Boosting #Global #YellowFever #Vaccine #Supply for #Epidemic #Preparedness: 3 Actions for #China and the #USA (Virol Sin., abstract)

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

Boosting Global Yellow Fever Vaccine Supply for Epidemic Preparedness: 3 Actions for China and the USA

Authors: Daniel R. Lucey, Kristen R. Kent

Perspective / First Online: 24 May 2019

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Yellow fever (YF) is an acute disease caused by a flavivirus that infects the liver. It can cause jaundice, bleeding, kidney damage, and death. No antiviral therapy exists. A vaccine does exist, however, and fortunately confers life-long immunity after a single dose (Monath et al.2016; WHO 2017a, b).

(…)

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Notes

Compliance with Ethical Standards

Conflict of interest: The authors declare that they have no conflict of interest.

Animal and Human Rights Statement: This article does not contain any studies with human or animal subjects performed by any of the authors.

Keywords: Yellow Fever; Vaccines; USA; China.

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Schlafen 11 Restricts #Flavivirus #Replication (J Virol., abstract)

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

Schlafen 11 Restricts Flavivirus Replication.

Federico Valdez, Julienne Salvador, Pedro M. Palermo, Jonathon E. Mohl, Kathryn A. Hanley, Douglas Watts, Manuel Llano

DOI: 10.1128/JVI.00104-19

 

ABSTRACT

Schlafen 11 (Slfn11) is an interferon-stimulated gene that controls synthesis of proteins by regulating tRNA abundance. Likely through this mechanism, Slfn11 has previously been shown to impair human immunodeficiency virus 1 (HIV-1) infection and the expression of codon-biased open reading frames. Because replication of positive-sense single-stranded RNA [(+)ssRNA] viruses requires the immediate translation of the incoming viral genome whereas negative-sense, single-stranded RNA [(-)ssRNA] viruses carry at infection an RNA replicase that makes multiple translation competent copies of the incoming viral genome, we reasoned that (+)ssRNA viruses will be more sensitive to the effect of Slfn11 on protein synthesis than (-)ssRNA viruses. To evaluate this hypothesis, we tested the effects of Slfn11 on the replication of a panel of ssRNA viruses in the human glioblastoma cell line A172, which naturally expresses Slfn11. Depletion of Slfn11 significantly increased the replication of (+)ssRNA viruses from the Flavivirus genus, including West Nile (WNV), dengue (DENV), and Zika virus (ZIKV) but had no significant effect on the replication of the (-)ssRNA viruses vesicular stomatitis (VSV, Rhabdoviridae family) and Rift Valley fever (RVFV, Phenuiviridae family). Quantification of the genome-containing viral particles to plaque forming units ratio indicated that Slfn11 impairs WNV infectivity. Intriguingly, Slfn11 prevented WNV-induced down-regulation of a subset of tRNAs implicated in the translation of 11.8% of the viral polyprotein. Low abundance tRNAs might promote optimal protein folding and enhance viral infectivity, as previously reported. In summary, this study demonstrates that Slfn11 restricts flavivirus replication by impairing viral infectivity.

 

AUTHOR SUMMARY

We provide evidence that the cellular protein Schlafen 11 (Slfn11) impairs replication of flaviviruses, including West Nile (WNV), dengue (DENV), and Zika virus (ZIKV). However, replication of single-stranded, negative RNA viruses was not affected. Specifically, Slfn11 decreases the infectivity of WNV potentially by preventing virus-induced modifications of the host tRNA repertoire that could lead to enhanced viral protein folding. Furthermore, we demonstrated that Slfn11 is not the limiting factor of this novel broad anti-viral pathway.

Copyright © 2019 American Society for Microbiology. All Rights Reserved.

Keywords: Flavivirus; Zika virus; WNV; Dengue fever; Interferons.

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#Serological #evidence of #Flavivirus #circulation in #human populations in Northern #Kenya: an assessment of disease risk 2016-2017 (Virol J., abstract)

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

Virol J. 2019 May 17;16(1):65. doi: 10.1186/s12985-019-1176-y.

Serological evidence of Flavivirus circulation in human populations in Northern Kenya: an assessment of disease risk 2016-2017.

Chepkorir E1,2, Tchouassi DP3, Konongoi SL4, Lutomiah J4, Tigoi C3, Irura Z5, Eyase F6, Venter M7, Sang R3.

