Special Issue "Mosquito-Specific Viruses: Their Role in Nature and Potential Use for Vector Control or Control of Arboviral Pathogens"

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

Deadline for manuscript submissions: closed (28 February 2021).

Special Issue Editors

Prof. Dr. Nikos Vasilakis
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Guest Editor
Department of Pathology and Center of Biodefense and Emerging Infectious Diseases; Center for Tropical Diseases; and Institute for Human Infection and Immunity University of Texas Medical Branch, 301 University Blvd, Galveston, TX 77555-0609, USA
Interests: basic research on evolution and pathogenesis of arthropod-borne viruses; quasispecies in transmission dynamics and emergence; and discovery and characterization of novel/new viruses
Special Issues and Collections in MDPI journals
Dr. Robert B. Tesh
E-Mail Website
Guest Editor
Departments of Pathology and of Microbiology and Immunology, Center of Biodefense and Emerging Infectious Diseases and Center for Tropical Diseases, University of Texas Medical Branch, Galveston, TX 77555-0609, USA
Interests: Epidemiology of arthropod-borne and other zoonotic viral diseases
Special Issues and Collections in MDPI journals

Special Issue Information

Dear Colleagues,

Recent studies utilizing next-generation sequencing and metagenomics have revealed an enormous diversity of RNA viruses in both vertebrates and invertebrates. Mosquitoes are of special interest, because many are vectors of arboviral pathogens. However, viruses which are pathogenic for humans, other mammals, and birds represent only a small fraction of the total mosquito virome. Mosquitoes also carry a large number of divergent mosquito-specific viruses (MSVs) belonging to diverse virus families and orders, such as Flaviridae, Togaviridae, Bunyavirales, Reoviridae, and Rhabdoviridae. Some of these MSVs are closely related genetically with important arbovirus pathogens, raising the question of how prior infection or co-infection with MSV affects the mosquito’s vector competence if it encounters a related arbovirus pathogen, or whether MSVs could be used to reduce a mosquito’s vector competence for a related pathogen and thus control certain arboviral diseases. Further, what other effects do MSVs have on a vector’s behavior, longevity, fecundity, and resistance/susceptibility to mosquito pathogens? These are important questions.

Unfortunately, most of the recently described MSVs are known only as a sequence or partial genetic sequence. Sequence data obtained in metagenomic studies can be used for genetic and phylogenetic analyses, allowing taxonomic placement (classification) of a new agent, and they can provide insight into virus diversity and evolution; but such data provide little or no information on the biological or phenotypic properties of the virus. To obtain the latter type of information, one generally needs an actual virus isolate that can be tested in experimental laboratory studies to determine the MSV’s growth characteristics and its effect on the mosquito host, including pathogenesis, increased susceptibility to or protection against mosquito pathogens, and potential effects on the insect’s vector competence for specific arboviral pathogens.

In this Special Issue, we encourage the submission of reports on the isolation and characterization of novel MSVs, of results of experimental studies of the MSV’s growth characteristics in various cell lines and mosquito species, as well as the MSV’s pathogenesis or protective effect on a given mosquito host, and its effects on the behavior and the vector competence of the insect.

Dr. Nikolaos Vasilakis
Dr. Robert Tesh
Guest Editors

Manuscript Submission Information

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Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2200 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

  • Mosquito-specific viruses
  • mosquito virome
  • epidemiology and pathogenesis of MSVs
  • vector competence
  • isolation and characterization of novel/new viruses
  • diversity and evolution of arthropod-borne viruses

Published Papers (7 papers)

