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Viruses, Volume 11, Issue 8 (August 2019)

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Open AccessReview
Diverse Mechanisms Underlie Enhancement of Enteric Viruses by the Mammalian Intestinal Microbiota
Viruses 2019, 11(8), 760; https://doi.org/10.3390/v11080760 (registering DOI)
Received: 26 June 2019 / Revised: 13 August 2019 / Accepted: 15 August 2019 / Published: 17 August 2019
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Abstract
Over the past two decades, there has been tremendous progress in understanding the impact of the intestinal microbiota on mammalian metabolism, physiology, and immune development and function. There has also been substantial advancement in elucidating the interplay between commensal and pathogenic bacteria. Relatively [...] Read more.
Over the past two decades, there has been tremendous progress in understanding the impact of the intestinal microbiota on mammalian metabolism, physiology, and immune development and function. There has also been substantial advancement in elucidating the interplay between commensal and pathogenic bacteria. Relatively more recently, researchers have begun to investigate the effect of the intestinal microbiota on viral pathogenesis. Indeed, a growing body of literature has reported that commensal bacteria within the mammalian intestinal tract enhance enteric virus infections through a variety of mechanisms. Commensal bacteria or bacterial glycans can increase the stability of enteric viruses, enhance virus binding to host receptors, modulate host immune responses in a proviral manner, expand the numbers of host cell targets, and facilitate viral recombination. In this review, we will summarize the current literature exploring these effects of the intestinal microbiota on enteric virus infections. Full article
(This article belongs to the Special Issue Viruses Ten-Year Anniversary)
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Open AccessArticle
A Novel RNA Virus Related to Sobemoviruses Confers Hypovirulence on the Phytopathogenic Fungus Sclerotinia sclerotiorum
Viruses 2019, 11(8), 759; https://doi.org/10.3390/v11080759 (registering DOI)
Received: 16 May 2019 / Revised: 12 August 2019 / Accepted: 15 August 2019 / Published: 16 August 2019
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Abstract
Infection by diverse mycoviruses is a common phenomenon in Sclerotinia sclerotiorum. In this study, the full genome of a single-stranded RNA mycovirus, tentatively named Hubei sclerotinia RNA virus 1 (HuSRV1), was determined in the hypovirulent strain 277 of S. sclerotiorum. The HuSRV1 genome [...] Read more.
Infection by diverse mycoviruses is a common phenomenon in Sclerotinia sclerotiorum. In this study, the full genome of a single-stranded RNA mycovirus, tentatively named Hubei sclerotinia RNA virus 1 (HuSRV1), was determined in the hypovirulent strain 277 of S. sclerotiorum. The HuSRV1 genome is 4492 nucleotides (nt) long and lacks a poly (A) tail at the 3ˊ- terminus. Sequence analyses showed that the HuSRV1 genome contains four putative open reading frames (ORFs). ORF1a was presumed to encode a protein with a conserved protease domain and a transmembrane domain. This protein is 27% identical to the P2a protein encoded by the subterranean clover mottle virus. ORF1b encodes a protein containing a conserved RNA-dependent RNA polymerase (RdRp) domain, which may be translated into a fusion protein by a -1 ribosome frameshift. This protein is 45.9% identical to P2b encoded by the sowbane mosaic virus. ORF2 was found to encode a putative coat protein, which shares 23% identical to the coat protein encoded by the olive mild mosaic virus. ORF3 was presumed to encode a putative protein with an unknown function. Evolutionary relation analyses indicated that HuSRV1 is related to members within Sobemovirus, but forms a unique phylogenetic branch, suggesting that HuSRV1 represents a new member within Solemoviridae. HuSRV1 virions, approximately 30 nm in diameter, were purified from strain 277. The purified virions were successfully introduced into virulent strain Ep-1PNA367, resulting in a new hypovirulent strain, which confirmed that HuSRV1 confers hypovirulence on S. sclerotiorum. Full article
(This article belongs to the Section Viruses of Plants, Fungi and Protozoa)
Open AccessReview
The Innate Antiviral Response in Animals: An Evolutionary Perspective from Flagellates to Humans
Viruses 2019, 11(8), 758; https://doi.org/10.3390/v11080758 (registering DOI)
Received: 27 June 2019 / Revised: 8 August 2019 / Accepted: 14 August 2019 / Published: 16 August 2019
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Abstract
Animal cells have evolved dedicated molecular systems for sensing and delivering a coordinated response to viral threats. Our understanding of these pathways is almost entirely defined by studies in humans or model organisms like mice, fruit flies and worms. However, new genomic and [...] Read more.
Animal cells have evolved dedicated molecular systems for sensing and delivering a coordinated response to viral threats. Our understanding of these pathways is almost entirely defined by studies in humans or model organisms like mice, fruit flies and worms. However, new genomic and functional data from organisms such as sponges, anemones and mollusks are helping redefine our understanding of these immune systems and their evolution. In this review, we will discuss our current knowledge of the innate immune pathways involved in sensing, signaling and inducing genes to counter viral infections in vertebrate animals. We will then focus on some central conserved players of this response including Toll-like receptors (TLRs), RIG-I-like receptors (RLRs) and cGAS-STING, attempting to put their evolution into perspective. To conclude, we will reflect on the arms race that exists between viruses and their animal hosts, illustrated by the dynamic evolution and diversification of innate immune pathways. These concepts are not only important to understand virus-host interactions in general but may also be relevant for the development of novel curative approaches against human disease. Full article
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Open AccessArticle
IFN-λ Decreases Murid Herpesvirus-4 Infection of the Olfactory Epithelium but Fails to Prevent Virus Reactivation in the Vaginal Mucosa
Viruses 2019, 11(8), 757; https://doi.org/10.3390/v11080757 (registering DOI)
Received: 26 June 2019 / Revised: 13 August 2019 / Accepted: 14 August 2019 / Published: 16 August 2019
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Abstract
Murid herpesvirus-4 (MuHV-4), a natural gammaherpesvirus of rodents, can infect the mouse through the nasal mucosa, where it targets sustentacular cells and olfactory neurons in the olfactory epithelium before it propagates to myeloid cells and then to B cells in lymphoid tissues. After [...] Read more.
