Transstadial #Transmission and Long-term Association of #CCHF #Virus in #Ticks Shapes #Genome Plasticity (Sci Rep., abstract)

[Source: Scientific Reports, full page: (LINK). Abstract, edited.]

Article | OPEN

Transstadial Transmission and Long-term Association of Crimean-Congo Hemorrhagic Fever Virus in Ticks Shapes Genome Plasticity

Han Xia, Andrew S. Beck, Aysen Gargili, Naomi Forrester, Alan D. T. Barrett & Dennis A. Bente

Scientific Reports 6, Article number: 35819 (2016) / doi:10.1038/srep35819

Received: 04 May 2016 – Accepted: 04 October 2016 – Published online: 24 October 2016

 

Abstract

The trade-off hypothesis, the current paradigm of arbovirus evolution, proposes that cycling between vertebrate and invertebrate hosts presents significant constraints on genetic change of arboviruses. Studying these constraints in mosquito-borne viruses has led to a new understanding of epizootics. The trade-off hypothesis is assumed to be applicable to tick-borne viruses too, although studies are lacking. Tick-borne Crimean-Congo hemorrhagic fever virus (CCHFV), a member of the family Bunyaviridae, is a major cause of severe human disease worldwide and shows an extraordinary amount of genetic diversity compared to other arboviruses, which has been linked to increased virulence and emergence in new environments. Using a transmission model for CCHFV, utilizing the main vector tick species and mice plus next generation sequencing, we detected a substantial number of consensus-level mutations in CCHFV recovered from ticks after only a single transstadial transmission, whereas none were detected in CCHFV obtained from the mammalian host. Furthermore, greater viral intra-host diversity was detected in the tick compared to the vertebrate host. Long-term association of CCHFV with its tick host for 1 year demonstrated mutations in the viral genome become fixed over time. These findings suggest that the trade-off hypothesis may not be accurate for all arboviruses.

Keywords: Arbovirus; Bunyavirus; CCHF; Ticks.

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Correlation Between #HLA-A, B and DRB1 #Alleles and #SFTS (PLoS Negl Trop Dis., abstract)

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

OPEN ACCESS / PEER-REVIEWED / RESEARCH ARTICLE

Correlation Between HLA-A, B and DRB1 Alleles and Severe Fever with Thrombocytopenia Syndrome

Shu-jun Ding , Yi Zhang , Xiao-mei Zhang, Xiao-lin Jiang, Bo Pang, Yong-hong Song, Jian-xing Wang, Yao-wen Pei, Chuan-fu Zhu , Xian-jun Wang , Xue-jie Yu

Published: October 19, 2016 / http://dx.doi.org/10.1371/journal.pntd.0005076

 

Abstract

Objective

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging hemorrhagic fever caused by a tick-borne bunyavirus (SFTSV) in East Asian countries. The role of human leukocyte antigen (HLA) in resistance and susceptibility to SFTSV is not known. We investigated the correlation of HLA locus A, B and DRB1 alleles with the occurrence of SFTS.

Methods

A total of 84 confirmed SFTS patients (patient group) and 501 unrelated non-SFTS patients (healthy individuals as control group) from Shandong Province were genotyped by PCR-sequence specific oligonucleotide probe (PCR-SSOP) for HLA-A, B and DRB1 loci.Allele frequency was calculated and compared using χ2 test or the Fisher’s exact test. A corrected P value was calculated with a bonferronis correction. Odds Ratio (OR) and 95% confidence intervals (CI) were calculated by Woolf’s method.

Results

A total of 11 HLA-A, 23 HLA-B and 12 HLA-DRB1 alleles were identified in the patient group, whereas 15 HLA-A, 30 HLA-B and 13 HLA-DRB1 alleles were detected in the control group. The frequencies of A*30 and B*13 in the SFTS patient group were lower than that in the control group (P = 0.0341 and 0.0085, Pc = 0.5115 and 0.252). The ORs of A*30 and B*13 in the SFTS patient group were 0.54 and 0.49, respectively. The frequency of two-locus haplotype A*30-B*13 was lower in the patient group than in the control group(5.59% versus 12.27%, P = 0.037,OR = 0.41, 95%CI = 0.18–0.96) without significance(Pc>0.05). A*30-B*13-DRB1*07 and A*02-B*15-DRB1*04 had strong associations with SFTS resistance and susceptibility respectively (Pc = 0.0412 and 0.0001,OR = 0.43 and 5.07).

