#Orthobunyavirus spike architecture and recognition by neutralizing #antibodies (Nat Commun., abstract)

[Source: Nature Communications, full page: (LINK). Abstract, edited.]

Article | OPEN | Published: 20 February 2019

Orthobunyavirus spike architecture and recognition by neutralizing antibodies

Jan Hellert, Andrea Aebischer, Kerstin Wernike, Ahmed Haouz, Emiliana Brocchi, Sven Reiche, Pablo Guardado-Calvo, Martin Beer & Félix A. Rey

Nature Communications, volume 10, Article number: 879 (2019)

 

Abstract

Orthobunyaviruses (OBVs) form a distinct genus of arthropod-borne bunyaviruses that can cause severe disease upon zoonotic transmission to humans. Antigenic drift or genome segment re-assortment have in the past resulted in new pathogenic OBVs, making them potential candidates for causing emerging zoonoses in the future. Low-resolution electron cryo-tomography studies have shown that OBV particles feature prominent trimeric spikes, but their molecular organization remained unknown. Here we report X-ray crystallography studies of four different OBVs showing that the spikes are formed by an N-terminal extension of the fusion glycoprotein Gc. Using Schmallenberg virus, a recently emerged OBV, we also show that the projecting spike is the major target of the neutralizing antibody response, and provide X-ray structures in complex with two protecting antibodies. We further show that immunization of mice with the spike domains elicits virtually sterilizing immunity, providing fundamental knowledge essential in the preparation for potential newly emerging OBV zoonoses.

Keywords: Orthobunyavirus; Zoonoses.

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#Vector #competence of biting #midges and #mosquitoes for #Shuni virus (PLoS Negl Trop Dis., abstract)

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

OPEN ACCESS /  PEER-REVIEWED / RESEARCH ARTICLE

Vector competence of biting midges and mosquitoes for Shuni virus

Tim W. R. Möhlmann , Judith Oymans, Paul J. Wichgers Schreur, Constantianus J. M. Koenraadt, Jeroen Kortekaas, Chantal B. F. Vogels

Published: February 12, 2019 / DOI: https://doi.org/10.1371/journal.pntd.0006609

 

Abstract

Background

Shuni virus (SHUV) is an orthobunyavirus that belongs to the Simbu serogroup. SHUV was isolated from diverse species of domesticated animals and wildlife, and is associated with neurological disease, abortions, and congenital malformations. Recently, SHUV caused outbreaks among ruminants in Israel, representing the first incursions outside the African continent. The isolation of SHUV from a febrile child in Nigeria and seroprevalence among veterinarians in South Africa suggests that the virus may have zoonotic potential as well. The high pathogenicity, extremely broad tropism, potential transmission via both biting midges and mosquitoes, and zoonotic features of SHUV require further investigation. This is important to accurately determine the risk for animal and human health, and to facilitate preparations for potential epidemics. To gain first insight into the potential involvement of biting midges and mosquitoes in SHUV transmission we have investigated the ability of SHUV to infect two species of laboratory-colonised biting midges and two species of mosquitoes.

Methodology/Principal findings

Culicoides nubeculosus, C. sonorensis, Culex pipiens pipiens, and Aedes aegypti were orally exposed to SHUV by providing an infectious blood meal. Biting midges showed high infection rates of approximately 40%-60%, whereas infection rates of mosquitoes were only 0–2%. Moreover, successful dissemination in both species of biting midges and no evidence for transmission by orally exposed mosquitoes was found.

Conclusions/Significance

The results of this study suggest that different species of Culicoides midges are efficient in SHUV transmission, while the involvement of mosquitoes has not been supported.

 

Author summary

Arthropod-borne (arbo)viruses are notorious for causing unpredictable and large-scale epidemics and epizootics. Apart from viruses such as West Nile virus and Rift Valley fever virus that are well-known to cause a significant impact on human and animal health, many arboviruses remain neglected. Shuni virus (SHUV) is a neglected virus with zoonotic characteristics that was recently associated with severe disease in livestock and wildlife. Isolations from field-collected biting midges and mosquitoes suggests that SHUV may be transmitted by these insects. In this study, four main vectors that transmit other arboviruses were selected to test their susceptibility to SHUV. Laboratory-reared biting midge species (Culicoides nubeculosus and C. sonorensis) and mosquito species (Culex pipiens pipiens and Aedes aegypti) were exposed to SHUV via an infectious blood meal. SHUV was able to successfully disseminate in both biting midge species, whereas no evidence of transmission by both mosquito species was found. Our results suggest that SHUV can be transmitted efficiently by diverse Culicoides species, and thereby that these insects could play a major role in the disease transmission cycle.

