Identifying target cells for a #tick-borne virus that causes #fatal #hemorrhagic fever (J Clin Invest., abstract)

[Source: Journal of Clinical Investigation, full page: (LINK). Abstract, edited.]

Identifying target cells for a tick-borne virus that causes fatal hemorrhagic fever

Satoko Yamaoka, Carla Weisend, and Hideki Ebihara

First published January 6, 2020

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Severe fever with thrombocytopenia syndrome (SFTS) is an emerging disease in China, South Korea, and Japan caused by the tick-borne SFTS virus (SFTSV). Severe and fatal SFTS presents as a hemorrhagic fever characterized by high viral load, uncontrolled inflammatory response, dysregulated adaptive immunity, coagulation abnormalities, hemorrhage, and multiorgan failure with up to 33% case fatality rates (CFRs). Despite its public health significance in Asia, vaccines and specific therapeutics against SFTS are still unavailable. A better understanding of the pathogenesis of SFTS is crucial to improving medical countermeasures against this devastating disease. In this issue of the JCI, Suzuki and colleagues analyzed histopathological samples from 22 individuals who succumbed to SFTS, and identified antibody-producing B cell–lineage plasmablasts and macrophages as principal target cells for SFTSV infection in fatal SFTS. Their results suggest that SFTSV-infected post–germinal center B cells, plasmablasts, and macrophages affect systemic immunopathology and dysregulation, which likely leads to fatal outcomes.

Keywords: SFTS; Immunopathology; Viral pathogenesis.

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#SFTS virus targets B cells in lethal #human #infections (J Clin Invest., abstract)

[Source: Journal of Clinical Investigation, full page: (LINK). Abstract, edited.]

Severe fever with thrombocytopenia syndrome virus targets B cells in lethal human infections

Tadaki Suzuki,1 Yuko Sato,1 Kaori Sano,1,2 Takeshi Arashiro,1 Harutaka Katano,1 Noriko Nakajima,1 Masayuki Shimojima,4 Michiyo Kataoka,1 Kenta Takahashi,1 Yuji Wada,1 Shigeru Morikawa,3 Shuetsu Fukushi,4 Tomoki Yoshikawa,4 Masayuki Saijo,4 and Hideki Hasegawa1,2,5

First published January 6, 2020

Related article: Identifying target cells for a tick-borne virus that causes fatal hemorrhagic fever, Satoko Yamaoka, … , Carla Weisend, Hideki Ebihara

Category: Commentary

 

Abstract

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging hemorrhagic fever caused by a tick-borne banyangvirus and is associated with high fatality. Despite increasing incidence of SFTS and serious public health concerns in East Asia, the pathogenesis of lethal SFTS virus (SFTSV) infection in humans is not fully understood. Numbers of postmortem examinations to determine target cells of the viral infection have so far been limited. Here we showed that B cells differentiating into plasmablasts and macrophages in secondary lymphoid organs were targets for SFTSV at the end stage of lethal infection, and the majority of SFTSV-infected cells were B cell–lineage lymphocytes. In affected individuals, B cell–lineage lymphocytes with SFTSV infection were widely distributed in both lymphoid and nonlymphoid organs, and infiltration of these cells into the capillaries of the organs could be observed occasionally. Moreover, a human plasmablastic lymphoma cell line, PBL-1, was susceptible to SFTSV propagation, and had a similar immunophenotype to that of target cells of SFTSV in fatal SFTS. PBL-1 can therefore provide a potential in vitro model for human SFTSV infection. These results extend our understanding of the pathogenesis of human lethal SFTSV infection, and can facilitate the development of SFTSV countermeasures.

Keywords: SFTS; Immunopathology; Viral pathogenesis.

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Cross-genotype protection of live-attenuated #vaccine candidate for #SFTS virus in a #ferret model (Proc Natl Acad Sci USA, abstract)

[Source: Proceedings of the National Academy of Sciences of the United States of America, full page: (LINK). Abstract, edited.]