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Research

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Article
Insect-Specific Flavivirus Replication in Mammalian Cells Is Inhibited by Physiological Temperature and the Zinc-Finger Antiviral Protein
Viruses 2021, 13(4), 573; https://0-doi-org.brum.beds.ac.uk/10.3390/v13040573 - 29 Mar 2021
Cited by 2 | Viewed by 1138
Abstract
The genus Flavivirus contains pathogenic vertebrate-infecting flaviviruses (VIFs) and insect-specific flaviviruses (ISF). ISF transmission to vertebrates is inhibited at multiple stages of the cellular infection cycle, via yet to be elucidated specific antiviral responses. The zinc-finger antiviral protein (ZAP) in vertebrate cells can [...] Read more.
The genus Flavivirus contains pathogenic vertebrate-infecting flaviviruses (VIFs) and insect-specific flaviviruses (ISF). ISF transmission to vertebrates is inhibited at multiple stages of the cellular infection cycle, via yet to be elucidated specific antiviral responses. The zinc-finger antiviral protein (ZAP) in vertebrate cells can bind CpG dinucleotides in viral RNA, limiting virus replication. Interestingly, the genomes of ISFs contain more CpG dinucleotides compared to VIFs. In this study, we investigated whether ZAP prevents two recently discovered lineage II ISFs, Binjari (BinJV) and Hidden Valley viruses (HVV) from replicating in vertebrate cells. BinJV protein and dsRNA replication intermediates were readily observed in human ZAP knockout cells when cultured at 34 °C. In ZAP-expressing cells, inhibition of the interferon response via interferon response factors 3/7 did not improve BinJV protein expression, whereas treatment with kinase inhibitor C16, known to reduce ZAP’s antiviral function, did. Importantly, at 34 °C, both BinJV and HVV successfully completed the infection cycle in human ZAP knockout cells evident from infectious progeny virus in the cell culture supernatant. Therefore, we identify vertebrate ZAP as an important barrier that protects vertebrate cells from ISF infection. This provides new insights into flavivirus evolution and the mechanisms associated with host switching. Full article
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Article
CXCL10 Signaling Contributes to the Pathogenesis of Arthritogenic Alphaviruses
Viruses 2020, 12(11), 1252; https://0-doi-org.brum.beds.ac.uk/10.3390/v12111252 - 02 Nov 2020
Cited by 1 | Viewed by 715
Abstract
Emerging and re-emerging arthritogenic alphaviruses, such as Chikungunya virus (CHIKV) and O’nyong nyong virus, cause acute and chronic crippling arthralgia associated with inflammatory immune responses. Approximately 50% of CHIKV-infected patients suffer from rheumatic manifestations that last 6 months to years. However, the physiological [...] Read more.
Emerging and re-emerging arthritogenic alphaviruses, such as Chikungunya virus (CHIKV) and O’nyong nyong virus, cause acute and chronic crippling arthralgia associated with inflammatory immune responses. Approximately 50% of CHIKV-infected patients suffer from rheumatic manifestations that last 6 months to years. However, the physiological functions of individual immune signaling pathways in the pathogenesis of alphaviral arthritis remain poorly understood. Here, we report that a deficiency in CXCL10, which is a chemoattractant for monocytes/macrophages/T cells, led to the same viremia as wild-type animals, but fewer immune infiltrates and lower viral loads in footpads at the peak of arthritic disease (6–8 days post infection). Macrophages constituted the largest immune cell population in footpads following infection, and were significantly reduced in Cxcl10−/− mice. The viral RNA loads in neutrophils and macrophages were reduced in Cxcl10−/− compared to wild-type mice. In summary, our results demonstrate that CXCL10 signaling promotes the pathogenesis of alphaviral disease and suggest that CXCL10 may be a therapeutic target for mitigating alphaviral arthritis. Full article
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Article
Genetic, Morphological and Antigenic Relationships between Mesonivirus Isolates from Australian Mosquitoes and Evidence for Their Horizontal Transmission
Viruses 2020, 12(10), 1159; https://0-doi-org.brum.beds.ac.uk/10.3390/v12101159 - 13 Oct 2020
Cited by 1 | Viewed by 890
Abstract