Conclusion

The host HLA class I polymorphism might play an important role with the occurrence of SFTS. Negative associations were observed with HLA-A*30, HLA-B*13 and Haplotype A*30-B*13, although the associations were not statistically significant. A*30-B*13-DRB1*07 had negative correlation with the occurrence of SFTS; in contrast, haplotype A*02-B*15-DRB1*04 was positively correlated with SFTS.

 

Author Summary

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging hemorrhagic fever caused by a tick-borne bunyavirus (SFTSV) in East Asian countries. The role of human leukocyte antigen (HLA) in resistance and susceptibility to SFTSV is not known. In this study, we investigated the correlation of HLA locus A, B and DRB1 alleles with the occurrence of SFTS. Our results have expanded the knowledge of the association of HLA genes with SFTS. Our study may be helpful to state the relationship between the occurrence of SFTS with HLA alleles or haplotypes and provide scientific basis for study on pathogenesis and vaccine development.

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Citation: Ding S-j, Zhang Y, Zhang X-m, Jiang X-l, Pang B, Song Y-h, et al. (2016) Correlation Between HLA-A, B and DRB1 Alleles and Severe Fever with Thrombocytopenia Syndrome. PLoS Negl Trop Dis 10(10): e0005076. doi:10.1371/journal.pntd.0005076

Editor: Aravinda M. de Silva, University of North Carolina at Chapel Hill, UNITED STATES

Received: April 20, 2016; Accepted: September 27, 2016; Published: October 19, 2016

Copyright: © 2016 Ding 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 by the National Natural Science Foundation of China (Grant No. 81102171), (http://www.nsfc.gov.cn) to SJD, Shandong Medical Science and Technology Development Program (Grant No. 2011HZ055), (http://www.sdws.gov.cn) to SJD, Shandong Province Science and Technology Development Plan (Grant No. 2012GHZ30031), (http://www.sdstc.gov.cn) to XMZ, and the Shandong Natural Science Foundation of China (Grant No.ZR2014HP030),(http://www.sdstc.gov.cn/eggs/1000007923.htm) to XlJ.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.

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#Bunyamwera #orthobunyavirus #glycoprotein precursor is processed by cellular signal peptidase and signal peptide peptidase (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.]

Bunyamwera orthobunyavirus glycoprotein precursor is processed by cellular signal peptidase and signal peptide peptidase

Xiaohong Shi a,1, Catherine H. Botting b, Ping Li a, Mark Niglas b, Benjamin Brennan a, Sally L. Shirran b, Agnieszka M. Szemiel a, and Richard M. Elliott a,2

Author Affiliations: [a]Medical Research Council–University of Glasgow Centre for Virus Research, University of Glasgow, Glasgow G61 1QH, United Kingdom; [b]Biomedical Sciences Research Complex, University of St. Andrews, St. Andrews KY16 9ST, United Kingdom

Edited by Peter Palese, Icahn School of Medicine at Mount Sinai, New York, NY, and approved June 17, 2016 (received for review February 29, 2016)

 

Significance

Bunyamwera virus (BUNV) is the prototype of the Orthobunyavirus genus and Bunyaviridae family that contains important human and animal pathogens. The cleavage mechanism of orthobunyavirus glycoprotein precursor (GPC) and the host proteases involved have not been clarified. Here we found that NSm and Gc contain their own internal signal peptides, which mediate the GPC cleavage by host signal peptidase and signal peptide peptidase (SPP). Furthermore, the NSm domain-I plays an important postcleavage role in cell fusion. Our data clarified the implication of host proteases in the processing of the orthobunyavirus GPC. This work identifies SPP as a potential intervention target, and the knowledge we gained will benefit preventive strategies against other orthobunyavirus infections.