Murid herpesvirus-4 (MuHV-4), a natural gammaherpesvirus of rodents, can infect the mouse through the nasal mucosa, where it targets sustentacular cells and olfactory neurons in the olfactory epithelium before it propagates to myeloid cells and then to B cells in lymphoid tissues. After establishment of latency in B cells, viral reactivation occurs in the genital tract in 80% of female mice, which can lead to spontaneous sexual transmission to co-housed males. Interferon-lambda (IFN-λ) is a key player of the innate immune response at mucosal surfaces and is believed to limit the transmission of numerous viruses by acting on epithelial cells. We used in vivo plasmid-mediated IFN-λ expression to assess whether IFN-λ could prophylactically limit MuHV-4 infection in the olfactory and vaginal mucosae. In vitro, IFN-λ decreased MuHV-4 infection in cells that overexpressed IFN-λ receptor 1 (IFNLR1). In vivo, prophylactic IFN-λ expression decreased infection of the olfactory epithelium but did not prevent virus propagation to downstream organs, such as the spleen where the virus establishes latency. In the olfactory epithelium, sustentacular cells readily responded to IFN-λ. In contrast, olfactory neurons did not respond to IFN-λ, thus, likely allowing viral entry. In the female genital tract, columnar epithelial cells strongly responded to IFN-λ, as did most vaginal epithelial cells, although with some variation from mouse to mouse. IFN-λ expression, however, failed to prevent virus reactivation in the vaginal mucosa. In conclusion, IFN-λ decreased MuHV-4 replication in the upper respiratory epithelium, likely by protecting the sustentacular epithelial cells, but it did not protect olfactory neurons and failed to block virus reactivation in the genital mucosa. Full article
(This article belongs to the Section Animal Viruses)
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Open AccessArticle
Herpes Simplex Virus Type 1–Encoded miR-H2-3p Manipulates Cytosolic DNA–Stimulated Antiviral Innate Immune Response by Targeting DDX41
Viruses 2019, 11(8), 756; https://doi.org/10.3390/v11080756
Received: 15 June 2019 / Revised: 28 July 2019 / Accepted: 6 August 2019 / Published: 15 August 2019
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Abstract
Herpes simplex virus type 1 (HSV-1), one of the human pathogens widely epidemic and transmitted among various groups of people in the world, often causes symptoms known as oral herpes or lifelong asymptomatic infection. HSV-1 employs many sophisticated strategies to escape host antiviral [...] Read more.
Herpes simplex virus type 1 (HSV-1), one of the human pathogens widely epidemic and transmitted among various groups of people in the world, often causes symptoms known as oral herpes or lifelong asymptomatic infection. HSV-1 employs many sophisticated strategies to escape host antiviral immune response based on its multiple coding proteins. However, the functions involved in the immune evasion of miRNAs encoded by HSV-1 during lytic (productive) infection remain poorly studied. Dual-luciferase reporter gene assay and bioinformatics revealed that Asp-Glu-Ala-Asp (DEAD)-box helicase 41 (DDX41), a cytosolic DNA sensor of the DNA-sensing pathway, was a putative direct target gene of HSV-1-encoded miR-H2-3p. The transfection of miR-H2-3p mimics inhibited the expression of DDX41 at the level of mRNA and protein, as well as the expression of interferon beta (IFN-β) and myxoma resistance protein I (MxI) induced by HSV-1 infection in THP-1 cells, and promoted the viral replication and its gene transcription. However, the transfection of miR-H2-3p inhibitor showed opposite effects. This finding indicated that HSV-1-encoded miR-H2-3p attenuated cytosolic DNA–stimulated antiviral immune response by manipulating host DNA sensor molecular DDX41 to enhance virus replication in cultured cells. Full article
(This article belongs to the Section Animal Viruses)
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Open AccessArticle
Development and Evaluation of a Duo Chikungunya Virus Real-Time RT-PCR Assay Targeting Two Regions within the Genome
Viruses 2019, 11(8), 755; https://doi.org/10.3390/v11080755
Received: 6 June 2019 / Revised: 10 August 2019 / Accepted: 12 August 2019 / Published: 15 August 2019
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Abstract
Chikungunya virus (CHIKV) re-emerged as a globalized health threat fifteen years ago. There are dozens of RT-PCR assays published. An inventory of the latter was made, and after in silico analysis, two assays were selected for their ability to detect strains belonging to [...] Read more.
Chikungunya virus (CHIKV) re-emerged as a globalized health threat fifteen years ago. There are dozens of RT-PCR assays published. An inventory of the latter was made, and after in silico analysis, two assays were selected for their ability to detect strains belonging to the five CHIKV genetic lineages. They were combined in order to provide a robust assay not affected by genetic point mutations and the resulting Duo CHIKV real-time RT-PCR assay was compared to the two parental single-plex tests against five strains belonging to the five genetic lineages. The Duo CHIKV assay performed equally, or better, in terms of sensitivity, specificity, linearity and signal intensity. Dual-target assays are better suited for viruses having the propensity to evolve into new variants via point mutations or major sequence deletions/insertions. Here, we demonstrated that combining two single systems into a dual-target assay did not impair sensitivity and specificity, and proved a potent diagnostic tool to face a potential emergence of CHIKV variants by newly evolving mutations. Full article
(This article belongs to the Special Issue Emerging Arboviruses)
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Open AccessArticle
Cyprinid Herpesvirus 3 Evolves in vitro through an Assemblage of Haplotypes that Alternatively become Dominant or Under-Represented
Viruses 2019, 11(8), 754; https://doi.org/10.3390/v11080754
Received: 28 June 2019 / Revised: 8 August 2019 / Accepted: 11 August 2019 / Published: 15 August 2019
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Abstract
Viruses are able to evolve in vitro by mutations after serial passages in cell cultures, which can lead to either a loss, or an increase, of virulence. Cyprinid herpesvirus 3 (CyHV-3), a 295-kb double-stranded DNA virus, is the etiological agent of the koi [...] Read more.
Viruses are able to evolve in vitro by mutations after serial passages in cell cultures, which can lead to either a loss, or an increase, of virulence. Cyprinid herpesvirus 3 (CyHV-3), a 295-kb double-stranded DNA virus, is the etiological agent of the koi herpesvirus disease (KHVD). To assess the influence of serial passages, an isolate of CyHV-3 (KHV-T) was passaged 99 times onto common carp brain (CCB) cells, and virus virulence was evaluated during passages through the experimental infections of common carp. After 78 CCB passages, the isolate was much less virulent than the original form. A comparative genomic analysis of these three forms of KHV-T (P0, P78 and P99) revealed a limited number of variations. The largest one was a deletion of 1363 bp in the predicted ORF150, which was detected in P78, but not in P99. This unexpected finding was confirmed by conventional PCR and digital PCR. The results presented here primarily suggest that, CyHV-3 evolves, at least in vitro, through an assemblage of haplotypes that alternatively become dominant or under-represented. Full article
(This article belongs to the Special Issue Recent Advances in Herpesviruses Research: What's in the Pipeline?)
