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1.
Vopr Virusol ; 66(4): 259-268, 2021 09 17.
Artigo em Russo | MEDLINE | ID: mdl-34545718

RESUMO

The virologists' attention to bats (Сhiroptera) changed in the late 20th century as the concept of emerging infections grew in popularity. Since the beginning of the COVID-19 pandemic, the number of publications on bat viruses has increased profoundly.History of the problem; biodiversity of Chiroptera and related viruses; medical and veterinary significance of some viral genera and subgenera (Lyssavirus, Henipavirus, Marburgvirus, Ebolavirus, Sarbecovirus, Merbecovirus), as well as problems of bat protection, are addressed in a concise form. Literature search was carried out in electronic databases, mainly for the period of 2000-2021. Publications in Russian that are poorly represented in English-language reviews are also included. The purpose of the review is to substantiate the importance of an interdisciplinary approach in the context of increased interest in the study of viral infections in bats. This review was written for researchers who have not previously dealt with this problem.Since the beginning of this century, the number of known virus species associated with bats has increased by an order of magnitude (>200). The families Rhabdoviridae, Coronaviridae, Paramyxoviridae are in the first ranks according to the number of findings, and the highest diversity of viruses has been established for the families Vespertilionidae, Pteropodidae, Molossidae. Interdisciplinary cooperation positively influences the efficiency, biological safety and practical significance of the ongoing research. The best results were achieved by multidisciplinary teams with good cross-training in several specialties. Many papers emphasize the need to balance health and conservation interests.The analysis of scientific publications indicates a change in research approaches in this area: from collecting individual facts within the framework of narrow specialties to a comprehensive assessment of new knowledge from ecological, evolutionary and socio-economic positions. Results of the research emphasize the need to maintain complex approaches addressing public health needs and environmental protection. The importance of bat-borne viral infections determines the necessity for correction and interdepartmental coordination of scientific research and surveillance of wildlife zoonoses in the Russian Federation.


Assuntos
COVID-19 , Quirópteros/virologia , Infecções por Paramyxoviridae , Paramyxoviridae , Infecções por Rhabdoviridae , Rhabdoviridae , SARS-CoV-2 , Zoonoses , Animais , COVID-19/epidemiologia , COVID-19/transmissão , Humanos , Infecções por Paramyxoviridae/epidemiologia , Infecções por Paramyxoviridae/transmissão , Infecções por Rhabdoviridae/epidemiologia , Infecções por Rhabdoviridae/transmissão , Zoonoses/epidemiologia , Zoonoses/virologia
2.
Eur J Med Chem ; 223: 113739, 2021 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-34375787

RESUMO

Diseases caused by rhabdoviruses have had a huge impact on the productive lives of the entire human population. The main problem is the lack of drugs for the treatment of this family of viruses. Infectious hematopoietic necrosis virus (IHNV), the causative agent of IHN, is a typical rhabdovirus which has caused huge losses to the salmonid industry. Therefore, in this study, IHNV was studied as a model to evaluate the antiviral activity of 35 novel coumarin derivatives. Coumarin A9 was specifically selected for further validation studies upon comparing the half maximum inhibitory concentration (IC50) of four screened candidate derivatives in epithelioma papulosum cyprinid (EPC) cells, as it exhibited an IC50 value of 2.96 µM against IHNV. The data revealed that A9 treatment significantly suppressed the virus-induced cytopathic effect (CPE) in EPC cells. In addition, A9 showed IC50 values of 1.68 and 2.12 µM for two other rhabdoviruses, spring viremia of carp virus and micropterus salmoides rhabdovirus, respectively. Furthermore, our results suggest that A9 exerts antiviral activity, but not by destroying the virus particles and interfering with the adsorption of IHNV. Moreover, we found that A9 had an inhibitory effect on IHNV-induced apoptosis in EPC cells, as reflected by the protection against cell swelling, formation of apoptotic bodies, and loss of cell morphology and nuclear division. There was a 19.05 % reduction in the number of apoptotic cells in the A9 treatment group compared with that in the IHNV group. In addition, enzyme activity assays proved that A9 suppressed the expression of caspase 3, 8 and 9. These results suggested that A9 inhibit viral replication, to some extent, by blocking IHNV-induced apoptosis. In an in vivo study, A9 exhibited an anti-rhabdovirus effect in virus-infected fish by substantially enhancing the survival rate. Consistent with the above results, A9 repressed IHNV gene expression in virus-sensitive tissues (brain, kidney and spleen) in the early stages of virus infection. Importantly, the data showed that horizontal transmission of IHNV was reduced by A9 in a static cohabitation challenge model, especially in fish that underwent bath treatment, suggesting that A9 might be a suitable therapeutic agent for IHNV in aquaculture. Therefore, coumarin derivatives can be developed as antiviral agents against rhabdoviruses.