 

Abstract

The M genome segment of Bunyamwera virus (BUNV)—the prototype of both the Bunyaviridae family and the Orthobunyavirus genus—encodes the glycoprotein precursor (GPC) that is proteolytically cleaved to yield two viral structural glycoproteins, Gn and Gc, and a nonstructural protein, NSm. The cleavage mechanism of orthobunyavirus GPCs and the host proteases involved have not been clarified. In this study, we investigated the processing of BUNV GPC and found that both NSm and Gc proteins were cleaved at their own internal signal peptides (SPs), in which NSm domain I functions as SPNSm and NSm domain V as SPGc. Moreover, the domain I was further processed by a host intramembrane-cleaving protease, signal peptide peptidase, and is required for cell fusion activities. Meanwhile, the NSm domain V (SPGc) remains integral to NSm, rendering the NSm topology as a two-membrane-spanning integral membrane protein. We defined the cleavage sites and boundaries between the processed proteins as follows: Gn, from residue 17–312 or nearby residues; NSm, 332–477; and Gc, 478–1433. Our data clarified the mechanism of the precursor cleavage process, which is important for our understanding of viral glycoprotein biogenesis in the genus Orthobunyavirus and thus presents a useful target for intervention strategies.

Bunyavirus – Bunyamwera virus – glycoprotein precursor processing – signal peptidase – signal peptide peptidase

Footnotes

1To whom correspondence should be addressed. Email: xiaohong.shi@glasgow.ac.uk.

2Deceased June 5, 2015.

Author contributions: X.S. and R.M.E. designed research; X.S., C.H.B., P.L., M.N., B.B., S.L.S., and A.M.S. performed research; C.H.B. and S.L.S. performed MS; X.S. analyzed data; and X.S. and R.M.E. wrote the paper.

The authors declare no conflict of interest.

This article is a PNAS Direct Submission.

This article contains supporting information online at http://www.pnas.org/lookup/suppl/doi:10.1073/pnas.1603364113/-/DCSupplemental.

Freely available online through the PNAS open access option.

Keywords: Research; Abstracts; Bunyavirus; Bunyamwera virus.

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#Canine #Infections and Partial S Segment #Sequence Analysis of #Toscana Virus in #Turkey (Vector Borne Zoo Dis., abstract)

[Source: Vector Borne and Zoonotic Diseases, full page: (LINK). Abstract, edited.]

Vector-Borne and Zoonotic Diseases

Canine Infections and Partial S Segment Sequence Analysis of Toscana Virus in Turkey

To cite this article: Dincer Ender, Karapinar Zeynep, Oktem Mert, Ozbaba Merve, Ozkul Aykut, and Ergunay Koray. Vector-Borne and Zoonotic Diseases. July 2016, ahead of print. doi:10.1089/vbz.2016.1979.

Online Ahead of Print: July 11, 2016

Author information: Ender Dincer,1 Zeynep Karapinar,2 Mert Oktem,3 Merve Ozbaba,4 Aykut Ozkul,5 and Koray Ergunay6

1Advanced Technology of Education, Research and Application Center, Mersin University, Mersin, Turkey. 2Department of Virology, Faculty of Veterinary Medicine, Yuzuncu Yıl University, Van, Turkey. 3Department of Biotechnology, Mersin University, Mersin, Turkey. 4Petical Veterinary Hospital, Mersin, Turkey. 5Department of Virology, Faculty of Veterinary Medicine, Ankara University, Ankara, Turkey. 6Virology Unit, Department of Medical Microbiology, Faculty of Medicine, Hacettepe University, Ankara, Turkey.

Address correspondence to: Koray Ergunay, Virology Unit, Department of Medical Microbiology, Faculty of Medicine, Hacettepe University, Morphology Building 3rd Floor, Sihhiye, Ankara 06100, Turkey, E-mail: ekoray@hacettepe.edu.tr

 

ABSTRACT

Introduction:

Toscana virus (TOSV) is a sandfly-borne bunyavirus with a significant public health impact. Preliminary studies have revealed TOSV exposure in dogs and they were suggested as potential reservoirs. This study was performed to characterize canine TOSV infections in an endemic region. Sequencing of TOSV small (S) segment in several previously identified specimens was also undertaken to reveal viral genealogy.

Materials and Methods:

Canine and feline plasma were collected in several districts of Mersin province, Mediterranean Anatolia, Turkey, during May–September, 2015. Phlebovirus RNA was screened through two nested polymerase chain reaction (PCR) assays, targeting S and large (L) segments of the viral genome. A kinetoplast minicircle nested PCR was employed for Leishmania DNA detection and typing. Previously collected TOSV-positive specimens from humans, dogs, cats, and sandflies from various regions in Turkey and Cyprus were further evaluated through the S segment PCR. All amplicons were characterized through sequencing.