The Mesoniviridae are a newly assigned family of viruses in the order Nidovirales. Unlike other nidoviruses, which include the Coronaviridae, mesoniviruses are restricted to mosquito hosts and do not infect vertebrate cells. To date there is little information on the morphological [...] Read more.
The Mesoniviridae are a newly assigned family of viruses in the order Nidovirales. Unlike other nidoviruses, which include the Coronaviridae, mesoniviruses are restricted to mosquito hosts and do not infect vertebrate cells. To date there is little information on the morphological and antigenic characteristics of this new group of viruses and a dearth of mesonivirus-specific research tools. In this study we determined the genetic relationships of recent Australian isolates of Alphamesonivirus 4 (Casuarina virus—CASV) and Alphamesonivirus 1 (Nam Dinh virus—NDiV), obtained from multiple mosquito species. Australian isolates of NDiV showed high-level similarity to the prototype NDiV isolate from Vietnam (99% nucleotide (nt) and amino acid (aa) identity). Isolates of CASV from Central Queensland were genetically very similar to the prototype virus from Darwin (95–96% nt and 91–92% aa identity). Electron microscopy studies demonstrated that virion diameter (≈80 nm) and spike length (≈10 nm) were similar for both viruses. Monoclonal antibodies specific to CASV and NDiV revealed a close antigenic relationship between the two viruses with 13/34 mAbs recognising both viruses. We also detected NDiV RNA on honey-soaked nucleic acid preservation cards fed on by wild mosquitoes supporting a possible mechanism of horizontal transmission between insects in nature. Full article
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Article
A Unique Relative of Rotifer Birnavirus Isolated from Australian Mosquitoes
Viruses 2020, 12(9), 1056; https://0-doi-org.brum.beds.ac.uk/10.3390/v12091056 - 22 Sep 2020
Cited by 2 | Viewed by 1024
Abstract
The family Birnaviridae are a group of non-enveloped double-stranded RNA viruses which infect poultry, aquatic animals and insects. This family includes agriculturally important pathogens of poultry and fish. Recently, next-generation sequencing technologies have identified closely related birnaviruses in Culex, Aedes and Anopheles mosquitoes. [...] Read more.
The family Birnaviridae are a group of non-enveloped double-stranded RNA viruses which infect poultry, aquatic animals and insects. This family includes agriculturally important pathogens of poultry and fish. Recently, next-generation sequencing technologies have identified closely related birnaviruses in Culex, Aedes and Anopheles mosquitoes. Using a broad-spectrum system based on detection of long double-stranded RNA, we have discovered and isolated a birnavirus from Aedes notoscriptus mosquitoes collected in northern New South Wales, Australia. Phylogenetic analysis of Aedes birnavirus (ABV) showed that it is related to Rotifer birnavirus, a pathogen of microscopic aquatic animals. In vitro cell infection assays revealed that while ABV can replicate in Aedes-derived cell lines, the virus does not replicate in vertebrate cells and displays only limited replication in Culex- and Anopheles-derived cells. A combination of SDS-PAGE and mass spectrometry analysis suggested that the ABV capsid precursor protein (pVP2) is larger than that of other birnaviruses and is partially resistant to trypsin digestion. Reactivity patterns of ABV-specific polyclonal and monoclonal antibodies indicate that the neutralizing epitopes of ABV are SDS sensitive. Our characterization shows that ABV displays a number of properties making it a unique member of the Birnaviridae and represents the first birnavirus to be isolated from Australian mosquitoes. Full article
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Article
Chikungunya Outbreak in the Republic of the Congo, 2019—Epidemiological, Virological and Entomological Findings of a South-North Multidisciplinary Taskforce Investigation
Viruses 2020, 12(9), 1020; https://0-doi-org.brum.beds.ac.uk/10.3390/v12091020 - 13 Sep 2020
Cited by 5 | Viewed by 1447
Abstract
The Republic of Congo (RoC) declared a chikungunya (CHIK) outbreak on 9 February 2019. We conducted a ONE-Human-Animal HEALTH epidemiological, virological and entomological investigation. Methods: We collected national surveillance and epidemiological data. CHIK diagnosis was based on RT-PCR and CHIKV-specific antibodies. Full CHIKV [...] Read more.