Assuntos
Antivirais/síntese química , Cumarínicos/química , Rhabdoviridae/efeitos dos fármacos , Animais , Antivirais/farmacologia , Antivirais/uso terapêutico , Apoptose/efeitos dos fármacos , Linhagem Celular , Cumarínicos/farmacologia , Cumarínicos/uso terapêutico , Regulação para Baixo/efeitos dos fármacos , Doenças dos Peixes/tratamento farmacológico , Doenças dos Peixes/mortalidade , Doenças dos Peixes/patologia , Humanos , Oncorhynchus mykiss/metabolismo , Oncorhynchus mykiss/virologia , Infecções por Rhabdoviridae/tratamento farmacológico , Infecções por Rhabdoviridae/mortalidade , Infecções por Rhabdoviridae/patologia , Relação Estrutura-Atividade , Taxa de Sobrevida , Proteínas Virais/genética , Proteínas Virais/metabolismo , Internalização do Vírus/efeitos dos fármacos
3.
J Immunol ; 207(3): 784-798, 2021 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-34290106

RESUMO

In mammals, cyclic GMP-AMP synthase (cGAS) recognizes cytosolic dsDNA to induce the type I IFN response. However, the functional role of cGAS in the IFN response of fish remains unclear or controversial. In this study, we report that cGAS orthologs from crucian carp Carassius auratus (CacGAS) and grass carp Ctenopharyngodon idellus (CicGAS) target the dsRNA sensor retinoic acid-inducible gene I (RIG-I) for negative regulation of the IFN response. First, poly(deoxyadenylic-deoxythymidylic) acid-, polyinosinic-polycytidylic acid-, and spring viremia of carp virus-induced IFN responses were impaired by overexpression of CacGAS and CicGAS. Then, CacGAS and CicGAS interacted with CiRIG-I and CiMAVS and inhibited CiRIG-I- and CiMAVS-mediated IFN induction. Moreover, the K63-linked ubiquitination of CiRIG-I and the interaction between CiRIG-I and CiMAVS were attenuated by CacGAS and CicGAS. Finally, CacGAS and CicGAS decreased CiRIG-I-mediated the cellular antiviral response and facilitated viral replication. Taken together, data in this study identify CacGAS and CicGAS as negative regulators in RIG-I-like receptor signaling, which extends the current knowledge regarding the role of fish cGAS in the innate antiviral response.


Assuntos
Proteínas de Peixes/genética , Interferon Tipo I/metabolismo , Nucleotidiltransferases/genética , Infecções por Rhabdoviridae/imunologia , Rhabdoviridae/fisiologia , Animais , Carpas , Cyprinidae , Proteínas de Peixes/imunologia , Proteínas de Peixes/metabolismo , Regulação da Expressão Gênica , Carpa Dourada , Células HEK293 , Humanos , Imunidade Inata/genética , Nucleotidiltransferases/imunologia , Nucleotidiltransferases/metabolismo , Transdução de Sinais , Ubiquitinação , Proteínas de Peixe-Zebra/genética
4.
Fish Shellfish Immunol ; 115: 142-149, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34147612

RESUMO

Both the activation and attenuation of MAVS/IFN signaling are critical for host defensing against viral infection and thus lead to an elaborate regulation of MAVS-mediated signaling. However, the regulatory mechanisms concerning MAVS/IFN signaling in teleost fish are not well understood. RIPK3 has been identified as a key regulator of necroptosis, apoptosis, and inflammatory signaling in human and mammals. Here we report the identification of the RIPK3 homologue from black carp Mylopharyngodon piceus (bcRIPK3) and describe its role in regulating MAVS/IFN signaling. qPCR results demonstrated that bcRIPK3 was transcriptionally activated in response to poly (I:C) or LPS stimulation. Immunoblot assay and immunofluorescent staining assay showed that bcRIPK3 was a cytosolic protein with molecular weights of 47 kDa. Like its mammalian counterparts, bcRIPK3 exhibited a conserved function in inducing cell death. The reporter assay and plaque assay showed that overexpression of bcRIPK3 restricted bcMAVS-activated transcription of the interferon promoters of black carp and zebrafish, and suppressed bcMAVS-mediated antiviral activity. Notably, EPC cells co-expressing bcRIPK3, bcRIPK1 and bcMAVS presented much attenuated antiviral activity than the cells co-expressing bcRIPK3 and bcMAVS; and the subsequent co-IP assay identified the interaction between bcRIPK3 and bcRIPK1. Our findings collectively elucidate for the first time in teleost that black carp RIPK3 interacts with RIPK1 to inhibit MAVS-mediated antiviral signaling.


Assuntos
Cyprinidae/genética , Cyprinidae/imunologia , Doenças dos Peixes/imunologia , Proteínas de Peixes/genética , Proteínas de Peixes/imunologia , Regulação da Expressão Gênica/imunologia , Imunidade Inata/genética , Proteínas Adaptadoras de Transdução de Sinal/química , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/imunologia , Sequência de Aminoácidos , Animais , Perfilação da Expressão Gênica/veterinária , Filogenia , Proteína Serina-Treonina Quinases de Interação com Receptores/química , Proteína Serina-Treonina Quinases de Interação com Receptores/genética , Proteína Serina-Treonina Quinases de Interação com Receptores/imunologia , Rhabdoviridae/fisiologia , Infecções por Rhabdoviridae/imunologia , Infecções por Rhabdoviridae/veterinária , Alinhamento de Sequência/veterinária
5.
Viruses ; 13(5)2021 05 03.
Artigo em Inglês | MEDLINE | ID: mdl-34063722

RESUMO

Vitis coignetiae samples were collected from several locations in the northern area of Japan, and virome analysis using a high-throughput sequencing technique was performed. The data indicated that some of the collected samples were in mixed infections by various RNA viruses. Among these viruses, three were identified as newly recognized species with support of sequence identity and phylogenetic analysis. The viruses have been provisionally named the Vitis varicosavirus, Vitis emaravirus, and Vitis crypticvirus, and were assigned to the genus Varicosavirus, Emaravirus, and Deltapartitivirus, respectively.


