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Viruses, Volume 11, Issue 5 (May 2019)

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Cover Story (view full-size image) This new report utilizes the classic genetic model system Drosophila melanogaster to study the [...] Read more.
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Open AccessArticle
Limited Sustained Local Transmission of HIV-1 CRF01_AE in New South Wales, Australia
Viruses 2019, 11(5), 482; https://doi.org/10.3390/v11050482 - 27 May 2019
Viewed by 828
Abstract
Australia’s response to the human immunodeficiency virus type 1 (HIV-1) pandemic led to effective control of HIV transmission and one of the world’s lowest HIV incidence rates—0.14%. Although there has been a recent decline in new HIV diagnoses in New South Wales (NSW), [...] Read more.
Australia’s response to the human immunodeficiency virus type 1 (HIV-1) pandemic led to effective control of HIV transmission and one of the world’s lowest HIV incidence rates—0.14%. Although there has been a recent decline in new HIV diagnoses in New South Wales (NSW), the most populous state in Australia, there has been a concomitant increase with non-B subtype infections, particularly for the HIV-1 circulating recombinant form CRF01_AE. This aforementioned CRF01_AE sampled in NSW, were combined with those sampled globally to identify NSW-specific viral clades. The population growth of these clades was assessed in two-year period intervals from 2009 to 2017. Overall, 109 NSW-specific clades were identified, most comprising pairs of sequences; however, five large clades comprising ≥10 sequences were also found. Forty-four clades grew over time with one or two sequences added to each in different two-year periods. Importantly, while 10 of these clades have seemingly discontinued, the remaining 34 were still active in 2016/2017. Seven such clades each comprised ≥10 sequences, and are representative of individual sub-epidemics in NSW. Thus, although the majority of new CRF01_AE infections were associated with small clades that rarely establish ongoing chains of local transmission, individual sub-epidemics are present and should be closely monitored. Full article
(This article belongs to the Section Animal Viruses)
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Open AccessArticle
Attenuation of Bluetongue Virus (BTV) in an in ovo Model Is Related to the Changes of Viral Genetic Diversity of Cell-Culture Passaged BTV
Viruses 2019, 11(5), 481; https://doi.org/10.3390/v11050481 - 26 May 2019
Viewed by 1025
Abstract
The embryonated chicken egg (ECE) is routinely used for the laboratory isolation and adaptation of Bluetongue virus (BTV) in vitro. However, its utility as an alternate animal model has not been fully explored. In this paper, we evaluated the pathogenesis of BTV in [...] Read more.
The embryonated chicken egg (ECE) is routinely used for the laboratory isolation and adaptation of Bluetongue virus (BTV) in vitro. However, its utility as an alternate animal model has not been fully explored. In this paper, we evaluated the pathogenesis of BTV in ovo using a pathogenic isolate of South African BTV serotype 3 (BTV-3) derived from the blood of an infected sheep. Endothelio- and neurotropism of BTV-3 were observed by immunohistochemistry of non-structural protein 1 (NS1), NS3, NS3/3a, and viral protein 7 (VP7) antigens. In comparing the pathogenicity of BTV from infectious sheep blood with cell-culture-passaged BTV, including virus propagated through a Culicoides-derived cell line (KC) or ECE, we found virus attenuation in ECE following cell-culture passage. Genomic analysis of the consensus sequences of segments (Seg)-2, -5, -6, -7, -8, -9, and -10 identified several nucleotide and amino-acid mutations among the cell-culture-propagated BTV-3. Deep sequencing analysis revealed changes in BTV-3 genetic diversity in various genome segments, notably a reduction of Seg-7 diversity following passage in cell culture. Using this novel approach to investigate BTV pathogenicity in ovo, our findings support the notion that pathogenic BTV becomes attenuated in cell culture and that this change is associated with virus quasispecies evolution. Full article
(This article belongs to the Special Issue Virus-Vector-Host Interactions of Culicoides-Borne Diseases)
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Open AccessReview
Inactivation of Dairy Bacteriophages by Thermal and Chemical Treatments
Viruses 2019, 11(5), 480; https://doi.org/10.3390/v11050480 - 25 May 2019
Viewed by 537
Abstract
This article provides information on the characteristics of diverse phages of lactic acid bacteria and highlights the incidence of their presence in different dairy fermentations. As it is known, thermal treatments on raw milk and use of sanitizers in the disinfection of surfaces [...] Read more.
This article provides information on the characteristics of diverse phages of lactic acid bacteria and highlights the incidence of their presence in different dairy fermentations. As it is known, thermal treatments on raw milk and use of sanitizers in the disinfection of surfaces and equipment are strategies usually applied in dairy to prevent bacteriophage infections. In this sense, this review mainly focuses on the existing data about the resistance against thermal treatments and sanitizers usually used in the dairy industry worldwide, and the differences found among bacteriophages of diverse genera are remarked upon. Also, we provide information concerning the problems that have arisen as a consequence of the potential presence of bacteriophages in cheese whey powder and derivatives when they are added in fermented dairy product manufacturing. Finally, some important conclusions on each topic are marked and checkpoints to be considered are suggested. Full article
Open AccessArticle
Characterization of Mutational Tolerance of a Viral RNA–Protein Interaction
Viruses 2019, 11(5), 479; https://doi.org/10.3390/v11050479 - 25 May 2019
Viewed by 706
Abstract
Replication of RNA viruses is generally markedly error-prone. Nevertheless, these viruses usually retain their identity under more or less constant conditions due to different mechanisms of mutation tolerance. However, there exists only limited information on quantitative aspects of the mutational tolerance of distinct [...] Read more.
