#Seroprevalence of #SFTS #Phlebovirus in Domesticated #Deer in South #Korea (Virol Sin., abstract)

[Source: Virologica Sinica, full page: (LINK). Abstract, edited.]

Seroprevalence of Severe Fever with Thrombocytopenia Syndrome Phlebovirus in Domesticated Deer in South Korea

Authors: Min-Ah Yu, Kwang-Min Yu, Su-Jin Park, Young-Il Kim, Norbert John Robles, Young-Jae Si, Eun-Ha Kim, Hyeok-Il Kwon, Hye Won Jeong, Min-Suk Song, Seok-Yong Kim, Young Ki Choi

Research Article / First Online: 25 June 2019

 

Abstract

Severe fever with thrombocytopenia syndrome phlebovirus (SFTSV) has a wide host range. Not only has it been found in humans, but also in many wild and domesticated animals. The infection of breeding deer on farms is a particularly worrisome public health concern due to the large amount of human contact and the diverse use of deer products, including raw blood. To investigate the prevalence of breeding domesticated deer, we examined the SFTSV infection rate on deer farms in South Korea from 2015 to 2017. Of the 215 collected blood samples, 0.9% (2/215) were found to be positive for viral RNA by PCR, and sequence analysis showed the highest homology with the KADGH human isolate. Both SFTSV-specific recombinant N and Gn protein-based ELISAs revealed that 14.0% (30/215) and 7.9% (17/215) of collected blood specimens were positive for SFTSV antibody. These results demonstrate that the breeding farm deer are exposed to SFTSV and could be a potential infection source for humans through direct contact or consumption of byproducts.

Keywords: Severe fever with thrombocytopenia syndrome phlebovirus (SFTSV) – Breeding deer – Seroprevalence – South Korea

 

Notes

Acknowledgements

We thank all involved staffs in the diagnosis of SFTS during this study. We thank veterinarians at Sejeong Farms for collecting the samples. This work was supported by the Ministry of Health & Welfare (government—wide R&D fund project for infectious disease research (HG18C0029).

Author Contributions

M-AY and YKC conceptualized the study. M-AY, KMY, S-JP, Y-IK, NJR, Y-JS, E-HK, and H-IK, conducted the investigation. HWJ, M-SS, S-YK and YKC wrote the paper.

 

Compliance with Ethical Stanadards

Conflict of interest

The authors do not have any competing interests to declare.

Animal and Human Rights Statement

This work was supported by the Ministry of Health & Welfare (government – wide R&D fund project for infectious disease research (HG18C0029). Deer serum samples for the study were collected with the deer owner’s approval, and the experiments were conducted under the guidelines of the Chungbuk National University.

Keywords: SFTS; Phlebovirus; Livestock; Deers; S. Korea.

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#RVF Virus and #YellowFever Virus in #Urine: A Potential #Source of #Infection (Virol Sin., summary)

[Source: Virologica Sinica, full page: (LINK). Summary, edited.]

Rift Valley Fever Virus and Yellow Fever Virus in Urine: A Potential Source of Infection

Authors: Meng Li, Beibei Wang, Liqiang Li, Gary Wong, Yingxia Liu, Jinmin Ma, Jiandong Li, Hongzhou Lu, Mifang Liang, Ang Li, Xiuqing Zhang, Yuhai Bi, Hui Zeng

Letter / First Online: 19 March 2019

___

Dear Editor,

In recent years, the incidence of human infections caused by emerging or re-emerging pathogens has rapidly increased. Diseases that were once regional now have the ability to spread globally in a short amount of time and pose a wider threat to public health (Weaver et al.2018). Yellow fever virus (YFV, family Flaviviridae, genus Flavivirus) is a mosquito-borne flavivirus that causes yellow fever in humans and has been endemic in Africa and Latin America for many years (Domingo et al. 2018). The most recent large-scale outbreak of YFV occurred in Brazil in which the mortality rate as of February 28, 2018 is 32.78% (WHO 2018). Rift Valley fever virus (RVFV, family Bunyaviridae, genus Phlebovirus) is another mosquito-borne virus and primarily circulates in Africa and the Middle East, and in recent years in Europe (Mansfield et al. 2015). During the initial stage of infection, most patients infected with YFV or RVFV present nonspecific symptoms such as fever, headache, and…

(…)

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Meng Li, Beibei Wang and Liqiang Li have contributed equally to this work.

