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Special Issue "Emerging Arboviruses"

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Animal Viruses".

Deadline for manuscript submissions: 14 February 2020

Special Issue Editor

Guest Editor
Prof. Dr. Remi N. Charrel

1. Unité des Virus Emergents, Aix Marseille Université, Marseille, France;
2. Emerging Pathogens Institute, University of Florida, Gainesville, Florida, USA
E-Mail
Interests: emerging arboviruses; arthropod-borne viruses; transmission; mosquitoes; tropical viral infections; viral zoonoses and respiratory infections

Special Issue Information

Dear Colleagues,

The emergence and re-emergence of arboviruses have occurred for centuries, but their rapid dispersion is more rapid and geographically extensive because of the intensive growth of global transportation systems, arthropod adaptation to urbanization, failure to contain mosquito populations and land perturbation.  Here we would like to address emerging arboviruses of human importance (such as Chikungunya, Zika, Yellow fever, West Nile, Toscana, Usutu, Japanese encephalitis, Spondweni, Oropouche, Mayaro, O'nyong nyong etc.) and of veterinary importance (such as Schmallenberg, Bluetongue, African swine fever, Usutu, West Nile, Rift Valley fever, Shuni, African horse sickness, Akabane, etc.). Research studies can be focused on epidemiology, development and evaluation of diagnostic assays, transmission pathways and cycles, natural cycles, virulence and clinical aspects. Studies aiming at virus discovery or at establishing the pathogenesis of viruses for either humans or animals are also within the scope of this Special Issue.

Prof. Dr. Remi Charrel
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Viruses is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1800 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • emergence
  • arthropod-borne virus
  • human importance
  • veterinary importance
  • diagnosis; preparedness and response
  • seroprevalence
  • epidemiology
  • transmission
  • virulence
  • animal models
  • antivirals

Published Papers (7 papers)