Replication of RNA viruses is generally markedly error-prone. Nevertheless, these viruses usually retain their identity under more or less constant conditions due to different mechanisms of mutation tolerance. However, there exists only limited information on quantitative aspects of the mutational tolerance of distinct viral functions. To address this problem, we used here as a model the interaction between a replicative cis-acting RNA element (oriL) of poliovirus and its ligand (viral protein 3CD). The mutational tolerance of a conserved tripeptide of 3CD, directly involved in this interaction, was investigated. Randomization of the relevant codons and reverse genetics were used to define the space of viability-compatible sequences. Surprisingly, at least 11 different amino acid substitutions in this tripeptide were not lethal. Several altered viruses exhibited wild-type-like phenotypes, whereas debilitated (but viable) genomes could increase their fitness by the acquisition of reversions or compensatory mutations. Together with our study on the tolerance of oriL (Prostova et al., 2015), the results demonstrate that at least 42 out of 51 possible nucleotide replacements within the two relevant genomic regions are viability-compatible. These results provide new insights into structural aspects of an important viral function as well as into the general problems of viral mutational robustness and evolution. Full article
(This article belongs to the Section Animal Viruses)
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Open AccessReview
Animals as Reservoir for Human Norovirus
Viruses 2019, 11(5), 478; https://doi.org/10.3390/v11050478 - 25 May 2019
Cited by 1 | Viewed by 1048
Abstract
Norovirus is the most common cause of non-bacterial gastroenteritis and is a burden worldwide. The increasing norovirus diversity is currently categorized into at least 10 genogroups which are further classified into more than 40 genotypes. In addition to humans, norovirus can infect a [...] Read more.
Norovirus is the most common cause of non-bacterial gastroenteritis and is a burden worldwide. The increasing norovirus diversity is currently categorized into at least 10 genogroups which are further classified into more than 40 genotypes. In addition to humans, norovirus can infect a broad range of hosts including livestock, pets, and wild animals, e.g., marine mammals and bats. Little is known about norovirus infections in most non-human hosts, but the close genetic relatedness between some animal and human noroviruses coupled with lack of understanding where newly appearing human norovirus genotypes and variants are emerging from has led to the hypothesis that norovirus may not be host restricted and might be able to jump the species barrier. We have systematically reviewed the literature to describe the diversity, prevalence, and geographic distribution of noroviruses found in animals, and the pathology associated with infection. We further discuss the evidence that exists for or against interspecies transmission including surveillance data and data from in vitro and in vivo experiments. Full article
(This article belongs to the Special Issue Noroviruses)
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Open AccessReview
Electron Microscopy in Discovery of Novel and Emerging Viruses from the Collection of the World Reference Center for Emerging Viruses and Arboviruses (WRCEVA)
Viruses 2019, 11(5), 477; https://doi.org/10.3390/v11050477 - 25 May 2019
Viewed by 848
Abstract
Since the beginning of modern virology in the 1950s, transmission electron microscopy (TEM) has been an important and widely used technique for discovery, identification and characterization of new viruses. Using TEM, viruses can be differentiated by their ultrastructure: shape, size, intracellular location and [...] Read more.
Since the beginning of modern virology in the 1950s, transmission electron microscopy (TEM) has been an important and widely used technique for discovery, identification and characterization of new viruses. Using TEM, viruses can be differentiated by their ultrastructure: shape, size, intracellular location and for some viruses, by the ultrastructural cytopathic effects and/or specific structures forming in the host cell during their replication. Ultrastructural characteristics are usually sufficient for the identification of a virus to the family level. In this review, we summarize 25 years of experience in identification of novel viruses from the collection of the World Reference Center for Emerging Viruses and Arboviruses (WRCEVA). Full article
(This article belongs to the Special Issue 6th Pan-American Dengue Research Network Meeting)
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Open AccessArticle
Co-Expression of Chicken IL-2 and IL-7 Enhances the Immunogenicity and Protective Efficacy of a VP2-Expressing DNA Vaccine against IBDV in Chickens
Viruses 2019, 11(5), 476; https://doi.org/10.3390/v11050476 - 24 May 2019
Viewed by 699
Abstract
Chicken infectious bursal disease (IBD) is still incompletely controlled worldwide. Although IBD virus (IBDV) VP2 DNA vaccine was considered a safe vaccine for IBD prevention, the immunogenicity by itself remains poor, resulting in the failure of effectively protecting chickens from infection. We and [...] Read more.
Chicken infectious bursal disease (IBD) is still incompletely controlled worldwide. Although IBD virus (IBDV) VP2 DNA vaccine was considered a safe vaccine for IBD prevention, the immunogenicity by itself remains poor, resulting in the failure of effectively protecting chickens from infection. We and others demonstrated that chicken IL-2 (chIL-2) and chIL-7 have the capacity to enhance the immunogenicity of the VP2 DNA vaccine. However, whether chIL-2 and chIL-7 can mutually enhance the immunogenicity of VP2 DNA vaccine and thereby augment the latter’s protection efficacy remains unknown. By using chIL-2/chIL-7 bicistronic gene vector to co-immunize the chickens together with the VP2 DNA vaccine, we now show that chIL-2 and chIL-7 significantly increased IBDV VP2-specific antibody titers, T cell proliferation, and IFN-γ production, resulting in the ultimate enhancement of vaccine-induced protection efficacy relative to that of chIL-2 or chIL-7 gene vectors alone. These results suggest that chIL-2 and chIL-7 can mutually enhance VP2 DNA vaccine’s efficacy, thereby establishing a concrete foundation for future optimization of IBDV VP2 DNA vaccine to prevent/treat chicken IBD. Full article
(This article belongs to the Section Antivirals & Vaccines)
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Open AccessErratum
Erratum: Singh, S. et al. Ocular Manifestations of Emerging Flaviviruses and the Blood–Retinal Barrier. Viruses 2018, 10, 530
Viruses 2019, 11(5), 475; https://doi.org/10.3390/v11050475 - 24 May 2019
Cited by 1 | Viewed by 670
Abstract
The authors wish to correct the following erratum in this paper [...] Full article
(This article belongs to the Section Animal Viruses)
Open AccessArticle
Detection Patterns of Porcine Parvovirus (PPV) and Novel Porcine Parvoviruses 2 through 6 (PPV2–PPV6) in Polish Swine Farms
Viruses 2019, 11(5), 474; https://doi.org/10.3390/v11050474 - 24 May 2019
Viewed by 629
Abstract
Porcine parvovirus (PPV) is a major causative agent in reproductive failure, but in the last two decades many novel porcine parvoviruses were described and designated as porcine parvovirus 2 through 6 (PPV2–PPV6). However, their role for pig health is largely unknown. The aim [...] Read more.
