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1.
Sci Rep ; 11(1): 16584, 2021 08 16.
Artigo em Inglês | MEDLINE | ID: mdl-34400676

RESUMO

Currently, there are increasing concerns about the possibility of a new epidemic due to emerging reports of Mayaro virus (MAYV) fever outbreaks in areas of South and Central America. Haemagogus mosquitoes, the primary sylvan vectors of MAYV are poorly characterized and a better understanding of the mosquito's viral transmission dynamics and interactions with MAYV and other microorganisms would be important in devising effective control strategies. In this study, a metatranscriptomic based approach was utilized to determine the prevalence of RNA viruses in field-caught mosquitoes morphologically identified as Haemagogus janthinomys from twelve (12) forest locations in Trinidad, West Indies. Known insect specific viruses including the Phasi Charoen-like and Humaiata-Tubiacanga virus dominated the virome of the mosquitoes throughout sampling locations while other viruses such as the avian leukosis virus, MAYV and several unclassified viruses had a narrower distribution. Additionally, assembled contigs from the Ecclesville location suggests the presence of a unique uncharacterized picorna-like virus. Mapping of RNA sequencing reads to reference mitochondrial sequences of potential feeding host animals showed hits against avian and rodent sequences, which putatively adds to the growing body of evidence of a potentially wide feeding host-range for the Haemagogus mosquito vector.


Assuntos
Culicidae/virologia , Vírus de RNA/isolamento & purificação , Viroma , Infecções por Alphavirus/epidemiologia , Infecções por Alphavirus/virologia , Animais , Sequência de Bases , Aves , Culicidae/microbiologia , Surtos de Doenças , Reservatórios de Doenças/virologia , Geografia Médica , Especificidade de Hospedeiro , Insetos Vetores/virologia , Filogenia , Proteobactérias/genética , Vírus de RNA/classificação , Vírus de RNA/genética , RNA Bacteriano/genética , RNA Bacteriano/isolamento & purificação , RNA Viral/genética , RNA Viral/isolamento & purificação , Roedores , Togaviridae/genética , Togaviridae/isolamento & purificação , Trinidad e Tobago/epidemiologia , Viroma/genética
2.
Sci Rep ; 11(1): 15374, 2021 07 28.
Artigo em Inglês | MEDLINE | ID: mdl-34321560

RESUMO

Mayaro virus (MAYV), which causes mayaro fever, is endemic to limited regions of South America that may expand due to the possible involvement of Aedes spp. mosquitoes in its transmission. Its effective control will require the accurate identification of infected individuals, which has been restricted to nucleic acid-based tests due to similarities with other emerging members of the Alphavirus genus of the Togaviridae family; both in structure and clinical symptoms. Serological tests have a more significant potential to expand testing at a reasonable cost, and their performance primarily reflects that of the antigen utilized to capture pathogen-specific antibodies. Here, we describe the assembly of a synthetic gene encoding multiple copies of antigenic determinants mapped from the nsP1, nsP2, E1, and E2 proteins of MAYV that readily expressed as a stable chimeric protein in bacteria. Its serological performance as the target in ELISAs revealed a high accuracy for detecting anti-MAYV IgM antibodies. No cross-reactivity was observed with serum from seropositive individuals for dengue, chikungunya, yellow fever, Zika, and other infectious diseases as well as healthy individuals. Our data suggest that this bioengineered antigen could be used to develop high-performance serological tests for MAYV infections.


Assuntos
Infecções por Alphavirus/diagnóstico , Alphavirus/imunologia , Epitopos/imunologia , Infecções por Togaviridae/diagnóstico , Aedes/virologia , Alphavirus/patogenicidade , Infecções por Alphavirus/imunologia , Infecções por Alphavirus/transmissão , Infecções por Alphavirus/virologia , Animais , Ensaio de Imunoadsorção Enzimática , Epitopos/genética , Epitopos/ultraestrutura , Feminino , Genes Sintéticos/genética , Genes Sintéticos/imunologia , Humanos , Imunoglobulina M/imunologia , Masculino , Testes Sorológicos , América do Sul/epidemiologia , Togaviridae/isolamento & purificação , Togaviridae/patogenicidade , Infecções por Togaviridae/imunologia , Infecções por Togaviridae/transmissão , Infecções por Togaviridae/virologia
3.
Sci Rep ; 10(1): 21431, 2020 12 08.
Artigo em Inglês | MEDLINE | ID: mdl-33293534

