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1.
Arch Virol ; 166(10): 2751-2762, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34341873

RESUMO

Ticks are important vector arthropods that transmit various pathogens to humans and other animals. Tick-borne viruses are of particular concern to public health as these are major agents of emerging and re-emerging infectious diseases. The Phenuiviridae family of tick-borne viruses is one of the most diverse groups and includes important human pathogenic viruses such as severe fever with thrombocytopenia syndrome virus. Phenuivirus-like sequences were detected during the surveillance of tick-borne viruses using RNA virome analysis from a pooled sample of Haemaphysalis formosensis ticks collected in Ehime, Japan. RT-PCR amplification and Sanger sequencing revealed the nearly complete viral genome sequence of all three segments. Comparisons of the viral amino acid sequences among phenuiviruses indicated that the detected virus shared 46%-70% sequence identity with known members of the Kaisodi group in the genus Uukuvirus. Furthermore, phylogenetic analysis of the viral proteins showed that the virus formed a cluster with the Kaisodi group viruses, suggesting that this was a novel virus, which was designated "Toyo virus" (TOYOV). Further investigation of TOYOV is needed, and it will contribute to understanding the natural history and the etiological importance of the Kaisodi group viruses.


Assuntos
Vírus de RNA de Sentido Negativo/classificação , Carrapatos/virologia , Sequência de Aminoácidos , Animais , Genoma Viral/genética , Humanos , Japão , Vírus de RNA de Sentido Negativo/genética , Vírus de RNA de Sentido Negativo/isolamento & purificação , Filogenia , RNA Viral/genética , Análise de Sequência de DNA , Proteínas Virais/genética , Viroma/genética
2.
Cells ; 10(6)2021 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-34200781

RESUMO

Infections by negative strand RNA viruses (NSVs) induce the formation of viral inclusion bodies (IBs) in the host cell that segregate viral as well as cellular proteins to enable efficient viral replication. The induction of those membrane-less viral compartments leads inevitably to structural remodeling of the cellular architecture. Recent studies suggested that viral IBs have properties of biomolecular condensates (or liquid organelles), as have previously been shown for other membrane-less cellular compartments like stress granules or P-bodies. Biomolecular condensates are highly dynamic structures formed by liquid-liquid phase separation (LLPS). Key drivers for LLPS in cells are multivalent protein:protein and protein:RNA interactions leading to specialized areas in the cell that recruit molecules with similar properties, while other non-similar molecules are excluded. These typical features of cellular biomolecular condensates are also a common characteristic in the biogenesis of viral inclusion bodies. Viral IBs are predominantly induced by the expression of the viral nucleoprotein (N, NP) and phosphoprotein (P); both are characterized by a special protein architecture containing multiple disordered regions and RNA-binding domains that contribute to different protein functions. P keeps N soluble after expression to allow a concerted binding of N to the viral RNA. This results in the encapsidation of the viral genome by N, while P acts additionally as a cofactor for the viral polymerase, enabling viral transcription and replication. Here, we will review the formation and function of those viral inclusion bodies upon infection with NSVs with respect to their nature as biomolecular condensates.


Assuntos
Corpos de Inclusão Viral , Vírus de RNA de Sentido Negativo , Infecções por Vírus de RNA , Animais , Humanos
3.
Arch Virol ; 166(10): 2829-2834, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34319452

RESUMO

Watermelon crinkle leaf-associated virus 1 and watermelon crinkle leaf-associated virus 2 (WCLaV-1 and WCLaV-2), two unclassified members of the order Bunyavirales, are phylogenetically related to members of the genus Coguvirus (family Phenuiviridae). The genome of both viruses was reported previously to be composed of three RNA segments. However, the terminal sequences of two genomic RNA segments, namely those encoding the putative movement protein (MP) and the nucleocapsid (NP) protein, remained undetermined. High-throughput sequencing of total RNA and small RNA preparations, combined with reverse transcription PCR amplification followed by sequencing, revealed that the WCLaV-1 and WCLaV-2 possess a bipartite genome consisting of a negative-sense RNA1, encoding the RNA-dependent RNA polymerase, and an ambisense RNA2, encoding the putative movement (MP) and nucleocapsid (NP) proteins. The two open reading frames of RNA2 are in opposite orientations and are separated by a long AU-rich intergenic region (IR) that may assume a hairpin conformation. RNA1 and RNA2 of both viruses share almost identical 5' and 3' termini, which are complementary to each other up to 20 nt. This genome organization is typical of members of the genus Coguvirus, with which WCLaV-1 and WCLaV-2 also share similar terminal 5' and 3' sequences of RNA1 and RNA2. These molecular features, together with phylogenetic reconstructions support the classification of WCLaV-1 and WCLaV2 as members of two new species in the genus Coguvirus.


