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Arbovirus Infections.

ABSTRACT: Arbovirus (arthropod-borne virus) infections are increasingly important causes of neurologic disease in the United States through both endemic transmission and travel-associated infections. This article reviews the major arbovirus infections that can cause neurologic disease likely to be encountered in the United States.West Nile virus continues to be an important cause of epidemic encephalitis, while emerging arbovirus infections such as dengue and chikungunya have rapidly expanded their geographic distribution. As emerging arboviruses expand in new geographic regions, neurologic abnormalities are reported in new patient populations.Emerging arbovirus infections are increasingly important causes of neurologic disease throughout the world and in the United States. While no US Food and Drug Administration (FDA)-approved therapy is yet available for these infections, prompt recognition and diagnosis from the consulting neurologist will ensure appropriate supportive care for the patient.

SUBMITTER: Beckham JD

PROVIDER: S-EPMC5089063 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature

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Arbovirus Infections.

Beckham J David JD Tyler Kenneth L KL

Continuum (Minneapolis, Minn.) 20151201 6 Neuroinfectious Disease

<h4>Purpose of review</h4>Arbovirus (arthropod-borne virus) infections are increasingly important causes of neurologic disease in the United States through both endemic transmission and travel-associated infections. This article reviews the major arbovirus infections that can cause neurologic disease likely to be encountered in the United States.<h4>Recent findings</h4>West Nile virus continues to be an important cause of epidemic encephalitis, while emerging arbovirus infections such as dengue ...[more]

PMID: 26633778

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Project description:Background: Arbovirus infections have steadily become a major pandemic threat. This study aimed at investigating the existence of host epigenetic markers arising from the principal arboviruses infections impacting on human health. We set to systematically review all published evidence describing any epigenetic modifications associated with infections from arboviruses, including, but not limited to, microRNAs, DNA methylation, and histone modifications. Methods: A comprehensive search was conducted using the electronic databases PubMed, Science Direct and Cochrane Library from inception to January 4th, 2018. We included reports describing original in vivo or in vitro studies investigating epigenetic changes related to arbovirus infections in either clinical subjects or human cell lines. Studies investigating epigenetic modifications related to the virus or the arthropod vector were excluded. A narrative synthesis of the findings was conducted, contextualizing comparative evidence from in vitro and in vivo studies. Results: A total of 853 unique references were identified and screened by two independent researchers. Thirty-two studies met the inclusion criteria and were reviewed. The evidence was centered mainly on microRNA and DNA methylation signatures implicated with secondary Dengue fever. Evidence for recent epidemic threats, such as the infections by Zika or Chikungunya viruses is still scant. Conclusions: Major epigenetic alterations found on arboviruses infections were miR-146, miR-30e and the Dicer complex. However, existing studies frequently tested distinct hypotheses resulting in a heterogeneity of methodological approaches. Whilst epigenetic signatures associated with arbovirus infections have been reported, existing studies have largely focused on a small number of diseases, particularly dengue. Validation of epigenetic signatures have an untapped potential, but concerted investigations are certainly required to deliver robust candidates of clinical utility for diagnosis, staging and prognosis of specific arboviral diseases.

Project description:Mosquitoes are known as important vectors of many arthropod-borne (arbo)viruses causing disease in humans. These include dengue (DENV) and Zika (ZIKV) viruses. The exogenous small interfering (si)RNA (exo-siRNA) pathway is believed to be the main antiviral defense in arthropods, including mosquitoes. During infection, double-stranded RNAs that form during viral replication and infection are cleaved by the enzyme Dicer 2 (Dcr2) into virus-specific 21 nt vsiRNAs, which are subsequently loaded into Argonaute 2 (Ago2). Ago2 then targets and subsequently cleaves complementary RNA sequences, resulting in degradation of the target viral RNA. Although various studies using silencing approaches have supported the antiviral activity of the exo-siRNA pathway in mosquitoes, and despite strong similarities between the siRNA pathway in the Drosophila melanogaster model and mosquitoes, important questions remain unanswered. The antiviral activity of Ago2 against different arboviruses has been previously demonstrated. However, silencing of Ago2 had no effect on ZIKV replication, whereas Dcr2 knockout enhanced its replication. These findings raise the question as to the role of Ago2 and Dcr2 in the control of arboviruses from different viral families in mosquitoes. Using a newly established Ago2 knockout cell line, alongside the previously reported Dcr2 knockout cell line, we investigated the impact these proteins have on the modulation of different arboviral infections. Infection of Ago2 knockout cell line with alpha- and bunyaviruses resulted in an increase of viral replication, but not in the case of ZIKV. Analysis of small RNA sequencing data in the Ago2 knockout cells revealed a lack of methylated siRNAs from different sources, such as acute and persistently infecting viruses-, TE- and transcriptome-derived RNAs. The results confirmed the importance of the exo-siRNA pathway in the defense against arboviruses, but highlights variability in its response to different viruses and the impact the siRNA pathway proteins have in controlling viral replication. Moreover, this established Ago2 knockout cell line can be used for functional Ago2 studies, as well as research on the interplay between the RNAi pathways.

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Arbovirus Infections.

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Arbovirus Infections.

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