Results:

A total of 210 specimens that comprise canine (76.2%) and feline (23.8%) plasma were screened. In three (1.9%) and two (1.3%) canine specimens, TOSV and Leishmania nucleic acids were detected, respectively. The TOSV strains were characterized as genotype B, and Leishmania infantum was identified in positive specimens. Twenty-four partial S segment sequences were amplified, which demonstrated a maximum intramural diversity of 3.88% in the nucleotide level. Sequence comparisons revealed significant similarities to particular genotype B strains characterized in Spain and France, whereas a notable divergence was observed among several TOSV strains. Single or recurrent amino acid substitutions were noted in eight residues of the viral nucleocapsid.

Discussion:

Canine infections of TOSV genotype B, with temporal and spatial association with L. infantum, were detected. Divergent TOSV S segment sequences with amino acid substitutions, presumably associated with host adaptation, were observed.

Keywords: Research; Abstracts; Toscana Virus; Bunyavirus; Dogs; Turkey.

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#Structure of a #phleboviral #envelope #glycoprotein reveals a consolidated model of membrane fusion (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.]

Structure of a phleboviral envelope glycoprotein reveals a consolidated model of membrane fusion

Steinar Halldorsson a, Anna-Janina Behrens b, Karl Harlos a, Juha T. Huiskonen a, Richard M. Elliott c, Max Crispin b, Benjamin Brennan c,1, and Thomas A. Bowden a,1

Author Affiliations: aDivision of Structural Biology, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, United Kingdom; bOxford Glycobiology Institute, Department of Biochemistry, University of Oxford, Oxford OX1 3QU, United Kingdom; cMRC–University of Glasgow Centre for Virus Research, Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G61 1QH, United Kingdom

Edited by Peter Palese, Icahn School of Medicine at Mount Sinai, New York, NY, and approved May 17, 2016 (received for review March 7, 2016)

 

Significance

Severe fever with thrombocytopenia syndrome virus (SFTSV) is a deadly tick-borne viral pathogen. Since first being reported in China in 2009, SFTSV has spread throughout South Korea and Japan, with mortality rates reaching up to 30%. The surface of the SFTSV virion is decorated by two glycoproteins, Gn and Gc. Here, we report the atomic-level structure of the Gc glycoprotein in a conformation formed during uptake of the virion into the host cell. Our analysis reveals the conformational changes that the Gc undergoes during host cell infection and provides structural evidence that these rearrangements are conserved with otherwise unrelated alpha- and flaviviruses.

 

Abstract

An emergent viral pathogen termed severe fever with thrombocytopenia syndrome virus (SFTSV) is responsible for thousands of clinical cases and associated fatalities in China, Japan, and South Korea. Akin to other phleboviruses, SFTSV relies on a viral glycoprotein, Gc, to catalyze the merger of endosomal host and viral membranes during cell entry. Here, we describe the postfusion structure of SFTSV Gc, revealing that the molecular transformations the phleboviral Gc undergoes upon host cell entry are conserved with otherwise unrelated alpha- and flaviviruses. By comparison of SFTSV Gc with that of the prefusion structure of the related Rift Valley fever virus, we show that these changes involve refolding of the protein into a trimeric state. Reverse genetics and rescue of site-directed histidine mutants enabled localization of histidines likely to be important for triggering this pH-dependent process. These data provide structural and functional evidence that the mechanism of phlebovirus–host cell fusion is conserved among genetically and patho-physiologically distinct viral pathogens.

emerging virus – phlebovirus – viral membrane fusion – bunyavirus – structure

 

Footnotes

1To whom correspondence may be addressed. Email: Thomas.Bowden@strubi.ox.ac.uk or Ben.Brennan@glasgow.ac.uk.

Author contributions: S.H., R.M.E., M.C., B.B., and T.A.B. designed research; S.H., A.-J.B., K.H., B.B., and T.A.B. performed research; S.H., A.-J.B., K.H., R.M.E., M.C., B.B., and T.A.B. analyzed data; and S.H., A.-J.B., J.T.H., M.C., B.B., and T.A.B. wrote the paper.

The authors declare no conflict of interest.

This article is a PNAS Direct Submission.

Data deposition: The crystallography, atomic coordinates, and structure factors have been deposited in the Protein Data Bank, http://www.pdb.org (PDB ID code 5G47).

This article contains supporting information online at http://www.pnas.org/lookup/suppl/doi:10.1073/pnas.1603827113/-/DCSupplemental.

Keywords: Research; Abstracts; SFTS; Phlebovirus; Bunyavirus; Flavivirus.

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