Assuntos
Citrullus/virologia , Genoma Viral/genética , Vírus de RNA de Sentido Negativo/genética , Sequência de Aminoácidos , Vírus de RNA de Sentido Negativo/classificação , Proteínas do Nucleocapsídeo/genética , Filogenia , Doenças das Plantas/virologia , Folhas de Planta/virologia , Proteínas do Movimento Viral em Plantas/genética , RNA Viral/genética , RNA Polimerase Dependente de RNA/genética , Análise de Sequência de DNA
4.
J Gen Virol ; 102(7)2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34269676

RESUMO

Type I interferons (IFNs) are a first line of defence against viral infections. Upon infection, a first small wave of early type I IFN, mainly IFN-ß and particularly IFN-α4, are induced and bind to the type I IFN receptor (IFNAR) to amplify the IFN response. It was shown for several viruses that robust type I IFN responses require this positive feedback loop via the IFNAR. Recently, we showed that infection of IFNAR knockout mice with the orthomyxovirus Thogoto virus lacking the ML open reading frame (THOV(ML-)) results in the expression of unexpected high amounts of type I IFN. To investigate if IFNAR-independent IFN responses are unique for THOV(ML-), we performed infection experiments with several negative-strand RNA viruses using different routes and dosages for infection. A variety of these viruses induced type I IFN responses IFNAR-independently when using the intraperitoneal (i.p.) route for infection. In vitro studies demonstrated that myeloid dendritic cells (mDC) are capable of producing IFNAR-independent IFN-α responses that are dependent on the expression of the adaptor protein mitochondrial antiviral-signalling protein (MAVS) whereas pDC where entirely depending on the IFNAR feedback loop in vitro. Thus, depending on dose and route of infection, the IFNAR feedback loop is not strictly necessary for robust type I IFN expression and an IFNAR-independent type I IFN production might be the rule rather than the exception for infections with numerous negative-strand RNA viruses.


Assuntos
Interferon-alfa/biossíntese , Vírus de RNA de Sentido Negativo/imunologia , Infecções por Vírus de RNA/imunologia , Receptor de Interferon alfa e beta/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Animais , Células Dendríticas/imunologia , Células Dendríticas/virologia , Camundongos , Camundongos Endogâmicos C57BL , Células Mieloides/imunologia , Células Mieloides/virologia , Infecções por Orthomyxoviridae/imunologia , Infecções por Orthomyxoviridae/virologia , Infecções por Vírus de RNA/virologia , Receptor de Interferon alfa e beta/genética , Thogotovirus , Carga Viral
5.
Annu Rev Phytopathol ; 59: 351-371, 2021 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-34077238

RESUMO

Rice stripe disease caused by Rice stripe virus (RSV) is one of the most devastating plant viruses of rice and causes enormous losses in production. RSV is transmitted from plant to plant by the small brown planthopper (Laodelphax striatellus) in a circulative-propagative manner. The recent reemergence of this pathogen in East Asia since 2000 has made RSV one of the most studied plant viruses over the past two decades. Extensive studies of RSV have resulted in substantial advances regarding fundamental aspects of the virus infection. Here, we compile and analyze recent information on RSV with a special emphasis on the strategies that RSV has adopted to establish infections. These advances include RSV replication and movement in host plants and the small brown planthopper vector, innate immunity defenses against RSV infection, epidemiology, and recent advances in the management of rice stripe disease. Understanding these issues will facilitate the design of novel antiviral therapies for management and contribute to a more detailed understanding of negative-sense virus-host interactions at the molecular level.