Cross-genotype protection of live-attenuated vaccine candidate for severe fever with thrombocytopenia syndrome virus in a ferret model

Kwang-Min Yu, Su-Jin Park, Min-Ah Yu, Young-Il Kim, Younho Choi, Jae U. Jung, Benjamin Brennan, and Young Ki Choi

PNAS first published December 9, 2019 / DOI: https://doi.org/10.1073/pnas.1914704116

Edited by Peter Palese, Icahn School of Medicine at Mount Sinai, New York, NY, and approved November 5, 2019 (received for review August 23, 2019)

 

Significance

Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging viral pathogen discovered in 2009. The virus is present in countries of East Asia and is transmitted through the bite of an infected Haemaphysalis longicornis tick. SFTSV disease is associated with high morbidity and is often fatal. Despite the incidence of disease, no antiviral therapy or vaccine has been approved for use. Here, we report and assess 2 live attenuated viruses as vaccine candidates in our recently described ferret model of infection. We show that the viruses caused no clinical disease or mortality in healthy animals. Immunized animals mounted a robust humoral immune response to a single dose of virus, and this response protected the animals from a lethal challenge.

 

Abstract

Severe fever with thrombocytopenia syndrome (SFTS) virus (SFTSV) is an emerging tick-borne virus classified within the Banyangvirus genus. SFTS disease has been reported throughout East Asia since 2009 and is characterized by high fever, thrombocytopenia, and leukopenia and has a 12 to 30% case fatality rate. Due to the recent emergence of SFTSV, there has been little time to conduct research into preventative measures aimed at combatting the virus. SFTSV is listed as one of the World Health Organization’s Prioritized Pathogens for research into antiviral therapeutics and vaccine development. Here, we report 2 attenuated recombinant SFTS viruses that induce a humoral immune response in immunized ferrets and confer complete cross-genotype protection to lethal challenge. Animals infected with rHB29NSsP102A or rHB2912aaNSs (both genotype D) had a reduced viral load in both serum and tissues and presented without high fever, thrombocytopenia, or mortality associated with infection. rHB29NSsP102A- or rHB2912aaNSs-immunized animals developed a robust anti-SFTSV immune response against cross-genotype isolates of SFTSV. This immune response was capable of neutralizing live virus in a focus-reduction neutralization test (FRNT) and was 100% protective against a cross-genotype lethal challenge with the CB1/2014 strain of SFTSV (genotype B). Thus, using our midsized, aged ferret infection model, we demonstrate 2 live attenuated vaccine candidates against the emerging pathogen SFTSV.

SFTS – emerging banyangvirus – live attenuated vaccine – ferret model – bunyavirus

Keywords: Bunyavirus; Banyangvirus; SFTS; Vaccines; Animal models.

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#Seroprevalance of #antibodies specific for #SFTS virus and the discovery of #asymptomatic #infections in #Henan Province, #China (PLOS Negl Trop Dis., abstract)

[Source: PLOS Neglected Tropical Diseases, full page: (LINK). Abstract, edited.]

OPEN ACCESS /  PEER-REVIEWED / RESEARCH ARTICLE

Seroprevalance of antibodies specific for severe fever with thrombocytopenia syndrome virus and the discovery of asymptomatic infections in Henan Province, China

Yanhua Du , Ningning Cheng , Yi Li, Haifeng Wang, Aiguo You, Jia Su, Yifei Nie, Hongxia Ma, Bianli Xu , Xueyong Huang

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Published: November 25, 2019 / DOI: https://doi.org/10.1371/journal.pntd.0007242 / This is an uncorrected proof.

 

Abstract

Background

Severe fever with thrombocytopenia syndrome (SFTS) is a severe emerging disease caused by SFTS virus (SFTSV), and the geographical distribution of SFTS has been increasing throughout China in recent years. To assess SFTSV-specific antibody seroprevalence, a cross-sectional study was conducted for healthy people in high SFTS endemic areas of Henan province in 2016.

Methods

This study used a stratified random sampling method to select 14 natural villages as the investigation sites. From April to May 2016, participants completed a questionnaire survey and serum samples were collected. All serum samples were subjected to ELISA to detect SFTSV-specific IgM and IgG. All IgM-positive samples were further tested by real-time RT-PCR, and isolation of virus from serum was attempted. Any participant who was IgM-positive was followed up with a month later to confirm health status.

Results

In total, 1463 healthy people participated in this study. The average seropositive rates for SFTSV-specific IgG and IgM were 10.46% (153/1463) and 0.82% (12/1463), respectively. IgM was detected in 12 individuals, and SFTSV RNA was detected in six of them. Virus was isolated from five of the six SFTSV RNA-positive individuals, and phylogenetic analyses revealed that all five isolates belonged to SFTSV group A. No IgM-positive participants exhibited any symptoms or other signs of illness at the one-month follow up.

