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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#Pathogen blocking in #Wolbachia-infected #Aedes aegypti is not affected by #Zika and #dengue virus co-infection (PLoS Negl Trop Dis., abstract)

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

OPEN ACCESS /  PEER-REVIEWED / RESEARCH ARTICLE

Pathogen blocking in Wolbachia-infected Aedes aegypti is not affected by Zika and dengue virus co-infection

Eric P. Caragata , Marcele N. Rocha , Thiago N. Pereira, Simone B. Mansur, Heverton L. C. Dutra, Luciano A. Moreira

Published: May 20, 2019 / DOI: https://doi.org/10.1371/journal.pntd.0007443 / This is an uncorrected proof.

 

Abstract

Background

Wolbachia’s ability to restrict arbovirus transmission makes it a promising tool to combat mosquito-transmitted diseases. Wolbachia-infected Aedes aegypti are currently being released in locations such as Brazil, which regularly experience concurrent outbreaks of different arboviruses. A. aegypti can become co-infected with, and transmit multiple arboviruses with one bite, which can complicate patient diagnosis and treatment.

Methodology/principle findings

Using experimental oral infection of A. aegypti and then RT-qPCR, we examined ZIKV/DENV-1 and ZIKV/DENV-3 co-infection in Wolbachia-infected A. aegypti and observed that Wolbachia-infected mosquitoes experienced lower prevalence of infection and viral load than wildtype mosquitoes, even with an extra infecting virus. Critically, ZIKV/DENV co-infection had no significant impact on Wolbachia’s ability to reduce viral transmission. Wolbachia infection also strongly altered expression levels of key immune genes Defensin C and Transferrin 1, in a virus-dependent manner.

Conclusions/significance

Our results suggest that pathogen interference in Wolbachia-infected A. aegypti is not adversely affected by ZIKV/DENV co-infection, which suggests that Wolbachia-infected A. aegypti will likely prove suitable for controlling mosquito-borne diseases in environments with complex patterns of arbovirus transmission.

 

Author summary

Wolbachia is an endosymbiotic bacterium that infects insects. It has been artificially transferred into Aedes aegypti, a mosquito species that can transmit medically important viruses including dengue, chikungunya, and Zika. Wolbachia in A. aegypti limits infection with these viruses, making the mosquitoes much less capable of transmitting them to people. In tropical areas, where these viral pathogens are commonly found, it is not unusual for outbreaks of different viruses to occur at the same time, which can complicate diagnosis and treatment for those afflicted. Mosquitoes with Wolbachia are currently being released into these areas to reduce transmission of these diseases. In our study, we assessed whether Wolbachia infection in A. aegypti mosquitoes could still effectively inhibit the dengue and Zika viruses if the mosquitoes were fed both viruses at the same time. We found that Wolbachia was still very effective at inhibiting the replication of both viruses in the mosquito, and likewise still greatly reduced the chance of transmission of either virus. Our results suggest that Wolbachia-infected mosquitoes should be able to limit infection with more than one virus, should they encounter them in the field.

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Citation: Caragata EP, Rocha MN, Pereira TN, Mansur SB, Dutra HLC, Moreira LA (2019) Pathogen blocking in Wolbachia-infected Aedes aegypti is not affected by Zika and dengue virus co-infection. PLoS Negl Trop Dis 13(5): e0007443. https://doi.org/10.1371/journal.pntd.0007443

Editor: Sujatha Sunil, International Centre for Genetic Engineering and Biotechnology, INDIA

Received: December 27, 2018; Accepted: May 7, 2019; Published: May 20, 2019

Copyright: © 2019 Caragata 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: This work was supported by FAPEMIG, CNPq, CAPES, the Brazilian Ministry of Health (DECIT/SVS), and a grant to Monash University from the Foundation for the National Institutes of Health through the Vector-Based Transmission of Control: Discovery Research (VCTR) program of the Grand Challenges in Global Health Initiatives of the Bill and Melinda Gates Foundation. 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: Zika Virus; Dengue Fever; Aedes aegypti; Wolbachia; Mosquitoes.

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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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#Neurological manifestations of #pediatric #arboviral #infections in the #Americas (J Clin Virol., abstract)

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

Journal of Clinical Virology / Available online 8 May 2019 / In Press, Accepted Manuscript

Neurological manifestations of pediatric arboviral infections in the Americas

Aline Almeida Bentes a,c,d, Erna Geessien Kroon b,d, Roberta Maiade Castro Romanelli a,d

{a} Faculdade de Medicina, Departamento de Pediatria, Universidade Federal de Minas Gerais, Av. Prof. Alfredo Balena, 190- Santa Efigênia, CEP 30130-100, Belo Horizonte, MG, Brazil; {b} Laboratório de Vírus, Departamento de Microbiologia, Universidade Federal de Minas Gerais, Minas Gerais, Brazil; {c} Hospital Infantil João Paulo II, FHEMIG, Minas Gerais, Brazil; {d} Faculty of Medicine of José do Rosário Vellano Univesity, Brazil

Received 8 February 2019, Revised 21 April 2019, Accepted 23 April 2019, Available online 8 May 2019. DOI: https://doi.org/10.1016/j.jcv.2019.04.006

 

Highlights

  • The neurological complications caused by DENV are based on three possible neuropathogenic mechanisms: invasion of the central (CNS) and peripheral (PNS) nervous systems; metabolic and vascular disorders and immune-mediated with different manifestations and sequelae.
  • Neurological manifestations of Zika acquired in children were remarkable and included hemiparesis, myelitis, Guillain-Barre syndrome, cortical infarction and behavioral changes.
  • The most common neurological manifestations found in children with Chikungunya infection were seizures, encephalitis, meningism and behavioral changes. Of these children, 5.6% died and 8.5% developed neuronal sequelae.