Assuntos
Hemípteros , Oryza , Tenuivirus , Animais , Vírus de RNA de Sentido Negativo , Doenças das Plantas , Tenuivirus/genética
6.
Arch Virol ; 166(7): 2045-2050, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33944994

RESUMO

A novel negative-stranded (ns) RNA virus tentatively named "Yunnan paris negative-stranded virus" (YPNSV), was isolated from Paris polyphylla var. yunnanensis plants exhibiting leaf chlorosis and mosaic symptoms in Yunnan. Its complete genome sequence was determined using Illumina and Sanger sequencing. YPNSV has a bipartite genome that consists of a negative-stranded (ns) RNA1 encoding the viral RNA-dependent RNA polymerase (RdRp, p251), an ambisense RNA2 coding for the putative movement protein (MP, p46) and nucleocapsid protein (NP, p39), with the two open reading frames separated by a long intergenic region that is rich in A and U. Sequence comparisons showed that the RdRp, MP, and NP of YPNSV are most similar to those of watermelon crinkle leaf-associated virus 2 (WCLaV-2), with 69.1%, 50.4%, and 60.9% amino acid sequence identity, respectively. Phylogenetic analysis based on deduced amino acid sequences of RdRp and NP showed that YPNSV clustered in a clade with coguviruses and that its closest known relative is WCLaV-2. Based on the above results, YPNSV should be regarded as a new member of genus Coguvirus, family Phenuiviridae.


Assuntos
Genoma Viral/genética , Melanthiaceae/virologia , Vírus de RNA de Sentido Negativo/genética , Sequência de Aminoácidos , China , Vírus de RNA de Sentido Negativo/classificação , Fases de Leitura Aberta , Filogenia , Doenças das Plantas/virologia , RNA Viral/genética , Proteínas Virais/genética
7.
Arch Virol ; 166(5): 1525-1528, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33721097

RESUMO

Here, we report the full-length genome sequence of a novel cogu-like virus identified in Brassica campestris L. ssp. Chinensis (B. campestris), an economically important vegetable in China. This virus, tentatively named "Brassica campestris chinensis coguvirus 1" (BCCoV1), has a bipartite genome that consists of two RNA molecules (RNA1 and RNA2). The negative-stranded (ns) RNA1 is 6757 nt in length, encoding the putative RNA-dependent RNA polymerase (RdRp), and the ambisense RNA2 is 3061 nt long, encoding the putative movement protein (MP) and nucleocapsid protein (NP). A homology search of the RdRp, MP, and NP showed that they are closely related to five other recently discovered negative-stranded RNA (nsRNA) viruses infecting plants, belonging to the new genus Coguvirus. Phylogenetic analysis of the 252-kDa RdRp confirmed the classification of this virus, showing that BCCoV1 possibly belongs to the genus Coguvirus, family Phenuiviridae, order Bunyavirales. The present study improves our understanding of the viral diversity in B. campestris and the evolution of nsRNA viruses.


Assuntos
Brassica rapa/virologia , Vírus de RNA de Sentido Negativo/classificação , Sequência de Bases , China , Genoma Viral/genética , Vírus de RNA de Sentido Negativo/genética , Filogenia , Doenças das Plantas/virologia , RNA Viral/genética , Verduras/virologia , Proteínas Virais/genética
8.
Sci Rep ; 11(1): 2977, 2021 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-33536558

RESUMO

Surface inactivation of human microbial pathogens has a long history. The Smith Papyrus (2600 ~ 2200 B.C.) described the use of copper surfaces to sterilize chest wounds and drinking water. Brass and bronze on doorknobs can discourage microbial spread in hospitals, and metal-base surface coatings are used in hygiene-sensitive environments, both as inactivators and modulators of cellular immunity. A limitation of these approaches is that the reactive oxygen radicals (ROS) generated at metal surfaces also damage human cells by oxidizing their proteins and lipids. Silicon nitride (Si3N4) is a non-oxide ceramic compound with known surface bacterial resistance. We show here that off-stoichiometric reactions at Si3N4 surfaces are also capable of inactivating different types of single-stranded RNA (ssRNA) viruses independent of whether their structure presents an envelop or not. The antiviral property of Si3N4 derives from a hydrolysis reaction at its surface and the subsequent formation of reactive nitrogen species (RNS) in doses that could be metabolized by mammalian cells but are lethal to pathogens. Real-time reverse transcription (RT)-polymerase chain reaction (PCR) tests of viral RNA and in situ Raman spectroscopy suggested that the products of Si3N4 hydrolysis directly react with viral proteins and RNA. Si3N4 may have a role in controlling human epidemics related to ssRNA mutant viruses.