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Open AccessReview
Reliable and Standardized Animal Models to Study the Pathogenesis of Bluetongue and Schmallenberg Viruses in Ruminant Natural Host Species with Special Emphasis on Placental Crossing
Viruses 2019, 11(8), 753; https://doi.org/10.3390/v11080753
Received: 27 May 2019 / Revised: 19 July 2019 / Accepted: 13 August 2019 / Published: 15 August 2019
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Abstract
Starting in 2006, bluetongue virus serotype 8 (BTV8) was responsible for a major epizootic in Western and Northern Europe. The magnitude and spread of the disease were surprisingly high and the control of BTV improved significantly with the marketing of BTV8 inactivated vaccines [...] Read more.
Starting in 2006, bluetongue virus serotype 8 (BTV8) was responsible for a major epizootic in Western and Northern Europe. The magnitude and spread of the disease were surprisingly high and the control of BTV improved significantly with the marketing of BTV8 inactivated vaccines in 2008. During late summer of 2011, a first cluster of reduced milk yield, fever, and diarrhoea was reported in the Netherlands. Congenital malformations appeared in March 2012 and Schmallenberg virus (SBV) was identified, becoming one of the very few orthobunyaviruses distributed in Europe. At the start of both epizootics, little was known about the pathogenesis and epidemiology of these viruses in the European context and most assumptions were extrapolated based on other related viruses and/or other regions of the World. Standardized and repeatable models potentially mimicking clinical signs observed in the field are required to study the pathogenesis of these infections, and to clarify their ability to cross the placental barrier. This review presents some of the latest experimental designs for infectious disease challenges with BTV or SBV. Infectious doses, routes of infection, inoculum preparation, and origin are discussed. Particular emphasis is given to the placental crossing associated with these two viruses. Full article
(This article belongs to the Special Issue Virus-Vector-Host Interactions of Culicoides-Borne Diseases)
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Open AccessArticle
Analysis of Synonymous Codon Usage Bias in Potato Virus M and Its Adaption to Hosts
Viruses 2019, 11(8), 752; https://doi.org/10.3390/v11080752
Received: 10 July 2019 / Revised: 12 August 2019 / Accepted: 13 August 2019 / Published: 14 August 2019
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Abstract
Potato virus M (PVM) is a member of the genus Carlavirus of the family Betaflexviridae and causes large economic losses of nightshade crops. Several previous studies have elucidated the population structure, evolutionary timescale and adaptive evolution of PVM. However, the synonymous codon usage [...] Read more.
Potato virus M (PVM) is a member of the genus Carlavirus of the family Betaflexviridae and causes large economic losses of nightshade crops. Several previous studies have elucidated the population structure, evolutionary timescale and adaptive evolution of PVM. However, the synonymous codon usage pattern of PVM remains unclear. In this study, we performed comprehensive analyses of the codon usage and composition of PVM based on 152 nucleotide sequences of the coat protein (CP) gene and 125 sequences of the cysteine-rich nucleic acid binding protein (NABP) gene. We observed that the PVM CP and NABP coding sequences were GC-and AU-rich, respectively, whereas U- and G-ending codons were preferred in the PVM CP and NABP coding sequences. The lower codon usage of the PVM CP and NABP coding sequences indicated a relatively stable and conserved genomic composition. Natural selection and mutation pressure shaped the codon usage patterns of PVM, with natural selection being the most important factor. The codon adaptation index (CAI) and relative codon deoptimization index (RCDI) analysis revealed that the greatest adaption of PVM was to pepino, followed by tomato and potato. Moreover, similarity Index (SiD) analysis showed that pepino had a greater impact on PVM than tomato and potato. Our study is the first attempt to evaluate the codon usage pattern of the PVM CP and NABP genes to better understand the evolutionary changes of a carlavirus. Full article
(This article belongs to the Section Viruses of Plants, Fungi and Protozoa)
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Open AccessReview
Trans-Acting RNA–RNA Interactions in Segmented RNA Viruses
Viruses 2019, 11(8), 751; https://doi.org/10.3390/v11080751
Received: 18 July 2019 / Revised: 8 August 2019 / Accepted: 11 August 2019 / Published: 14 August 2019
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Abstract
RNA viruses represent a large and important group of pathogens that infect a broad range of hosts. Segmented RNA viruses are a subclass of this group that encode their genomes in two or more molecules and package all of their RNA segments in [...] Read more.
RNA viruses represent a large and important group of pathogens that infect a broad range of hosts. Segmented RNA viruses are a subclass of this group that encode their genomes in two or more molecules and package all of their RNA segments in a single virus particle. These divided genomes come in different forms, including double-stranded RNA, coding-sense single-stranded RNA, and noncoding single-stranded RNA. Genera that possess these genome types include, respectively, Orbivirus (e.g., Bluetongue virus), Dianthovirus (e.g., Red clover necrotic mosaic virus) and Alphainfluenzavirus (e.g., Influenza A virus). Despite their distinct genomic features and diverse host ranges (i.e., animals, plants, and humans, respectively) each of these viruses uses trans-acting RNA–RNA interactions (tRRIs) to facilitate co-packaging of their segmented genome. The tRRIs occur between different viral genome segments and direct the selective packaging of a complete genome complement. Here we explore the current state of understanding of tRRI-mediated co-packaging in the abovementioned viruses and examine other known and potential functions for this class of RNA–RNA interaction. Full article
(This article belongs to the Special Issue Viruses Ten-Year Anniversary)
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Open AccessArticle
Proteomics Computational Analyses Suggest that the Antennavirus Glycoprotein Complex Includes a Class I Viral Fusion Protein (α-Penetrene) with an Internal Zinc-Binding Domain and a Stable Signal Peptide
Viruses 2019, 11(8), 750; https://doi.org/10.3390/v11080750
Received: 20 July 2019 / Revised: 6 August 2019 / Accepted: 13 August 2019 / Published: 14 August 2019
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Abstract
A metatranscriptomic study of RNA viruses in cold-blooded vertebrates identified two related viruses from frogfish (Antennarius striatus) that represent a new genus Antennavirus in the family Arenaviridae (Order: Bunyavirales). Computational analyses were used to identify features common to class I [...] Read more.