RESUMO

In the event of an unpredictable viral outbreak requiring high/maximum biosafety containment facilities (i.e. BSL3 and BSL4), X-ray irradiation has the potential to relieve pressures on conventional diagnostic bottlenecks and expediate work at lower containment. Guided by Monte Carlo modelling and in vitro 1-log10 decimal-reduction value (D-value) predictions, the X-ray photon energies required for the effective inactivation of zoonotic viruses belonging to the medically important families of Flaviviridae, Nairoviridae, Phenuiviridae and Togaviridae are demonstrated. Specifically, it is shown that an optimized irradiation approach is attractive for use in a multitude of downstream detection and functional assays, as it preserves key biochemical and immunological properties. This study provides evidence that X-ray irradiation can support emergency preparedness, outbreak response and front-line diagnostics in a safe, reproducible and scalable manner pertinent to operations that are otherwise restricted to higher containment BSL3 or BSL4 laboratories.


Assuntos
Vírus de RNA/fisiologia , RNA Viral/genética , Inativação de Vírus , Raios X/efeitos adversos , Animais , Chlorocebus aethiops , Defesa Civil , Contenção de Riscos Biológicos , Células Alimentadoras , Humanos , Método de Monte Carlo , Nairovirus/fisiologia , Nairovirus/efeitos da radiação , Vírus de RNA/efeitos da radiação , RNA Viral/efeitos da radiação , Análise de Sequência de RNA , Togaviridae/fisiologia , Togaviridae/efeitos da radiação , Células Vero , Zoonoses Virais/prevenção & controle , Zika virus/fisiologia , Zika virus/efeitos da radiação
4.
Viruses ; 12(11)2020 11 16.
Artigo em Inglês | MEDLINE | ID: mdl-33207797

RESUMO

Delivering transgenes to human cells through transduction with viral vectors constitutes one of the most encouraging approaches in gene therapy. Lentivirus-derived vectors are among the most promising vectors for these approaches. When the genetic modification of the cell must be performed in vivo, efficient specific transduction of the cell targets of the therapy in the absence of off-targeting constitutes the Holy Grail of gene therapy. For viral therapy, this is largely determined by the characteristics of the surface proteins carried by the vector. In this regard, an important property of lentiviral vectors is the possibility of being pseudotyped by envelopes of other viruses, widening the panel of proteins with which they can be armed. Here, we discuss how this is achieved at the molecular level and what the properties and the potentialities of the different envelope proteins that can be used for pseudotyping these vectors are.


Assuntos
Terapia Genética , Vetores Genéticos , Genoma Viral , Lentivirus/genética , Proteínas do Envelope Viral/genética , Genômica , Humanos , Biologia Molecular , Paramyxovirinae/genética , Paramyxovirinae/metabolismo , Rhabdoviridae/genética , Rhabdoviridae/metabolismo , Togaviridae/genética , Togaviridae/metabolismo , Transdução Genética , Proteínas do Envelope Viral/metabolismo , Internalização do Vírus
5.
Parasit Vectors ; 13(1): 508, 2020 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-33032645

RESUMO

BACKGROUND: Mayaro virus (Togaviridae) is an endemic arbovirus of the Americas with epidemiological similarities with the agents of other more prominent diseases such as dengue (Flaviviridae), Zika (Flaviviridae), and chikungunya (Togaviridae). It is naturally transmitted in a sylvatic/rural cycle by Haemagogus spp., but, potentially, it could be incorporated and transmitted in an urban cycle by Aedes aegypti, a vector widely disseminated in the Americas. METHODS: The Mayaro arbovirus dynamics was simulated mathematically in the colombian population in the eight biogeographical provinces, bearing in mind the vector's population movement between provinces through passive transport via truck cargo. The parameters involved in the virus epidemiological dynamics, as well as the vital rates of Ae. aegypti in each of the biogeographical provinces were obtained from the literature. These data were included in a meta-population model in differential equations, represented by a model structured by age for the dynamic population of Ae. aegypti combined with an epidemiological SEI/SEIR-type model. In addition, the model was incorporated with a term of migration to represent the connectivity between the biogeographical provinces. RESULTS: The vital rates and the development cycle of Ae. aegypti varied between provinces, having greater biological potential between 23 °C and 28 °C in provinces of Imerí, biogeographical Chocó, and Magdalena, with respect to the North-Andean Moorland (9.33-21.38 °C). Magdalena and Maracaibo had the highest flow of land cargo. The results of the simulations indicate that Magdalena, Imerí, and biogeographical Chocó would be the most affected regarding the number of cases of people infected by Mayaro virus over time. CONCLUSIONS: The temperature in each of the provinces influences the local population dynamics of Ae. aegypti and passive migration via transport of land cargo plays an important role on how the Mayaro virus would be disseminated in the human population. Once this arbovirus begins an urban cycle, the most-affected departments would be Antioquia, Santander, Norte de Santander, Cesar (Provinces of Magdalena), and Valle del Cauca, and Chocó (biogeographical province of Chocó), which is why vector control programmes must aim their efforts at these departments and include some type of vector control to the transport of land cargo to avoid a future Mayaro epidemic.