Assuntos
Cerâmica/química , Desinfecção/instrumentação , Vírus de RNA de Sentido Negativo/química , Vírus de RNA de Cadeia Positiva/química , Compostos de Silício/química , Animais , Gatos , Cães , Hidrólise , Macaca mulatta , Células Madin Darby de Rim Canino , Teste de Materiais , Mutação , Vírus de RNA de Sentido Negativo/genética , Vírus de RNA de Cadeia Positiva/genética , Espécies Reativas de Nitrogênio/química , Propriedades de Superfície
9.
J Virol ; 95(9)2021 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-33536170

RESUMO

N 6-Methyladenosine (m6A) is the most abundant internal RNA modification catalyzed by host RNA methyltransferases. As obligate intracellular parasites, many viruses acquire m6A methylation in their RNAs. However, the biological functions of viral m6A methylation are poorly understood. Here, we found that viral m6A methylation serves as a molecular marker for host innate immunity to discriminate self from nonself RNA and that this novel biological function of viral m6A methylation is universally conserved in several families in nonsegmented negative-sense (NNS) RNA viruses. Using m6A methyltransferase (METTL3) knockout cells, we produced m6A-deficient virion RNAs from the representative members of the families Pneumoviridae, Paramyxoviridae, and Rhabdoviridae and found that these m6A-deficient viral RNAs triggered significantly higher levels of type I interferon compared to the m6A-sufficient viral RNAs, in a RIG-I-dependent manner. Reconstitution of the RIG-I pathway revealed that m6A-deficient virion RNA induced higher expression of RIG-I, bound to RIG-I more efficiently, enhanced RIG-I ubiquitination, and facilitated RIG-I conformational rearrangement and oligomerization. Furthermore, the m6A binding protein YTHDF2 is essential for suppression of the type I interferon signaling pathway, including by virion RNA. Collectively, our results suggest that several families in NNS RNA viruses acquire m6A in viral RNA as a common strategy to evade host innate immunity.IMPORTANCE The nonsegmented negative-sense (NNS) RNA viruses share many common replication and gene expression strategies. There are no vaccines or antiviral drugs for many of these viruses. We found that representative members of the families Pneumoviridae, Paramyxoviridae, and Rhabdoviridae among the NNS RNA viruses acquire m6A methylation in their genome and antigenome as a means to escape recognition by host innate immunity via a RIG-I-dependent signaling pathway. Viral RNA lacking m6A methylation induces a significantly higher type I interferon response than m6A-sufficient viral RNA. In addition to uncovering m6A methylation as a common mechanism for many NNS RNA viruses to evade host innate immunity, this study discovered a novel strategy to enhance type I interferon responses, which may have important applications in vaccine development, as robust innate immunity will likely promote the subsequent adaptive immunity.


Assuntos
Adenosina/análogos & derivados , Interações entre Hospedeiro e Microrganismos/imunologia , Interferon Tipo I/imunologia , Vírus de RNA de Sentido Negativo , Infecções por Vírus de RNA , RNA Viral/genética , Células A549 , Adenosina/genética , Regulação Viral da Expressão Gênica , Técnicas de Inativação de Genes , Humanos , Imunidade Inata , Metiltransferases/genética , Vírus de RNA de Sentido Negativo/genética , Vírus de RNA de Sentido Negativo/imunologia , Vírus de RNA de Sentido Negativo/patogenicidade , Processamento Pós-Transcricional do RNA , Infecções por Vírus de RNA/imunologia , Infecções por Vírus de RNA/virologia
10.
Arch Virol ; 166(4): 1241-1245, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33566195

RESUMO

Here, we report the complete genome sequence of chrysanthemum mosaic-associated virus (ChMaV), a putative new member of the genus Emaravirus. The ChMaV genome comprises seven negative-sense RNA segments (RNAs 1, 2, 3a, 3b, 4, 5, and 6), and the amino acid sequences of its RNA-dependent RNA polymerase (RNA1), glycoprotein precursor (RNA2), nucleocapsid protein (RNA3), and movement protein (RNA4) showed the closest relationship to pear chlorotic leaf spot-associated virus. Phylogenetic analysis showed that it clusters with emaraviruses whose host plants originate from East Asia.


