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1.
Nat Commun ; 12(1): 1362, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33649317

RESUMO

Therapeutic application of RNA viruses as oncolytic agents or gene vectors requires a tight control of virus activity if toxicity is a concern. Here we present a regulator switch for RNA viruses using a conditional protease approach, in which the function of at least one viral protein essential for transcription and replication is linked to autocatalytical, exogenous human immunodeficiency virus (HIV) protease activity. Virus activity can be en- or disabled by various HIV protease inhibitors. Incorporating the HIV protease dimer in the genome of vesicular stomatitis virus (VSV) into the open reading frame of either the P- or L-protein resulted in an ON switch. Here, virus activity depends on co-application of protease inhibitor in a dose-dependent manner. Conversely, an N-terminal VSV polymerase tag with the HIV protease dimer constitutes an OFF switch, as application of protease inhibitor stops virus activity. This technology may also be applicable to other potentially therapeutic RNA viruses.


Assuntos
Vírus de RNA/genética , Vírus de RNA/fisiologia , Replicação Viral/genética , Animais , Linhagem Celular Tumoral , Genoma Viral , Protease de HIV/química , Protease de HIV/metabolismo , Inibidores da Protease de HIV/farmacologia , Humanos , Camundongos Endogâmicos NOD , Fosfoproteínas/metabolismo , Multimerização Proteica , Vírus de RNA/efeitos dos fármacos , Vesiculovirus/efeitos dos fármacos , Vesiculovirus/genética , Vesiculovirus/fisiologia , Replicação Viral/efeitos dos fármacos
2.
PLoS One ; 16(3): e0246981, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33730017

RESUMO

Nidoviruses and arenaviruses are the only known RNA viruses encoding a 3'-5' exonuclease domain (ExoN). The proofreading activity of the ExoN domain has played a key role in the growth of nidoviral genomes, while in arenaviruses this domain partakes in the suppression of the host innate immune signaling. Sequence and structural homology analyses suggest that these proteins have been hijacked from cellular hosts many times. Analysis of the available nidoviral ExoN sequences reveals a high conservation level comparable to that of the viral RNA-dependent RNA polymerases (RdRp), which are the most conserved viral proteins. Two highly preserved zinc fingers are present in all nidoviral exonucleases, while in the arenaviral protein only one zinc finger can be identified. This is in sharp contrast with the reported lack of zinc fingers in cellular ExoNs, and opens the possibility of therapeutic strategies in the struggle against COVID-19.


Assuntos
Exonucleases/genética , Domínios Proteicos/genética , RNA Viral/genética , Proteínas Virais/genética , Sequência de Aminoácidos , Arenavirus/genética , Humanos , Imunidade Inata/genética , Nidovirales/genética , Vírus de RNA/genética , /genética , Dedos de Zinco/genética
3.
Mol Cell ; 81(6): 1187-1199.e5, 2021 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-33581076

RESUMO

Type I interferons (IFNs) are critical cytokines in the host defense against invading pathogens. Sustained production of IFNs, however, is detrimental to the host, as it provokes autoimmune diseases. Thus, the expression of IFNs is tightly controlled. We report that the mRNA 5' cap-binding protein 4EHP plays a key role in regulating type I IFN concomitant with controlling virus replication, both in vitro and in vivo. Mechanistically, 4EHP suppresses IFN-ß production by effecting the miR-34a-induced translational silencing of Ifnb1 mRNA. miR-34a is upregulated by both RNA virus infection and IFN-ß induction, prompting a negative feedback regulatory mechanism that represses IFN-ß expression via 4EHP. These findings demonstrate the direct involvement of 4EHP in virus-induced host response, underscoring a critical translational silencing mechanism mediated by 4EHP and miR-34a to impede sustained IFN production. This study highlights an intrinsic regulatory function for miRNA and the translation machinery in maintaining host homeostasis.