Assuntos
Aedes , Infecções por Alphavirus/transmissão , Modelos Teóricos , Togaviridae , Aedes/virologia , Infecções por Alphavirus/epidemiologia , Animais , Arbovírus , Colômbia/epidemiologia , Humanos , Modelos Estatísticos , Controle de Mosquitos , Mosquitos Vetores/virologia , Dinâmica Populacional/estatística & dados numéricos
6.
PLoS Pathog ; 16(6): e1008513, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32555677

RESUMO

The ability of the endosymbiont Wolbachia pipientis to restrict RNA viruses is presently being leveraged to curb global transmission of arbovirus-induced diseases. Past studies have shown that virus replication is limited early in arthropod cells colonized by the bacterium, although it is unclear if this phenomenon is replicated in mosquito cells that first encounter viruses obtained through a vertebrate blood meal. Furthermore, these cellular events neither explain how Wolbachia limits dissemination of viruses between mosquito tissues, nor how it prevents transmission of infectious viruses from mosquitoes to vertebrate host. In this study, we try to address these issues using an array of mosquito cell culture models, with an additional goal being to identify a common viral target for pathogen blocking. Our results establish the viral RNA as a cellular target for Wolbachia-mediated inhibition, with the incoming viral RNA experiencing rapid turnover following internalization in cells. This early block in replication in mosquito cells initially infected by the virus thus consequently reduces the production of progeny viruses from these same cells. However, this is not the only contributor to pathogen blocking. We show that the presence of Wolbachia reduces the per-particle infectivity of progeny viruses on naïve mosquito and vertebrate cells, consequently limiting virus dissemination and transmission, respectively. Importantly, we demonstrate that this aspect of pathogen blocking is independent of any particular Wolbachia-host association and affects viruses belonging to Togaviridae and Flaviviridae families of RNA viruses. Finally, consistent with the idea of the viral RNA as a target, we find that the encapsidated virion RNA is less infectious for viruses produced from Wolbachia-colonized cells. Collectively, our findings present a common mechanism of pathogen blocking in mosquitoes that establish a link between virus inhibition in the cell to virus dissemination and transmission.


Assuntos
Flavivirus/metabolismo , RNA Viral/metabolismo , Togaviridae/metabolismo , Wolbachia/metabolismo , Aedes , Animais , Linhagem Celular , Chlorocebus aethiops , Cricetinae , Drosophila melanogaster , Flavivirus/genética , RNA Viral/genética , Togaviridae/genética , Células Vero , Wolbachia/genética
7.
Am J Trop Med Hyg ; 102(1): 195-201, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31769401

RESUMO

Tonate virus (TONV) is an arbovirus discovered in 1973 in French Guiana (FG) belonging to the Venezuelan equine encephalitis virus complex, Alphavirus genus. Only few publications and cases have been reported in FG. The objectives of the present study were to describe the clinical picture of TONV and to compare its presentation with that of dengue virus (DENV). A retrospective study was performed in Cayenne hospital from 2003 to 2016 including all patients exclusively positive for TONV IgM and not for other alphaviruses. They were classified as high probability: typical clinical picture of arbovirus infection (i.e., fever, chills, headaches, muscle, and joint pains) and IgM seroconversion; medium probability: typical clinical picture + single positive IgM on a unique serum sample without control; and low probability: atypical clinical picture of infection and single positive IgM. Only patients with high and medium probability were included in the analysis and compared with a gender- and age-matched control group of DENV diagnosed by NS1 antigen (two controls per case). During the study period, 45 cases of TONV were included and compared with 90 cases of DENV. Twenty-eight (62.2%) were men; the median age was 34 years (IQ [22-49]). In the bivariate analysis, variables significantly associated with TONV versus DENV were the presence of cough (33.3% versus 10.3%) and anemia (32.5% versus 11.1%) and the absence of nausea (4.4% versus 32.2%), rash (2.2% versus 27.4%), fatigue (17.8% versus 41.0%), anorexia (6.7% versus 30.1%), muscle pain (42.2% versus 61.4%), headache (53.3% versus 70.8%), leukopenia (9.8% versus 44.4), and lymphopenia (42.5% versus 89.9%). There were no cases with severe neurological involvement, and there were no deaths. Tonate virus may be evoked as a cause of fever in patients living or returning from the Amazonian area. Positive TONV IgM does not prove the diagnosis and should not preclude from searching for alternative infectious diagnoses.