 

Abstract

Dengue, Zika, Chikungunya and yellow fever viruses are arboviruses transmitted by the mosquito Aedes aegypti. These viruses exhibit marked neurotropism but have rarely been studied. Here, we conduct an integrative review of the neurological manifestations caused by these arboviruses in the pediatric population. Data on patients under 18 years of age were extracted from literature databases. The most frequently reported neurological manifestations were encephalitis, meningitis, seizures, hypotonia, paresis, and behavioral changes. This review highlights the importance of accurately diagnosing these arboviral infections in children and adolescents with neurological manifestations.

Keywords: neurological manifestations – Dengue virus – Zika virus – Chikungunya virus – Yellow fever virus

© 2019 Elsevier B.V. All rights reserved.

Keywords: Arbovirus; Neurology; Zika virus; Chikungunya fever; Dengue Fever; Pediatrics; Encephalitis; Meningitis.

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Joint #Estimation of Relative #Risk for #Dengue and #Zika #Infections, #Colombia, 2015–2016 (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 6—June 2019 / Research

Joint Estimation of Relative Risk for Dengue and Zika Infections, Colombia, 2015–2016

Daniel Adyro Martínez-Bello1  , Antonio López-Quílez, and Alexander Torres Prieto

Author affiliations: University of Valencia, Valencia, Spain (D.A. Martínez-Bello, A. López-Quílez); Secretary of Health of the Department of Santander, Bucaramanga, Colombia (A. Torres Prieto)

 

Abstract

We jointly estimated relative risk for dengue and Zika virus disease (Zika) in Colombia, establishing the spatial association between them at the department and city levels for October 2015–December 2016. Cases of dengue and Zika were allocated to the 87 municipalities of 1 department and the 293 census sections of 1 city in Colombia. We fitted 8 hierarchical Bayesian Poisson joint models of relative risk for dengue and Zika, including area- and disease-specific random effects accounting for several spatial patterns of disease risk (clustered or uncorrelated heterogeneity) within and between both diseases. Most of the dengue and Zika high-risk municipalities varied in their risk distribution; those for Zika were in the northern part of the department and dengue in the southern to northeastern parts. At city level, spatially clustered patterns of dengue high-risk census sections indicated Zika high-risk areas. This information can be used to inform public health decision making.

Keywords: Zika Virus; Dengue fever; Colombia.

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The possible role of cross-reactive #dengue virus #antibodies in #Zika virus #pathogenesis (PLoS Pathog., abstract)

[Source: PLoS Pathogens, full page: (LINK). Abstract, edited.]

OPEN ACCESS / REVIEW

The possible role of cross-reactive dengue virus antibodies in Zika virus pathogenesis

Thomas Langerak , Noreen Mumtaz , Vera I. Tolk, Eric C. M. van Gorp, Byron E. Martina, Barry Rockx, Marion P. G. Koopmans

Published: April 18, 2019 / DOI: https://doi.org/10.1371/journal.ppat.1007640

 

Abstract

Zika virus (ZIKV) has been known for decades to circulate in Africa and Asia. However, major complications of a ZIKV infection have recently become apparent for reasons that are still not fully elucidated. One of the hypotheses for the seemingly increased pathogenicity of ZIKV is that cross-reactive dengue antibodies can enhance a ZIKV infection through the principle of antibody-dependent enhancement (ADE). Recently, ADE in ZIKV infection has been studied, but conclusive evidence for the clinical importance of this principle in a ZIKV infection is lacking. Conversely, the widespread circulation of ZIKV in dengue virus (DENV)-endemic regions raises new questions about the potential contribution of ZIKV antibodies to DENV ADE. In this review, we summarize the results of the evidence to date and elaborate on other possible detrimental effects of cross-reactive flavivirus antibodies, both for ZIKV infection and the risk of ZIKV-related congenital anomalies, DENV infection, and dengue hemorrhagic fever.

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Citation: Langerak T, Mumtaz N, Tolk VI, van Gorp ECM, Martina BE, Rockx B, et al. (2019) The possible role of cross-reactive dengue virus antibodies in Zika virus pathogenesis. PLoS Pathog 15(4): e1007640. https://doi.org/10.1371/journal.ppat.1007640

Editor: Tom C. Hobman, University of Alberta, CANADA

Published: April 18, 2019

Copyright: © 2019 Langerak 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.

Funding: This project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement ZikAlliance No 734548 and from the ZikaRisk project of ZonMw under project number 522003001. 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: Zika Virus; Dengue Fever; Immunopathology; A.D.E.

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