Assuntos
Fator de Iniciação 4E em Eucariotos/imunologia , Imunidade Inata , MicroRNAs/imunologia , Biossíntese de Proteínas/imunologia , Infecções por Vírus de RNA/imunologia , Vírus de RNA/imunologia , Animais , Fator de Iniciação 4E em Eucariotos/genética , Células HEK293 , Humanos , Interferon beta/genética , Interferon beta/imunologia , Camundongos , Camundongos Transgênicos , MicroRNAs/genética , Infecções por Vírus de RNA/genética , Vírus de RNA/genética
4.
Microbiome ; 9(1): 37, 2021 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-33522966

RESUMO

BACKGROUND: Viruses are a significant player in many biosphere and human ecosystems, but most signals remain "hidden" in metagenomic/metatranscriptomic sequence datasets due to the lack of universal gene markers, database representatives, and insufficiently advanced identification tools. RESULTS: Here, we introduce VirSorter2, a DNA and RNA virus identification tool that leverages genome-informed database advances across a collection of customized automatic classifiers to improve the accuracy and range of virus sequence detection. When benchmarked against genomes from both isolated and uncultivated viruses, VirSorter2 uniquely performed consistently with high accuracy (F1-score > 0.8) across viral diversity, while all other tools under-detected viruses outside of the group most represented in reference databases (i.e., those in the order Caudovirales). Among the tools evaluated, VirSorter2 was also uniquely able to minimize errors associated with atypical cellular sequences including eukaryotic genomes and plasmids. Finally, as the virosphere exploration unravels novel viral sequences, VirSorter2's modular design makes it inherently able to expand to new types of viruses via the design of new classifiers to maintain maximal sensitivity and specificity. CONCLUSION: With multi-classifier and modular design, VirSorter2 demonstrates higher overall accuracy across major viral groups and will advance our knowledge of virus evolution, diversity, and virus-microbe interaction in various ecosystems. Source code of VirSorter2 is freely available ( https://bitbucket.org/MAVERICLab/virsorter2 ), and VirSorter2 is also available both on bioconda and as an iVirus app on CyVerse ( https://de.cyverse.org/de ). Video abstract.


Assuntos
Vírus de DNA/classificação , Genoma Viral/genética , Metagenômica , Vírus de RNA/classificação , Software , Vírus de DNA/genética , Ecossistema , Humanos , Vírus de RNA/genética
5.
Viruses ; 13(1)2021 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-33477448

RESUMO

Liquid-liquid phase separation (LLPS) represents a major physiochemical principle to organize intracellular membrane-less structures. Studies with non-segmented negative-sense (NNS) RNA viruses have uncovered a key role of LLPS in the formation of viral inclusion bodies (IBs), sites of viral protein concentration in the cytoplasm of infected cells. These studies further reveal the structural and functional complexity of viral IB factories and provide a foundation for their future research. Herein, we review the literature leading to the discovery of LLPS-driven formation of IBs in NNS RNA virus-infected cells and the identification of viral scaffold components involved, and then outline important questions and challenges for IB assembly and disassembly. We discuss the functional implications of LLPS in the life cycle of NNS RNA viruses and host responses to infection. Finally, we speculate on the potential mechanisms underlying IB maturation, a phenomenon relevant to many human diseases.


Assuntos
Infecções por Vírus de RNA/virologia , Vírus de RNA/genética , RNA Viral , Animais , Interações Hospedeiro-Patógeno , Humanos , Extração Líquido-Líquido , Vírus de RNA/isolamento & purificação , Proteínas Virais/genética , Proteínas Virais/metabolismo , Fenômenos Fisiológicos Virais , Replicação Viral
6.
Biochim Biophys Acta Gen Subj ; 1865(3): 129839, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33412226

RESUMO

Mitochondria are multi-functioning organelles that participate in a wide range of biologic processes from energy metabolism to cellular suicide. Mitochondria are also involved in the cellular innate immune response against microorganisms or environmental irritants, particularly in mammals. Mitochondrial-mediated innate immunity is achieved by the activation of two discrete signaling pathways, the NLR family pyrin domain-containing 3 inflammasomes and the retinoic acid-inducible gene I-like receptor pathway. In both pathways, a mitochondrial outer membrane adaptor protein, called mitochondrial antiviral signaling MAVS, and mitochondria-derived components play a key role in signal transduction. In this review, we discuss current insights regarding the fundamental phenomena of mitochondrial-related innate immune responses, and review the specific roles of various mitochondrial subcompartments in fine-tuning innate immune signaling events. We propose that specific targeting of mitochondrial functions is a potential therapeutic approach for the management of infectious diseases and autoinflammatory disorders with an excessive immune response.