Conclusions

This study identified a relatively high incidence of SFTSV-specific antibody seropositivity in healthy people in Xinyang city. Moreover, our data provide the first evidence for asymptomatic SFTSV infections, which may have significant implications for SFTS outbreak control.

 

Author summary

Severe fever with thrombocytopenia syndrome (SFTS) is a severe emerging infectious disease caused by SFTS virus (SFTSV) that was first discovered in rural areas of China. Henan province has had the largest number of SFTS cases in China every year since the disease was discovered, however, seropositivity for SFTSV-specific antibodies in healthy people in this region is still not clear. To address this issue, a cross-sectional survey was performed in high endemic areas from April to May 2016. The results showed that SFTSV seroprevalence was relatively high and possibly increasing. Notably, SFTSV RNA, as well as virus itself, was isolated from specimens obtained from healthy people. This study confirmed there are asymptomatic SFTSV infections in humans, and it is the first to report SFTSV isolation from healthy people.

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Citation: Du Y, Cheng N, Li Y, Wang H, You A, Su J, et al. (2019) Seroprevalance of antibodies specific for severe fever with thrombocytopenia syndrome virus and the discovery of asymptomatic infections in Henan Province, China. PLoS Negl Trop Dis 13(11): e0007242. https://doi.org/10.1371/journal.pntd.0007242

Editor: Abdallah M. Samy, Faculty of Science, Ain Shams University (ASU), EGYPT

Received: February 10, 2019; Accepted: October 4, 2019; Published: November 25, 2019

Copyright: © 2019 Du et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: All relevant data are within the manuscript and its Supporting Information files.

Funding: H.X.Y received grants from the National Natural Science Foundation of China (NO 81573204 https://isisn.nsfc.gov.cn/egrantweb/) and Henan provincial medical science and technology program (grant no.2018010029) .X.B.L. recieved a grant from the National Natural Science Foundation of China (NO 81773500 https://isisn.nsfc.gov.cn/egrantweb/).D.Y.H received a grant from Henan provincial medical science and technology program (grant no.2018020510). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: The authors have declared that no competing interests exist.

Keywords: Serology; Seroprevalence; SFTS; Henan; China.

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A #nomogram to predict #mortality in patients with #SFTS at the early stage—A multicenter study in #China (PLOS Negl Trop Dis., abstract)

[Source: PLOS Neglected Tropical Diseases, full page: (LINK). Abstract, edited.]

OPEN ACCESS /  PEER-REVIEWED / RESEARCH ARTICLE

A nomogram to predict mortality in patients with severe fever with thrombocytopenia syndrome at the early stage—A multicenter study in China

Lin Wang , Gang Wan , Yi Shen , Zhenghua Zhao , Ling Lin , Wei Zhang, Rui Song, Di Tian, Jing Wen, Yongxiang Zhao, Xiaoli Yu, Li Liu, Yang Feng,  [ … ], Wei Li

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Published: November 25, 2019 / DOI: https://doi.org/10.1371/journal.pntd.0007829 / This is an uncorrected proof.

 

Abstract

Background

Severe fever with thrombocytopenia syndrome (SFTS) caused by the SFTS virus is an emerging infectious disease that was first identified in the rural areas of China in 2011. Severe cases often result in death due to multiple organ failure. To date, there are still numerous problems remain unresolved in SFTS, including unclear pathogenesis, lack of specific treatment, and no effective vaccines available.

Aim

To analyze the clinical information of patients with early-stage SFTS and to establish a nomogram for the mortality risk.

Methods

Between April 2011 and December 2018, data on consecutive patients who were diagnosed with SFTS were prospectively collected from five medical centers distributed in central and northeastern China. Multivariable Cox analyses were used to identify the factors independently associated with mortality. A nomogram for mortality was established using those factors.

Results

During the study period, 429 consecutive patients were diagnosed with SFTS at the early stage of the disease (within 7 days of fever), among whom 69 (16.1%) died within 28 days. The multivariable Cox proportional hazard regression analysis showed that low lymphocyte percentage, early-stage encephalopathy, and elevated concentration of serum LDH and BUN were independent risk factors for fatal outcomes. Received-operating characteristic curves for 7-, 14-, and 28-days survival had AUCs of 0.944 (95% CI: 0.920–0.968), 0.924 (95% CI: 0.896–0.953), and 0.924 (95% CI: 0.895–0.952), respectively. Among low-risk patients, 6 patients died (2.2%). Among moderate-risk patients, 25 patients died (24.0%, hazard ratio (HR) = 11.957). Among high-risk patients, the mortality rate was 69.1% (HR = 57.768).