Electronic supplementary material

The online version of this article ( https://doi.org/10.1007/s12250-019-00096-2) contains supplementary material, which is available to authorized users.

 

Notes

Acknowledgements

This work is supported by grants from the National Science and Technology Major Project of China (2016ZX10004222 and 2016YFC1200800), Strategic Priority Research Program of the Chinese Academy of Sciences (XDB29010102), Sanming Project of Medicine in Shenzhen (SZSM201412003), Shenzhen Municipal Government of China (JCYJ20160427151920801) and Beijing Municipal Science & Technology Commission (Z161100000116049), and the National Natural Science Foundation of China (NSFC) International Cooperation and Exchange Program (816110193). Y.B. is supported by the NSFC Outstanding Young Scholars (31822055) and Youth Innovation Promotion Association of Chinese Academy of Sciences (CAS) (2017122).

 

Compliance with Ethical Standards

Conflict of interest

The authors declare that they have no conflict of interest.

Animal and Human Rights Statement

Informed consent was obtained from all patients for the collection and use of all clinical specimens. This article does not contain any studies with animal subjects performed by any of the authors.

Keywords: Flavivirus; Phlebovirus; Yellow Fever; Rift Valley Fever.

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Quantitative #proteomic analysis reveals unfolded protein response involved in #SFTS virus #infection (J Virol., abstract)

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

Quantitative proteomic analysis reveals unfolded protein response involved in severe fever with thrombocytopenia syndrome virus infection

Lei-Ke Zhang, Bo Wang, Qilin Xin, Weijuan Shang, Shu Shen, Gengfu Xiao, Fei Deng, Hualin Wang, Zhihong Hu, Manli Wang

DOI: 10.1128/JVI.00308-19

 

ABSTRACT

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging, highly pathogenic, infectious disease caused by infection with a newly discovered tick-borne phlebovirus, SFTS virus (SFTSV). Limited information on the molecular mechanism of SFTSV infection and pathogenesis impedes the development of effective vaccines and drugs for SFTS prevention and treatment. In this study, an isobaric tag for relative and absolute quantification (iTRAQ)-based quantitative proteomic analysis of SFTSV-infected HEK 293 cells was performed to explore dynamic host cellular protein responses towards SFTSV infection. A total of 433 out of 5,606 host proteins involved in different biological processes were differentially regulated by SFTSV infection. The proteomic results highlighted a potential role of endoplasmic reticular stress-triggered unfolded protein response (UPR) in SFTSV infection. Further functional studies confirmed that all three major branches of the UPR, including the PRKR-like endoplasmic reticulum kinase (PERK), the activating transcription factor-6 (ATF6) and the inositol-requiring protein-1 (IRE1)-X-box-binding protein 1 (XBP1) pathways, were activated by SFTSV. However, only the former two pathways play a crucial role in SFTSV infection. Furthermore, expression of SFTSV glycoprotein (GP) alone was sufficient to stimulate the UPR, while suppression of PERK and ATF6 notably decreased GP expression. Interestingly, two other newly discovered phleboviruses, Heartland virus (HRTV) and Guertu virus (GTV), also stimulated the UPR, suggesting a common mechanism shared by these genetically related phleboviruses. This study provides a global view to our knowledge on how host cells respond to SFTSV infection and highlights that host cell UPR plays an important role in phlebovirus infection.

 

IMPORTANCE

Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging tick-borne bunyavirus that causes severe fever with thrombocytopenia syndrome in humans, with a mortality rate reaching up to 30% in some outbreaks. There are currently no FDA-approved vaccines or specific antivirals available against SFTSV. To comprehensively understand the molecular interactions occurring between SFTSV and the host cell, we exploit quantitative proteomic approach to investigate the dynamic host cellular responses to SFTSV infection. The results highlight multiple biological processes being regulated by SFTSV infection. Among these, we focused on exploration of the mechanism of how SFTSV infection stimulates the host cell’s unfolded protein response (UPR) and identified the UPR as a common feature shared by SFTSV-related new emerging phleboviruses. This study, for the first time to our knowledge, provides a global map for host cellular responses to SFTSV infection and highlighted potential host targets for further research.

Copyright © 2019 Zhang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.

Keywords: Phlebovirus; Bunyavirus; SFTS; Viral pathogenesis.