A metatranscriptomic study of RNA viruses in cold-blooded vertebrates identified two related viruses from frogfish (Antennarius striatus) that represent a new genus Antennavirus in the family Arenaviridae (Order: Bunyavirales). Computational analyses were used to identify features common to class I viral fusion proteins (VFPs) in antennavirus glycoproteins, including an N-terminal fusion peptide, two extended alpha-helices, an intrahelical loop, and a carboxyl terminal transmembrane domain. Like mammarenavirus and hartmanivirus glycoproteins, the antennavirus glycoproteins have an intracellular zinc-binding domain and a long virion-associated stable signal peptide (SSP). The glycoproteins of reptarenaviruses are also class I VFPs, but do not contain zinc-binding domains nor do they encode SSPs. Divergent evolution from a common progenitor potentially explains similarities of antennavirus, mammarenavirus, and hartmanivirus glycoproteins, with an ancient recombination event resulting in a divergent reptarenavirus glycoprotein. Full article
(This article belongs to the Special Issue Emerging Viruses: Surveillance, Prevention, Evolution and Control)
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Open AccessArticle
Selection of Bacteriophages to Control In Vitro 24 h Old Biofilm of Pseudomonas aeruginosa Isolated from Drinking and Thermal Water
Viruses 2019, 11(8), 749; https://doi.org/10.3390/v11080749
Received: 12 June 2019 / Revised: 10 August 2019 / Accepted: 11 August 2019 / Published: 13 August 2019
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Abstract
Pseudomonas aeruginosa is an opportunistic pathogen that causes public healthcare issues. In moist environments, this Gram-negative bacterium persists through biofilm-associated contamination on surfaces. Bacteriophages are seen as a promising alternative strategy to chemical biocides. This study evaluates the potential of nine lytic bacteriophages [...] Read more.
Pseudomonas aeruginosa is an opportunistic pathogen that causes public healthcare issues. In moist environments, this Gram-negative bacterium persists through biofilm-associated contamination on surfaces. Bacteriophages are seen as a promising alternative strategy to chemical biocides. This study evaluates the potential of nine lytic bacteriophages as biocontrol treatments against nine environmental P. aerginosa isolates. The spot test method is preliminarily used to define the host range of each virus and to identify their minimum infectious titer, depending on the strain. Based on these results, newly isolated bacteriophages 14.1, LUZ7, and B1 are selected and assessed on a planktonic cell culture of the most susceptible isolates (strains MLM, D1, ST395E, and PAO1). All liquid infection assays are achieved in a mineral minimum medium that is much more representative of real moist environments than standard culture medium. Phages 14.1 and LUZ7 eliminate up to 90% of the PAO1 and D1 bacterial strains. Hence, their effectiveness is evaluated on the 24 h old biofilms of these strains, established on a stainless steel coupon that is characteristic of materials found in thermal and industrial environments. The results of quantitative PCR viability show a maximum reduction of 1.7 equivalent Log CFU/cm2 in the coupon between treated and untreated surfaces and shed light on the importance of considering the entire virus/host/environment system for optimizing the treatment. Full article
(This article belongs to the Special Issue Bacteriophages and Biofilms)
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Open AccessArticle
ZIKV Envelope Domain-Specific Antibodies: Production, Purification and Characterization
Viruses 2019, 11(8), 748; https://doi.org/10.3390/v11080748
Received: 19 June 2019 / Revised: 8 August 2019 / Accepted: 11 August 2019 / Published: 13 August 2019
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Abstract
Infection with Zika virus (ZIKV) came first to public attention after it was found to be associated with congenital microcephaly during the outbreak in Brazil (2015–2016). Diagnosis of ZIKV suffers from extensive cross-reactivity with other Flaviviruses, which are circulating in many ZIKV [...] Read more.
Infection with Zika virus (ZIKV) came first to public attention after it was found to be associated with congenital microcephaly during the outbreak in Brazil (2015–2016). Diagnosis of ZIKV suffers from extensive cross-reactivity with other Flaviviruses, which are circulating in many ZIKV epidemic areas. Due to the fatal outcome of ZIKV infection during pregnancy, detailed knowledge about neutralizing and non-neutralizing epitopes is crucial for the development of robust detection systems of protective antibodies. Therefore, additional information about ZIKV immunogenicity and antibody response is required. In this project, we report the production, purification and characterization of six different polyclonal antibodies against ZIKV envelope (E) protein. The produced antibodies bind to isolated ZIKV E protein as well as to the surface of ZIKV particles, interestingly without being potently neutralizing. Surface plasmon resonance measurement showed that these antibodies bind with high affinity to ZIKV E protein. Epitope mapping revealed that the epitopes are distributed among the three ZIKV E domains with seven binding sites. These identified binding sites overlap only partially with the previously described epitopes recognized by neutralizing antibodies, which is in accordance with their lack of potent neutralizing activity. Additionally, these antibodies showed neither cross-reactivity nor potent neutralizing activity against West Nile virus, a related flavivirus. The gained set of data helps to extend our understanding about the distribution of neutralizing and non-/weak-neutralizing epitopes in ZIKV E protein, and provides a rationale for ZIKV vaccine design and development of robust detection assays for neutralizing antibodies. Full article
(This article belongs to the Section Animal Viruses)
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Open AccessArticle
Establishment of Primary Transgenic Human Airway Epithelial Cell Cultures to Study Respiratory Virus–Host Interactions
Viruses 2019, 11(8), 747; https://doi.org/10.3390/v11080747
Received: 5 July 2019 / Revised: 9 August 2019 / Accepted: 9 August 2019 / Published: 13 August 2019
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Abstract
Primary human airway epithelial cell (hAEC) cultures represent a universal platform to propagate respiratory viruses and characterize their host interactions in authentic target cells. To further elucidate specific interactions between human respiratory viruses and important host factors in the airway epithelium, it is [...] Read more.
Primary human airway epithelial cell (hAEC) cultures represent a universal platform to propagate respiratory viruses and characterize their host interactions in authentic target cells. To further elucidate specific interactions between human respiratory viruses and important host factors in the airway epithelium, it is important to make hAEC cultures amenable to genetic modification. However, the short and finite lifespan of primary cells in cell culture creates a bottleneck for the genetic modification of these cultures. In the current study, we show that the incorporation of the Rho-associated protein kinase (ROCK) inhibitor (Y-27632) during cell propagation extends the life span of primary human cells in vitro and thereby facilitates the incorporation of lentivirus-based expression systems. Using fluorescent reporters for fluorescence-activated cell sorting (FACS)-based sorting, we generated homogenously fluorescent hAEC cultures that differentiate normally after lentiviral transduction. As a proof-of-principle, we demonstrate that host gene expression can be modulated post-differentiation via inducible short hairpin (sh)RNA-mediated knockdown. Importantly, functional characterization of these transgenic hAEC cultures with exogenous poly (I:C), as a proxy for virus infection, demonstrates that such modifications do not influence the host innate immune response. Moreover, the propagation kinetics of both human coronavirus 229E (HCoV-229E) and human respiratory syncytial virus (hRSV) were not affected. Combined, these results validate our newly established protocol for the genetic modification of hAEC cultures, thereby unlocking a unique potential for detailed molecular characterization of virus–host interactions in human respiratory epithelium. Full article
(This article belongs to the Section Animal Viruses)
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Open AccessArticle
In Silico Identification of Novel Aromatic Compounds as Potential HIV-1 Entry Inhibitors Mimicking Cellular Receptor CD4
Viruses 2019, 11(8), 746; https://doi.org/10.3390/v11080746
Received: 10 July 2019 / Revised: 31 July 2019 / Accepted: 1 August 2019 / Published: 13 August 2019
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Abstract
Despite recent progress in the development of novel potent HIV-1 entry/fusion inhibitors, there are currently no licensed antiviral drugs based on inhibiting the critical interactions of the HIV-1 envelope gp120 protein with cellular receptor CD4. In this connection, studies on the design of [...] Read more.