Assuntos
Genoma Viral , Sequenciamento de Nucleotídeos em Larga Escala , Rhabdoviridae/classificação , Rhabdoviridae/genética , Vitis/virologia , Sequência de Bases , Fases de Leitura Aberta , Filogenia , Doenças das Plantas/virologia , RNA Viral , Rhabdoviridae/isolamento & purificação , Viroma , Sequenciamento Completo do Genoma
6.
Exp Appl Acarol ; 84(2): 365-388, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34061290

RESUMO

Citrus leprosis is a viral disease vectored by the mites Brevipalpus californicus and Brevipalpus yothersi. This work aimed to determine the potential areas for establishment of both mites and viruses in Mexico, based on the geographical distribution of the hosts and the climatic suitability for the vectors. Life tables of both mites were constructed to determine their thermal requirements-base temperature and degree-days required to complete life cycle-and population growth parameters-net reproduction rate, generation time, and intrinsic growth rate. For this, the mites were confined in Citrus aurantium fruits at 20, 22.5, 25 or 30 °C, 60 ± 5% RH and L14:D10 h photoperiod. Maps were generated where the climatic suitability for establishment of the mites and the citrus leprosis viruses was estimated in citrus-producing municipalities. The climatic suitability was determined through historical temperature records to calculate the potential number of generations per year, and ecological niche modeling based on collecting localities and bioclimatic variables using the algorithm Maxent. The base temperature was 9.5 °C for B. californicus and 10.2 °C for B. yothersi; degree-days required to reach adulthood were 372.1 and 331.7 °C, respectively. Potential sites for establishment of B. yothersi are mostly lowlands, whereas for B. californicus they are both lowlands and highlands. Temperature data indicate that B. californicus has fewer sites where it can develop > 16 generations per year than B. yothersi. According to our results, the sites where citrus leprosis is most likely to present high incidence are the sweet orange cultivars bordering the Gulf of Mexico.


Assuntos
Citrus , Ácaros , Rhabdoviridae , Animais , México , Doenças das Plantas
7.
Arch Virol ; 166(7): 1985-1990, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33881618

RESUMO

The genomes of three putative novel viruses, tentatively named "Bacopa monnieri virus 1" (BmV1), "Bacopa monnieri virus 2" (BmV2), and "Bacopa monnieri virus 3" (BmV3) were identified in the transcriptome dataset of a medicinally important herb - water hyssop (Bacopa monnieri (L.) Wettst.). The BmV1 and BmV2 genomes resemble those of plant rhabdoviruses. The 13.3-kb-long BmV1 genome contains eight antisense ORFs in the order 3' l-N-P2'-P-P3-M-G-P6-L-t 5', with P2' ORF overlapping with P, while the 13.2-kb BmV2 genome contains six interspersed ORFs in the antisense orientation (3' l-N-P-P3-M-G-L-t 5'). The 8-kb BmV3 genome possesses five overlapping ORFs, with ORFs 2 to 5 being similar to those of solendoviruses. Based on genome organization, sequence similarity, and phylogeny, BmV1, BmV2, and BmV3 can be regarded as new members of the genera Cytorhabdovirus, Betanucleorhabdovirus, and Solendovirus, respectively.


Assuntos
Bacopa/genética , Bacopa/virologia , Caulimoviridae/genética , Genoma Viral/genética , Rhabdoviridae/genética , Transcriptoma/genética , Fases de Leitura Aberta/genética , Filogenia , Plantas Medicinais/genética
8.
Front Immunol ; 12: 654758, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33897703

RESUMO

The mucosa of vertebrates is a particularly complex but dynamic environment in which the host constantly interacts with trillions of commensal microorganisms and pathogens. Although the internal and external mucosal microbiomes with immune defense of mammals have been well investigated, the relationship between mucosal microbes and their host's immune responses has not been systematically understood in the early vertebrates. In this study, we compared the composition and distribution of mucosal microbiota in common carp (Cyprinus carpio), and found that there were significant differences of microbiota between in the internal (gut) and external mucosal (buccal mucosa, gills and skin) tissues. Next, we successfully constructed an infection model with spring viremia of carp virus (SVCV). Specifically, following viral infection, the immune and antiviral related genes showed different up-regulation in all selected mucosal tissues while significant morphological changes were only found in external tissues including buccal mucosa, gills and skin. Using 16S rRNA gene sequence, we revealed that the abundance of Proteobacteria in mucosal tissues including buccal mucosa, gills and gut showed increased trend after viral infection, whereas the abundance of Fusobacteria significantly decreased in gut. In addition, the loss of dominant commensal microorganisms and increased colonization of opportunistic bacteria were discovered in the mucosal surfaces indicating that a secondary bacterial infection might occur in these mucosal tissues after viral infection. Overall, our results firstly point out the distribution of internal and external mucosal microbiota and analyze the changes of mucosal microbiota in common carp after SVCV infection, which may indicated that the potential role of mucosal microbiota in the antiviral process in early vertebrates.