Assuntos
Dengue/diagnóstico , Dengue/patologia , Infecções por Togaviridae/diagnóstico , Infecções por Togaviridae/patologia , Togaviridae , Adolescente , Adulto , Idoso , Estudos de Casos e Controles , Criança , Pré-Escolar , Dengue/epidemiologia , Feminino , Guiana Francesa/epidemiologia , Humanos , Lactente , Masculino , Meningite Viral/epidemiologia , Meningite Viral/virologia , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
8.
PLoS Pathog ; 15(9): e1007934, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31479495

RESUMO

Mayaro virus (MAYV) is an arbovirus that circulates in Latin America and is emerging as a potential threat to public health. Infected individuals develop Mayaro fever, a severe inflammatory disease characterized by high fever, rash, arthralgia, myalgia and headache. The disease is often associated with a prolonged arthralgia mediated by a chronic inflammation that can last months. Although the immune response against other arboviruses, such as chikungunya virus (CHIKV), dengue virus (DENV) and Zika virus (ZIKV), has been extensively studied, little is known about the pathogenesis of MAYV infection. In this study, we established models of MAYV infection in macrophages and in mice and found that MAYV can replicate in bone marrow-derived macrophages and robustly induce expression of inflammasome proteins, such as NLRP3, ASC, AIM2, and Caspase-1 (CASP1). Infection performed in macrophages derived from Nlrp3-/-, Aim2-/-, Asc-/-and Casp1/11-/-mice indicate that the NLRP3, but not AIM2 inflammasome is essential for production of inflammatory cytokines, such as IL-1ß. We also determined that MAYV triggers NLRP3 inflammasome activation by inducing reactive oxygen species (ROS) and potassium efflux. In vivo infections performed in inflammasome-deficient mice indicate that NLRP3 is involved with footpad swelling, inflammation and pain, establishing a role of the NLRP3 inflammasome in the MAYV pathogenesis. Accordingly, we detected higher levels of caspase1-p20, IL-1ß and IL-18 in the serum of MAYV-infected patients as compared to healthy individuals, supporting the participation of the NLRP3-inflammasome during MAYV infection in humans.


Assuntos
Infecções por Alphavirus/imunologia , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Adulto , Idoso , Infecções por Alphavirus/metabolismo , Animais , Proteínas de Transporte/metabolismo , Caspase 1/metabolismo , Vírus Chikungunya/metabolismo , Vírus da Dengue/metabolismo , Modelos Animais de Doenças , Feminino , Humanos , Inflamassomos/imunologia , Inflamação/metabolismo , Macrófagos/imunologia , Macrófagos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Pessoa de Meia-Idade , Proteína 3 que Contém Domínio de Pirina da Família NLR/imunologia , Espécies Reativas de Oxigênio/metabolismo , Togaviridae/patogenicidade , Zika virus/metabolismo
9.
Recurso na Internet em Português | LIS - Localizador de Informação em Saúde, LIS-bvsms | ID: lis-46581

RESUMO

A Febre do Mayaro é uma doença infecciosa febril aguda, cujo quadro clínico geralmente é de curso benigno, semelhante à Dengue e à Chikungunya. A Febre do Mayaro compõe a lista nacional de doenças de notificação compulsória imediata, conforme Portaria de Consolidação nº 4, de 28 de setembro de 2017.