Author information: 1 International Centre of Insect Physiology and Ecology, P. O. Box 30772-00100, Nairobi, Kenya. echepkorir@icipe.org. 2 Center for Viral Zoonoses, Department of Medical Virology, University of Pretoria, P. O. Box 323, Arcadia, 0007, South Africa. echepkorir@icipe.org. 3 International Centre of Insect Physiology and Ecology, P. O. Box 30772-00100, Nairobi, Kenya. 4 Center for Virus Research, Kenya Medical Research Institute, P. O. Box 54628-00200, Nairobi, Kenya. 5 Division of Disease Surveillance and Response, Ministry of Health, P. O. Box 20781-00202, Nairobi, Kenya. 6 Jomo Kenyatta University of Agriculture and Technology, P.O. Box 606, Village Market, Nairobi, Kenya. 7 Center for Viral Zoonoses, Department of Medical Virology, University of Pretoria, P. O. Box 323, Arcadia, 0007, South Africa.

 

Abstract

BACKGROUND:

Yellow fever, Dengue, West Nile and Zika viruses are re-emerging mosquito-borne Flaviviruses of public health concern. However, the extent of human exposure to these viruses and associated disease burden in Kenya and Africa at large remains unknown. We assessed the seroprevalence of Yellow fever and other Flaviviruses in human populations in West Pokot and Turkana Counties of Kenya. These areas border Uganda, South Sudan and Ethiopia where recent outbreaks of Yellow fever and Dengue have been reported, with possibility of spillover to Kenya.

METHODOLOGY:

Human serum samples collected through a cross-sectional survey in West Pokot and Turkana Counties were screened for neutralizing antibodies to Yellow fever, Dengue-2, West Nile and Zika virus using the Plaque Reduction Neutralization Test (PRNT). Seroprevalence was compared by county, site and important human demographic characteristics. Adjusted odds ratios (aOR) were estimated using Firth logistic regression model.

RESULTS:

Of 877 samples tested, 127 neutralized with at least one of the four flaviviruses (14.5, 95% CI 12.3-17.0%), with a higher proportion in Turkana (21.1%, n = 87/413) than in West Pokot (8.6%, n = 40/464). Zika virus seroprevalence was significantly higher in West Pokot (7.11%) than in Turkana County (0.24%; χ2 P < 0.0001). A significantly higher Yellow fever virus seroprevalence was also observed in Turkana (10.7%) compared to West Pokot (1.29%; χ2 P < 0.0001). A high prevalence of West Nile virus was detected in Turkana County only (10.2%) while Dengue was only detected in one sample, from West Pokot. The odds of infection with West Nile virus was significantly higher in males than in females (aOR = 2.55, 95% CI 1.22-5.34). Similarly, the risk of Zika virus infection in West Pokot was twice higher in males than females (aOR = 2.01, 95% CI 0.91-4.41).

CONCLUSION:

Evidence of neutralizing antibodies to West Nile and Zika viruses indicates that they have been circulating undetected in human populations in these areas. While the observed Yellow Fever prevalence in Turkana and West Pokot Counties may imply virus activity, we speculate that this could also be as a result of vaccination following the Yellow Fever outbreak in the Omo river valley, South Sudan and Uganda across the border.

KEYWORDS: Dengue virus; Flaviviruses risk assessment; Northern Kenya; Plaque reduction neutralization test; Seroprevalence; West Nile virus; Yellow fever virus; Zika virus

PMID: 31101058 DOI: 10.1186/s12985-019-1176-y

Keywords: Flavivirus; WNV; Zika Virus; Dengue Fever; Yellow Fever; Serology; Seroprevalence; Kenya.