Assuntos
Doenças dos Peixes/imunologia , Doenças dos Peixes/virologia , Interações Hospedeiro-Patógeno/imunologia , Imunidade nas Mucosas , Microbiota , Rhabdoviridae/imunologia , Animais , Biomarcadores , Biologia Computacional/métodos , Disbiose , Doenças dos Peixes/patologia , Expressão Gênica , Imuno-Histoquímica , Metagenoma , Metagenômica/métodos , Membrana Mucosa/imunologia , Membrana Mucosa/microbiologia
9.
PLoS Pathog ; 17(3): e1009438, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33735323

RESUMO

Circular RNAs (circRNAs) represent a class of widespread and diverse covalently closed circular endogenous RNAs that exert crucial functions in regulating gene expression in mammals. However, the function and regulation mechanism of circRNAs in lower vertebrates are still unknown. Here, we discovered a novel circRNA derived from Deltex E3 ubiquitin ligase 1 (Dtx1) gene, namely, circDtx1, which was related to the antiviral responses in teleost fish. Results indicated that circDtx1 played essential roles in host antiviral immunity and inhibition of SCRV replication. Our study also found a microRNA miR-15a-5p, which could inhibit antiviral immune response and promote viral replication by targeting TRIF. Moreover, we also found that the antiviral effect inhibited by miR-15a-5p could be reversed with the circDtx1. In mechanism, our data revealed that circDtx1 was a competing endogenous RNA (ceRNA) of TRIF by sponging miR-15a-5p, leading to activation of the NF-κB/IRF3 pathway, and then enhancing the innate antiviral responses. Our results indicated that circRNAs played a regulatory role in immune responses in teleost fish.


Assuntos
Proteínas Adaptadoras de Transporte Vesicular/biossíntese , Doenças dos Peixes/imunologia , Regulação da Expressão Gênica/genética , Fator Regulador 3 de Interferon/imunologia , MicroRNAs/imunologia , RNA Circular/imunologia , Animais , Regulação para Baixo , Imunidade Inata/imunologia , Perciformes , Rhabdoviridae/imunologia , Infecções por Rhabdoviridae/imunologia
10.
Front Immunol ; 12: 581786, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33717065

RESUMO

Cholesterol is essential for building and maintaining cell membranes and is critical for several steps in the replication cycle of viruses, especially for enveloped viruses. In mammalian cells virus infections lead to the accumulation of the oxysterol 25-hydroxycholesterol (25HC), an antiviral factor, which is produced from cholesterol by the cholesterol 25 hydroxylase (CH25H). Antiviral responses based on CH25H are not well studied in fish. Therefore, in the present study putative genes encoding for CH25H were identified and amplified in common carp and rainbow trout cells and an HPLC-MS method was applied for determination of oxysterol concentrations in these cells under virus infection. Our results give some evidence that the activation of CH25H could be a part of the antiviral response against a broad spectrum of viruses infecting fish, in both common carp and rainbow trout cells in vitro. Quantification of oxysterols showed that fibroblastic cells are capable of producing 25HC and its metabolite 7α,25diHC. The oxysterol 25HC showed an antiviral activity by blocking the entry of cyprinid herpesvirus 3 (CyHV-3) into KFC cells, but not spring viremia of carp virus (SVCV) or common carp paramyxovirus (Para) in the same cells, or viral haemorrhagic septicaemia virus (VHSV) and infectious pancreatic necrosis virus (IPNV) into RTG-2 cells. Despite the fact that the CH25H based antiviral response coincides with type I IFN responses, the stimulation of salmonid cells with recombinant type I IFN proteins from rainbow trout could not induce ch25h_b gene expression. This provided further evidence, that the CH25H-response is not type I IFN dependent. Interestingly, the susceptibility of CyHV-3 to 25HC is counteracted by a downregulation of the expression of the ch25h_b gene in carp fibroblasts during CyHV-3 infection. This shows a unique interplay between oxysterol based immune responses and immunomodulatory abilities of certain viruses.


Assuntos
Antivirais/imunologia , Herpesviridae/imunologia , Hidroxicolesteróis/imunologia , Rhabdoviridae/imunologia , Animais , Antivirais/metabolismo , Carpas/genética , Carpas/metabolismo , Carpas/virologia , Linhagem Celular , Proteínas de Peixes/genética , Proteínas de Peixes/imunologia , Proteínas de Peixes/metabolismo , Regulação da Expressão Gênica/imunologia , Herpesviridae/fisiologia , Interações Hospedeiro-Patógeno/imunologia , Hidroxicolesteróis/metabolismo , Interferon Tipo I/genética , Interferon Tipo I/imunologia , Interferon Tipo I/metabolismo , Oncorhynchus mykiss/genética , Oncorhynchus mykiss/metabolismo , Rhabdoviridae/fisiologia , Internalização do Vírus , Replicação Viral/imunologia
11.
Front Immunol ; 12: 647202, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33659012