Assuntos
Dengue , Febre de Chikungunya , Infecções por Arbovirus , Togaviridae , Infecções por Alphavirus , Febre Amarela
10.
Molecules ; 24(8)2019 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-31010179

RESUMO

Silymarin flavonolignans are well-known agents that typically possess antioxidative, anti-inflammatory, and hepatoprotective functions. Recent studies have also documented the antiviral activities of silymarin and its derivatives against several viruses, including the flaviviruses (hepatitis C virus and dengue virus), togaviruses (Chikungunya virus and Mayaro virus), influenza virus, human immunodeficiency virus, and hepatitis B virus. This review will describe some of the latest preclinical and clinical studies detailing the antiviral profiles of silymarin and its derivatives, and discuss their relevance for antiviral drug development.


Assuntos
Antivirais/farmacologia , Flavonolignanos/farmacologia , Silimarina/farmacologia , Antivirais/química , Vírus Chikungunya/efeitos dos fármacos , Vírus da Dengue/efeitos dos fármacos , Flavivirus/efeitos dos fármacos , Flavonolignanos/química , HIV/efeitos dos fármacos , Hepacivirus/efeitos dos fármacos , Silimarina/química , Togaviridae/efeitos dos fármacos
11.
J Mol Biol ; 431(12): 2283-2297, 2019 05 31.
Artigo em Inglês | MEDLINE | ID: mdl-30998933

RESUMO

Mayaro virus (MAYV) is a member of Togaviridae family, which also includes Chikungunya virus as a notorious member. MAYV recently emerged in urban areas of the Americas, and this emergence emphasized the current paucity of knowledge about its replication cycle. The macro domain (MD) of MAYV belongs to the N-terminal region of its non-structural protein 3, part of the replication complex. Here, we report the first structural and dynamical characterization of a previously unexplored Alphavirus MD investigated through high-resolution NMR spectroscopy, along with data on its ligand selectivity and binding properties. The structural analysis of MAYV MD reveals a typical "macro" (ßßαßßαßαßα) fold for this polypeptide, while NMR-driven interaction studies provide in-depth insights into MAYV MD-ligand adducts. NMR data in concert with thermodynamics and biochemical studies provide convincing experimental evidence for preferential binding of adenosine diphosphate ribose (ADP-r) and adenine-rich RNAs to MAYV MD, thus shedding light on the structure-function relationship of a previously unexplored viral MD. The emerging differences with any other related MD are expected to enlighten distinct functions.


Assuntos
Nucleotídeos/metabolismo , RNA/metabolismo , Infecções por Togaviridae/virologia , Togaviridae/metabolismo , Proteínas não Estruturais Virais/metabolismo , Adenosina Difosfato Ribose/metabolismo , Humanos , Modelos Moleculares , Ligação Proteica , Domínios Proteicos , Infecções por Togaviridae/metabolismo , Proteínas não Estruturais Virais/química
12.
PLoS Negl Trop Dis ; 13(2): e0007042, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30730897

RESUMO

Mayaro virus (MAYV) of the genus alphavirus is a mosquito-transmitted emerging infectious disease that causes an acute febrile illness, rash, headaches, and nausea that may turn into incapacitating, persistent arthralgias in some victims. Since its discovery in Trinidad in 1954, cases of MAYV infection have largely been confined there and to the northern countries of South America, but recently, MAYV cases have been reported in some island nations in the Caribbean Sea. Accompanying these reports is evidence that new vectors, including Aedes spp. mosquitos, recently implicated in the global spread of Zika and chikungunya viruses, are competent for MAYV transmission, which, if true, could facilitate the spread of MAYV beyond its current range. Despite its status as an emerging virus, there are no licensed vaccines to prevent MAYV infection nor therapeutics to treat it. Here, we describe the development and testing of a novel DNA vaccine, scMAYV-E, that encodes a synthetically-designed consensus MAYV envelope sequence. In vivo electroporation-enhanced immunization of mice with this vaccine induced potent humoral responses including neutralizing antibodies as well as robust T-cell responses to multiple epitopes in the MAYV envelope. Importantly, these scMAYV-E-induced immune responses protected susceptible mice from morbidity and mortality following a MAYV challenge.