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Cross- #Protection of #Dengue Virus #Infection against #Congenital #Zika #Syndrome, Northeastern #Brazil (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 8—August 2019 / Research

Cross-Protection of Dengue Virus Infection against Congenital Zika Syndrome, Northeastern Brazil

Celia Pedroso1, Carlo Fischer1, Marie Feldmann1, Manoel Sarno, Estela Luz, Andrés Moreira-Soto, Renata Cabral, Eduardo Martins Netto, Carlos Brites, Beate M. Kümmerer, and Jan Felix Drexler

Author affiliations: Universidade Federal de Bahia, Salvador, Brazil (C. Pedroso, M. Sarno, E. Luz, R. Cabral, E. Martins Netto, C. Brites); Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin Humbolt-Universität zu Berlin and Berlin Institute of Health, Institute of Virology, Berlin, Germany (C. Fischer, A. Moreira-Soto, J.F. Drexler); University of Bonn Medical Centre, Bonn, Germany (M. Feldmann, B.M. Kümmerer); German Centre for Infection Research (B.M. Kümmerer, J.F. Drexler)

 

Abstract

The Zika virus outbreak in Latin America resulted in congenital malformations, called congenital Zika syndrome (CZS). For unknown reasons, CZS incidence was highest in northeastern Brazil; one potential explanation is that dengue virus (DENV)–mediated immune enhancement may promote CZS development. In contrast, our analyses of historical DENV genomic data refuted the hypothesis that unique genome signatures for northeastern Brazil explain the uneven dispersion of CZS cases. To confirm our findings, we performed serotype-specific DENV neutralization tests in a case–control framework in northeastern Brazil among 29 Zika virus–seropositive mothers of neonates with CZS and 108 Zika virus–seropositive control mothers. Neutralization titers did not differ significantly between groups. In contrast, DENV seroprevalence and median number of neutralized serotypes were significantly lower among the mothers of neonates with CZS. Supported by model analyses, our results suggest that exposure to multitypic DENV infection may protect from, rather than enhance, development of CZS.

Keywords: Flavivirus; Dengue Fever; Zika Virus; A.D.E.; Congenital Zika Syndrome; Pregnancy; Brazil; Seroprevalence.

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Discovery of novel #crustacean and #cephalopod #flaviviruses: insights into evolution and circulation of flaviviruses between marine invertebrate and vertebrate hosts (J Virol., abstract)

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

Discovery of novel crustacean and cephalopod flaviviruses: insights into evolution and circulation of flaviviruses between marine invertebrate and vertebrate hosts

Rhys Parry, Sassan Asgari

DOI: 10.1128/JVI.00432-19

 

ABSTRACT

Most described flaviviruses (family, Flaviviridae) are disease-causing pathogens of vertebrates maintained in zoonotic cycles between mosquitoes or ticks and vertebrate hosts. Poor sampling of flaviviruses outside vector-borne flaviviruses, such as Zika virus and dengue virus, have presented a narrow understanding of flavivirus diversity and evolution. In this study, we discovered three crustacean flaviviruses (Gammarus chevreuxi flavivirus, Gammarus pulex flavivirus and Crangon crangon flavivirus) and two cephalopod flaviviruses (Southern Pygmy squid flavivirus and Firefly squid flavivirus). Bayesian and Maximum-Likelihood phylogenetic methods demonstrate that crustacean flaviviruses form a well-supported clade and share a more closely related ancestor to terrestrial vector-borne flaviviruses than classical insect-specific flaviviruses. In addition, we identify variants of Wenzhou shark flavivirus in multiple gazami crab (Portunus trituberculatus) populations with active replication supported by evidence of an active RNA interference (RNAi) response. This suggests Wenzhou shark flavivirus moves horizontally between sharks and gazami crabs in ocean ecosystems. Analyses of the mono and dinucleotide composition of marine flaviviruses compared to flaviviruses with known host status suggest some marine flaviviruses share a nucleotide bias similar to vector-borne flaviviruses. Further, we identify crustacean flavivirus endogenous viral elements that are closely related to terrestrial vector-borne flaviviruses. Taken together, these data provide evidence of flaviviruses circulating between marine vertebrates and invertebrates, expand our understanding of flavivirus host range and offer potential insights into the evolution and emergence of terrestrial vector-borne flaviviruses.

 

Importance

Some flaviviruses are known to cause disease in vertebrates and typically transmitted by blood-feeding arthropods such as ticks and mosquitoes. While an ever-increasing number of insect-specific flaviviruses have been described, we have a narrow understanding of flavivirus incidence and evolution. To expand this understanding, we discovered a number of novel flaviviruses infecting a range of crustaceans and cephalopod hosts. Phylogenetic analyses of these novel marine flaviviruses suggests that crustacean flaviviruses share a close ancestor to all terrestrial vector-borne flaviviruses, and squid flaviviruses are the most divergent of all known flaviviruses to date. Additionally, our results indicate horizontal transmission of a marine flavivirus between crabs and sharks. Taken together these data suggests flaviviruses move horizontally between invertebrates and vertebrates in ocean ecosystems. This study demonstrates that flavivirus invertebrate-vertebrate host associations have arisen in flaviviruses at least twice and may potentially provide insights into the emergence or origin of terrestrial vector-borne flaviviruses.