Porcine parvovirus (PPV) is a major causative agent in reproductive failure, but in the last two decades many novel porcine parvoviruses were described and designated as porcine parvovirus 2 through 6 (PPV2–PPV6). However, their role for pig health is largely unknown. The aim of this study was to better understand the on-farm prevalence of PPVs in different age groups of pigs, and to assess the diagnostic applicability of testing different diagnostic materials. In total, 271 oral fluids, 1244 serum samples, and 1238 fecal samples were collected from 3–21-week-old pigs from 19 farms, and after pooling by 4–6, tested by real-time PCR. The results showed that PPVs are widely spread in Poland and that the highest detection rates were obtained for oral fluids (ranging from 10.7% (PPV1) to 48.7% (PPV2)). Fattening pigs were the age group with the most frequent detection of PPVs (ranging from 8.6% (PPV1) to 49.1% (PPV2)). Porcine parvoviruses were detected mostly in growing-finishing pigs and the infection persisted until the late fattening period, which may suggest the chronic character of the infection (especially for PPV2, which was found to commonly infect animals of all ages). Particularly low Ct values detected for PPV2, PPV3, PPV5, and PPV6 in serum pools from some farms suggested that these viruses may cause high levels of viremia in one or more individuals included in these pools. Further studies are needed to quantify the levels of PPVs viremia and to assess the impact in co-infections with other, often endemic pig viruses, such as porcine circovirus type 2 (PCV2) and porcine reproductive and respiratory syndrome virus (PRRSV). Full article
(This article belongs to the Special Issue Porcine Viruses 2019)
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Open AccessArticle
Transcriptome Response of Female Culicoides sonorensis Biting Midges (Diptera: Ceratopogonidae) to Early Infection with Epizootic Hemorrhagic Disease Virus (EHDV-2)
Viruses 2019, 11(5), 473; https://doi.org/10.3390/v11050473 - 24 May 2019
Viewed by 556
Abstract
Female Culicoides sonorensis biting midges are vectors of epizootic hemorrhagic disease virus (EHDV), which causes morbidity and mortality in wild and domesticated ruminants. The aims in this study were to identify key changes in female midge transcriptome profiles occurring during early infection with [...] Read more.
Female Culicoides sonorensis biting midges are vectors of epizootic hemorrhagic disease virus (EHDV), which causes morbidity and mortality in wild and domesticated ruminants. The aims in this study were to identify key changes in female midge transcriptome profiles occurring during early infection with EHDV-2. Midges were fed either negative control bloodmeals or bloodmeals containing EHDV-2 and transcriptomes were acquired at 36 h through deep sequencing. Reads were de novo assembled into a transcriptome comprised of 18,754 unigenes. Overall, there were 2401 differentially expressed unigenes and ~60% were downregulated in response to the virus (953 up; 1448 down). Downstream Gene Ontology enrichment, KEGG pathway mapping, and manual analyses were used to identify the effect of virus ingestion at both the gene and pathway levels. Downregulated unigenes were predominantly assigned to pathways related to cell/tissue structure and integrity (actin cytoskeleton, adherens junction, focal adhesion, hippo signaling), calcium signaling, eye morphogenesis and axon guidance. Unigenes attributed to sensory functions (especially vision), behavior, learning and memory were largely downregulated. Upregulated unigenes included those coding for innate immune processes, olfaction and photoreceptor pigments. Our results suggest that midges respond to virus infection as soon as 36 h post-ingestion, and that EHDV-2 may have a significant phenotypic effect on sensory and neural tissues. Full article
(This article belongs to the Special Issue Virus-Vector-Host Interactions of Culicoides-Borne Diseases)
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Open AccessArticle
Wheat streak mosaic virus P1 Binds to dsRNAs without Size and Sequence Specificity and a GW Motif Is Crucial for Suppression of RNA Silencing
Viruses 2019, 11(5), 472; https://doi.org/10.3390/v11050472 - 24 May 2019
Cited by 2 | Viewed by 640
Abstract
Wheat streak mosaic virus (WSMV; genus Tritimovirus; family Potyviridae) is an economically important virus infecting wheat in the Great Plains region of the USA. Previously, we reported that the P1 protein of WSMV acts as a viral suppressor of RNA silencing. [...] Read more.