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Citation: Möhlmann TWR, Oymans J, Wichgers Schreur PJ, Koenraadt CJM, Kortekaas J, Vogels CBF (2019) Vector competence of biting midges and mosquitoes for Shuni virus. PLoS Negl Trop Dis 13(2): e0006609. https://doi.org/10.1371/journal.pntd.0006609

Editor: David Harley, University of Queensland, AUSTRALIA

Received: May 31, 2018; Accepted: June 13, 2018; Published: February 12, 2019

Copyright: © 2019 Möhlmann 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

Funding: TWRM, CJMK, and CBFV received funding from the Global One Health strategic programme of Wageningen University and Research, and JO, PJWS, and JK received funding from the Dutch Ministry of Agriculture, Nature and Food Quality; project WOT-01-001-033. 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: Orthobunyavirus; Shuni virus; Arbovirus; Mosquitoes; Midges.

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#Vector competence of biting #midges and #mosquitoes for #Shuni virus (PLoS Negl Trop Dis., abstract)

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

OPEN ACCESS /  PEER-REVIEWED / RESEARCH ARTICLE

Vector competence of biting midges and mosquitoes for Shuni virus

Tim W. R. Möhlmann , Judith Oymans, Paul J. Wichgers Schreur, Constantianus J. M. Koenraadt, Jeroen Kortekaas, Chantal B. F. Vogels

Published: December 7, 2018 / DOI: https://doi.org/10.1371/journal.pntd.0006993

 

Abstract

Background

Shuni virus (SHUV) is an orthobunyavirus that belongs to the Simbu serogroup. SHUV was isolated from diverse species of domesticated animals and wildlife, and is associated with neurological disease, abortions, and congenital malformations. Recently, SHUV caused outbreaks among ruminants in Israel, representing the first incursions outside the African continent. The isolation of SHUV from a febrile child in Nigeria and seroprevalence among veterinarians in South Africa suggests that the virus may have zoonotic potential as well. The high pathogenicity, extremely broad tropism, potential transmission via both biting midges and mosquitoes, and zoonotic features warrants prioritization of SHUV for further research. Additional knowledge is essential to accurately determine the risk for animal and human health, and to assess the risk of future epizootics and epidemics. To gain first insights into the potential involvement of arthropod vectors in SHUV transmission, we have investigated the ability of SHUV to infect and disseminate in laboratory-reared biting midges and mosquitoes.

Methodology/Principal findings

Culicoides nubeculosus, C. sonorensis, Culex pipiens pipiens, and Aedes aegypti were orally exposed to SHUV by providing an infectious blood meal. Biting midges showed high infection rates of approximately 40–60%, whereas infection rates of mosquitoes were lower than 2%. SHUV successfully disseminated in both species of biting midges, but no evidence of transmission in orally exposed mosquitoes was found.

Conclusions/Significance

The results of this study show that different species of Culicoides biting midges are susceptible to infection and dissemination of SHUV, whereas the two mosquito species tested were found not to be susceptible.

 

Author summary

Arthropod-borne (arbo)viruses are notorious for causing unpredictable and large-scale epidemics and epizootics. Apart from viruses such as West Nile virus and Rift Valley fever virus that are well known to have a significant impact on human and animal health, many arboviruses remain neglected. Shuni virus (SHUV) is a neglected virus with zoonotic potential that was recently associated with severe disease in livestock and wildlife. Isolations of SHUV from field-collected biting midges and mosquitoes suggests that SHUV may be transmitted by these insects. Laboratory-reared biting midge species (Culicoides nubeculosus and C. sonorensis) and mosquito species (Culex pipiens pipiens and Aedes aegypti), that are known to transmit other arboviruses, were exposed to SHUV via an infectious blood meal. SHUV was able to successfully disseminate in both biting midge species, whereas no evidence of infection or transmission in both mosquito species was found. Our results show that SHUV infects and disseminates in two different Culicoides species, suggesting that these insects could play an important role in the disease transmission cycle.