RESUMO

The innate immune organs and cells detect the invasion of pathogenic microorganisms, which trigger the innate immune response. A proper immune response can protect the organisms from pathogen invasion. However, excessive immunity can destroy immune homeostasis, leading to uncontrolled inflammation or pathogen transmission. Evidence shows that the miRNA-mediated immune regulatory network in mammals has had a significant impact, but the antibacterial and antiviral responses involved in miRNAs need to be further studied in lower vertebrates. Here, we report that miR-2187 as a negative regulator playing a critical role in the antiviral and antibacterial response of miiuy croaker. We find that pathogens such as Vibrio anguillarum and Siniperca chuatsi rhabdovirus (SCRV) can up-regulate the expression of miR-2187. Elevated miR-2187 is capable of reducing the production of inflammatory factors and antiviral genes by targeting TRAF6, thereby avoiding excessive inflammatory response. Furthermore, we proved that miR-2187 modulates innate immunity through TRAF6-mediated NF-κB and IRF3 signaling pathways. The above results indicate that miR-2187 acts as an immune inhibitor involved in host antibacterial and antiviral responses, thus enriching the immune regulatory network of the interaction between host and pathogen in lower vertebrates.


Assuntos
Proteínas de Peixes/genética , Fator Regulador 3 de Interferon/genética , MicroRNAs/genética , NF-kappa B/genética , Perciformes/genética , Fator 6 Associado a Receptor de TNF/genética , Animais , Sequência de Bases , Células Cultivadas , Citocinas/genética , Citocinas/imunologia , Citocinas/metabolismo , Doenças dos Peixes/genética , Doenças dos Peixes/microbiologia , Doenças dos Peixes/virologia , Proteínas de Peixes/metabolismo , Regulação da Expressão Gênica/imunologia , Interações Hospedeiro-Patógeno/imunologia , Imunidade Inata/genética , Imunidade Inata/imunologia , Fator Regulador 3 de Interferon/metabolismo , NF-kappa B/metabolismo , Perciformes/microbiologia , Perciformes/virologia , Rhabdoviridae/imunologia , Rhabdoviridae/fisiologia , Homologia de Sequência do Ácido Nucleico , Transdução de Sinais/genética , Transdução de Sinais/imunologia , Fator 6 Associado a Receptor de TNF/metabolismo , Vibrio/imunologia , Vibrio/fisiologia
12.
Arch Virol ; 166(6): 1615-1622, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33774730

RESUMO

We identified a novel plant rhabdovirus infecting native joá (Solanum aculeatissimum) plants in Brazil. Infected plants showed yellow blotches on the leaves, and typical enveloped bacilliform rhabdovirus particles associated with the nucleus were seen in thin sections by electron microscopy. The virus could be graft-transmitted to healthy joá and tomato plants but was not mechanically transmissible. RT-PCR using degenerate plant rhabdovirus L gene primers yielded an amplicon from extracted total RNA, the sequence of which was similar to those of alphanucleorhabdoviruses. Based on close sequence matches, especially with the type member potato yellow dwarf virus (PYDV), we adopted a degenerate-primer-walking strategy towards both genome ends. The complete genome of joá yellow blotch-associated virus (JYBaV) is comprised of 12,965 nucleotides, is less than 75% identical to that of its closest relative PYDV, and clusters with PYDV and other alphanucleorhabdoviruses in L protein phylogenetic trees, suggesting that it should be taxonomically classified in a new species in the genus Alphanucleorhabdovirus, family Rhabdoviridae. The genome organization of JYBaV is typical of the 'PYDV-like' subgroup of alphanucleorhabdoviruses, with seven genes (N-X-P-Y-M-G-L) separated by conserved intergenic regions and flanked by partly complementary 3' leader and 5' trailer regions.


Assuntos
Doenças das Plantas/virologia , Rhabdoviridae/isolamento & purificação , Solanum/virologia , Brasil , Genoma Viral , Filogenia , Folhas de Planta/virologia , Vírus de Plantas , Rhabdoviridae/genética
13.
PLoS Pathog ; 17(2): e1009317, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33600488

RESUMO

The transmembrane protein 33 (TMEM33) was originally identified as an endoplasmic reticulum (ER) protein that influences the tubular structure of the ER and modulates intracellular calcium homeostasis. However, the role of TMEM33 in antiviral immunity in vertebrates has not been elucidated. In this article, we demonstrate that zebrafish TMEM33 is a negative regulator of virus-triggered interferon (IFN) induction via two mechanisms: mitochondrial antiviral signaling protein (MAVS) ubiquitination and a decrease in the kinase activity of TANK binding kinase 1 (TBK1). Upon stimulation with viral components, tmem33 was remarkably upregulated in the zebrafish liver cell line. The IFNφ1 promoter (IFNφ1pro) activity and mRNA level induced by retinoic acid-inducible gene (RIG)-I-like receptors (RLRs) were significantly inhibited by TMEM33. Knockdown of TMEM33 increased host ifn transcription. Subsequently, we found that TMEM33 was colocalized in the ER and interacted with the RLR cascades, whereas MAVS was degraded by TMEM33 during the K48-linked ubiquitination. On the other hand, TMEM33 reduced the phosphorylation of mediator of IFN regulatory factor 3 (IRF3) activation (MITA)/IRF3 by acting as a decoy substrate of TBK1, which was also phosphorylated. A functional domain assay revealed that the N-terminal transmembrane domain 1 (TM1) and TM2 regions of TMEM33 were necessary for IFN suppression. Finally, TMEM33 significantly attenuated the host cellular antiviral capacity by blocking the IFN response. Taken together, our findings provide insight into the different mechanisms employed by TMEM33 in cellular IFN-mediated antiviral process.