Copyright © 2019 American Society for Microbiology. All Rights Reserved.

Keywords: Flavivirus; Crustacean flavivirus; Cephalopod flavivirus; Wildlife.

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The #Human Upper #Respiratory Tract #Epithelium Is Susceptible to #Flaviviruses (Front Microbiol., abstract)

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

Front Microbiol. 2019 Apr 16;10:811. doi: 10.3389/fmicb.2019.00811. eCollection 2019.

The Human Upper Respiratory Tract Epithelium Is Susceptible to Flaviviruses.

Vielle NJ1,2,3, García-Nicolás O1,2, Oliveira Esteves BI1,2, Brügger M1,2,3, Summerfield A1,2, Alves MP1,2.

Author information: 1 Institute of Virology and Immunology, Bern, Switzerland. 2 Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of Bern, Bern, Switzerland. 3 Graduate School of Cellular and Biomedical Sciences, University of Bern, Bern, Switzerland.

 

Abstract

Flaviviruses replicate in a wide variety of species and have a broad cellular tropism. They are isolated from various body fluids, and Zika virus (ZIKV), Japanese encephalitis virus (JEV), and West Nile virus (WNV) RNAs have been detected in nasopharyngeal swabs. Consequently, we evaluated the cellular tropism and host responses upon ZIKV, JEV, WNV, and Usutu virus (USUV) infection using a relevant model of the human upper respiratory tract epithelium based on primary human nasal epithelial cells (NECs) cultured at the air-liquid interface. NECs were susceptible to all the viruses tested, and confocal analysis showed evidence of infection of ciliated and non-ciliated cells. Each flavivirus productively infected NECs, leading to apical and basolateral live virus shedding with particularly high basal release for JEV and WNV. As demonstrated by a paracellular permeability assay, the integrity of the epithelium was not affected by flavivirus infection, suggesting an active release of live virus through the basolateral surface. Also, we detected a significant secretion of interferon type III and the pro-inflammatory cytokine IP-10/CXCL10 upon infection with JEV. Taken together, our data suggest that the human upper respiratory tract epithelium is a target for flaviviruses and could potentially play a role in the spread of infection to other body compartments through basolateral virus release. Undoubtedly, further work is required to evaluate the risks and define the adapted measures to protect individuals exposed to flavivirus-contaminated body fluids.

KEYWORDS: air-liquid interface cultures; flavivirus; nasal epithelial cells; non-vector borne transmission; respiratory epithelium; upper respiratory tract

PMID: 31057517 PMCID: PMC6477545 DOI: 10.3389/fmicb.2019.00811

Keywords: Flavivirus; Viral pathogenesis.

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#Arboviral #screening of invasive #Aedes species in northeastern #Turkey: #WNV circulation and detection of insect-only viruses (PLoS Negl Trop Dis., abstract)

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

OPEN ACCESS /  PEER-REVIEWED / RESEARCH ARTICLE

Arboviral screening of invasive Aedes species in northeastern Turkey: West Nile virus circulation and detection of insect-only viruses

Mustafa M. Akıner, Murat Öztürk, Aykut Buğra Başer, Filiz Günay, Sabri Hacıoğlu, Annika Brinkmann, Nergis Emanet, Bülent Alten, Aykut Özkul, Andreas Nitsche, Yvonne-Marie Linton, Koray Ergünay

Published: May 6, 2019 / DOI: https://doi.org/10.1371/journal.pntd.0007334 / This is an uncorrected proof.

 

Abstract

Background

The recent reports of Aedes aegypti and Ae. albopictus populations in Turkey, in parallel with the territorial expansion identified in several surrounding countries, have raised concerns about the establishment and re-establishment of these invasive Aedes mosquitoes in Turkey. This cross-sectional study was performed to detect Aedes aegypti and Ae. albopictus in regions of recent incursions, and screen for viral pathogens known to be transmitted elsewhere by these species.