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#SandFly–Associated #Phlebovirus with Evidence of Neutralizing #Antibodies in #Humans, #Kenya (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 4—April 2019 / Research

Sand Fly–Associated Phlebovirus with Evidence of Neutralizing Antibodies in Humans, Kenya

David P. Tchouassi  , Marco Marklewitz, Edith Chepkorir, Florian Zirkel1, Sheila B. Agha, Caroline C. Tigoi, Edith Koskei, Christian Drosten, Christian Borgemeister, Baldwyn Torto, Sandra Junglen2  , and Rosemary Sang2

Author affiliations: International Centre of Insect Physiology and Ecology, Nairobi, Kenya (D.P. Tchouassi, E. Chepkorir, S.B. Agha, C.C. Tigoi, B. Torto, R. Sang); Charité-Universitätsmedizin Berlin, Berlin, Germany (M. Marklewitz, F. Zirkel, C. Drosten, S. Junglen); German Center for Infection Research, Berlin (M. Marklewitz, F. Zirkel. C. Drosten, S. Junglen); Center for Virus Research, Kenya Medical Research Institute, Nairobi (E. Koskei, R. Sang); University of Bonn, Bonn, Germany (C. Borgemeister)

 

Abstract

We describe a novel virus, designated Ntepes virus (NPV), isolated from sand flies in Kenya. NPV has the characteristic phlebovirus trisegmented genome architecture and is related to, but distinct from, Gabek Forest phlebovirus. Diverse cell cultures derived from wildlife, livestock, and humans were susceptible to NPV, with pronounced permissiveness in swine and rodent cells. NPV infection of newborn mice caused rapid and fatal illness. Permissiveness for NPV replication in sand fly cells, but not mosquito cells, suggests a vector-specific adaptation. Specific neutralizing antibodies were found in 13.9% (26/187) of human serum samples taken at the site of isolation of NPV as well as a disparate site in northeastern Kenya, suggesting a wide distribution. We identify a novel human-infecting arbovirus and highlight the importance of rural areas in tropical Africa for arbovirus surveillance as well as extending arbovirus surveillance to include hematophagous arthropods other than mosquitoes.

Keywords: Phlebovirus; Human; Ntepes virus; Kenya.

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Single dose of a #rVSV-based #vaccine elicits complete protection against #SFTS virus (npj Vaccines, abstract)

[Source: npj Vaccines, full page: (LINK). Abstract, edited.]

Article | OPEN | Published: 25 January 2019

Single dose of a rVSV-based vaccine elicits complete protection against severe fever with thrombocytopenia syndrome virus

Fangfang Dong,  Dandan Li,  Dan Wen,  Suhua Li,  Chaoyue Zhao,  Yue Qi,  Rohit K. Jangra,  Cuiping Wu,  Dequan Xia,  Xing Zhang,  Fei Deng,  Kartik Chandran,  Zhen Zou, Fei Yuan & Aihua Zheng

npj Vaccines, volume 4, Article number: 5 (2019)

 

Abstract

Severe fever with thrombocytopenia virus (SFTSV) is an emerging tick-borne phlebovirus that causes lethal human disease, for which there are no licensed antiviral vaccines or therapies. Herein, we developed a live attenuated recombinant vesicular stomatitis virus (rVSV)-based vaccine candidate expressing the SFTSV Gn/Gc glycoproteins (rVSV-SFTSV/AH12-GP). High titers of cross-protective, broadly neutralizing antibodies were elicited by a single dose of rVSV-SFTSV/AH12-GP in both immunocompetent and immunocompromised mice against multiple strains of SFTSV and the related but distinct phlebovirus Heartland virus (HRTV). Remarkably, complete protection against lethal challenge with SFTSV was conferred in young and old immunocompromised mice irrespective of any pre-existing vector-specific immunity. Collectively, these results suggest that a rVSV vector expressing SFTSV glycoproteins is a promising candidate vaccine against two emerging phleboviruses associated with severe human diseases.

Keywords: Phlebovirus; SFTS virus; Vaccines; Animal models.