Wheat streak mosaic virus (WSMV; genus Tritimovirus; family Potyviridae) is an economically important virus infecting wheat in the Great Plains region of the USA. Previously, we reported that the P1 protein of WSMV acts as a viral suppressor of RNA silencing. In this study, we delineated the minimal region of WSMV P1 and examined its mechanisms in suppression of RNA silencing. We found that the 25 N-terminal amino acids are dispensable, while deletion of a single amino acid at the C-terminal region completely abolished the RNA silencing suppression activity of P1. Electrophoretic mobility shift assays with in vitro expressed P1 revealed that the P1 protein formed complexes with green fluorescent protein-derived 180-nt dsRNA and 21 and 24-nt ds-siRNAs, and WSMV coat protein-specific 600-nt dsRNA. These data suggest that the P1 protein of WSMV binds to dsRNAs in a size- and sequence-independent manner. Additionally, in vitro dicing assay with human Dicer revealed that the P1 protein efficiently protects dsRNAs from processing by Dicer into siRNAs, by forming complexes with dsRNA. Sequence comparison of P1-like proteins from select potyvirid species revealed that WSMV P1 harbors a glycine-tryptophan (GW) motif at the C-terminal region. Disruption of GW motif in WSMV P1 through W303A mutation resulted in loss of silencing suppression function and pathogenicity enhancement, and abolished WSMV viability. These data suggest that the mechanisms of suppression of RNA silencing of P1 proteins of potyvirid species appear to be broadly conserved in the family Potyviridae. Full article
(This article belongs to the Special Issue Plant Immunity to Virus Infections)
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Open AccessReview
Exploiting the Legacy of the Arbovirus Hunters
Viruses 2019, 11(5), 471; https://doi.org/10.3390/v11050471 - 23 May 2019
Viewed by 969
Abstract
In recent years, it has become evident that a generational gap has developed in the community of arbovirus research. This apparent gap is due to the dis-investment of training for the next generation of arbovirologists, which threatens to derail the rich history of [...] Read more.
In recent years, it has become evident that a generational gap has developed in the community of arbovirus research. This apparent gap is due to the dis-investment of training for the next generation of arbovirologists, which threatens to derail the rich history of virus discovery, field epidemiology, and understanding of the richness of diversity that surrounds us. On the other hand, new technologies have resulted in an explosion of virus discovery that is constantly redefining the virosphere and the evolutionary relationships between viruses. This paradox presents new challenges that may have immediate and disastrous consequences for public health when yet to be discovered arboviruses emerge. In this review we endeavor to bridge this gap by providing a historical context for the work being conducted today and provide continuity between the generations. To this end, we will provide a narrative of the thrill of scientific discovery and excitement and the challenges lying ahead. Full article
(This article belongs to the Special Issue 6th Pan-American Dengue Research Network Meeting)
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Open AccessConference Report
“French Phage Network” Annual Conference 2018—Fourth Meeting Report
Viruses 2019, 11(5), 470; https://doi.org/10.3390/v11050470 - 23 May 2019
Viewed by 666
Abstract
The present meeting report aims to cover the scientific activities of the 4th French Bacteriophage Network (Phages.fr) symposium which took place during 24th–25th September 2018, at the Agora du Haut-Carré in Talence (France). The hosting institute was University Bordeaux and 72 participants attended [...] Read more.
The present meeting report aims to cover the scientific activities of the 4th French Bacteriophage Network (Phages.fr) symposium which took place during 24th–25th September 2018, at the Agora du Haut-Carré in Talence (France). The hosting institute was University Bordeaux and 72 participants attended the meeting from both public and private sectors, coming from France, Belgium, Ireland, Germany, Portugal and Canada. The scientific program was structured in three themed oral sessions entitled “ecology and evolution”, “bacteriophage-host molecular interaction”, and “therapy and biotechnology applications” consisting of 21 oral presentations, including three keynote lectures, and a presentation of the activities of the Spanish bacteriophage network. A poster session included 22 presentations. Full article
(This article belongs to the Section Bacterial Viruses)
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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 - 23 May 2019
Viewed by 644
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 AccessReview
Don’t Shut the Stable Door after the Phage Has Bolted—The Importance of Bacteriophage Inactivation in Food Environments
Viruses 2019, 11(5), 468; https://doi.org/10.3390/v11050468 - 22 May 2019
Cited by 1 | Viewed by 966
Abstract
In recent years, a new potential measure against foodborne pathogenic bacteria was rediscovered—bacteriophages. However, despite all their advantages, in connection to their widespread application in the food industry, negative consequences such as an uncontrolled phage spread as well as a development of phage [...] Read more.
In recent years, a new potential measure against foodborne pathogenic bacteria was rediscovered—bacteriophages. However, despite all their advantages, in connection to their widespread application in the food industry, negative consequences such as an uncontrolled phage spread as well as a development of phage resistant bacteria can occur. These problems are mostly a result of long-term persistence of phages in the food production environment. As this topic has been neglected so far, this article reviews the current knowledge regarding the effectiveness of disinfectant strategies for phage inactivation and removal. For this purpose, the main commercial phage products, as well as their application fields are first discussed in terms of applicable inactivation strategies and legal regulations. Secondly, an overview of the effectiveness of disinfectants for bacteriophage inactivation in general and commercial phages in particular is given. Finally, this review outlines a possible strategy for users of commercial phage products in order to improve the effectiveness of phage inactivation and removal after application. Full article
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Open AccessArticle
Enterovirus A71 VP1 Variation A289T Decreases the Central Nervous System Infectivity via Attenuation of Interactions between VP1 and Vimentin In Vitro and In Vivo
Viruses 2019, 11(5), 467; https://doi.org/10.3390/v11050467 - 22 May 2019
Viewed by 528
Abstract
Vimentin (VIM) is a surface receptor for enterovirus-A71, mediating the initial binding and subsequent increase in EV-A71 infectivity. The caspid protein VP1 variation, A289T, is reportedly closely associated with less severe central nervous system (CNS) infections in humans. However, it is unclear whether [...] Read more.
