger in the fatal group (correlation coefficient −0.940) than in the non-fatal group (correlation coefficient −0.345). Conclusion: In this study, we established a correlation between SFTS viral load and Ct values for estimating the initial viral load and early predicting prognosis. These results are expected to offer valuable insights for SFTS patient treatment and prognosis prediction. Full article
(This article belongs to the Special Issue Severe Fever with Thrombocytopenia Syndrome Virus 3.0)
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9 pages, 1162 KiB  
Brief Report
High Seroprevalence of Severe Fever with Thrombocytopenia Syndrome Virus Infection among the Dog Population in Thailand
by Keita Ishijima, Thanmaporn Phichitraslip, Nattakarn Naimon, Preeyaporn Ploypichai, Benyapa Kriebkajon, Torntun Chinarak, Jirasin Sridaphan, Anamika Kritiyakan, Noppadol Prasertsincharoen, Sathaporn Jittapalapong, Kanate Tangcham, Worawut Rerkamnuaychoke, Yudai Kuroda, Masakatsu Taira, Kango Tatemoto, Eunsil Park, Milagros Virhuez-Mendoza, Yusuke Inoue, Michiko Harada, Tsukasa Yamamoto, Ayano Nishino, Aya Matsuu and Ken Maedaadd Show full author list remove Hide full author list
Viruses 2023, 15(12), 2403; https://doi.org/10.3390/v15122403 - 11 Dec 2023
Cited by 4 | Viewed by 2299
Abstract
Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne zoonotic disease caused by the SFTS virus (SFTSV). In Thailand, three human cases of SFTS were reported in 2019 and 2020, but there was no report of SFTSV infection in animals. Our study [...] Read more.
Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne zoonotic disease caused by the SFTS virus (SFTSV). In Thailand, three human cases of SFTS were reported in 2019 and 2020, but there was no report of SFTSV infection in animals. Our study revealed that at least 16.6% of dogs in Thailand were seropositive for SFTSV infection, and the SFTSV-positive dogs were found in several districts in Thailand. Additionally, more than 70% of the serum samples collected at one shelter possessed virus-neutralization antibodies against SFTSV and the near-complete genome sequences of the SFTSV were determined from one dog in the shelter. The dog SFTSV was genetically close to those from Thailand and Chinese patients and belonged to genotype J3. These results indicated that SFTSV has already spread among animals in Thailand. Full article
(This article belongs to the Special Issue Severe Fever with Thrombocytopenia Syndrome Virus 3.0)
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