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Citation: Möhlmann TWR, Oymans J, Wichgers Schreur PJ, Koenraadt CJM, Kortekaas J, Vogels CBF (2018) Vector competence of biting midges and mosquitoes for Shuni virus. PLoS Negl Trop Dis 12(12): e0006993. https://doi.org/10.1371/journal.pntd.0006993

Editor: Hans-Peter Fuehrer, University of Veterinary Medicine, Vienna, AUSTRIA

Received: June 19, 2018; Accepted: November 12, 2018; Published: December 7, 2018

Copyright: © 2018 Möhlmann 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.

Funding: TWRM, CJMK, and CBFV received funding from the Global One Health strategic programme of Wageningen University and Research, and JO, PJWS, and JK received funding from the Dutch Ministry of Agriculture, Nature and Food Quality; project WOT-01-001-033. 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: Orthobunyavirus; Arbovirus; Shuni Virus; Midges; Mosquitoes.

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Vertical #transmission of naturally occurring #Bunyamwera and insect-specific #flavivirus #infections in #mosquitoes from islands and mainland shores of Lakes Victoria and Baringo in #Kenya (PLoS Negl Trop Dis., abstract)

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

OPEN ACCESS /  PEER-REVIEWED / RESEARCH ARTICLE

Vertical transmission of naturally occurring Bunyamwera and insect-specific flavivirus infections in mosquitoes from islands and mainland shores of Lakes Victoria and Baringo in Kenya

Yvonne Ukamaka Ajamma, Thomas Ogao Onchuru , Daniel O. Ouso , David Omondi, Daniel K. Masiga, Jandouwe Villinger

Published: November 19, 2018 / DOI: https://doi.org/10.1371/journal.pntd.0006949 / This is an uncorrected proof.

 

Abstract

Background

Many arboviruses transmitted by mosquitoes have been implicated as causative agents of both human and animal illnesses in East Africa. Although epidemics of arboviral emerging infectious diseases have risen in frequency in recent years, the extent to which mosquitoes maintain pathogens in circulation during inter-epidemic periods is still poorly understood. This study aimed to investigate whether arboviruses may be maintained by vertical transmission via immature life stages of different mosquito vector species.

Methodology

We collected immature mosquitoes (egg, larva, pupa) on the shores and islands of Lake Baringo and Lake Victoria in western Kenya and reared them to adults. Mosquito pools (≤25 specimens/pool) of each species were screened for mosquito-borne viruses by high-resolution melting analysis and sequencing of multiplex PCR products of genus-specific primers (alphaviruses, flaviviruses, phleboviruses and Bunyamwera-group orthobunyaviruses). We further confirmed positive samples by culturing in baby hamster kidney and Aedes mosquito cell lines and re-sequencing.

Principal findings

Culex univittatus (2/31pools) and Anopheles gambiae (1/77 pools) from the Lake Victoria region were positive for Bunyamwera virus, a pathogenic virus that is of public health concern. In addition, Aedes aegypti (3/50), Aedes luteocephalus (3/13), Aedes spp. (2/15), and Culex pipiens (1/140) pools were positive for Aedes flaviviruses at Lake Victoria, whereas at Lake Baringo, three pools of An. gambiae mosquitoes were positive for Anopheles flavivirus. These insect-specific flaviviruses (ISFVs), which are presumably non-pathogenic to vertebrates, were found in known medically important arbovirus and malaria vectors.

Conclusions

Our results suggest that not only ISFVs, but also a pathogenic arbovirus, are naturally maintained within mosquito populations by vertical transmission, even in the absence of vertebrate hosts. Therefore, virus and vector surveillance, even during inter-epidemics, and the study of vector-arbovirus-ISFV interactions, may aid in identifying arbovirus transmission risks, with the potential to inform control strategies that lead to disease prevention.

 

Author summary

The East African region is endemic to diverse mosquito-transmitted arboviruses, though little is known about the role of vertical transmission in maintaining these viruses within mosquito vector populations during inter-epidemic periods. We sampled mosquito larvae from the Lake Baringo and Lake Victoria regions of Kenya and reared them to adults in the laboratory before screening them for mosquito-associated viruses by multiplex RT-PCR-HRM, cell culture, and sequencing. From the Lake Victoria region, we detected the arbovirus, Bunyamwera, which can cause febrile illness in humans, in Culex univittatus and vector competent Anopheles gambiaemosquitoes. We also identified diverse insect-specific flaviviruses in Aedes aegypti, Aedes luteocephalus, Aedes spp. and Culex pipiens mosquitoes. From the Lake Baringo region, we detected Anopheles flavivirus in An. gambiae mosquitoes. These findings demonstrate that naturally occurring vertical transmission potentially maintains viruses in circulation within the sampled vector species populations. Therefore, mosquitoes may potentially transmit a pathogenic arbovirus during their first bite after emergence. Because various insect-specific flaviviruses have recently been found to either inhibit or enhance replication of specific arboviruses in mosquitoes, their vertical transmission, as observed in this study, has implications as to their potential impact on both horizontal and vertical transmission of medically important arboviruses.