Vimentin (VIM) is a surface receptor for enterovirus-A71, mediating the initial binding and subsequent increase in EV-A71 infectivity. The caspid protein VP1 variation, A289T, is reportedly closely associated with less severe central nervous system (CNS) infections in humans. However, it is unclear whether VIM is associated with a reduction in CNS infections of EV-A71 in the presence of A289T. We investigated whether VIM served as a receptor for EV-A71 in the presence of an A298T substitution in VP1. EV-A71-289A and EV-A71-289T were used to infect human rhabdomyosarcoma cells, control human brain microvascular endothelial cells (HBMECs), and VIM-knockout (KO) HBMECs and inoculated BALB/c mice, SV129 mice, and VIM-KO SV129 mice. Furthermore, we cloned VP1-289A-Flag and VP1-289T-Flag proteins for co-immunoprecipitation analysis. Analysis of viral function revealed that the capacity of viral attachment, replication, and protein synthesis and secretion decreased in HBMECs during an EV-A71-289A infection, the infectivity being higher than that of EV-A71-289T upon VIM-KO. Histopathological and immunohistochemical analyses of brain tissue revealed that cerebral cortical damage was more extensive in EV-A71-289A than in EV-A71-289T infections in control SV129 mice; however, no significant difference was observed upon VIM-KO. Co-immunoprecipitation analysis revealed an interaction between VP1 and VIM, which was attenuated in VP1 harboring A289T; however, this attenuation was reversed by VIM (1-58) peptide. The A289T variation of VP1 specifically decreased the virulence of EV-A71 in HBMECs, and the attenuated interaction between VP1 harboring the A289T variation and VIM essentially decreased the CNS infectivity of EV-A71 in vitro and vivo. Full article
(This article belongs to the Special Issue Enteroviruses)
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Open AccessArticle
Amentoflavone Inhibits HSV-1 and ACV-Resistant Strain Infection by Suppressing Viral Early Infection
Viruses 2019, 11(5), 466; https://doi.org/10.3390/v11050466 - 22 May 2019
Viewed by 634
Abstract
Infection of Herpes simplex virus 1 (HSV-1) induces severe clinical disorders, such as herpes simplex encephalitis and keratitis. Acyclovir (ACV) is the current therapeutic drug against viral infection and ACV-resistant strains have gradually emerged, leading to the requirement for novel antiviral agents. In [...] Read more.
Infection of Herpes simplex virus 1 (HSV-1) induces severe clinical disorders, such as herpes simplex encephalitis and keratitis. Acyclovir (ACV) is the current therapeutic drug against viral infection and ACV-resistant strains have gradually emerged, leading to the requirement for novel antiviral agents. In this study, we exhibited the antiviral activity of amentoflavone, a naturally occurring biflavonoid, toward HSV-1 and ACV-resistant strains. Amentoflavone significantly inhibited infection of HSV-1 (F strain), as well as several ACV-resistant strains including HSV-1/106, HSV-1/153 and HSV-1/Blue at high concentrations. Time-of-drug-addition assay further revealed that amentoflavone mainly impaired HSV-1 early infection. More detailed study demonstrated that amentoflavone affected cofilin-mediated F-actin reorganization and reduced the intracellular transportation of HSV-1 from the cell membrane to the nucleus. In addition, amentoflavone substantially decreased transcription of viral immediate early genes. Collectively, amentoflavone showed strong antiviral activity against HSV-1 and ACV-resistant strains, and amentoflavone could be a promising therapeutic candidate for HSV-1 pathogenesis. Full article
(This article belongs to the Section Animal Viruses)
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Open AccessArticle
Evolution of the Piscine orthoreovirus Genome Linked to Emergence of Heart and Skeletal Muscle Inflammation in Farmed Atlantic Salmon (Salmo salar)
Viruses 2019, 11(5), 465; https://doi.org/10.3390/v11050465 - 22 May 2019
Cited by 1 | Viewed by 638
Abstract
Heart and skeletal muscle inflammation (HSMI) in farmed Atlantic salmon (Salmo salar) was first diagnosed in Norway in 1999. The disease is caused by Piscine orthoreovirus-1 (PRV-1). The virus is prevalent in farmed Atlantic salmon, but not always associated with disease. [...] Read more.
Heart and skeletal muscle inflammation (HSMI) in farmed Atlantic salmon (Salmo salar) was first diagnosed in Norway in 1999. The disease is caused by Piscine orthoreovirus-1 (PRV-1). The virus is prevalent in farmed Atlantic salmon, but not always associated with disease. Phylogeny and sequence analyses of 31 PRV-1 genomes collected over a 30-year period from fish with or without HSMI, grouped the viral sequences into two main monophylogenetic clusters, one associated with HSMI and the other with low virulent PRV-1 isolates. A PRV-1 strain from Norway sampled in 1988, a decade before the emergence of HSMI, grouped with the low virulent HSMI cluster. The two distinct monophylogenetic clusters were particularly evident for segments S1 and M2. Only a limited number of amino acids were unique to the association with HSMI, and they all located to S1 and M2 encoded proteins. The observed co-evolution of the S1-M2 pair coincided in time with the emergence of HSMI in Norway, and may have evolved through accumulation of mutations and/or segment reassortment. Sequences of S1-M2 suggest selection of the HSMI associated pair, and that this segment pair has remained almost unchanged in Norwegian salmon aquaculture since 1997. PRV-1 strains from the North American Pacific Coast and Faroe Islands have not undergone this evolution, and are more closely related to the PRV-1 precursor strains not associated with clinical HSMI. Full article
(This article belongs to the Section Animal Viruses)
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Open AccessArticle
Transcriptome Analysis Shows That IFN-I Treatment and Concurrent SAV3 Infection Enriches MHC-I Antigen Processing and Presentation Pathways in Atlantic Salmon-Derived Macrophage/Dendritic Cells
Viruses 2019, 11(5), 464; https://doi.org/10.3390/v11050464 - 22 May 2019
Viewed by 494
Abstract
Type I interferons (IFNs) have been shown to play an important role in shaping adaptive immune responses in addition to their antiviral properties in immune cells. To gain insight into the impact of IFN-I-induced pathways involved in early adaptive immune responses, i.e., antigen-presenting [...] Read more.