Assuntos
Chrysanthemum/virologia , Genoma Viral/genética , Vírus do Mosaico/genética , Vírus de RNA de Sentido Negativo/genética , Doenças das Plantas/virologia , Sequência de Aminoácidos , Sequência de Bases , Vírus do Mosaico/classificação , Vírus de RNA de Sentido Negativo/classificação , Filogenia , RNA Viral/genética , Proteínas Virais/genética
11.
Sci Rep ; 10(1): 20364, 2020 11 23.
Artigo em Inglês | MEDLINE | ID: mdl-33230226

RESUMO

Tilapia lake virus (TiLV) causes high mortality and high economic losses in tilapines. We describe an experimental challenge study focusing on early post challenge innate immune responses. Nile tilapia (Oreochromis niloticus) were infected with 105 TCID50/mL TiLV intraperitoneally, followed by virus quantification, histopathology and gene expression analysis in target (brain/liver) and lymphoid (spleen/headkidney) organs at 3, 7, 12, 17, and 34 days post challenge (dpc). Onset of mortality was from 21 dpc, and cumulative mortality was 38.5% by 34 dpc. Liver and kidney histopathology developed over the period 3-17 dpc, characterized by anisocytosis, anisokaryocytosis, and formation of multinucleated hepatocytes. Viral loads were highest at early time (3 dpc) in liver, spleen and kidney, declining towards 34 dpc. In brain, viral titer peaked 17 dpc. Innate sensors, TLRs 3/7 were inversely correlated with virus titer in brain and headkidney, and IFN-ß and Mx showed a similar pattern. All organs showed increased mRNA IgM expression over the course of infection. Overall, high virus titers downplay innate responses, and an increase is seen when viral titers decline. In silico modeling found that TiLV segments 4, 5 and 10 carry nucleolar localization signals. Anti-viral effects of TiLV facilitate production of virus at early stage of infection.


Assuntos
Ciclídeos/imunologia , Doenças dos Peixes/imunologia , Interações Hospedeiro-Patógeno/imunologia , Imunidade Inata , Vírus de RNA de Sentido Negativo/patogenicidade , Animais , Anticorpos Antivirais/biossíntese , Anticorpos Antivirais/genética , Encéfalo/imunologia , Encéfalo/virologia , Ciclídeos/virologia , Doenças dos Peixes/mortalidade , Doenças dos Peixes/patologia , Doenças dos Peixes/virologia , Regulação da Expressão Gênica , Hepatócitos/imunologia , Hepatócitos/virologia , Imunoglobulina M/biossíntese , Imunoglobulina M/genética , Interferon beta/genética , Interferon beta/imunologia , Rim/imunologia , Rim/virologia , Fígado/imunologia , Fígado/virologia , Vírus de RNA de Sentido Negativo/crescimento & desenvolvimento , Vírus de RNA de Sentido Negativo/imunologia , Baço/imunologia , Baço/virologia , Análise de Sobrevida , Fatores de Tempo , Receptor 3 Toll-Like/genética , Receptor 3 Toll-Like/imunologia , Receptor 7 Toll-Like/genética , Receptor 7 Toll-Like/imunologia
12.
Viruses ; 12(8)2020 07 30.
Artigo em Inglês | MEDLINE | ID: mdl-32751700

RESUMO

Negative strand RNA viruses (NSVs) include many important human pathogens, such as influenza virus, Ebola virus, and rabies virus. One of the unique characteristics that NSVs share is the assembly of the nucleocapsid and its role in viral RNA synthesis. In NSVs, the single strand RNA genome is encapsidated in the linear nucleocapsid throughout the viral replication cycle. Subunits of the nucleocapsid protein are parallelly aligned along the RNA genome that is sandwiched between two domains composed of conserved helix motifs. The viral RNA-dependent-RNA polymerase (vRdRp) must recognize the protein-RNA complex of the nucleocapsid and unveil the protected genomic RNA in order to initiate viral RNA synthesis. In addition, vRdRp must continuously translocate along the protein-RNA complex during elongation in viral RNA synthesis. This unique mechanism of viral RNA synthesis suggests that the nucleocapsid may play a regulatory role during NSV replication.


Assuntos
Vírus de RNA de Sentido Negativo/fisiologia , Vírus de RNA de Sentido Negativo/ultraestrutura , Proteínas do Nucleocapsídeo/química , Nucleocapsídeo/química , Nucleocapsídeo/fisiologia , Genoma Viral , Modelos Moleculares , Vírus de RNA de Sentido Negativo/química , Vírus de RNA de Sentido Negativo/genética , Nucleocapsídeo/genética , Nucleocapsídeo/ultraestrutura , Proteínas do Nucleocapsídeo/metabolismo , Conformação Proteica , Dobramento de Proteína , RNA Viral/biossíntese , RNA Viral/genética , RNA Viral/metabolismo , RNA Polimerase Dependente de RNA/metabolismo
13.
Virus Res ; 286: 198079, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32599089