Assuntos
Doenças Transmissíveis Emergentes/prevenção & controle , Infecções por Togaviridae/prevenção & controle , Togaviridae/classificação , Vacinas Virais/imunologia , Transferência Adotiva , Animais , Sobrevivência Celular , Chlorocebus aethiops , Doenças Transmissíveis Emergentes/virologia , Feminino , Engenharia Genética , Células HEK293 , Humanos , Macrófagos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Receptor de Interferon alfa e beta/genética , Baço/citologia , Vacinas de DNA/imunologia , Células Vero
13.
PLoS One ; 14(1): e0209993, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30640927

RESUMO

The objective of this study was to characterize the prevalence of viral encephalitis due to arbovirus infection of the Togaviridae and Flaviviridae families in São Paulo, Brazil. A total of 500 cerebrospinal fluid (CSF) samples collected between August 2012 and January 2013, from patients with symptoms of acute encephalitis were analyzed. Findings suggestive of viral encephalitis-elevations in cell concentration, glucose and total protein-were observed in 234 (46.8%) samples, designated as Group 1. The remaining 266 samples comprised Group 2. All samples were tested for Flaviviruses (dengue virus 1, 2, 3 and 4, yellow fever virus and West Nile virus), Alphavirus (NS5 region) and enterovirus by RT- PCR and for herpesviruses and enteroviruses using CLART-Entherpex. A presumptive viral etiological agent was detected in 26 samples (5.2%), 18 (8.0%) in Group 1 and 8 (3.0%) in Group 2. In Group 1 human herpesviruses were detected in 9 cases, enteroviruses in 7 cases, dengue viruses (DENV) in 2 CSFs and St. Louis encephalitis virus (SLEV) in one case. In Group 2 there were 3 CSFs positive for human herpesviruses, 2 for enteroviruses, 2 for DENV and 1 for SLEV. Detection of arboviruses, even though present in a minority of infected patients, identifies these viruses as a probable etiological agent of encephalitis. This is of special concern in regions where this class of viruses is endemic and has been linked to other recent epidemics.


Assuntos
Arbovírus/isolamento & purificação , Encefalite Viral/epidemiologia , Encefalite Viral/virologia , Flaviviridae/isolamento & purificação , Togaviridae/isolamento & purificação , Adolescente , Adulto , Brasil/epidemiologia , Criança , Pré-Escolar , Estudos Transversais , Vírus da Dengue/isolamento & purificação , Vírus da Encefalite de St. Louis/isolamento & purificação , Encefalite Viral/líquido cefalorraquidiano , Enterovirus/isolamento & purificação , Feminino , Herpesviridae/isolamento & purificação , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Epidemiologia Molecular , Adulto Jovem
14.
Virus Genes ; 55(2): 127-137, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30632016

RESUMO

The advancement in high-throughput sequencing technology and bioinformatics tools has spurred a new age of viral discovery. Arthropods is the largest group of animals and has shown to be a major reservoir of different viruses, including a group known as insect-specific viruses (ISVs). The majority of known ISVs have been isolated from mosquitoes and shown to belong to viral families associated with animal arbovirus pathogens, such as Flaviviridae, Togaviridae and Phenuiviridae. These insect-specific viruses have a strict tropism and are unable to replicate in vertebrate cells, these properties are interesting for many reasons. One is that these viruses could potentially be utilised as biocontrol agents using a similar strategy as for Wolbachia. Mosquitoes infected with the viral agent could have inferior vectorial capacity of arboviruses resulting in a decrease of circulating arboviruses of public health importance. Moreover, insect-specific viruses are thought to be ancestral to arboviruses and could be used to study the evolution of the switch from single-host to dual-host. In this review, we discuss new discoveries and hypothesis in the field of arboviruses and insect-specific viruses.


Assuntos
Arbovírus/genética , Vírus de Insetos/genética , Viroses/genética , Replicação Viral/genética , Animais , Arbovírus/patogenicidade , Culicidae/genética , Culicidae/virologia , Flaviviridae/genética , Flaviviridae/patogenicidade , Sequenciamento de Nucleotídeos em Larga Escala , Insetos Vetores/virologia , Vírus de Insetos/patogenicidade , Controle Biológico de Vetores , Especificidade da Espécie , Togaviridae/genética , Togaviridae/patogenicidade , Viroses/virologia
15.
Braz J Microbiol ; 49 Suppl 1: 260-261, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30166269

RESUMO

Rio Negro virophage (RNV) was co-isolated with a strain of mimivirus named sambavirus, from Brazilian Amazon. We report the near complete genome sequence of RNV, the first virophage isolated in Brazil. We also present new microscopical data demonstrating that RNV particles have similar dimensions to that described to sputnik virophages.