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Two conserved #aminoacids within the #NSs of #SFTS #phlebovirus are essential for anti- #interferon activity (J Virol., abstract)

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

Two conserved amino acids within the NSs of SFTS phlebovirus are essential for anti-interferon activity

Miyu Moriyama 1, Manabu Igarashi 2,3, Takumi Koshiba 4, Takashi Irie 5, Ayato Takada 2,3 and Takeshi Ichinohe 1*

Author Affiliations: 1 Division of Viral Infection, Department of Infectious Disease Control, International Research Center for Infectious Diseases, Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo 108-8639, Japan; 2 Division of Global Epidemiology, Research Center for Zoonosis Control, Hokkaido University, Kita-ku, Sapporo 001-0020, Japan; 3 Global Station for Zoonosis Control, Global Institution for Collaborative Research and Education (GI-CoRE), Hokkaido University, Kita-ku, Sapporo 001-0020, Japan; 4 Department of Biology, Faculty of Sciences, Kyushu University, Higashi-ku, Fukuoka 812-8581, Japan; 5 Department of Virology, Institute of Biomedical & Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan

 

ABSTRACT

The nonstructural protein (NSs) of severe fever with thrombocytopenia syndrome phlebovirus (SFTSV) sequesters TANK-binding kinase 1 (TBK1) into NSs-induced cytoplasmic structures to inhibit the phosphorylation and nuclear translocation of interferon regulatory factor 3 (IRF3) and subsequent interferon beta (IFN-β) production. Although the C-terminal region of SFTSV NSs (NSs66-249) has been linked to the formation of NSs-induced cytoplasmic structures and inhibition of host IFN-β responses, the role of the N-terminal region in antagonising host antiviral responses remains to be defined. Herein, we demonstrate that two conserved amino acids at positions 21 and 23 in the SFTSV and heartland virus (HRTV) NSs are essential for suppression of IRF3 phosphorylation and IFN-β mRNA expression following infection with SFTSV or recombinant influenza virus lacking the NS1 gene. Surprisingly, formation of SFTSV/HRTV NSs-induced cytoplasmic structures is not essential for inhibition of host antiviral responses. Rather, association between SFTSV/HRTV NSs and TBK1 is required for suppression of mitochondrial antiviral signalling protein (MAVS)-mediated activation of IFN-β promoter activity. Although the SFTSV NSs did not prevent ubiquitination of TBK1, they associate with TBK1 though its N-terminal kinase domain (residues 1-307) to block the autophosphorylation of TBK1. Further, we found that both wild-type and 21/23A mutant NSs of SFTSV suppressed the NLRP3 inflammasome-dependent IL-1β secretion, suggesting that the importance of these residues is restricted to TBK1-dependent IFN signalling. Together, our findings strongly implicate the two conserved amino acids at positions 21 and 23 of SFTSV/HRTV NSs in the inhibition of host interferon responses.

 

Importance

Recognition of viruses by host innate immune systems plays a critical role not only in providing resistance to viral infection, but also in initiation of antigen-specific adaptive immune responses against viruses. Severe fever with thrombocytopenia syndrome (SFTS) is a newly emerging infectious disease caused by the SFTS phlebovirus (SFTSV), a highly pathogenic tick-borne phlebovirus. The 294 amino acid nonstructural protein (NSs) of SFTSV associates with TANK-binding kinase 1 (TBK1), a key regulator of host innate antiviral immunity, to inhibit interferon beta (IFN-β) production and enhance viral replication. Herein, we demonstrate that two conserved amino acids at positions 21 and 23 in the NSs of SFTSV and heartland virus, another tick-borne phlebovirus, are essential for association with TBK1 and suppression of IFN-β production. Our results provide important insight into the molecular mechanisms by which SFTSV NSs helps to counteract host antiviral strategies.

 

FOOTNOTES

*Corresponding author. Takeshi Ichinohe, Division of Viral Infection, Department of Infectious Disease Control, International Research Center for Infectious Diseases, Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo 108-8639, Japan. Tel: +81-3-6409-2125; E-mail: ichinohe@ims.u-tokyo.ac.jp

Copyright © 2018 American Society for Microbiology. All Rights Reserved.

Keywords: SFTS; Phlebovirus; Viral Pathogenesis.

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Isolation and sequencing of #Dashli virus, a novel #Sicilian-like virus in #sandflies from #Iran; genetic and phylogenetic evidence for the creation of one novel species within the Phlebovirus genus in the Bunyaviridae family (PLoS Negl Trop Dis., abstract)

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

OPEN ACCESS /  PEER-REVIEWED / RESEARCH ARTICLE

Isolation and sequencing of Dashli virus, a novel Sicilian-like virus in sandflies from Iran; genetic and phylogenetic evidence for the creation of one novel species within the Phlebovirusgenus in the Bunyaviridae family

Cigdem Alkan , Vahideh Moin Vaziri  , Nazli Ayhan, Mehdi Badakhshan, Laurence Bichaud, Nourina Rahbarian, Ezat-Aldin Javadian, Bulent Alten, Xavier de Lamballerie, Remi N. Charrel

Published: December 27, 2017 / DOI: https://doi.org/10.1371/journal.pntd.0005978 /  This is an uncorrected proof.