Conclusion

We established a simple and practical clinical scoring system, through which we can identify critically ill patients and provide intensive medical intervention for patients as soon as possible to reduce mortality.

 

Author summary

We established a SFTS nomogram scoring system, which is the first nomogram for this disease. According to this nomogram, patients were divided into three levels of mortality risk: low, moderate, and high. This scoring system is helpful to identify critically ill patients, allowing for early intervention and intensive care, which may contribute to reducing the mortality of SFTS.

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Citation: Wang L, Wan G, Shen Y, Zhao Z, Lin L, Zhang W, et al. (2019) A nomogram to predict mortality in patients with severe fever with thrombocytopenia syndrome at the early stage—A multicenter study in China. PLoS Negl Trop Dis 13(11): e0007829. https://doi.org/10.1371/journal.pntd.0007829

Editor: Benjamin L. Makepeace, University of Liverpool, UNITED KINGDOM

Received: April 12, 2019; Accepted: October 4, 2019; Published: November 25, 2019

Copyright: © 2019 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: All relevant data are within the manuscript.

Funding: This study was supported by the Special Fund For High-level Talents in Beijing Health System Project (2011-3-079), Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding Support (XMLX201502 and XMLX201602) and the National Science and Technology Major Project of China (2018ZX09711003). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: The authors have declared that no competing interests exist.

Keywords: SFTS; China.

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Severe fever with thrombocytopenia syndrome (#SFTS) treated with a novel #antiviral medication, #favipiravir (T-705) (Infection, abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Infection. 2019 Oct 31. doi: 10.1007/s15010-019-01364-9. [Epub ahead of print]

Severe fever with thrombocytopenia syndrome (SFTS) treated with a novel antiviral medication, favipiravir (T-705).

Song R1, Chen Z2, Li W3.

Author information: 1 Center of Infectious Disease, Beijing Ditan Hospital, Capital Medical University, 8 Jingshun East Street, Chaoyang District, 100015, Beijing, People’s Republic of China. 2 Center of Infectious Disease, Beijing Ditan Hospital, Capital Medical University, 8 Jingshun East Street, Chaoyang District, 100015, Beijing, People’s Republic of China. zhccmu@sina.com. 3 Cancer Center, Beijing Ditan Hospital, Capital Medical University, 8 Jingshun East Street, Chaoyang District, 100015, Beijing, People’s Republic of China. vision988@126.com.

 

Abstract

BACKGROUND:

Severe fever and thrombocytopenia syndrome (SFTS) is an acute illness with a high mortality (16.2-29.1%). Unfortunately, there is no specific cure or vaccine for SFTS.

METHODS:

In this open-label study, two patients with SFTS were treated with favipiravir, a new antiviral drug.

RESULTS:

Patients had a sustainable virologic, immunologic and symptomatic recovery.

CONCLUSIONS:

Favipiravir may be a prosiming drug for the treatment of SFTS.

KEYWORDS: Favipiravir; SFTS; Severe fever and thrombocytopenia syndrome

PMID: 31673977 DOI: 10.1007/s15010-019-01364-9

Keywords: Antivirals; Favipiravir; SFTS.

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#SFTS Virus #RNA in #Semen, #Japan (Emerg Infect Dis., abstract)

[Source: US Centers for Disease Control and Prevention (CDC), Emerging Infectious Diseases Journal, full page: (LINK). Abstract, edited.]

Volume 25, Number 11—November 2019 / Research Letter

Severe Fever with Thrombocytopenia Syndrome Virus RNA in Semen, Japan

Satoru Koga, Takahiro Takazono  , Tsuyoshi Ando, Daisuke Hayasaka, Masato Tashiro, Tomomi Saijo, Shintaro Kurihara, Motohiro Sekino, Kazuko Yamamoto, Yoshifumi Imamura, Taiga Miyazaki, Katsunori Yanagihara, Kouichi Morita, Koichi Izumikawa, and Hiroshi Mukae

Author affiliations: Nagasaki University, Nagasaki, Japan

 

Abstract

Severe fever with thrombocytopenia syndrome virus (SFTSV) can be transmitted between humans. We describe a case of severe fever with thrombocytopenia syndrome (in which SFTSV RNA was detected in semen after its disappearance from serum. Our findings indicate possible sexual transmission of this emerging virus.

Keywords: SFTS; Human.

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