Despite recent progress in the development of novel potent HIV-1 entry/fusion inhibitors, there are currently no licensed antiviral drugs based on inhibiting the critical interactions of the HIV-1 envelope gp120 protein with cellular receptor CD4. In this connection, studies on the design of new small-molecule compounds able to block the gp120-CD4 binding are still of great value. In this work, in silico design of drug-like compounds containing the moieties that make the ligand active towards gp120 was performed within the concept of click chemistry. Complexes of the designed molecules bound to gp120 were then generated by molecular docking and optimized using semiempirical quantum chemical method PM7. Finally, the binding affinity analysis of these ligand/gp120 complexes was performed by molecular dynamic simulations and binding free energy calculations. As a result, five top-ranking compounds that mimic the key interactions of CD4 with gp120 and show the high binding affinity were identified as the most promising CD4-mimemic candidates. Taken together, the data obtained suggest that these compounds may serve as promising scaffolds for the development of novel, highly potent and broad anti-HIV-1 therapeutics. Full article
(This article belongs to the Special Issue Viral Entry Pathways)
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Open AccessReview
A Comprehensive Superposition of Viral Polymerase Structures
Viruses 2019, 11(8), 745; https://doi.org/10.3390/v11080745
Received: 19 July 2019 / Revised: 7 August 2019 / Accepted: 11 August 2019 / Published: 13 August 2019
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Abstract
Nucleic acid polymerases are essential enzymes that replicate the genomes of both RNA and DNA viruses. These enzymes are generally encoded by viruses themselves so as to provide biochemical functions and control elements that differ from those of the host cell polymerases. The [...] Read more.
Nucleic acid polymerases are essential enzymes that replicate the genomes of both RNA and DNA viruses. These enzymes are generally encoded by viruses themselves so as to provide biochemical functions and control elements that differ from those of the host cell polymerases. The core active site structure used by all replicative polymerases is highly conserved and composed of two key aspartate residues from the conserved motifs A and C, but beyond this there is significant divergence among structures. These differences can make it difficult to select which portions of structures to align for comparisons, yet there are extended structural similarities within different groups of viral polymerases that should clearly be considered to generate optimal alignments. This manuscript describes a comprehensive structure-based superposition of every viral polymerase structure solved thus far based on an alignment-tree approach wherein aligned regions grow in complexity as similarity among polymerases increases. The result is a set of 646 structures that have been aligned into a single common orientation. This provides a convenient resource for directly comparing viral polymerases and illustrating structural conservation among them. It also sets the stage for detailed bioinformatics analysis to further assess common structural features. The full set of protein data bank (PDB) formatted files is publicly available via the Polymerase Structures community page at the Zenodo.org open data repository. Full article
(This article belongs to the Special Issue Structure-Function Relationships in Viral Polymerases)
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Open AccessArticle
Isolation and Full-Length Sequence Analysis of a Pestivirus from Aborted Lamb Fetuses in Italy
Viruses 2019, 11(8), 744; https://doi.org/10.3390/v11080744
Received: 24 July 2019 / Revised: 8 August 2019 / Accepted: 10 August 2019 / Published: 13 August 2019
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Abstract
Pestiviruses are distributed worldwide and are responsible for a variety of economically important diseases. They are not very host-specific, and thus sheep can be infected by well-known pestiviruses like bovine viral diarrhea virus (BVDV) and border disease virus (BDV), as well as by [...] Read more.
Pestiviruses are distributed worldwide and are responsible for a variety of economically important diseases. They are not very host-specific, and thus sheep can be infected by well-known pestiviruses like bovine viral diarrhea virus (BVDV) and border disease virus (BDV), as well as by other recently discovered pestivirus species. The aim of this study is to describe the isolation and characterization of four pestivirus strains detected in aborted lamb fetuses from a single farm in the Brescia province (Northern Italy). A total of twelve aborted fetuses were collected and examined. After necropsy, organs were tested for the presence of infectious agents known as potential causes of abortion (Brucella spp., Listeria spp., Coxiella burnetii, Chlamydophila spp., Mycoplasma spp., Neospora caninum, and Toxoplasma gondii), and submitted to viral identification by isolation on Madin Darby bovine kidney (MDBK) cell culture and by PCR assay for Schmallenberg virus and pan-pestivirus RT-PCR real time assay. Three viral strains (Ovine/IT/1756/2017, Ovine/IT/338710-2/2017, and Ovine/IT/338710-3/2017) were isolated in the absence of cytopathic effects (CPEs) in cell cultures and identified with RT-PCR. Another pestivirus strain (Ovine/IT/16235-2/2018) was detected by PCR, but was not successfully isolated. Complete sequence genomic data of the three isolated viruses showed that they were highly similar, differed genetically from known pestivirus species, and were closely related to classical swine fever virus (CSFV). Beyond the identification of new ovine pestiviruses, this study indicates that a systematic diagnostic approach is important to identify the presence and map the distribution of both known and emerging pestiviruses. Full article
(This article belongs to the Special Issue Emerging Viruses: Surveillance, Prevention, Evolution and Control)
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Open AccessArticle
Serological Screening for Coronavirus Infections in Cats
Viruses 2019, 11(8), 743; https://doi.org/10.3390/v11080743
Received: 5 July 2019 / Revised: 8 August 2019 / Accepted: 9 August 2019 / Published: 13 August 2019
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Abstract
Coronaviruses (CoVs) are widespread among mammals and birds and known for their potential for cross-species transmission. In cats, infections with feline coronaviruses (FCoVs) are common. Several non-feline coronaviruses have been reported to infect feline cells as well as cats after experimental infection, supported [...] Read more.