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Research

Open AccessArticle
Establishment of a Cell Culture Model of Persistent Flaviviral Infection: Usutu Virus Shows Sustained Replication during Passages and Resistance to Extinction by Antiviral Nucleosides
Viruses 2019, 11(6), 560; https://doi.org/10.3390/v11060560
Received: 22 March 2019 / Revised: 2 June 2019 / Accepted: 15 June 2019 / Published: 17 June 2019
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Abstract
Chronic viral disease constitutes a major global health problem, with several hundred million people affected and an associated elevated number of deaths. An increasing number of disorders caused by human flaviviruses are related to their capacity to establish a persistent infection. Here we [...] Read more.
Chronic viral disease constitutes a major global health problem, with several hundred million people affected and an associated elevated number of deaths. An increasing number of disorders caused by human flaviviruses are related to their capacity to establish a persistent infection. Here we show that Usutu virus (USUV), an emerging zoonotic flavivirus linked to sporadic neurologic disease in humans, can establish a persistent infection in cell culture. Two independent lineages of Vero cells surviving USUV lytic infection were cultured over 82 days (41 cell transfers) without any apparent cytopathology crisis associated. We found elevated titers in the supernatant of these cells, with modest fluctuations during passages but no overall tendency towards increased or decreased infectivity. In addition to full-length genomes, viral RNA isolated from these cells at passage 40 revealed the presence of defective genomes, containing different deletions at the 5’ end. These truncated transcripts were all predicted to encode shorter polyprotein products lacking membrane and envelope structural proteins, and most of non-structural protein 1. Treatment with different broad-range antiviral nucleosides revealed that USUV is sensitive to these compounds in the context of a persistent infection, in agreement with previous observations during lytic infections. The exposure of infected cells to prolonged treatment (10 days) with favipiravir and/or ribavirin resulted in the complete clearance of infectivity in the cellular supernatants (decrease of ~5 log10 in virus titers and RNA levels), although modest changes in intracellular viral RNA levels were recorded (<2 log10 decrease). Drug withdrawal after treatment day 10 resulted in a relapse in virus titers. These results encourage the use of persistently-infected cultures as a surrogate system in the identification of improved antivirals against flaviviral chronic disease. Full article
(This article belongs to the Special Issue Emerging Arboviruses)
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Open AccessArticle
Host Immune Response to ZIKV in an Immunocompetent Embryonic Mouse Model of Intravaginal Infection
Viruses 2019, 11(6), 558; https://doi.org/10.3390/v11060558
Received: 21 May 2019 / Revised: 11 June 2019 / Accepted: 14 June 2019 / Published: 17 June 2019
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Abstract
Zika virus (ZIKV) only induces mild symptoms in adults; however, it can cause congenital Zika syndrome (CZS), including microcephaly. Most of the knowledge on ZIKV pathogenesis was gained using immunocompromised mouse models, which do not fully recapitulate human pathology. Moreover, the study of [...] Read more.
Zika virus (ZIKV) only induces mild symptoms in adults; however, it can cause congenital Zika syndrome (CZS), including microcephaly. Most of the knowledge on ZIKV pathogenesis was gained using immunocompromised mouse models, which do not fully recapitulate human pathology. Moreover, the study of the host immune response to ZIKV becomes challenging in these animals. Thus, the main goal of this study was to develop an immunocompetent mouse model to study the ZIKV spread and teratogeny. FVB/NJ immune competent dams were infected intravaginally with ZIKV during the early stage of pregnancy. We found that the placentae of most fetuses were positive for ZIKV, while the virus was detected in the brain of only about 42% of the embryos. To investigate the host immune response, we measured the expression of several inflammatory factors. Embryos from ZIKV-infected dams had an increased level of inflammatory factors, as compared to Mock. Next, we compared the gene expression levels in embryos from ZIKV-infected dams that were either negative or positive for ZIKV in the brain. The mRNA levels of viral response genes and cytokines were increased in both ZIKV-positive and negative brains. Interestingly, the levels of chemokines associated with microcephaly in humans, including CCL2 and CXCL10, specifically increased in embryos harboring ZIKV in the embryo brains. Full article
(This article belongs to the Special Issue Emerging Arboviruses)
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Open AccessArticle
Presence of Antibodies against Sindbis Virus in the Israeli Population: A Nationwide Cross-Sectional Study
Viruses 2019, 11(6), 542; https://doi.org/10.3390/v11060542
Received: 18 March 2019 / Revised: 5 June 2019 / Accepted: 7 June 2019 / Published: 11 June 2019
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Abstract
Sindbis virus (SINV) is a mosquito-borne alphavirus circulating globally. SINV outbreaks have been mainly reported in North-European countries. In Israel, SINV was detected in 6.3% of mosquito pools; however, SINV infection in humans has rarely been diagnosed. A serologic survey to detect SINV [...] Read more.