Assuntos
Interações Hospedeiro-Patógeno/imunologia , Imunidade Inata , Mitocôndrias/imunologia , Infecções por Vírus de RNA/imunologia , Vírus de RNA/imunologia , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/imunologia , Animais , Proteína DEAD-box 58/genética , Proteína DEAD-box 58/imunologia , Regulação da Expressão Gênica , Interações Hospedeiro-Patógeno/genética , Humanos , Inflamassomos , MicroRNAs/genética , MicroRNAs/imunologia , Mitocôndrias/genética , Mitocôndrias/virologia , Membranas Mitocondriais/imunologia , Membranas Mitocondriais/virologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/imunologia , Infecções por Vírus de RNA/genética , Infecções por Vírus de RNA/patologia , Infecções por Vírus de RNA/virologia , Vírus de RNA/genética , Vírus de RNA/patogenicidade , Receptores Imunológicos/genética , Receptores Imunológicos/imunologia , Transdução de Sinais
7.
Arch Virol ; 166(2): 659-664, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33404858

RESUMO

The bisegmented genome of a novel double-stranded (ds) RNA mycovirus, named "Aspergillus nidulans partitivirus 1" (AnPV1), isolated from the fungus Aspergillus nidulans strain HJ5-47, was sequenced and analyzed. AnPV1 contains two segments, AnPV1-1 and AnPV1-2. AnPV1-1 has 1837 bp with an open reading frame (ORF) that potentially encodes a putative RNA-dependent RNA polymerase (RdRp) of 572 amino acids (aa). AnPV1-2 has 1583 bp with an ORF encoding a putative capsid protein (CP) of 488 aa. Phylogenetic analyses indicated that AnPV1 and related viruses clustered in a group that could represent a new unclassified genus in the family Partitiviridae.


Assuntos
Aspergillus nidulans/virologia , Micovírus/genética , Genoma Viral/genética , Vírus de RNA/genética , Sequência de Aminoácidos , Sequência de Bases , Proteínas do Capsídeo/genética , Fases de Leitura Aberta/genética , Filogenia , RNA de Cadeia Dupla/genética , RNA Viral/genética , Análise de Sequência de DNA/métodos
8.
Arch Virol ; 166(2): 665-669, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33409550

RESUMO

A putative mycovirus belonging to the proposed family "Fusariviridae" was discovered in Setosphaeria turcica by sequencing a double-stranded RNA extracted from this phytopathogenic fungus. The virus was tentatively named "Setosphaeria turcica fusarivirus 1" (StFV1). StFV1 has a genome comprising 6685 nucleotides. The genome contains three open reading frames (ORF). The largest ORF, ORF1, is preceded by an untranslated region (UTR) of 16 nucleotides and separated from ORF2 by an intergenic region of 63 nucleotides. The smallest ORF, ORF3, overlaps ORF2 by 16 nucleotides and is followed by a 3'-UTR of 82 nucleotides. The protein encoded by ORF1 is 71.8%, 67.4% and 68.1% identical to the RNA-dependent RNA polymerases (RdRps) of Pleospora typhicola fusarivirus 1 (PtFV1), Plasmopara viticola lesion-associated fusarivirus 1 (PvlaFV1), and Plasmopara viticola lesion-associated fusarivirus 3 (PvlaFV3), respectively, but has less than 47% amino acid sequence identity to the RdRps of other fusariviruses. To our knowledge, this is the first fusarivirus discovered in S. turcica and the first virus to be identified in this fungus using conventional cloning methods.


Assuntos
Ascomicetos/virologia , Vírus de RNA/genética , Regiões 3' não Traduzidas/genética , Sequência de Aminoácidos , Genoma Viral/genética , Nucleotídeos/genética , Fases de Leitura Aberta/genética , Filogenia , RNA de Cadeia Dupla/genética , RNA Viral/genética , /genética
9.
PLoS Pathog ; 17(1): e1009033, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33411764