 

Abstract

Phlebotomine sandflies are vectors of phleboviruses that cause sandfly fever or meningitis with significant implications for public health. Although several strains of these viruses had been isolated in Iran in the late 1970’s, there was no recent data about the present situation at the outset of this study. Entomological investigations performed in 2009 and 2011 in Iran collected 4,770 sandflies from 10 different regions. Based on morphological identification, they were sorted into 315 pools according to species, sex, trapping station and date of capture. A phlebovirus, provisionally named Dashli virus (DASHV), was isolated from one pool of Sergentomyia spp, and subsequently DASHV RNA was detected in a second pool of Phlebotomus papatasi. Genetic and phylogenetic analyses based on complete coding genomic sequences indicated that (i) DASHV is most closely related to the Iranian isolates of Sandfly fever Sicilian virus [SFSV], (ii) there is a common ancestor to DASHV, Sandfly fever Sicilian- (SFS) and SFS-like viruses isolated in Italy, India, Turkey, and Cyprus (lineage I), (iii) DASHV is more distantly related with Corfou and Toros viruses (lineage II) although common ancestry is supported with 100% bootstrap, (iii) lineage I can be subdivided into sublineage Ia including all SFSV, SFCV and SFTV except those isolated in Iran which forms sublineage Ib (DASHV). Accordingly, we suggest to approve Sandfly fever Sicilian virus species consisting of the all aforementioned viruses. Owing that most of these viruses have been identified in human patients with febrile illness, DASHV should be considered as a potential human pathogen in Iran.

 

Author summary

Phlebotomine sandflies are vectors of phleboviruses that cause sandfly fever or meningitis with significant implications for public health. Although several strains of these viruses had been isolated in Iran in the late 1970’s, there was no recent data about the present situation at the outset of this study. Entomological investigations performed in 2009 and 2011 in Iran collected 4,770 sandflies from 10 different regions. A phlebovirus, provisionally named Dashli virus (DASHV), was isolated / detected in two pools. DASHV strain was isolated in cell culture and complete genome sequence was determined. Sequence analysis indicated that (i) DASHV is most closely related to the Iranian isolates of Sandfly fever Sicilian virus [SFSV], a virus that is known to cause self-resolutive incapacitating febrile illness in humans, (ii) there is a common ancestor to DASHV and all other variants of SFSV isolated in Italy, India, Turkey, and Cyprus (lineage I), (iii) DASHV is more distantly related with Corfou and Toros viruses (lineage II) although common ancestry is supported with 100% bootstrap, (iii) lineage I can be subdivided into sublineage Ia including all SFSV strains, whereas Iranian viruses are most closely related and should be individualized as DASHV (sublineage Ib). Although discovered first in the 1940’s, SFSV is still listed as “tentative species” by the International Committee for Taxonomy of Viruses. Based on the results described in this study, we propose to approve Sandfly fever Sicilian virus species. Owing that most of these viruses have been identified in human patients with febrile illness, DASHV should be considered as a potential human pathogen in Iran.

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Citation: Alkan C, Moin Vaziri V, Ayhan N, Badakhshan M, Bichaud L, Rahbarian N, et al. (2017) Isolation and sequencing of Dashli virus, a novel Sicilian-like virus in sandflies from Iran; genetic and phylogenetic evidence for the creation of one novel species within the Phlebovirus genus in the Bunyaviridae family. PLoS Negl Trop Dis 11(12): e0005978. https://doi.org/10.1371/journal.pntd.0005978

Editor: Mary Ann McDowell, University of Notre Dame, UNITED STATES

Received: January 19, 2017; Accepted: September 20, 2017; Published: December 27, 2017

Copyright: © 2017 Alkan 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 paper and its Supporting Information files.

Funding: This work was supported through funds received from EU grant FP7-261504 EDENext and this paper is catalogued by the EDENext Steering Committee as EDENext???(http://www.edenext.eu), the European Virus Archive goes Global (EVAg) project in the European Union’s Horizon 2020 research and innovation programme under grant agreement No 653316 (http://global.european-virus-archive.com/). The work of RNC and BA was done under the frame of EurNegVec (TD1303) COST Action. 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: Phlebovirus; Bunyavirus; Sandflies; Iran; Dashly Virus; Viral Meningitis.

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