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Citation: Ajamma YU, Onchuru TO, Ouso DO, Omondi D, Masiga DK, Villinger J (2018) Vertical transmission of naturally occurring Bunyamwera and insect-specific flavivirus infections in mosquitoes from islands and mainland shores of Lakes Victoria and Baringo in Kenya. PLoS Negl Trop Dis 12(11): e0006949. https://doi.org/10.1371/journal.pntd.0006949

Editor: Michael J. Turell, INDEPENDENT RESEARCHER, UNITED STATES

Received: May 3, 2018; Accepted: October 26, 2018; Published: November 19, 2018

Copyright: © 2018 Ajamma 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 ISFV sequences are available from the GenBank nucleotide database (accession MG372051-MG372060, MK015647- MK015648).

Funding: This work was supported by the Swedish International Development Cooperation Agency (Sida) (www.sida.se), grant number 75000529 to YUA as an African Regional Postgraduate Programme in Insect Science (ARPPIS) scholar; and institutional financial support from UK Aid (www.ukaiddirect.org) from the UK Government; Sida; the Swiss Agency for Development and Cooperation (SDC) (www.eda.admin.ch/sdc); and the Kenyan Government (www.mygov.go.ke). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The views expressed herein do not necessarily reflect the official opinion of the donors.

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

Keywords: Arbovirus; Flavivirus; Orthobunyavirus; Bunyamwera Virus; Mosquitoes; Culex spp.; Anopheles spp.; Kenya.

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#Virological and #Serological Responses of #Sheep and #Cattle to Experimental #Schmallenberg Virus #Infection (Vector Borne Zoo Dis., abstract)

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

Virological and Serological Responses of Sheep and Cattle to Experimental Schmallenberg Virus Infection

Abaineh D. Endalew, Igor Morozov, A. Sally Davis, Natasha N. Gaudreault, Kerstin Wernike, Bhupinder Bawa, Mark G. Ruder, Barbara S. Drolet, D. Scott McVey, Vinay Shivanna, Wenjun Ma, Bonto Faburay, William C. Wilson, and Juergen A. Richt

Published Online: 15 Aug 2018 / DOI: https://doi.org/10.1089/vbz.2018.2297

 

Abstract

Schmallenberg virus (SBV) is an orthobunyavirus in the Simbu serogroup that emerged in Germany in late 2011 and was mostly associated with a mild transient disease of sheep and cattle. SBV is transmitted by biting midges (Culicoidesspecies) and causes abortions, stillbirths, and congenital defects in naïve pregnant ruminants. Two separate studies were conducted with a primary objective of better understanding the virological and serological responses of sheep and cattle to different SBV isolates after experimental infection. The second objective was to produce immunoreagents and challenge materials for use in future vaccine and diagnostics research. These studies were carried out using the following infectious inocula: (i) infectious serum (IS) (ii) cell culture-grown virus, and (iii) infectious lamb brain homogenate. The responses were assessed in both species throughout the course of the experiment. SBV RNA in serum (RNAemia) was detected as early as 2 (in sheep) and 3 (in cattle) days postinfection (dpi) and peaked on 3 and 4 dpi in cattle and sheep, respectively. Cattle had higher levels of RNAemia compared with sheep. Experimental infection with IS resulted in the highest level of RNAemia in both species followed by cell culture-grown virus. A delayed, low level RNAemia was detected in cattle inoculated with infectious sheep brain. Isolation of SBV was only possible from 4 dpi sera from all cattle inoculated with IS and one sheep inoculated with cell culture-derived virus. SBV neutralizing antibodies were first detected on 14 dpi in both species. No specific gross and microscopic lesions were observed in either study. In conclusion, these studies highlight not only the difference in viremia and anti-SBV antibody level against the different SBV isolates, but also the extent of the response in the two host species.

Keywords: Schmallenberg virus; Orthobunyavirus; Cattle; Sheep; Animal Models.