Assuntos
Acanthamoeba/virologia , Genoma Viral , Togaviridae/genética , Virófagos/genética , Brasil , Microscopia Eletrônica de Transmissão , Fases de Leitura Aberta , Filogenia , Togaviridae/isolamento & purificação , Togaviridae/ultraestrutura , Virófagos/isolamento & purificação , Virófagos/ultraestrutura
16.
MULTIMED ; 22(3)2018. ilus
Artigo em Espanhol | CUMED | ID: cum-74697

RESUMO

La infección por virus de la rubeola es benigna, sin embargo, si se contrae durante el embarazo pueden presentarse malformaciones congénitas. Se presenta un caso de gestante portadora de rubeola en el primer trimestre de la gestación (no vacunada); en el segundo trimestre se toma muestra de sangre y se detectó titulación de anticuerpos IgM e IgG contra la rubeola; y el neonato desde el nacimiento presenta manifestaciones como crecimiento intrauterino retardado, ictericia precoz, cataratas congénitas (bilateral) y soplo cardiaco y que 5 días después en estudio ecocardiográfico se concluye como una cardiopatía congénita (estenosis de la arteria pulmonar); se confirma con los títulos elevados de IgG e IgM en el neonato lo cual evidencia un caso confirmado, esta infección prenatal es evitable por medio de la inmunización contra la rubeola en la infancia o en la mujer adolescente(AU)


Rubella virus infection is benign, however, congenital malformations can occur if contracted during pregnancy. We present a case of a pregnant woman with rubella in the first trimester of gestation (not vaccinated); in the second trimester a blood sample was taken and IgM and IgG antibodies against rubella were detected; and the newborn from birth has manifestations such as delayed intrauterine growth, early jaundice, congenital cataracts (bilateral) and heart murmur and that 5 days later in echocardiographic study concludes as a congenital heart disease (stenosis of the pulmonary artery); it is confirmed with the elevated IgG and IgM titres in the neonate, which evidences a confirmed case, this prenatal infection is preventable by means of immunization against rubella in childhood or in adolescent women(EU)


Assuntos
Humanos , Feminino , Gravidez , Adulto Jovem , Síndrome da Rubéola Congênita , Rubéola (Sarampo Alemão) , Togaviridae/patogenicidade , Imunização
17.
Sci Rep ; 8(1): 6889, 2018 05 02.
Artigo em Inglês | MEDLINE | ID: mdl-29720714

RESUMO

Wolbachia, an intracellular endosymbiont present in up to 70% of all insect species, has been suggested as a sustainable strategy for the control of arboviruses such as Dengue, Zika and Chikungunya. As Mayaro virus outbreaks have also been reported in Latin American countries, the objective of this study was to evaluate the vector competence of Brazilian field-collected Ae. aegypti and the impact of Wolbachia (wMel strain) upon this virus. Our in vitro studies with Aag2 cells showed that Mayaro virus can rapidly multiply, whereas in wMel-infected Aag2 cells, viral growth was significantly impaired. In addition, C6/36 cells seem to have alterations when infected by Mayaro virus. In vivo experiments showed that field-collected Ae. aegypti mosquitoes are highly permissive to Mayaro virus infection, and high viral prevalence was observed in the saliva. On the other hand, Wolbachia-harboring mosquitoes showed significantly impaired capability to transmit Mayaro virus. Our results suggest that the use of Wolbachia-harboring mosquitoes may represent an effective mechanism for the reduction of Mayaro virus transmission throughout Latin America.


Assuntos
Aedes/virologia , Mosquitos Vetores/virologia , Togaviridae/fisiologia , Replicação Viral , Wolbachia/patogenicidade , Aedes/microbiologia , Animais , Linhagem Celular , Células Cultivadas , Feminino , Humanos , Mosquitos Vetores/microbiologia , Simbiose , Togaviridae/patogenicidade , Infecções por Togaviridae/transmissão
18.
J Gen Virol ; 99(6): 761-762, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29745869

RESUMO

The Togaviridae is a family of small, enveloped viruses with single-stranded, positive-sense RNA genomes of 10-12 kb. Within the family, the genus Alphavirus includes a large number of diverse species, while the genus Rubivirus includes the single species Rubella virus. Most alphaviruses are mosquito-borne and are pathogenic in their vertebrate hosts. Many are important human and veterinary pathogens (e.g. chikungunya virus and eastern equine encephalitis virus). Rubella virus is transmitted by respiratory routes among humans. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the taxonomy of the Togaviridae, which is available at www.ictv.global/report/togaviridae.