Type I interferons (IFNs) have been shown to play an important role in shaping adaptive immune responses in addition to their antiviral properties in immune cells. To gain insight into the impact of IFN-I-induced pathways involved in early adaptive immune responses, i.e., antigen-presenting pathways, in an Atlantic salmon-derived (Salmo salar L.) macrophage cell line (TO-cells), we used a comparative de novo transcriptome analysis where cells were treated with IFN-I or kept untreated and concurrently infected with salmonid alphavirus subtype 3 (SAV3). We found that concurrent treatment of TO-cells with IFN-I and SAV3 infection (SAV3/IFN+) significantly enriched the major histocompatibility complex class I (MHC-I) pathway unlike the non-IFN-I treated TO-cells (SAV3/IFN) that had lower expression levels of MHC-I pathway-related genes. Genes such as the proteasomal activator (PA28) and β-2 microglobulin (β2M) were only differentially expressed in the SAV3/IFN+ cells and not in the SAV3/IFN cells. MHC-I pathway genes like heat shock protein 90 (Hsp90), transporter of antigen associated proteins (TAPs) and tapasin had higher expression levels in the SAV3/IFN+ cells than in the SAV3/IFN cells. There were no MHC-II pathway-related genes upregulated in SAV3/IFN+-treated cells, and cathepsin S linked to the degradation of endosomal antigens in the MHC-II pathway was downregulated in the SAV3/IFN cells. Overall, our findings show that concurrent IFN-I treatment of TO-cells and SAV3 infection enriched gene expression linked to the MHC-I antigen presentation pathway. Data presented indicate a role of type I IFNs in strengthening antigen processing and presentation that may facilitate activation particularly of CD8+ T-cell responses following SAV3 infection, while SAV3 infection alone downplayed MHC-II pathways. Full article
(This article belongs to the Section Antivirals & Vaccines)
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Open AccessReview
Herpes Virus, Oral Clinical Signs and QoL: Systematic Review of Recent Data
Viruses 2019, 11(5), 463; https://doi.org/10.3390/v11050463 - 21 May 2019
Cited by 5 | Viewed by 1052
Abstract
This manuscript aims to highlight all the clinical features of the herpes virus, with a particular focus on oral manifestations and in the maxillofacial district about Herpes Simplex Virus-1 (HSV-1) and Herpes Simplex Virus-2 (HSV-2). Oral herpes virus is a very common and [...] Read more.
This manuscript aims to highlight all the clinical features of the herpes virus, with a particular focus on oral manifestations and in the maxillofacial district about Herpes Simplex Virus-1 (HSV-1) and Herpes Simplex Virus-2 (HSV-2). Oral herpes virus is a very common and often debilitating infectious disease for patients, affecting oral health and having important psychological implications. The collection of relevant data comes from the scientific databases Pubmed, Embase; initially this collection obtained an extremely high number of results, 1415. After applying the inclusion and exclusion criteria, as well as a manual screening, the results included in this review were limited to 14. The results were expressed by evaluating all the signs and symptoms that this pathology entails during the study, paying attention to the characteristics linked to the quality of life and the psychological implications. This pathology has numerous therapies, which often make the healing phase of the manifestations of this viral pathology more comfortable. The therapies currently used for the treatment of this viral infection are pharmacological, topical, systemic, or instrumental, for example with laser devices. Full article
(This article belongs to the Special Issue Recent Advances in Herpesviruses Research: What's in the Pipeline?)
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 - 21 May 2019
Cited by 1 | Viewed by 761
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
Equine Parvovirus-Hepatitis Frequently Detectable in Commercial Equine Serum Pools
Viruses 2019, 11(5), 461; https://doi.org/10.3390/v11050461 - 21 May 2019
Viewed by 828
Abstract
An equine parvovirus-hepatitis (EqPV-H) has been recently identified in association with equine serum hepatitis, also known as Theiler’s disease. This disease was first described by Arnold Theiler in 1918 and is often observed after applications with blood products in equines. So far, the [...] Read more.
An equine parvovirus-hepatitis (EqPV-H) has been recently identified in association with equine serum hepatitis, also known as Theiler’s disease. This disease was first described by Arnold Theiler in 1918 and is often observed after applications with blood products in equines. So far, the virus has only been described in the USA and China. In this study, we evaluated the presence of EqPV-H in several commercial serum samples to assess the potential risk of virus transmission by equine serum-based products for medical and research applications. In 11 out of 18 commercial serum samples, EqPV-H DNA was detectable with a viral load up to 105 copies/mL. The same serum batches as well as three additional samples were also positive for antibodies against the EqPV-H VP1 protein. The countries of origin with detectable viral genomes included the USA, Canada, New Zealand, Italy, and Germany, suggesting a worldwide distribution of EqPV-H. Phylogenetic analysis of the EqPV-H NS1 sequence in commercial serum samples revealed high similarities in viral sequences from different geographical areas. As horse sera are commonly used for the production of anti-sera, which are included in human and veterinary medical products, these results implicate the requirement for diagnostic tests to prevent EqPV-H transmission. Full article
(This article belongs to the Special Issue New Insights into Parvovirus Research)
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Open AccessReview
Enteroviruses: A Gut-Wrenching Game of Entry, Detection, and Evasion
Viruses 2019, 11(5), 460; https://doi.org/10.3390/v11050460 - 21 May 2019
Viewed by 1035
Abstract
Enteroviruses are a major source of human disease, particularly in neonates and young children where infections can range from acute, self-limited febrile illness to meningitis, endocarditis, hepatitis, and acute flaccid myelitis. The enterovirus genus includes poliovirus, coxsackieviruses, echoviruses, enterovirus 71, and enterovirus D68. [...] Read more.