Assuntos
Regulação da Expressão Gênica , Interferons/metabolismo , Fígado/metabolismo , Proteínas de Membrana/metabolismo , Infecções por Rhabdoviridae/virologia , Proteínas de Peixe-Zebra/metabolismo , Animais , Fígado/imunologia , Fígado/virologia , Proteínas de Membrana/genética , Fosforilação , Rhabdoviridae/fisiologia , Infecções por Rhabdoviridae/imunologia , Infecções por Rhabdoviridae/metabolismo , Ubiquitinação , Peixe-Zebra , Proteínas de Peixe-Zebra/genética
14.
Prev Vet Med ; 188: 105288, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33551191

RESUMO

Spring viremia of carp virus (SVCV) is a rhabdovirus of the Sprivivirus genus and the etiological agent of an internationally regulated aquatic animal disease in several fish species, including koi carp Cyprinus carpio L. The virus has a complex lifecycle with both acute and persistent stages of infection and can cause high mortality in affected populations. In this study, the diagnostic repeatability (within laboratory agreement) and reproducibility (between laboratory agreement) of 3 tests were investigated to assess their fitness as SVCV diagnostic tools. The tests, reverse transcription quantitative polymerase chain reaction (RT-qPCR) assays targeting either the SVCV glycoprotein (Q1G) or nucleoprotein (Q2N) genes and virus isolation by cell culture (VI), were performed in a blinded study with four Canadian laboratories. Test panels consisted of duplicate sets of 100 tissue samples collected from 3 SVCV prevalence populations of koi: a low-prevalence negative reference population (n = 20 fish) as well as moderate- (n = 50 fish) and high-prevalence (n = 30 fish) populations of koi experimentally infected with SVCV. The Q1G and Q2N tests were performed with kidney tissue in 3 laboratories and with brain tissue in 1 laboratory whereas pools of kidney, spleen and gill tissues were tested with the VI assay in 2 laboratories. Agreement of binary results was evaluated using the observed proportion of agreement, Cohen's kappa and Gwet's agreement coefficient (AC1) whereas the concordance correlation coefficient (ccc) and Bland Altman's limit of agreement were used to evaluate agreement of the RT-qPCR continuous data. Gwet's AC1 provided a more stable estimate of agreement than Cohen's kappa. Overall, high repeatability (AC1, 0.78-0.90) and reproducibility (AC1, 0.74-0.89) were observed for the Q1G and Q2N tests when kidney tissue was used. Lower agreement estimates of repeatability (AC1, 0.54-0.77) and reproducibility (AC1, 0.50-0.80) were obtained for the VI test. RT-qPCR reproducibility was low with kidney-brain tissue pairs (AC1, 0.09-0.46) and high with inter-test pairs of brain (AC1, 0.76-0.86) or kidney tissue (0.75-0.86). Tissue-specific differences in virus load affected test precision and informed final tissue selection. Repeatability (ccc, 0.94-0.97) and reproducibility (ccc, 0.91-0.97) estimates of agreement for paired continuous data from the RT-qPCR assays were similarly high with kidney tissue and lower with paired brain (ccc, 0.15-0.83) and kidney-brain tissues (ccc, 0.01-0.55). The high precision of Q1G and Q2N with kidney tissue suggests that the tests are performing similarly and are suitable candidates for assessment of their diagnostic accuracy.


Assuntos
Carpas , Testes Diagnósticos de Rotina/veterinária , Doenças dos Peixes/diagnóstico , Infecções por Rhabdoviridae/veterinária , Rhabdoviridae/isolamento & purificação , Animais , Doenças dos Peixes/virologia , Reprodutibilidade dos Testes , Infecções por Rhabdoviridae/diagnóstico , Infecções por Rhabdoviridae/virologia
15.
J Virol ; 95(9)2021 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-33568507