Coronaviruses (CoVs) are widespread among mammals and birds and known for their potential for cross-species transmission. In cats, infections with feline coronaviruses (FCoVs) are common. Several non-feline coronaviruses have been reported to infect feline cells as well as cats after experimental infection, supported by their ability to engage the feline receptor ortholog for cell entry. However, whether cats might become naturally infected with CoVs of other species is unknown. We analyzed coronavirus infections in cats by serological monitoring. In total 137 cat serum samples and 25 FCoV type 1 or type 2-specific antisera were screened for the presence of antibodies against the S1 receptor binding subunit of the CoV spike protein, which is immunogenic and possesses low amino acid sequence identity among coronavirus species. Seventy-eight sera were positive for antibodies that recognized one or more coronavirus S1s whereas 1 serum exclusively reacted with human coronavirus 229E (HCoV-229E) and two sera exclusively reacted with porcine delta coronavirus (PDCoV). We observed antigenic cross-reactivity between S1s of type 1 and type 2 FCoVs, and between FCoV type 1 and porcine epidemic diarrhea virus (PEDV). Domain mapping of antibody epitopes indicated the presence of conserved epitope(s) particularly in the CD domains of S1. The cross-reactivity of FCoV type 1 and PEDV was also observed at the level of virus neutralization. To conclude, we provide the first evidence of antigenic cross-reactivity among S1 proteins of coronaviruses, which should be considered in the development of serological diagnoses. In addition, the potential role of cats in cross-species transmission of coronaviruses cannot be excluded. Full article
(This article belongs to the Special Issue Feline Viruses and Viral Diseases)
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Open AccessArticle
Inhibitory Effects of Antiviral Drug Candidates on Canine Parvovirus in F81 cells
Viruses 2019, 11(8), 742; https://doi.org/10.3390/v11080742
Received: 22 May 2019 / Revised: 12 July 2019 / Accepted: 18 July 2019 / Published: 13 August 2019
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Abstract
Canine parvovirus (CPV) is a common etiological agent of acute enteritis, which occurs globally in domestic and wild carnivores. Despite the widespread use of inactivated or live attenuated vaccines, the emergence of antigenic variants and the influence of maternal antibodies have raised some [...] Read more.
Canine parvovirus (CPV) is a common etiological agent of acute enteritis, which occurs globally in domestic and wild carnivores. Despite the widespread use of inactivated or live attenuated vaccines, the emergence of antigenic variants and the influence of maternal antibodies have raised some concerns regarding the efficacy of commercial vaccines. While no specific antiviral therapy for CPV infection exists, the only treatment option for the infection is supportive therapy based on symptoms. Thus, there is an urgent medical need to develop antiviral therapeutic options to reduce the burden of CPV-related disease. In this study, a cytopathic effect (CPE)-based high-throughput screening assay was used to screen CPV inhibitors from a Food and Drug Administration (FDA)-approved drug library. After two rounds of screening, seven out of 1430 screened drugs were found to have >50% CPE inhibition. Three drugs—Nitazoxanide, Closantel Sodium, and Closantel—with higher anti-CPV effects were further evaluated in F81 cells by absolute PCR quantification and indirect immunofluorescence assay (IFA). The inhibitory effects of all three drugs were dose-dependent. Time of addition assay indicated that the drugs inhibited the early processes of the CPV replication cycle, and the inhibition effects were relatively high within 2 h postinfection. Western blot assay also showed that the three drugs had broad-spectrum antiviral activity against different subspecies of three CPV variants. In addition, antiapoptotic effects were observed within 12 h in Nitazoxanide-treated F81 cells regardless of CPV infection, while Closantel Sodium- or Closantel-treated cells had no pro- or antiapoptotic effects. In conclusion, Nitazoxanide, Closantel Sodium, and Closantel can effectively inhibit different subspecies of CPV. Since the safety profiles of FDA-approved drugs have already been extensively studied, these three drugs can potentially become specific and effective anti-CPV drugs. Full article
(This article belongs to the Section Antivirals & Vaccines)
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Open AccessReview
Pathogenesis of Hypervirulent Fowl Adenovirus Serotype 4: The Contributions of Viral and Host Factors
Viruses 2019, 11(8), 741; https://doi.org/10.3390/v11080741
Received: 18 July 2019 / Revised: 9 August 2019 / Accepted: 10 August 2019 / Published: 12 August 2019
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Abstract
Since 2015, severe outbreaks of hepatitis-hydropericardium syndrome (HHS), caused by hypervirulent fowl adenovirus serotype 4 (FAdV-4), have emerged in several provinces in China, posing a great threat to poultry industry. So far, factors contributing to the pathogenesis of hypervirulent FAdV-4 have not been [...] Read more.
Since 2015, severe outbreaks of hepatitis-hydropericardium syndrome (HHS), caused by hypervirulent fowl adenovirus serotype 4 (FAdV-4), have emerged in several provinces in China, posing a great threat to poultry industry. So far, factors contributing to the pathogenesis of hypervirulent FAdV-4 have not been fully uncovered. Elucidation of the pathogenesis of FAdV-4 will facilitate the development of effective FAdV-4 vaccine candidates for the control of HHS and vaccine vector. The interaction between pathogen and host defense system determines the pathogenicity of the pathogen. Therefore, the present review highlights the knowledge of both viral and host factors contributing to the pathogenesis of hypervirulent FAdV-4 strains to facilitate the related further studies. Full article
(This article belongs to the Special Issue Viral Evasion or Suppression of Host Immunity)
Open AccessArticle
Screening of Duck Tembusu Virus NS3 Interacting Host Proteins and Identification of Its Specific Interplay Domains
Viruses 2019, 11(8), 740; https://doi.org/10.3390/v11080740
Received: 12 July 2019 / Revised: 19 July 2019 / Accepted: 2 August 2019 / Published: 12 August 2019
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Abstract
NS3 protein is a member of the non-structural protein of duck Tembusu virus (DTMUV), which contains three domains, each of which has serine protease, nucleotide triphosphatase, and RNA helicase activities, respectively. It performs a variety of biological functions that are involved in the [...] Read more.
NS3 protein is a member of the non-structural protein of duck Tembusu virus (DTMUV), which contains three domains, each of which has serine protease, nucleotide triphosphatase, and RNA helicase activities, respectively. It performs a variety of biological functions that are involved in the regulation of the viral life cycle and host immune response. Based on the yeast two-hybrid system, we successfully transformed pGBKT7-NS3 bait plasmid into Y2H Gold, tested it to prove that it has no self-activation and toxicity, and then hybridized it with the prey yeast strain of the duck embryo fibroblast cDNA library for screening. After high-stringency selection, positive alignment with the National Center for Biotechnology Information database revealed nine potential interactive proteins: MGST1, ERCC4, WIF1, WDR75, ACBD3, PRDX1, RPS7, ND5, and LDHA. The most interesting one (PRDX1) was selected to be verified with full-length NS3 protein and its three domains S7/DEXDc/HELICc using yeast regressive verification and GST Pull-Down assay. It denoted that PRDX1 does indeed interact with HELICc domains of NS3. NS3 is involved in the RNA uncoiling process of viral replication, which may cause mitochondrial overload to create oxidative stress (OS) during DTMUV attack. We deduced that the HELICc domain binding partner PRDX1, which regulates the p38/mitogen-activated protein kinase pathway (p38/MAPK) to avert OS, causing apoptosis, making it possible for viruses to escape host immune responses. Full article
(This article belongs to the Special Issue Flavivirus Replication and Pathogenesis)
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Open AccessArticle
Antibiotic Minocycline Prevents Respiratory Syncytial Virus Infection
Viruses 2019, 11(8), 739; https://doi.org/10.3390/v11080739
Received: 10 July 2019 / Revised: 5 August 2019 / Accepted: 7 August 2019 / Published: 11 August 2019
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Abstract
Treatment drugs, besides their specific activity, often have multiple effects on the body. The undesired effect of the drug may be repurposed as therapeutics, saving significant investigative time and effort. Minocycline has anti-cancer, anti-oxidant, anti-inflammatory, and anti-apoptotic properties. Presently, minocycline is also known [...] Read more.