RESUMO

The p53 transcription factor plays a key role both in cancer and in the cell-intrinsic response to infections. The ORFEOME project hypothesized that novel p53-virus interactions reside in hitherto uncharacterized, unknown, or hypothetical open reading frames (orfs) of human viruses. Hence, 172 orfs of unknown function from the emerging viruses SARS-Coronavirus, MERS-Coronavirus, influenza, Ebola, Zika (ZIKV), Chikungunya and Kaposi Sarcoma-associated herpesvirus (KSHV) were de novo synthesized, validated and tested in a functional screen of p53 signaling. This screen revealed novel mechanisms of p53 virus interactions and two viral proteins KSHV orf10 and ZIKV NS2A binding to p53. Originally identified as the target of small DNA tumor viruses, these experiments reinforce the notion that all viruses, including RNA viruses, interfere with p53 functions. These results validate this resource for analogous systems biology approaches to identify functional properties of uncharacterized viral proteins, long non-coding RNAs and micro RNAs.


Assuntos
Doenças Transmissíveis Emergentes/virologia , Vírus de RNA/metabolismo , Transdução de Sinais/genética , Proteína Supressora de Tumor p53/metabolismo , Vírus Chikungunya/genética , Vírus Chikungunya/metabolismo , Coronavirus/genética , Coronavirus/metabolismo , Ebolavirus/genética , Ebolavirus/metabolismo , Herpesvirus Humano 8/genética , Herpesvirus Humano 8/metabolismo , Humanos , Vírus da Influenza A/genética , Vírus da Influenza A/metabolismo , Fases de Leitura Aberta , Vírus de RNA/genética , Proteína Supressora de Tumor p53/genética , Proteínas não Estruturais Virais/metabolismo , Zika virus/genética , Zika virus/metabolismo
10.
Arch Virol ; 166(3): 973-976, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33427965

RESUMO

In this study, a new double-stranded RNA (dsRNA) virus, Alternaria tenuissima partitivirus 1 (AttPV1), was isolated from Alternaria tenuissima strain XJ-BZ-2-6, a phytopathogenic fungus infecting cotton in China. The genome of AttPV1 comprised three dsRNAs of 1,785 nt (dsRNA1), 1,545 nt (dsRNA2), and 1,537 nt (dsRNA3) in length, the nucleotide sequence of which was determined using reverse transcription polymerase chain reaction, random-primed clones, and RNA-ligase-mediated rapid amplification of cDNA ends. dsRNA1 had a single open reading frame encoding a putative 61.54-kDa RNA-dependent RNA polymerase (RdRp). dsRNA2 and dsRNA3 were predicted to encode putative coat proteins (CPs) of 47.90 kDa and 46.25 kDa, respectively. The RdRp domain shared 63.54-73.17% amino acid sequence identity with members of the genus Gammapartitivirus. Phylogenetic trees based on RdRp or CP sequences showed that AttPV1 clustered with members of the genus Gammapartitivirus. Hence, these results indicate that AttPV1 is a new gammapartitivirus from A. tenuissima.


Assuntos
Alternaria/virologia , Micovírus/genética , Genoma Viral/genética , Vírus de RNA/genética , RNA Viral/genética , Sequência de Aminoácidos , Sequência de Bases , Proteínas do Capsídeo/genética , China , Micovírus/classificação , Micovírus/isolamento & purificação , Gossypium/microbiologia , Fases de Leitura Aberta/genética , Doenças das Plantas/microbiologia , Vírus de RNA/classificação , Vírus de RNA/isolamento & purificação , RNA de Cadeia Dupla/genética , Alinhamento de Sequência , Proteínas Virais/genética
11.
Arch Virol ; 166(3): 977-981, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33427966

RESUMO

Here, we report a novel partitivirus infecting Metarhizium brunneum, which was designated "Metarhizium brunneum partitivirus 2" (MbPV2). The complete genome of MbPV2 consists of two segments, dsRNA1 and dsRNA2, with each dsRNA possessing a single open reading frame (ORF). dsRNA1 (1,775 bp) encodes a conserved RNA-dependent RNA polymerase (RdRp) with the highest sequence similarity to Plasmopara viticola associated partitivirus 1 (PvAPV1), while dsRNA2 (1,568 bp) encodes a coat protein (CP) with the highest sequence similarity to Colletotrichum partitivirus 1 (CtParV1). Phylogenetic analysis based on RdRp sequences showed that MbPV2 is a new member of the genus Gammapartitivirus, family Partitiviridae. This is the first report of a gammapartitivirus that infects the entomopathogenic fungus Metarhizium brunneum.