Enteroviruses are a major source of human disease, particularly in neonates and young children where infections can range from acute, self-limited febrile illness to meningitis, endocarditis, hepatitis, and acute flaccid myelitis. The enterovirus genus includes poliovirus, coxsackieviruses, echoviruses, enterovirus 71, and enterovirus D68. Enteroviruses primarily infect by the fecal–oral route and target the gastrointestinal epithelium early during their life cycles. In addition, spread via the respiratory tract is possible and some enteroviruses such as enterovirus D68 are preferentially spread via this route. Once internalized, enteroviruses are detected by intracellular proteins that recognize common viral features and trigger antiviral innate immune signaling. However, co-evolution of enteroviruses with humans has allowed them to develop strategies to evade detection or disrupt signaling. In this review, we will discuss how enteroviruses infect the gastrointestinal tract, the mechanisms by which cells detect enterovirus infections, and the strategies enteroviruses use to escape this detection. Full article
(This article belongs to the Special Issue Viruses Ten-Year Anniversary)
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Open AccessReview
West Nile Virus Associations in Wild Mammals: An Update
Viruses 2019, 11(5), 459; https://doi.org/10.3390/v11050459 - 21 May 2019
Cited by 1 | Viewed by 571
Abstract
Although West Nile virus (WNV) is generally thought to circulate among mosquitoes and birds, several historic and recent works providing evidence of WNV activity in wild mammals have been published. Indeed, a previous review tabulated evidence of WNV exposure in at least 100 [...] Read more.
Although West Nile virus (WNV) is generally thought to circulate among mosquitoes and birds, several historic and recent works providing evidence of WNV activity in wild mammals have been published. Indeed, a previous review tabulated evidence of WNV exposure in at least 100 mammalian species. Herein, we provide an update on WNV activity in wild and select other mammals that have been reported since the last major review article on this subject was published in early 2013. Of interest, new species, such as Hoffman’s two-toed sloths (Choloepus hoffmanni), are now included in the growing list of wild mammals that have been naturally exposed to WNV. Furthermore, new instances of WNV viremia as well as severe disease presumably caused by this virus have been reported in wild mammals (e.g., the Virginia opossum [Didelphis virginiana]) from natural and semi-captive (e.g., zoological institution) settings. Regrettably, few recent challenge studies have been conducted on wild mammals, which would provide key information as to their potential role(s) in WNV cycles. Largely based on these recent findings, important future lines of research are recommended to assess which mammalian species are commonly exposed to WNV, which mammal species develop viremias sufficient for infecting mosquitoes, and which mammal species might be negatively affected by WNV infection at the species or population level. Full article
(This article belongs to the Special Issue West Nile Virus 2019)
Open AccessReview
Competitive Cooperation of Hemagglutinin and Neuraminidase during Influenza A Virus Entry
Viruses 2019, 11(5), 458; https://doi.org/10.3390/v11050458 - 20 May 2019
Cited by 1 | Viewed by 1091
Abstract
The hemagglutinin (HA) and neuraminidase (NA) of influenza A virus possess antagonistic activities on interaction with sialic acid (SA), which is the receptor for virus attachment. HA binds SA through its receptor-binding sites, while NA is a receptor-destroying enzyme by removing SAs. The [...] Read more.
The hemagglutinin (HA) and neuraminidase (NA) of influenza A virus possess antagonistic activities on interaction with sialic acid (SA), which is the receptor for virus attachment. HA binds SA through its receptor-binding sites, while NA is a receptor-destroying enzyme by removing SAs. The function of HA during virus entry has been extensively investigated, however, examination of NA has long been focused to its role in the exit of progeny virus from infected cells, and the role of NA in the entry process is still under-appreciated. This review summarizes the current understanding of the roles of HA and NA in relation to each other during virus entry. Full article
(This article belongs to the Special Issue Viral Entry Pathways)
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Open AccessReview
Roles of Hepatitis B Virus Mutations in the Viral Reactivation after Immunosuppression Therapies
Viruses 2019, 11(5), 457; https://doi.org/10.3390/v11050457 - 19 May 2019
Viewed by 736
Abstract
Reactivation of hepatitis B virus (HBV) is a major problem in patients receiving chemotherapy for malignant diseases or immunosuppression therapies. It has been thought that a reduction in the immune responses might result in the reactivation of HBV replication from covalently closed circular [...] Read more.
Reactivation of hepatitis B virus (HBV) is a major problem in patients receiving chemotherapy for malignant diseases or immunosuppression therapies. It has been thought that a reduction in the immune responses might result in the reactivation of HBV replication from covalently closed circular DNA (cccDNA) residing in hepatocytes. However, not only the host’s immune status, but also viral mutations have been reported to be associated with reactivation. Especially, several case reports about amino acid mutations in hepatitis B surface antigen (HBsAg) that escape from immune reactions have been reported, and recent reports showed that the frequencies of such mutations are higher than previously expected. In this review, we summarize the characteristics of viral mutations, including immune escape mutations in HBV-reactivated patients, and discuss their significance. Full article
(This article belongs to the Special Issue Hepatitis B Virus Reactivation)
Open AccessReview
Genetic Variability and Evolution of Hepatitis E Virus
Viruses 2019, 11(5), 456; https://doi.org/10.3390/v11050456 - 18 May 2019
Viewed by 863
Abstract
Hepatitis E virus (HEV) is a single-stranded positive-sense RNA virus. HEV can cause both acute and chronic hepatitis, with the latter usually occurring in immunocompromised patients. Modes of transmission range from the classic fecal–oral route or zoonotic route, to relatively recently recognized but [...] Read more.