Methodology

Mosquitoes were collected at several locations in Artvin, Rize and Trabzon provinces of the Black Sea region during 2016–2017, identified morphologically, pooled and analyzed via generic or specific nucleic acid amplification assays. Viruses in positive pools were identified by product sequencing, cell culture inoculation and next generation sequencing (NGS) in selected specimens.

Principal findings

The study group comprised 791 specimens. Aedes albopictus was the most abundant species in all locations (89.6%), followed by Ae. aegypti (7.8%) and Culex pipiens (2.5%). Mosquitoes were screened for viruses in 65 pools where fifteen (23.1%) were reactive. The infecting strains was identified as West Nile virus (WNV) in 5 pools (7.7%) with Ae. albopictus or Cx. pipiensmosquitoes. The obtained WNV sequences phylogenetically grouped with local and global lineage 1 clade 1a viruses. In 4 (6.2%) and 6 (9.2%) pools, respectively, cell fusing agent virus (CFAV) and Aedes flavivirus (AEFV) sequences were characterized. NGS provided a near-complete AEFV genome in a pool of Ae. albopictus. The strain is provisionally called “AEFV-Turkey”, and functional analysis of the genome revealed several conserved motifs and regions associated with virus replication. Merida-like virus Turkey (MERDLVT), a recently-described novel rhabdovirus, was also co-detected in a Cx. pipiens pool also positive for WNV.

Conclusions/Significance

Invasive Aedes mosquitoes are established in certain locations of northeastern Turkey. Herein we conclusively show the role of these species in WNV circulation in the region. Biosurveillance is imperative to monitor the spread of these species further into Asia Minor and to detect possible introduction of pathogens.

 

Author summary

Mosquitoes can transmit viruses to susceptible humans during blood-feeding. The presence and establishment of particular mosquito species within a region is the prerequisite for the introduction and emergence of the diseases transmitted by that species. Aedes mosquitoes transmit dengue and yellow fever, as well as recently-emergent chikungunya and Zika viruses to susceptible humans. Mosquitoes were collected in the Black Sea region of Anatolia, NE Turkey, where invasive Aedes mosquitoes have recently encroached, and specimens were screened for a variety of viruses. We observed particular Aedes species that are associated with disease transmission, suggesting that these species have been established in the region. We did not detect dengue, yellow fever, chikungunya or Zika viruses, but West Nile virus was found in several pools of these invasive species. Moreover, we detected a number of related viruses that exclusively infect mosquitoes, identified for the first time in Anatolia. Using advanced sequencing technologies, the near-complete genome of a new Aedes flavivirus (AEFV-Turkey) was achieved.

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Citation: Akıner MM, Öztürk M, Başer AB, Günay F, Hacıoğlu S, Brinkmann A, et al. (2019) Arboviral screening of invasive Aedes species in northeastern Turkey: West Nile virus circulation and detection of insect-only viruses. PLoS Negl Trop Dis 13(5): e0007334. https://doi.org/10.1371/journal.pntd.0007334

Editor: Pattamaporn Kittayapong, Faculty of Science, Mahidol University, THAILAND

Received: January 3, 2019; Accepted: March 26, 2019; Published: May 6, 2019

This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

Data Availability: The nucleotide sequences characterized in this study are deposited and can be accessed at the GenBank via the following accession numbers: MF361262, MF361264, MF361265, MF361263, MF361267, MF361268, MK251047, MK251048, MK251049, MK251050, MK251051, MK251052, MK251053, MK251054, MK251055 and MK251056. All remaining data are within the paper and its Supporting Information files.

Funding: This study was supported in part by the Armed Forces Health Surveillance Board, Global Emerging Infections Surveillance and Response System (AFHSB-GEIS), United States of America (FY18 award P0034_18_WR (PI: Yvonne-Marie Linton) under US Army subcontract W911QY-16-C-0160). BA and FG were also included in AIM-COST. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The material to be published reflects the views of the authors and should not be construed to represent those of the US Department of the Army or the US Department of Defense.

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

Keywords: Flavivirus; Rhabdovirus; Mosquitoes; WNV; Aedes albopictus; Culex spp.; Turkey; Merida-like Turkey virus.

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