Assuntos
Micovírus/genética , Genoma Viral/genética , Metarhizium/virologia , Vírus de RNA/genética , RNA Viral/genética , Sequência de Aminoácidos , Proteínas do Capsídeo/genética , Micovírus/classificação , Micovírus/isolamento & purificação , Fases de Leitura Aberta/genética , Vírus de RNA/classificação , Vírus de RNA/isolamento & purificação , RNA de Cadeia Dupla/genética , Alinhamento de Sequência , Análise de Sequência de RNA
12.
Am J Infect Control ; 49(4): 464-468, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33347935

RESUMO

BACKGROUND: Schools represent high occupancy environments and well-documented high-risk locations for the transmission of respiratory viruses. The goal of this study was to report on the area density, occurrence, and type of respiratory viruses on desks in primary school classrooms. METHODS: Quantitative reverse transcription polymerase chain reaction (qPCR) techniques were employed to measure nucleic acid area densities from a broad range of human adenoviruses and rhinoviruses, as well as coronavirus OC43, influenza A, and norovirus GI. Every two weeks, virus monitoring was conducted on the desks of four primary school classrooms in Colorado, USA, during the 2019 respiratory virus season. RESULTS: DNA and RNA from respiratory viruses and norovirus were recovered from more than 20% of the desks sampled; occurrence patterns that indicate a greater than 60% probability of encountering any virus, if more than five desks were occupied in a day. Rhinoviruses and adenoviruses were the most commonly detected viruses as judged by the composite of occurrence and number of gene copies recovered. Desktop adenosine triphosphate monitoring did not predict the recovery of viral genomic materials on desks. School desks can be commonly contaminated with respiratory viruses. CONCLUSIONS: Genomic surveys of the identity, distribution and abundance of human viruses on "high-touch" surfaces, can help inform risk assessments, design cleaning interventions, and may be useful for infection surveillance.


Assuntos
Decoração de Interiores e Mobiliário , Vírus de RNA/isolamento & purificação , Infecções Respiratórias/virologia , Instituições Acadêmicas , Colorado/epidemiologia , DNA Viral/isolamento & purificação , Humanos , Vigilância da População , Vírus de RNA/genética , RNA Viral/isolamento & purificação , Reação em Cadeia da Polimerase em Tempo Real , Infecções Respiratórias/epidemiologia , Medição de Risco
13.
J Med Virol ; 93(4): 1843-1846, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33314219

RESUMO

In this commentary, we shed light on the role of the mammalian target of rapamycin (mTOR) pathway in viral infections. The mTOR pathway has been demonstrated to be modulated in numerous RNA viruses. Frequently, inhibiting mTOR results in suppression of virus growth and replication. Recent evidence points towards modulation of mTOR in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We discuss the current literature on mTOR in SARS-CoV-2 and highlight evidence in support of a role for mTOR inhibitors in the treatment of coronavirus disease 2019.


Assuntos
/tratamento farmacológico , Vírus de RNA/fisiologia , Serina-Treonina Quinases TOR/antagonistas & inibidores , Animais , Antivirais/farmacologia , Antivirais/uso terapêutico , Humanos , Coronavírus da Síndrome Respiratória do Oriente Médio/genética , Coronavírus da Síndrome Respiratória do Oriente Médio/patogenicidade , Coronavírus da Síndrome Respiratória do Oriente Médio/fisiologia , Vírus de RNA/genética , Vírus de RNA/patogenicidade , /patogenicidade , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismo , Replicação Viral
14.
Viruses ; 13(1)2020 12 23.
Artigo em Inglês | MEDLINE | ID: mdl-33374584