RESUMO

Virus communities of forest fungi remain poorly characterized. In this study, we detected two new viruses co-infecting an isolate of the polypore fungus Bondarzewia berkeleyi using high-throughput sequencing. One of them was a putative new partitivirus designated as Bondarzewia berkeleyi partitivirus 1 (BbPV1), with two linear dsRNA genome segments of 1928 and 1863 bp encoding a putative RNA-dependent RNA polymerase (RdRP) of 591 aa and a putative capsid protein of 538 aa. The other virus, designated as Bondarzewia berkeleyi negative-strand RNA virus 1 (BbNSRV1), had a non-segmented negative-sense RNA genome of 10,983 nt and was related to members of family Mymonaviridae. The BbNSRV1 genome includes six predicted open reading frames (ORFs) of 279, 425, 230, 174, 200 and 1970 aa. The longest ORF contained conserved regions corresponding to Mononegavirales RdRP and mRNA-capping enzyme region V constituting the mononegavirus Large protein. In addition, a low level of sequence identity was detected between the putative nucleocapsid protein-coding ORF2 of Lentinula edodes negative-strand RNA virus 1 and BbNSRV1. The viruses characterized in this study are the first ones described in Bondarzewia spp., and BbNSRV1 is the second mymona-like virus described in a basidiomycete host.


Assuntos
Basidiomycota/virologia , Coinfecção/virologia , Vírus de RNA de Sentido Negativo/classificação , Filogenia , Vírus de RNA/classificação , Proteínas do Capsídeo/genética , Genoma Viral , Vírus de RNA de Sentido Negativo/isolamento & purificação , Fases de Leitura Aberta/genética , Vírus de RNA/isolamento & purificação , RNA Viral/genética
14.
Antiviral Res ; 178: 104750, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32205137

RESUMO

Picornaviridae are positive-sense single stranded RNA viruses with a similar genomic structure lacking a cap at the 5' end, but with a highly structured 5'-untranslated region (UTR) containing an internal ribosome entry site (IRES). IRES allows ribosomes to be recruited by the viral RNA and initiate translation in a cap-independent manner. Coxsackie virus type B (CV-B) belong to Picornaviridae and are widespread in human population. They usually cause subclinical infections but, occasionally, also severe diseases with various clinical manifestations. CV-B have no specific therapy. DEAD-box polypeptide 3 (DDX3) is a member of the Asp-Glu-Ala-Asp (DEAD)-box family with an ATP-dependent RNA unwinding helicase activity. Recently, several positive-sense single strand RNA viruses have been shown to need DDX3 for their translation. Here, we show that several DDX3 inhibitors reduced CV-B replication and production of viral protein, particularly when added within 12 h of infection. Based on in vitro and in silico data, we hypothesized that DDX3 inhibitors hamper interaction between DDX3 and viral IRES in a stereodynamic fashion. Accordingly, the DDX3 inhibitors tested have no activity against the Vesicular Stomatitis virus and Measles virus, which are negative-sense single stranded RNA viruses and use cap-dependent translation. This study suggests that DDX3 is required by RNA viruses lacking a cap and show that this enzyme is a valuable target to design antiviral molecules against CV-B. Thus, DDX3 is dispensable for cap-dependent translation, but required for translation of transcripts containing secondary structure in their UTRs.


Assuntos
Antivirais/farmacologia , RNA Helicases DEAD-box/antagonistas & inibidores , Enterovirus Humano B/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Antivirais/química , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , RNA Helicases DEAD-box/metabolismo , Enterovirus Humano B/classificação , Enterovirus Humano B/fisiologia , Inibidores Enzimáticos/química , Humanos , Concentração Inibidora 50 , Sítios Internos de Entrada Ribossomal , Células KB , Vírus do Sarampo/efeitos dos fármacos , Vírus do Sarampo/fisiologia , Vírus de RNA de Sentido Negativo/efeitos dos fármacos , Vírus de RNA de Sentido Negativo/fisiologia , Conformação de Ácido Nucleico , Vírus de RNA de Cadeia Positiva/efeitos dos fármacos , Vírus de RNA de Cadeia Positiva/fisiologia , RNA Viral/química , RNA Viral/genética , RNA Viral/metabolismo , Ribavirina/farmacologia , Sorogrupo , Vesiculovirus/efeitos dos fármacos , Vesiculovirus/fisiologia , Ensaio de Placa Viral , Proteínas Virais/biossíntese , Replicação Viral/efeitos dos fármacos
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