RESUMO

The use of unique cell surface markers to target and eradicate HIV-infected cells has been a longstanding objective of HIV-1 cure research. This approach, however, overlooks the possibility that intracellular changes present within HIV-infected cells may serve as valuable therapeutic targets. For example, the identification of dysregulated antiviral signaling in cancer has led to the characterization of oncolytic viruses capable of preferentially killing cancer cells. Since impairment of cellular antiviral machinery has been proposed as a mechanism by which HIV-1 evades immune clearance, we hypothesized that HIV-infected macrophages (an important viral reservoir in vivo) would be preferentially killed by the interferon-sensitive oncolytic Maraba virus MG1. We first showed that HIV-infected monocyte-derived macrophages (MDM) were more susceptible to MG1 infection and killing than HIV-uninfected cells. As MG1 is highly sensitive to type I interferons (IFN-I), we then investigated whether we could identify IFN-I signaling differences between HIV-infected and uninfected MDM and found evidence of impaired IFN-α responsiveness within HIV-infected cells. Finally, to assess whether MG1 could target a relevant, primary cell reservoir of HIV-1, we investigated its effects in alveolar macrophages (AM) obtained from effectively treated individuals living with HIV-1. As observed with in vitro-infected MDM, we found that HIV-infected AM were preferentially eliminated by MG1. In summary, the oncolytic rhabdovirus MG1 appears to preferentially target and kill HIV-infected cells via impairment of antiviral signaling pathways and may therefore provide a novel approach to an HIV-1 cure.IMPORTANCE Human immunodeficiency virus type 1 (HIV-1) remains a treatable, but incurable, viral infection. The establishment of viral reservoirs containing latently infected cells remains the main obstacle in the search for a cure. Cure research has also focused on only one cellular target of HIV-1 (the CD4+ T cell) while largely overlooking others (such as macrophages) that contribute to HIV-1 persistence. In this study, we address these challenges by describing a potential strategy for the eradication of HIV-infected macrophages. Specifically, we show that an engineered rhabdovirus-initially developed as a cancer therapy-is capable of preferential infection and killing of HIV-infected macrophages, possibly via the same altered antiviral signaling seen in cancer cells. As this rhabdovirus is currently being explored in phase I/II clinical trials, there is potential for this approach to be readily adapted for use within the HIV-1 cure field.


Assuntos
Antirretrovirais/uso terapêutico , Infecções por HIV/terapia , Interferon-alfa/uso terapêutico , Macrófagos/virologia , Vírus Oncolíticos/fisiologia , Rhabdoviridae/fisiologia , Animais , Chlorocebus aethiops , Células HEK293 , HIV-1 , Humanos , Células Vero
16.
Arch Virol ; 166(4): 1253-1257, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33575895

RESUMO

Deep-sequencing analysis of a chrysanthemum plant with yellow dwarf symptoms led to the discovery of a novel putative cytorhabdovirus, here tentatively named "chrysanthemum yellow dwarf associated virus" (CYDaV). Its negative-sense single-stranded RNA genome comprises 14,086 nucleotides and contains eight open reading frames in the order 3' leader-N-P'-P-P3-M-G-P6-L-5' trailer. CYDaV shares moderate sequence similarity (< 54.2% nucleotide and 51% amino acid sequence identity) with its cytorhabdovirus counterparts in cognate genes. Phylogenetic analysis showed that CYDaV clustered with strong support with alfalfa dwarf virus, raspberry vein chlorosis virus, and strawberry crinkle virus. These findings suggest that CYDaV should be considered a novel member of the genus Cytorhabdovirus, family Rhabdoviridae.


Assuntos
Chrysanthemum/virologia , Doenças das Plantas/virologia , Rhabdoviridae/genética , Sequência de Aminoácidos , Sequência de Bases , Genoma Viral/genética , Fases de Leitura Aberta , Filogenia , RNA Viral/genética , Rhabdoviridae/classificação , Homologia de Sequência
17.
Arch Virol ; 166(2): 655-658, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33394170

RESUMO

RNA was extracted from 'Hugh Dickson' rose leaves displaying virus-like symptoms in Maryland, USA. Using high-throughput sequencing, we identified a new virus, tentatively named "rose virus R". This virus has a negative-sense, single-stranded RNA genome and exhibits genomic features of a rhabdovirus, including a genome organization of 3'-N-P-P3-M-G-P6-L-5' and a gene junction region consensus sequence 3'-AUUUAUUUUGACUCUA-5'. Rose virus R is phylogenetically related to cytorhabdoviruses, and the nucleotide and amino acid sequences of rose virus R and related cytorhabdoviruses have diverged considerably, suggesting that rose virus R should be classified as a member of a novel species in the genus Cytorhabdovirus.


Assuntos
Doenças das Plantas/virologia , Rosa/virologia , Vírus não Classificados/genética , Sequência de Aminoácidos , Genoma Viral/genética , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Nucleotídeos/genética , Filogenia , RNA Viral/genética , Rhabdoviridae/genética , Proteínas Virais/genética , Sequenciamento Completo do Genoma/métodos
18.
Fish Shellfish Immunol ; 111: 83-93, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33513437

RESUMO

Tumor necrosis factor receptor 1 (TNFR1) associated death domain protein (TRADD) is a pivotal adaptor in TNF signaling pathway and up-regulates MAVS/IFN signaling pathway in human and mammal. However, the role of TRADD in teleost fish remains obscure. To reveal the function of teleost TRADD in the innate immune response, the TRADD homologue (bcTRADD) of black carp (Mylopharyngodon piceus) has been cloned and the function of bcTRADD is investigated in this study, which shares similar functional domain to its mammalian counterpart. bcTRADD mRNA expression level increased in response to different stimuli, including LPS, poly (I:C) and virus infection in host cells. bcTRADD activated the transcriptional activity of NF-κB promoter in the reporter assay; however, showed hardly any effect on the transcriptional activity of IFN promoter. It was interesting that black carp mitochondria antiviral signaling protein (bcMAVS)-activated IFN promoter transcription were dramatically depressed by bcTRADD and the C-terminal death domain of bcTRADD was indispensable for its regulation of bcMAVS. Accordingly, the plaque assay result showed that EPC cells co-expressing bcMAVS and bcTRADD presented much attenuated antiviral activity than EPC cells expressing bcMAVS alone. Knockdown of bcTRADD slightly promoted the antiviral ability of the host cells against SVCV. The current data support the conclusion that bcTRADD suppresses MAVS-mediated antiviral signaling, which is different to its mammalian counterpart.