The Republic of Congo (RoC) declared a chikungunya (CHIK) outbreak on 9 February 2019. We conducted a ONE-Human-Animal HEALTH epidemiological, virological and entomological investigation. Methods: We collected national surveillance and epidemiological data. CHIK diagnosis was based on RT-PCR and CHIKV-specific antibodies. Full CHIKV genome sequences were obtained by Sanger and MinION approaches and Bayesian tree phylogenetic analysis was performed. Mosquito larvae and 215 adult mosquitoes were collected in different villages of Kouilou and Pointe-Noire districts and estimates of Aedes (Ae.) mosquitos’ CHIKV-infectious bites obtained. We found two new CHIKV sequences of the East/Central/South African (ECSA) lineage, clustering with the recent enzootic sub-clade 2, showing the A226V mutation. The RoC 2019 CHIKV strain has two novel mutations, E2-T126M and E2-H351N. Phylogenetic suggests a common origin from 2016 Angola strain, from which it diverged around 1989 (95% HPD 1985–1994). The infectious bite pattern was similar for 2017, 2018 and early 2019. One Ae. albopictus pool was RT-PCR positive. The 2019 RoC CHIKV strain seems to be recently introduced or be endemic in sylvatic cycle. Distinct from the contemporary Indian CHIKV isolates and in contrast to the original Central-African strains (transmitted by Ae. aegypti), it carries the A226V mutation, indicating an independent adaptive mutation in response to vector replacement (Ae. albopictus vs Ae. aegypti). Full article
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Article
Characterization of Port Bolivar Virus, a Novel Entomobirnavirus (Birnaviridae) Isolated from Mosquitoes Collected in East Texas, USA
Viruses 2020, 12(4), 390; https://0-doi-org.brum.beds.ac.uk/10.3390/v12040390 - 31 Mar 2020
Cited by 1 | Viewed by 1151
Abstract
This report describes and characterizes a novel entomobirnavirus, designated Port Bolivar virus (PTBV), that was isolated from a pool of Aedes sollicitans mosquitoes collected in a saltwater marsh in East Texas, USA. Full genome sequencing and phylogenetic analyses indicate that PTBV is distinct [...] Read more.
This report describes and characterizes a novel entomobirnavirus, designated Port Bolivar virus (PTBV), that was isolated from a pool of Aedes sollicitans mosquitoes collected in a saltwater marsh in East Texas, USA. Full genome sequencing and phylogenetic analyses indicate that PTBV is distinct but genetically related to Drosophila X virus and mosquito X virus, which are assigned to species in the genus Entomobirnavirus, family Birnaviridae. PTBV produced cytopathic effect (CPE) in cultures of mosquito (C6/36) cells, but not in Vero cell cultures. Ultrastructural studies of PTBV in infected C6/36 cells demonstrated unenveloped virus particles about 55 nm in diameter. Full article
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Review

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Review
Superinfection Exclusion in Mosquitoes and Its Potential as an Arbovirus Control Strategy
Viruses 2020, 12(11), 1259; https://0-doi-org.brum.beds.ac.uk/10.3390/v12111259 - 05 Nov 2020
Cited by 2 | Viewed by 1042
Abstract
The continuing emergence of arbovirus disease outbreaks around the world, despite the use of vector control strategies, warrants the development of new strategies to reduce arbovirus transmission. Superinfection exclusion, a phenomenon whereby a primary virus infection prevents the replication of a second closely [...] Read more.
The continuing emergence of arbovirus disease outbreaks around the world, despite the use of vector control strategies, warrants the development of new strategies to reduce arbovirus transmission. Superinfection exclusion, a phenomenon whereby a primary virus infection prevents the replication of a second closely related virus, has potential to control arbovirus disease emergence and outbreaks. This phenomenon has been observed for many years in plants, insects and mammalian cells. In this review, we discuss the significance of identifying novel vector control strategies, summarize studies exploring arbovirus superinfection exclusion and consider the potential for this phenomenon to be the basis for novel arbovirus control strategies. Full article
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