Treatment drugs, besides their specific activity, often have multiple effects on the body. The undesired effect of the drug may be repurposed as therapeutics, saving significant investigative time and effort. Minocycline has anti-cancer, anti-oxidant, anti-inflammatory, and anti-apoptotic properties. Presently, minocycline is also known to show anti-viral activity against Influenza virus, Japanese encephalitis virus, Simian immunodeficiency virus, Human immunodeficiency virus and West Nile virus. Here, we investigate the effect of minocycline on Respiratory syncytial virus (RSV), a common respiratory virus that causes severe mortality and morbidity in infants, children, and older adult populations. Currently, there is no effective vaccine or treatment for RSV infection; hence, there is a critical need for alternative and effective drug choices. Our study shows that minocycline reduces the RSV-mediated cytopathic effect and prevents RSV infection. This is the first study demonstrating the anti-viral activity of minocycline against RSV. Full article
(This article belongs to the Section Antivirals & Vaccines)
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Open AccessArticle
Generation of Virus- and dsRNA-Derived siRNAs with Species-Dependent Length in Insects
Viruses 2019, 11(8), 738; https://doi.org/10.3390/v11080738
Received: 15 July 2019 / Revised: 7 August 2019 / Accepted: 8 August 2019 / Published: 11 August 2019
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Abstract
Double-stranded RNA (dsRNA) molecules of viral origin trigger a post-transcriptional gene-silencing mechanism called RNA interference (RNAi). Specifically, virally derived dsRNA is recognized and cleaved by the enzyme Dicer2 into short interfering RNAs (siRNAs), which further direct sequence-specific RNA silencing, ultimately silencing replication of [...] Read more.
Double-stranded RNA (dsRNA) molecules of viral origin trigger a post-transcriptional gene-silencing mechanism called RNA interference (RNAi). Specifically, virally derived dsRNA is recognized and cleaved by the enzyme Dicer2 into short interfering RNAs (siRNAs), which further direct sequence-specific RNA silencing, ultimately silencing replication of the virus. Notably, RNAi can also be artificially triggered by the delivery of gene-specific dsRNA, thereby leading to endogenous gene silencing. This is a widely used technology that holds great potential to contribute to novel pest control strategies. In this regard, research efforts have been set to find methods to efficiently trigger RNAi in the field. In this article, we demonstrate the generation of dsRNA- and/or virus-derived siRNAs—the main RNAi effectors—in six insect species belonging to five economically important orders (Lepidoptera, Orthoptera, Hymenoptera, Coleoptera, and Diptera). In addition, we describe that the siRNA length distribution is species-dependent. Taken together, our results reveal interspecies variability in the (antiviral) RNAi mechanism in insects and show promise to contribute to future research on (viral-based) RNAi-triggering mechanisms in this class of animals. Full article
(This article belongs to the Special Issue Insect Viruses and Pest Management)
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Open AccessEditorial
Bacteriophage-Based Biotechnological Applications
Viruses 2019, 11(8), 737; https://doi.org/10.3390/v11080737
Received: 24 July 2019 / Accepted: 8 August 2019 / Published: 10 August 2019
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Abstract
Phages have shown a high biotechnological potential with numerous applications. The advent of high-resolution microscopy techniques aligned with omic and molecular tools are revealing innovative phage features and enabling new processes that can be further exploited for biotechnological applications in a wide variety [...] Read more.
Phages have shown a high biotechnological potential with numerous applications. The advent of high-resolution microscopy techniques aligned with omic and molecular tools are revealing innovative phage features and enabling new processes that can be further exploited for biotechnological applications in a wide variety of fields. This special issue is a collection of original and review articles focusing on the most recent advances in phage-based biotechnology with applications for human benefit. Full article
(This article belongs to the Special Issue Biotechnological Applications of Phage and Phage-Derived Proteins)
Open AccessReview
The Development and Use of Reporter Influenza B Viruses
Viruses 2019, 11(8), 736; https://doi.org/10.3390/v11080736
Received: 3 July 2019 / Revised: 31 July 2019 / Accepted: 2 August 2019 / Published: 9 August 2019
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Abstract
Influenza B viruses (IBVs) are major contributors to total human influenza disease, responsible for ~1/3 of all infections. These viruses, however, are relatively less studied than the related influenza A viruses (IAVs). While it has historically been assumed that the viral biology and [...] Read more.
Influenza B viruses (IBVs) are major contributors to total human influenza disease, responsible for ~1/3 of all infections. These viruses, however, are relatively less studied than the related influenza A viruses (IAVs). While it has historically been assumed that the viral biology and mechanisms of pathogenesis for all influenza viruses were highly similar, studies have shown that IBVs possess unique characteristics. Relative to IAV, IBV encodes distinct viral proteins, displays a different mutational rate, has unique patterns of tropism, and elicits different immune responses. More work is therefore required to define the mechanisms of IBV pathogenesis. One valuable approach to characterize mechanisms of microbial disease is the use of genetically modified pathogens that harbor exogenous reporter genes. Over the last few years, IBV reporter viruses have been developed and used to provide new insights into the host response to infection, viral spread, and the testing of antiviral therapeutics. In this review, we will highlight the history and study of IBVs with particular emphasis on the use of genetically modified viruses and discuss some remaining gaps in knowledge that can be addressed using reporter expressing IBVs. Full article
(This article belongs to the Special Issue Non-A Influenza)
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Open AccessArticle
Production of Recombinant EAV with Tagged Structural Protein Gp3 to Study Artervirus Minor Protein Localization in Infected Cells
Viruses 2019, 11(8), 735; https://doi.org/10.3390/v11080735
Received: 5 July 2019 / Revised: 29 July 2019 / Accepted: 7 August 2019 / Published: 9 August 2019
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Abstract
Equine arteritis virus (EAV) is a prototype member of the Arterivirus family, comprising important pathogens of domestic animals. Minor glycoproteins of Arteriviruses are responsible for virus entry and cellular tropism. The experimental methods for studying minor Arterivirus proteins are limited because of the [...] Read more.