Assuntos
Togaviridae/classificação , Togaviridae/genética , Animais , Vírus Chikungunya/genética , Genoma Viral , Humanos , Vírus da Rubéola/genética , Togaviridae/patogenicidade
19.
Trends Microbiol ; 26(7): 598-610, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29268982

RESUMO

Viruses from the Coronaviridae, Togaviridae, and Hepeviridae families ​all contain genes that encode a conserved protein domain, called a macrodomain; however, the role of this domain during infection has remained enigmatic. The recent discovery that mammalian macrodomain proteins enzymatically remove ADP-ribose, a common post-translation modification, from proteins has led to an outburst of studies describing both the enzymatic activity and function of viral macrodomains. These new studies have defined these domains as de-ADP-ribosylating enzymes, which indicates that these viruses have evolved to counteract antiviral ADP-ribosylation, likely mediated by poly-ADP-ribose polymerases (PARPs). Here, we comprehensively review this rapidly expanding field, describing the structures and enzymatic activities of viral macrodomains, and discussing their roles in viral replication and pathogenesis.


Assuntos
Domínios Proteicos , Proteínas não Estruturais Virais/química , Replicação Viral , Vírus/genética , Vírus/patogenicidade , Adenosina Difosfato Ribose/metabolismo , Coronaviridae/genética , Coronaviridae/patogenicidade , Hepevirus/genética , Hepevirus/patogenicidade , Histonas , Poli(ADP-Ribose) Polimerases , Processamento de Proteína Pós-Traducional , Togaviridae/genética , Togaviridae/patogenicidade , Proteínas não Estruturais Virais/metabolismo , Vírus/enzimologia
20.
J Virol ; 92(6)2018 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-29263275

RESUMO

Oncolytic virotherapy is an emerging treatment modality that uses replication-competent viruses to destroy cancer cells. M1 is a naturally occurring alphavirus (Togaviridae) which shows potent oncolytic activities against many cancers. Accumulation of unfolded proteins during virus replication leads to a transcriptional/translational response known as the unfolded protein response (UPR), which might counteract the antitumor effect of the oncolytic virus. In this report, we show that either pharmacological or biological inhibition of IRE1α or PERK, but not ATF6, substantially increases the oncolytic effects of the M1 virus. Moreover, inhibition of IRE1α blocks M1 virus-induced autophagy, which restricts the antitumor effects of the M1 virus through degradation of viral protein, in glioma cells. In addition, IRE1α suppression significantly increases the oncolytic effect of M1 virus in an orthotopic glioma model. From a molecular pathology study, we found that IRE1α is expressed at lower levels in higher-grade gliomas, suggesting greater antitumor efficacy of the oncolytic virus M1. Taken together, these findings illustrate a defensive mechanism of glioma cells against the oncolytic virus M1 and identify possible approaches to enhance the oncolytic viral protein accumulation and the subsequent lysis of tumor cells.IMPORTANCE Although oncolytic virotherapy is showing great promise in clinical applications, not all patients are benefiting. Identifying inhibitory signals in refractory cancer cells for each oncolytic virus would provide a good chance to increase the therapeutic effect. Here we describe that infection with the oncolytic virus M1 triggers the unfolded protein response (UPR) and subsequent autophagy, while blocking the UPR-autophagy axis significantly potentiates the antitumor efficacy of M1 in vitro and in vivo A survey of cancer tissue banks revealed that IRE1α, a key element in the UPR pathway, is commonly downregulated in higher-grade human gliomas, suggesting favorable prospects for the application of M1. Our work provides a potential predictor and target for enhancement of the therapeutic effectiveness of the M1 virus. We predict that the mechanism-based combination therapy will promote cancer virotherapy in the future.


Assuntos
Autofagia/imunologia , Endorribonucleases/deficiência , Glioma/terapia , Proteínas de Neoplasias/deficiência , Terapia Viral Oncolítica , Vírus Oncolíticos , Proteínas Serina-Treonina Quinases/deficiência , Togaviridae , Animais , Autofagia/genética , Linhagem Celular Tumoral , Chlorocebus aethiops , Cricetinae , Endorribonucleases/imunologia , Feminino , Glioma/genética , Glioma/imunologia , Humanos , Camundongos Endogâmicos BALB C , Camundongos Nus , Proteínas de Neoplasias/imunologia , Proteínas Serina-Treonina Quinases/imunologia , Resposta a Proteínas não Dobradas/genética , Resposta a Proteínas não Dobradas/imunologia , Células Vero , Ensaios Antitumorais Modelo de Xenoenxerto
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