Hepatitis E virus (HEV) is a single-stranded positive-sense RNA virus. HEV can cause both acute and chronic hepatitis, with the latter usually occurring in immunocompromised patients. Modes of transmission range from the classic fecal–oral route or zoonotic route, to relatively recently recognized but increasingly common routes, such as via the transfusion of blood products or organ transplantation. Extrahepatic manifestations, such as neurological, kidney and hematological abnormalities, have been documented in some limited cases, typically in patients with immune suppression. HEV has demonstrated extensive genomic diversity and a variety of HEV strains have been identified worldwide from human populations as well as growing numbers of animal species. The genetic variability and constant evolution of HEV contribute to its physiopathogenesis and adaptation to new hosts. This review describes the recent classification of the Hepeviridae family, global genotype distribution, clinical significance of HEV genotype and genomic variability and evolution of HEV. Full article
(This article belongs to the Special Issue Hepatitis E Virus)
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Open AccessArticle
Characteristics of the Life Cycle of Porcine Deltacoronavirus (PDCoV) In Vitro: Replication Kinetics, Cellular Ultrastructure and Virion Morphology, and Evidence of Inducing Autophagy
Viruses 2019, 11(5), 455; https://doi.org/10.3390/v11050455 - 18 May 2019
Cited by 1 | Viewed by 689
Abstract
Porcine deltacoronavirus (PDCoV) causes severe diarrhea and vomiting in affected piglets. The aim of this study was to establish the basic, in vitro characteristics of the life cycle such as replication kinetics, cellular ultrastructure, virion morphology, and induction of autophagy of PDCoV. Time-course [...] Read more.
Porcine deltacoronavirus (PDCoV) causes severe diarrhea and vomiting in affected piglets. The aim of this study was to establish the basic, in vitro characteristics of the life cycle such as replication kinetics, cellular ultrastructure, virion morphology, and induction of autophagy of PDCoV. Time-course analysis of viral subgenomic and genomic RNA loads and infectious titers indicated that one replication cycle of PDCoV takes 5 to 6 h. Electron microscopy showed that PDCoV infection induced the membrane rearrangements with double-membrane vesicles and large virion-containing vacuoles. The convoluted membranes structures described in alpha- and beta-coronavirus were not observed. PDCoV infection also increased the number of autophagosome-like vesicles in the cytoplasm of cells, and the autophagy response was detected by LC3 I/II and p62 Western blot analysis. For the first time, this study presents the picture of the PDCoV infection cycle, which is crucial to help elucidate the molecular mechanism of deltacoronavirus replication. Full article
(This article belongs to the Special Issue Porcine Viruses 2019)
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Open AccessArticle
Still Something to Discover: Novel Insights into Escherichia coli Phage Diversity and Taxonomy
Viruses 2019, 11(5), 454; https://doi.org/10.3390/v11050454 - 17 May 2019
Viewed by 1022
Abstract
The aim of this study was to gain further insight into the diversity of Escherichia coli phages followed by enhanced work on taxonomic issues in that field. Therefore, we present the genomic characterization and taxonomic classification of 50 bacteriophages against E. coli isolated [...] Read more.
The aim of this study was to gain further insight into the diversity of Escherichia coli phages followed by enhanced work on taxonomic issues in that field. Therefore, we present the genomic characterization and taxonomic classification of 50 bacteriophages against E. coli isolated from various sources, such as manure or sewage. All phages were examined for their host range on a set of different E. coli strains, originating, e.g., from human diagnostic laboratories or poultry farms. Transmission electron microscopy revealed a diversity of morphotypes (70% Myo-, 22% Sipho-, and 8% Podoviruses), and genome sequencing resulted in genomes sizes from ~44 to ~370 kb. Annotation and comparison with databases showed similarities in particular to T4- and T5-like phages, but also to less-known groups. Though various phages against E. coli are already described in literature and databases, we still isolated phages that showed no or only few similarities to other phages, namely phages Goslar, PTXU04, and KWBSE43-6. Genome-based phylogeny and classification of the newly isolated phages using VICTOR resulted in the proposal of new genera and led to an enhanced taxonomic classification of E. coli phages. Full article
(This article belongs to the Special Issue Diversity and Evolution of Phage Genomes)
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Open AccessArticle
Global Transcriptomic Analysis Reveals Insights into the Response of ‘Etrog’ Citron (Citrus medica L.) to Citrus Exocortis Viroid Infection
Viruses 2019, 11(5), 453; https://doi.org/10.3390/v11050453 - 17 May 2019
Viewed by 638
Abstract
Citrus exocortis viroid (CEVd) is the causal agent of citrus exocortis disease. We employed CEVd-infected ‘Etrog’ citron as a system to study the feedback regulation mechanism using transcriptome analysis in this study. Three months after CEVd infection, the transcriptome of fresh leaves was [...] Read more.
Citrus exocortis viroid (CEVd) is the causal agent of citrus exocortis disease. We employed CEVd-infected ‘Etrog’ citron as a system to study the feedback regulation mechanism using transcriptome analysis in this study. Three months after CEVd infection, the transcriptome of fresh leaves was analyzed, and 1530 differentially expressed genes were detected. The replication of CEVd in citron induced upregulation of genes encoding key proteins that were involved in the RNA silencing pathway such as Dicer-like 2, RNA-dependent RNA polymerase 1, argonaute 2, argonaute 7, and silencing defective 3, as well as those genes encoding proteins that are related to basic defense responses. Many genes involved in secondary metabolite biosynthesis and chitinase activity were upregulated, whereas other genes related to cell wall and phytohormone signal transduction were downregulated. Moreover, genes encoding disease resistance proteins, pathogenicity-related proteins, and heat shock cognate 70 kDa proteins were also upregulated in response to CEVd infection. These results suggest that basic defense and RNA silencing mechanisms are activated by CEVd infection, and this information improves our understanding of the pathogenesis of viroids in woody plants. Full article
(This article belongs to the Special Issue Viroid-2018: International Conference on Viroids and Viroid-Like RNAs)
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