Equine arteritis virus (EAV) is a prototype member of the Arterivirus family, comprising important pathogens of domestic animals. Minor glycoproteins of Arteriviruses are responsible for virus entry and cellular tropism. The experimental methods for studying minor Arterivirus proteins are limited because of the lack of antibodies and nested open reading frames (ORFs). In this study, we generated recombinant EAV with separated ORFs 3 and 4, and Gp3 carrying HA-tag (Gp3-HA). The recombinant viruses were stable on passaging and replicated in titers similar to the wild-type EAV. Gp3-HA was incorporated into the virion particles as monomers and as a Gp2/Gp3-HA/Gp4 trimer. Gp3-HA localized in ER and, to a lesser extent, in the Golgi, it also co-localized with the E protein but not with the N protein. The co-localization of Gp3-HA and the E protein with ERGIC was reduced. Moreover, EAV with Gp3-HA could become a valuable research tool for identifying host cell factors during infection and the role of Gp3 in virus attachment and entry. Full article
(This article belongs to the Section Animal Viruses)
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Open AccessErratum
Erratum: Yang, Y.; et al. A Novel Roseosiphophage Isolated from the Oligotrophic South China Sea. Viruses 2017, 9, 109
Viruses 2019, 11(8), 734; https://doi.org/10.3390/v11080734
Received: 5 August 2019 / Accepted: 7 August 2019 / Published: 8 August 2019
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Abstract
The authors wish to make the following changes to their paper [...] Full article
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Open AccessReview
Virophages of Giant Viruses: An Update at Eleven
Viruses 2019, 11(8), 733; https://doi.org/10.3390/v11080733
Received: 12 July 2019 / Revised: 31 July 2019 / Accepted: 2 August 2019 / Published: 8 August 2019
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Abstract
The last decade has been marked by two eminent discoveries that have changed our perception of the virology field: The discovery of giant viruses and a distinct new class of viral agents that parasitize their viral factories, the virophages. Coculture and metagenomics have [...] Read more.
The last decade has been marked by two eminent discoveries that have changed our perception of the virology field: The discovery of giant viruses and a distinct new class of viral agents that parasitize their viral factories, the virophages. Coculture and metagenomics have actively contributed to the expansion of the virophage family by isolating dozens of new members. This increase in the body of data on virophage not only revealed the diversity of the virophage group, but also the relevant ecological impact of these small viruses and their potential role in the dynamics of the microbial network. In addition, the isolation of virophages has led us to discover previously unknown features displayed by their host viruses and cells. In this review, we present an update of all the knowledge on the isolation, biology, genomics, and morphological features of the virophages, a decade after the discovery of their first member, the Sputnik virophage. We discuss their parasitic lifestyle as bona fide viruses of the giant virus factories, genetic parasites of their genomes, and then their role as a key component or target for some host defense mechanisms during the tripartite virophage–giant virus–host cell interaction. We also present the latest advances regarding their origin, classification, and definition that have been widely discussed. Full article
(This article belongs to the Section Viruses of Plants, Fungi and Protozoa)
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Open AccessArticle
Antiviral and Immunomodulatory Activity of Silver Nanoparticles in Experimental RSV Infection
Viruses 2019, 11(8), 732; https://doi.org/10.3390/v11080732
Received: 29 May 2019 / Revised: 30 July 2019 / Accepted: 6 August 2019 / Published: 8 August 2019
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Abstract
Respiratory syncytial virus (RSV) is an important etiological agent of respiratory infection in children for which no specific treatment option is available. The RSV virion contains two surface glycoproteins (F and G) that are vital for the initial phases of infection, making them [...] Read more.
Respiratory syncytial virus (RSV) is an important etiological agent of respiratory infection in children for which no specific treatment option is available. The RSV virion contains two surface glycoproteins (F and G) that are vital for the initial phases of infection, making them critical targets for RSV therapeutics. Recent studies have identified the broad-spectrum antiviral properties of silver nanoparticles (AgNPs) against respiratory pathogens, such as adenovirus, parainfluenza, and influenza. AgNPs achieve this by attaching to viral glycoproteins, blocking entry into the host cell. The objective of this study was to evaluate the antiviral and immunomodulatory effects of AgNPs in RSV infection. Herein we demonstrate AgNP-mediated reduction in RSV replication, both in epithelial cell lines and in experimentally infected BALB/c mice. Marked reduction in pro-inflammatory cytokines (i.e., IL-1α, IL-6, TNF-α) and pro-inflammatory chemokines (i.e., CCL2, CCL3, CCL5) was also observed. Conversely, CXCL1, G-CSF, and GM-CSF were increased in RSV-infected mice treated with AgNPs, consistent with an increase of neutrophil recruitment and activation in the lung tissue. Following experimental antibody-dependent depletion of neutrophils, the antiviral effect of AgNPs in mice treated was ablated. To our knowledge, this is the first in vivo report demonstrating antiviral activity of AgNPs during RSV infection. Full article
(This article belongs to the Section Antivirals & Vaccines)
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Open AccessArticle
Field Evaluation of Deltamethrin and Ivermectin Applications to Cattle on Culicoides Host-Alighting, Blood-Feeding, and Emergence
Viruses 2019, 11(8), 731; https://doi.org/10.3390/v11080731
Received: 2 July 2019 / Revised: 30 July 2019 / Accepted: 2 August 2019 / Published: 8 August 2019
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Abstract
The impact of topical applications of deltamethrin and ivermectin to cattle on Culicoides spp. landing and blood-feeding was studied in this work using sticky traps mounted on Friesian heifers’ backs. There was no effect of the insecticides on total numbers of Culicoides trapped [...] Read more.
The impact of topical applications of deltamethrin and ivermectin to cattle on Culicoides spp. landing and blood-feeding was studied in this work using sticky traps mounted on Friesian heifers’ backs. There was no effect of the insecticides on total numbers of Culicoides trapped or the proportion engorged. Deltamethrin and ivermectin treatment did not prevent blood-feeding on these animals. Deltamethrin did result in significant Culicoides mortality as evidenced by the numbers of dead midges combed from heifers’ upper flanks. The proximity of engorged midges on traps to dead midges in the hair suggests that blood-feeding took place despite midges receiving an ultimately lethal dose of deltamethrin. Ivermectin application resulted in a smaller proportion of nulliparous than parous females caught. There was no significant effect of ivermectin on the numbers of Culicoides that emerged from dung samples (but p was small at 0.095 for the Obsoletus group Culicoides). In cases of suspect animal imports, pour-on or spray applications of deltamethrin could reduce the risk of onward transmission of bluetongue virus. Full article
(This article belongs to the Special Issue Virus-Vector-Host Interactions of Culicoides-Borne Diseases)
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