RESUMO

Hematophagous insects act as the major reservoirs of infectious agents due to their intimate contact with a large variety of vertebrate hosts. Lutzomyia longipalpis is the main vector of Leishmania chagasi in the New World, but its role as a host of viruses is poorly understood. In this work, Lu. longipalpis RNA libraries were subjected to progressive assembly using viral profile HMMs as seeds. A sequence phylogenetically related to fungal viruses of the genus Mitovirus was identified and this novel virus was named Lul-MV-1. The 2697-base genome presents a single gene coding for an RNA-directed RNA polymerase with an organellar genetic code. To determine the possible host of Lul-MV-1, we analyzed the molecular characteristics of the viral genome. Dinucleotide composition and codon usage showed profiles similar to mitochondrial DNA of invertebrate hosts. Also, the virus-derived small RNA profile was consistent with the activation of the siRNA pathway, with size distribution and 5' base enrichment analogous to those observed in viruses of sand flies, reinforcing Lu. longipalpis as a putative host. Finally, RT-PCR of different insect pools and sequences of public Lu. longipalpis RNA libraries confirmed the high prevalence of Lul-MV-1. This is the first report of a mitovirus infecting an insect host.


Assuntos
Genoma Viral , Interações entre Hospedeiro e Microrganismos , Orthoreovirus/genética , Psychodidae/classificação , Psychodidae/virologia , Animais , Códon , Uso do Códon , Amplificação de Genes , Genômica/métodos , Sequenciamento de Nucleotídeos em Larga Escala , Cadeias de Markov , Filogenia , Prevalência , Interferência de RNA , Vírus de RNA/genética , RNA Interferente Pequeno/genética
15.
Viruses ; 13(1)2020 12 22.
Artigo em Inglês | MEDLINE | ID: mdl-33375071

RESUMO

Bats are often claimed to be a major source for future viral epidemics, as they are associated with several viruses with zoonotic potential. Here we describe the presence and biodiversity of bats associated with intensive pig farms devoted to the production of heavy pigs in northern Italy. Since chiropters or signs of their presence were not found within animal shelters in our study area, we suggest that fecal viruses with high environmental resistance have the highest likelihood for spillover through indirect transmission. In turn, we investigated the circulation of mammalian orthoreoviruses (MRVs), coronaviruses (CoVs) and astroviruses (AstVs) in pigs and bats sharing the same environment. Results of our preliminary study did not show any bat virus in pigs suggesting that spillover from these animals is rare. However, several AstVs, CoVs and MRVs circulated undetected in pigs. Among those, one MRV was a reassortant strain carrying viral genes likely acquired from bats. On the other hand, we found a swine AstV and a MRV strain carrying swine genes in bat guano, indicating that viral exchange at the bat-pig interface might occur more frequently from pigs to bats rather than the other way around. Considering the indoor farming system as the most common system in the European Union (EU), preventive measures should focus on biosecurity rather than displacement of bats, which are protected throughout the EU and provide critical ecosystem services for rural settings.


Assuntos
Quirópteros , Suínos , Animais , Biodiversidade , Quirópteros/virologia , Vírus de DNA/classificação , Vírus de DNA/genética , Ecossistema , Filogenia , Vírus de RNA/classificação , Vírus de RNA/genética , Vírus Reordenados/genética , Suínos/virologia , Doenças dos Suínos/epidemiologia , Doenças dos Suínos/transmissão , Doenças dos Suínos/virologia , Viroses/veterinária
16.
Viruses ; 13(1)2020 12 25.
Artigo em Inglês | MEDLINE | ID: mdl-33375657

RESUMO

Chinese jujube (Ziziphus jujuba Mill.) is a native fruit crop in China. Leaf mottle and dapple fruit disease is prevalent in cultivated jujube plants grown at Aksu in Xinjiang Uygur Autonomous Region of China. Jujube yellow mottle-associated virus (JYMaV), a tentative member in the genus Emaravirus, was recently identified from mottle-diseased jujube plants grown in Liaoning Province in China, but its incidence and genetic diversity in China is unknown. In this study, the genome sequences of three JYMaV isolates from two jujube cultivars and one jujube variant were determined by high-throughput sequencing (HTS) for small RNA and rRNA-depleted RNA coupled with RT-PCR assays. Comparison of these sequences together with sequences of the viral RNA segments derived by primer set 3C/5H-based RT-PCR revealed that genetic diversity was present in the virus populations and high sequence variation occurred at the non-translational regions of each of the viral genomic segments. Field investigation confirmed the close association of the virus with leaf mottle symptoms of jujube plants. Furthermore, this study revealed that P5 encoded in the viral RNA5 displayed a nuclear localization feature differing from the plasmodesma (PD) subcellular localization of the virus movement protein (P4), and the two proteins could interact with each other in the BiFC assays. Our study provides a snapshot of JYMaV genetic diversity in its natural hosts.