Sindbis virus (SINV) is a mosquito-borne alphavirus circulating globally. SINV outbreaks have been mainly reported in North-European countries. In Israel, SINV was detected in 6.3% of mosquito pools; however, SINV infection in humans has rarely been diagnosed. A serologic survey to detect SINV IgG antibodies was conducted to evaluate the seroprevalence of SINV in the Israeli population. In total, 3145 serum samples collected in 2011–2014, representing all age and population groups in Israel, were assessed using an indirect ELISA assay, and a neutralization assay was performed on all ELISA-positive samples. The prevalence rates of SINV IgG antibodies were calculated. Logistic regressions models were applied to assess the association between demographic characteristics and SINV seropositivity. Overall, 113 (3.6%) and 59 (1.9%) samples were positive for ELISA and neutralization SINV IgG, respectively. Multivariable analysis demonstrated that SINV seropositivity was significantly associated with older age and residence outside metropolitan areas. These results demonstrate that, despite no outbreaks or clinical presentation, SINV infects the human population in Israel. Seropositivity is countrywide, more frequent in people of older age, and less diffuse in Israel’s metropolitan areas. Seroprevalence studies from other countries will add to our understanding of the global burden of SINV and the risk for potential SINV outbreaks. Full article
(This article belongs to the Special Issue Emerging Arboviruses)
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Open AccessArticle
Detection of a Novel Phlebovirus (Drin Virus) from Sand Flies in Albania
Viruses 2019, 11(5), 469; https://doi.org/10.3390/v11050469
Received: 17 April 2019 / Revised: 20 May 2019 / Accepted: 21 May 2019 / Published: 23 May 2019
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Abstract
Phlebotomine sand flies are generalist vectors with significant implications for public health. They are able to transmit phleboviruses that cause sand fly fever, headaches, or meningitis in humans. Albania is a country in Southeast Europe with a typical Mediterranean climate which provides convenient [...] Read more.
Phlebotomine sand flies are generalist vectors with significant implications for public health. They are able to transmit phleboviruses that cause sand fly fever, headaches, or meningitis in humans. Albania is a country in Southeast Europe with a typical Mediterranean climate which provides convenient conditions for the presence of sand flies. Hence, the circulation of phleboviruses, such as the Toscana and Balkan viruses, has been recently described in the country. We followed a virus discovery approach on sand fly samples collected in 2015 and 2016 in seven regions of Albania, with the aim to investigate and characterize potentially circulating phleboviruses in phlebotomine sand flies. A presumed novel phlebovirus was detected in a pool consisting of 24 Phlebotomus neglectus males. The virus was provisionally named the Drin virus after a river near the locality of Kukës, where the infected sand flies were trapped. Genetic and phylogenetic analysis revealed that the Drin virus is closely related to the Corfou (CFUV) virus, isolated in the 1980s from Phlebotomus major sand flies on the eponymous island of Greece, and may also be involved in human infections because of its similarity to the sand fly fever Sicilian virus. The latter justifies further studies to specifically address this concern. Together with recent findings, this study confirms that Albania and the Balkan peninsula are hot spots for phleboviruses. Full article
(This article belongs to the Special Issue Emerging Arboviruses)
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Open AccessCommunication
First Isolation and Phylogenetic Analyses of Tick-Borne Encephalitis Virus in Lower Saxony, Germany
Viruses 2019, 11(5), 462; https://doi.org/10.3390/v11050462
Received: 15 March 2019 / Revised: 16 May 2019 / Accepted: 18 May 2019 / Published: 21 May 2019
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Abstract
Tick-borne encephalitis (TBE) is the most important tick-borne arboviral disease in Europe. Presently, the main endemic regions in Germany are located in the southern half of the country. Although recently, sporadic human TBE cases were reported outside of these known endemic regions. The [...] Read more.
Tick-borne encephalitis (TBE) is the most important tick-borne arboviral disease in Europe. Presently, the main endemic regions in Germany are located in the southern half of the country. Although recently, sporadic human TBE cases were reported outside of these known endemic regions. The detection and characterization of invading TBE virus (TBEV) strains will considerably facilitate the surveillance and assessment of this important disease. In 2018, ticks were collected by flagging in several locations of the German federal state of Lower Saxony where TBEV-infections in humans (diagnosed clinical TBE disease or detection of TBEV antibodies) were reported previously. Ticks were pooled according to their developmental stage and tested for TBEV-RNA by RT-qPCR. Five of 730 (0.68%) pools from Ixodes spp. ticks collected in the areas of “Rauher Busch” and “Barsinghausen/Mooshuette” were found positive for TBEV-RNA. Phylogenetic analysis of the whole genomes and E gene sequences revealed a close relationship between the two TBEV isolates, which cluster with a TBEV strain from Poland isolated in 1971. This study provides first data on the phylogeny of TBEV in the German federal state of Lower Saxony, outside of the known TBE endemic areas of Germany. Our results support the hypothesis of an east-west invasion of TBEV strains in Western Europe. Full article
(This article belongs to the Special Issue Emerging Arboviruses)
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Open AccessArticle
A Functional Ubiquitin-Proteasome System is Required for Efficient Replication of New World Mayaro and Una Alphaviruses
Viruses 2019, 11(4), 370; https://doi.org/10.3390/v11040370
Received: 26 March 2019 / Revised: 18 April 2019 / Accepted: 19 April 2019 / Published: 23 April 2019