Assuntos
Carpas/genética , Carpas/imunologia , Doenças dos Peixes/imunologia , Regulação da Expressão Gênica/imunologia , Imunidade Inata/genética , Proteína de Domínio de Morte Associada a Receptor de TNF/genética , Proteína de Domínio de Morte Associada a Receptor de TNF/imunologia , Sequência de Aminoácidos , Animais , Linhagem Celular , Proteínas de Peixes/química , Proteínas de Peixes/genética , Proteínas de Peixes/imunologia , Perfilação da Expressão Gênica/veterinária , Células HEK293 , Humanos , Lipopolissacarídeos/farmacologia , Filogenia , Poli I-C/farmacologia , Rhabdoviridae/fisiologia , Infecções por Rhabdoviridae/imunologia , Infecções por Rhabdoviridae/veterinária , Alinhamento de Sequência/veterinária , Proteína de Domínio de Morte Associada a Receptor de TNF/química
19.
Viruses ; 13(1)2021 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-33466539

RESUMO

Bats, the second largest order of mammals worldwide, harbor specific characteristics such as sustaining flight, a special immune system, unique habits, and ecological niches. In addition, they are the natural reservoirs of a variety of emerging or re-emerging zoonotic pathogens. Rhabdoviridae is one of the most diverse families of RNA viruses, which consists of 20 ecologically diverse genera, infecting plants, mammals, birds, reptiles, and fish. To date, three bat-related genera are described, named Lyssavirus, Vesiculovirus, and Ledantevirus. However, the prevalence and the distribution of these bat-related rhabdoviruses remain largely unknown, especially in China. To fill this gap, we performed a large molecular retrospective study based on the real-time reverse transcription polymerase chain reaction (RT-qPCR) detection of lyssavirus in bat samples (1044 brain and 3532 saliva samples, from 63 different bat species) originating from 21 provinces of China during 2006-2018. None of them were positive for lyssavirus, but six bat brains (0.6%) of Rhinolophus bat species, originating from Hubei and Hainan provinces, were positive for vesiculoviruses or ledanteviruses. Based on complete genomes, these viruses were phylogenetically classified into three putative new species, tentatively named Yinshui bat virus (YSBV), Taiyi bat virus (TYBV), and Qiongzhong bat virus (QZBV). These results indicate the novel rhabdoviruses circulated in different Chinese bat populations.


Assuntos
Quirópteros/virologia , Genoma Viral , Filogenia , Infecções por Rhabdoviridae/veterinária , Rhabdoviridae/classificação , Animais , Encéfalo/virologia , China/epidemiologia , Estudos Retrospectivos , Rhabdoviridae/isolamento & purificação , Infecções por Rhabdoviridae/epidemiologia , Infecções por Rhabdoviridae/virologia , Saliva/virologia , Vesiculovirus/classificação
20.
J Fish Dis ; 44(6): 675-687, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33423323

RESUMO

As one of the piscine rhabdoviruses, Siniperca chuatsi rhabdovirus (SCRV) has caused considerable losses to mandarin fish aquaculture industry. RNA-seq, as efficient transcriptome research method, has been widely used to study the immune response of fish to pathogens. This study reported the effect of SCRV infection at 0, 24 and 60 hr on S. chuatsi at the transcriptome level. A total of 61,527 unigenes with high quality were obtained, and 3,095, 1,854 and 227 differentially expressed genes (DEGs) were labelled between the Sc24 and Sc0 groups, the Sc60 and Sc0 groups and the Sc60 and Sc24 groups, respectively. Genes involved in innate and adaptive immunity were highlighted. In Gene Ontology analysis, the DEGs that participated in immune response, innate immune response and the regulation of apoptotic process were identified as enriched classes. Kyoto Encyclopedia of Genes and Genomes pathway results indicated that most DEGs caused by SCRV infection were identified in the immune system (retinoic acid-inducible gene-I-like receptor/Toll-like receptor/nucleotide-binding oligomerization domain-like receptor/C-type lectin receptor signalling pathway), cellular processes, cell growth and death (p53 signalling pathway, cellular senescence, apoptosis and phagosome), and metabolism. Quantitative real-time PCR was used to further verify the expression levels of 15 immune-related DEGs. The transcriptome database obtained in this study provided further in-depth insight into the immune response of S. chuatsi against SCRV.


Assuntos
Imunidade Adaptativa/genética , Doenças dos Peixes/imunologia , Proteínas de Peixes/imunologia , Regulação da Expressão Gênica/imunologia , Imunidade Inata/genética , Perciformes/genética , Perciformes/imunologia , Transcriptoma/imunologia , Animais , Apoptose , Doenças dos Peixes/virologia , Proteínas de Peixes/genética , Perfilação da Expressão Gênica , Ontologia Genética , Rhabdoviridae/fisiologia , Infecções por Rhabdoviridae/imunologia , Infecções por Rhabdoviridae/veterinária , Infecções por Rhabdoviridae/virologia
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