Assuntos
Bunyaviridae/classificação , Bunyaviridae/genética , Ziziphus/virologia , Bunyaviridae/isolamento & purificação , Bunyaviridae/ultraestrutura , China , Variação Genética , Genoma Viral , Genômica/métodos , Sequenciamento de Nucleotídeos em Larga Escala , Fases de Leitura Aberta , Fenótipo , Filogenia , Doenças das Plantas/virologia , Folhas de Planta/virologia , Vírus de RNA/genética , RNA Viral , Análise de Sequência de RNA
17.
Arch Virol ; 165(10): 2379-2384, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32761427

RESUMO

In this study, we determined the complete genome sequence of a new blunervirus isolated from tomato plants grown in an open field in Italy in the fall of 2018. Like other blunerviruses, the RNA genome of this virus is quadripartite, positive-sense, and single-stranded. Excluding the polyA tail present in each segment, the RNAs 1 and 2 are 5790 nucleotides (nt) and 3621 nt in size, respectively, and each contains a single open reading frame (ORF). The RNAs 3 and 4 are 2842 and 1924 nt long and encode five and two ORFs, respectively. BLASTp analysis of the predicted products of RNA1 and RNA2 ORF1 showed the highest sequence identity (31% and 42%) to tea plant necrotic ring blotch virus (TPNRBV), while the protein encoded by RNA 4 ORF2 had the highest sequence identity (38%) to blueberry necrotic ring blotch virus (BNRBV). These are the only two recognized members in the genus Blunervirus. When the RNA3 ORF3 and ORF5 products were compared with the blunerviruses-encoded proteins, they had the highest sequence identity (30% and 32%) to their TPNRBV-encoded homologs; however, general comparisons showed stronger matches to two different proteins from Acinetobacter baumannii. The proteins encoded by ORFs 1, 2 and 4 of RNA3 and ORF 1 of RNA4 showed no significant BLASTp hits to any known proteins in the databases. Given the limited genetic similarity of this virus to those currently available in the databases, we suggest that this is a new virus, for which we propose the name "tomato fruit blotch virus" (ToFBV). A distinct isolate of the same virus was also detected in Australia.


Assuntos
Genoma Viral , Lycopersicon esculentum/virologia , Filogenia , Vírus de RNA/genética , Proteínas Virais/genética , Austrália , Sequência de Bases , Produtos Agrícolas/virologia , Itália , Fases de Leitura Aberta , Doenças das Plantas/virologia , Vírus de RNA/classificação , Vírus de RNA/isolamento & purificação , RNA Viral/genética , Alinhamento de Sequência
18.
Nucleic Acids Res ; 48(16): 9285-9300, 2020 09 18.
Artigo em Inglês | MEDLINE | ID: mdl-32785642

RESUMO

The genomes of RNA viruses contain regulatory elements of varying complexity. Many plus-strand RNA viruses employ largescale intra-genomic RNA-RNA interactions as a means to control viral processes. Here, we describe an elaborate RNA structure formed by multiple distant regions in a tombusvirus genome that activates transcription of a viral subgenomic mRNA. The initial step in assembly of this intramolecular RNA complex involves the folding of a large viral RNA domain, which generates a discontinuous binding pocket. Next, a distally-located protracted stem-loop RNA structure docks, via base-pairing, into the binding site and acts as a linchpin that stabilizes the RNA complex and activates transcription. A multi-step RNA folding pathway is proposed in which rate-limiting steps contribute to a delay in transcription of the capsid protein-encoding viral subgenomic mRNA. This study provides an exceptional example of the complexity of genome-scale viral regulation and offers new insights into the assembly schemes utilized by large intra-genomic RNA structures.