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Abstract
Mayaro (MAYV) and Una (UNAV) are emerging arboviruses belonging to the Alphavirus genus of the Togaviridae family. These viruses can produce febrile disease with symptoms such as fever, headache, myalgia, skin rash and incapacitating poly-arthralgia. Serological studies indicate that both viruses are circulating [...] Read more.
Mayaro (MAYV) and Una (UNAV) are emerging arboviruses belonging to the Alphavirus genus of the Togaviridae family. These viruses can produce febrile disease with symptoms such as fever, headache, myalgia, skin rash and incapacitating poly-arthralgia. Serological studies indicate that both viruses are circulating in different countries in Latin America. Viruses need the host cell machinery and resources to replicate effectively. One strategy to find new antivirals consists of identifying key cellular pathways or factors that are essential for virus replication. In this study, we analyzed the role of the ubiquitin-proteasome system (UPS) in MAYV and UNAV replication. Vero-E6 or HeLa cells were treated with the proteasome inhibitors MG132 or Lactacystin, and viral progeny production was quantified using a plaque assay method. In addition, the synthesis of viral proteins was analyzed by Western blot and confocal microscopy. Our results indicate that treatment with proteasome inhibitors decreases MAYV and UNAV protein synthesis, and also causes a significant dose-dependent decrease in MAYV and UNAV replication. Proteasome activity seems to be important at the early stages of MAYV replication. These findings suggest that the ubiquitin-proteasome system is a possible pharmacological target to inhibit these neglected alphaviruses. Full article
(This article belongs to the Special Issue Emerging Arboviruses)
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Open AccessArticle
Experimental Infection of Sand Flies by Massilia Virus and Viral Transmission by Co-Feeding on Sugar Meal
Viruses 2019, 11(4), 332; https://doi.org/10.3390/v11040332
Received: 14 March 2019 / Revised: 29 March 2019 / Accepted: 31 March 2019 / Published: 9 April 2019
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Abstract
Background: Massilia virus (MASV) is a phlebovirus isolated from Phlebotomus perniciosus in various regions of southwestern Europe. It is closely related to human pathogens such as Toscana virus and sandfly fever Naples virus. The natural cycle of phleboviruses is poorly understood. Indeed, experimental [...] Read more.
Background: Massilia virus (MASV) is a phlebovirus isolated from Phlebotomus perniciosus in various regions of southwestern Europe. It is closely related to human pathogens such as Toscana virus and sandfly fever Naples virus. The natural cycle of phleboviruses is poorly understood. Indeed, experimental studies demonstrate that transovarial and sexual transmission are not efficient enough for the maintenance of the virus in nature and to date there is no convincing evidence that a species of vertebrates is the reservoir of the virus. Here, we studied various transmission routes of MASV taking advantage of experimental colonies representing different species of sand flies. Methodology/Principal findings: In P. perniciosus, four sources of infection were compared: (i) Virus-seeded larval food to the first instar larvae (L1), or (ii) to the fourth instar larvae (L4), (iii) virus-seeded blood meal to adult females, and (iv) virus-seeded sugar meal to adults of both sexes. From 875 adults emerged from infected L1 and L4, only three were positive. In females infected by bloodmeal the infection rate was high before defecation, then it decreased drastically; MASV RNA was detected in only 5 out of 27 post-defecation. Surprisingly, the most efficient route of infection was observed after intake of virus-seeded sugar meal: 72% of females (79/110) and 52% of males (51/99) were found to be MASV RNA-positive. In addition, MASV-infected sandflies regurgitated virus particules into the sugar drop and MASV RNA was detectable in this drop for at least 24 h after regurgitation. MASV RNA was detected in about one third of the P. perniciosus exposed to this sugar drop contaminated by regurgitation. Sugar meal infection was also tested with six other species of sand flies. In males, there were no significant differences in infection rates when compared to P. perniciosus. In females, most species tested showed high infection rate at the beginning but then significant gradual decrease in infection rate during the experiment. Conclusions/Significance: We present the first description of arboviral infection of a dipteran vector using sugar meal. In all seven sand fly species tested, MASV was detected for two weeks post-infection. Our results showed that MASV can be transmitted between P. perniciosus either through co-feeding or via an infected sugar source such as plant sap. These newly described routes of horizontal transmission may play an important role in the circulation of phleboviruses in nature. Full article
(This article belongs to the Special Issue Emerging Arboviruses)
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Planned Papers

The below list represents only planned manuscripts. Some of these manuscripts have not been received by the Editorial Office yet. Papers submitted to MDPI journals are subject to peer-review.

Title: First isolation and phylogenetic analyses of tick-borne encephalitis virus in Lower Saxony, Germany
Authors: Mathias Boelke, Malena Bestehorn, Birgit Marchwald, Mareike Kubinski, Katrin Liebig, Julien Glanz, Claudia Schulz, Gerhard Dobler, Masyar Monazahian, Stefanie Christine Becker *

Title: A functional ubiquitin-proteasome system is required for efficient replication of New World Mayaro and Una Alphaviruses
Authors: Yessica Y. Llamas-González, Dalkiria Campos, Juan M. Pascale, Juan Arbiza, José González-Santamaría *

 
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