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Association of #Batai Virus #Infection and #Encephalitis in Harbor #Seals, #Germany, 2016 (Emerg Infect Dis., abstract)

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

Volume 24, Number 9—September 2018 / Dispatch

Association of Batai Virus Infection and Encephalitis in Harbor Seals, Germany, 2016

Wendy K. Jo1, Vanessa M. Pfankuche1, Annika Lehmbecker, Byron Martina, Ana Rubio-Garcia, Stefanie Becker, Jochen Kruppa, Klaus Jung, Daniela Klotz, Julia Metzger, Martin Ludlow, Wolfgang Baumgärtner, Erhard van der Vries2, and Albert Osterhaus

Author affiliations: University of Veterinary Medicine Hannover, Hannover, Germany (W.K. Jo, V.M. Pfankuche, A. Lehmbecker, S. Becker, J. Kruppa, K. Jung, D. Klotz, J. Metzger, M. Ludlow, W. Baumgärtner, E. van der Vries, A. Osterhaus); Center for Systems Neuroscience, Hannover (W.K. Jo, V.M. Pfankuche, W. Baumgärtner, A. Osterhaus); Artemis One Health, Delft, the Netherlands (B. Martina, A. Osterhaus); Seal Centre Pieterburen, the Netherlands (A. Rubio-Garcia)

 

Abstract

We isolated Batai virus (from the brain of a euthanized, 26-year-old, captive harbor seal with meningoencephalomyelitis in Germany. We provide evidence that this orthobunyavirus can naturally infect the central nervous system of a mammal. The full-genome sequence showed differences from a previously reported virus isolate from a mosquito in Germany.

Keywords: Orthobunyavirus; Batai virus; Wildlife; Germany.

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#Human #Orthobunyavirus #Infections, Tefé, Amazonas, #Brazil (PLoS Curr., abstract)

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

PLoS Curr. 2018 Mar 22;10. pii: ecurrents.outbreaks.7d65e5eb6ef75664da68905c5582f7f7. doi: 10.1371/currents.outbreaks.7d65e5eb6ef75664da68905c5582f7f7.

Human Orthobunyavirus Infections, Tefé, Amazonas, Brazil.

Naveca FG1, Nascimento VA1, Souza VC1, de Figueiredo RMP2.

Author information: 1 Laboratório de Ecologia de Doenças Transmissíveis na Amazônia, Instituto Leônidas e Maria Deane – Fiocruz Amazônia, Manaus, Amazonas, Brazil. 2 Gerência de Virologia, Fundação de Medicina Tropical Doutor Heitor Vieira Dourado, Manaus, Amazonas, Brazil.

 

Abstract

INTRODUCTION:

Several orthobunyaviruses are important arthropod-borne pathogens, responsible for a variety of diseases in humans, from acute febrile illness to encephalitis.

METHODS:

We collected serum samples from a series of dengue suspected cases in Tefé, a mid-size city located in the interior of the Amazonas state, Brazil. Viral RNA extraction was performed, and specimens were tested for dengue virus using RT-PCR. Thirty dengue negative samples were further tested for Mayaro virus (MAYV) and Oropouche virus (OROV) using an RT-qPCR protocol previously described. Positive samples were characterized by MegaBLAST analysis over the entire nucleotide collection of the main public databases, and also by maximum likelihood phylogenetic reconstruction of the S genome segment.

RESULTS:

We detected nine OROV or OROV-like positive cases among 30 patients reporting fever and headache, as the most common symptoms. The closest nucleotide sequence returned from the MegaBLAST analysis belongs to an OROV isolated in Peru 2008. Moreover, all Tefé samples grouped in the same clade with the OROV reference sequence and other closely-related OROV-like viruses.

DISCUSSION:

Dengue viruses are still the most important arbovirus worldwide, causing hundreds of millions of infections every year. Nonetheless, other arboviruses like chikungunya virus, Zika virus, and yellow fever virus have emerged in the last few years and are now a public health concern in several countries. OROV is believed to have caused more than 500,000 febrile infections in Brazil over recent decades. Therefore, the results described in this study strengthen that this arbovirus, and its closely-related recombinants, should be under continuous surveillance, at least in the endemic countries of Latin America.

KEYWORDS: Brazil; Mayaro; Oropouche; Orthobunyavirus; arbovirus; dengue; infectious diseases

PMID: 29623245 PMCID: PMC5878103 DOI: 10.1371/currents.outbreaks.7d65e5eb6ef75664da68905c5582f7f7

Keywords: Orthobunyavirus; Mayaro Virus; Oropouche Virus; Brazil.

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