Assuntos
Genoma Viral/genética , Conformação de Ácido Nucleico , Vírus de RNA/ultraestrutura , Proteínas Virais/genética , Pareamento de Bases , Vírus de RNA/genética , RNA Viral/genética , RNA Viral/ultraestrutura , Tombusvirus/genética , Tombusvirus/ultraestrutura , Transcrição Genética , Proteínas Virais/ultraestrutura , Replicação Viral/genética
19.
PLoS Pathog ; 16(8): e1008759, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32745135

RESUMO

Ticks (order: Ixodida) are a highly diverse and ecologically important group of ectoparasitic blood-feeding organisms. One such species, the seabird tick (Ixodes uriae), is widely distributed around the circumpolar regions of the northern and southern hemispheres. It has been suggested that Ix. uriae spread from the southern to the northern circumpolar region millions of years ago and has remained isolated in these regions ever since. Such a profound biographic subdivision provides a unique opportunity to determine whether viruses associated with ticks exhibit the same evolutionary patterns as their hosts. To test this, we collected Ix. uriae specimens near a Gentoo penguin (Pygoscelis papua) colony at Neko harbour, Antarctica, and from migratory birds-the Razorbill (Alca torda) and the Common murre (Uria aalge)-on Bonden island, northern Sweden. Through meta-transcriptomic next-generation sequencing we identified 16 RNA viruses, seven of which were novel. Notably, we detected the same species, Ronne virus, and two closely related species, Bonden virus and Piguzov virus, in both hemispheres indicating that there have been at least two cross-circumpolar dispersal events. Similarly, we identified viruses discovered previously in other locations several decades ago, including Gadgets Gully virus, Taggert virus and Okhotskiy virus. By identifying the same or closely related viruses in geographically disjunct sampling locations we provide evidence for virus dispersal within and between the circumpolar regions. In marked contrast, our phylogenetic analysis revealed no movement of the Ix. uriae tick hosts between the same locations. Combined, these data suggest that migratory birds are responsible for the movement of viruses at both local and global scales.


Assuntos
Doenças das Aves/epidemiologia , Aves/parasitologia , Interações Hospedeiro-Parasita , Ixodes/fisiologia , Infecções por Vírus de RNA/virologia , Vírus de RNA/classificação , Infestações por Carrapato/veterinária , Animais , Doenças das Aves/parasitologia , Filogenia , Infecções por Vírus de RNA/genética , Vírus de RNA/genética , Vírus de RNA/isolamento & purificação , Infestações por Carrapato/epidemiologia , Infestações por Carrapato/parasitologia
20.
Lancet Gastroenterol Hepatol ; 5(10): 940-947, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32730785

RESUMO

Major gains in reducing the burden of hepatitis C are now possible because of the discovery of a cure. The prevention of premature deaths and increased workforce participation among people who are cured are likely to provide substantial indirect economic benefits. We developed an investment case for hepatitis C for the six WHO world regions, which, to our knowledge, is the first to consider both indirect and direct economic benefits in this context. Scaling up of testing and treatment to reach the 2030 WHO hepatitis C elimination targets was estimated to prevent 2·1 million (95% credible interval 1·3-3·2 million) hepatitis C-related deaths and 10 million (4-14 million) new hepatitis C virus infections globally between 2018 and 2030. This elimination strategy was estimated to cost US$41·5 billion (33·1-48·7 billion) in testing, treatment, and health care between 2018 and 2030 ($23·4 billion more than the status quo scenario of no testing or treatment scale up), with a global average of $885 (654-1189) per disability-adjusted life-year averted at 2030. Compared with the status quo scenario, the elimination scenario generated $46·1 billion (35·9-53·8 billion) in cumulative productivity gains by 2030. These indirect costs made elimination cost-saving by 2027, with a net economic benefit of $22·7 billion (17·1-27·9 billion) by 2030. This model shows that countries might be underestimating the true burden of hepatitis C and will benefit from investing in elimination.


Assuntos
Erradicação de Doenças/economia , Saúde Global/economia , Hepatite C/tratamento farmacológico , Efeitos Psicossociais da Doença , Análise Custo-Benefício , Erradicação de Doenças/métodos , Custos de Cuidados de Saúde , Hepacivirus/genética , Hepatite C/epidemiologia , Hepatite C/prevenção & controle , Hepatite C/transmissão , Humanos , Masculino , Modelos Teóricos , Mortalidade Prematura/tendências , Prevalência , Vírus de RNA/genética , Recursos Humanos/estatística & dados numéricos , Organização Mundial da Saúde/organização & administração
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