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  1 / 216 MEDLINE  
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[PMID]:28449693
[Au] Autor:Mariën J; Borremans B; Gryseels S; Soropogui B; De Bruyn L; Bongo GN; Becker-Ziaja B; de Bellocq JG; Günther S; Magassouba N; Leirs H; Fichet-Calvet E
[Ad] Endereço:Evolutionary Ecology Group, University of Antwerp, Antwerp, Belgium. Joachim.marien@uantwerpen.be.
[Ti] Título:No measurable adverse effects of Lassa, Morogoro and Gairo arenaviruses on their rodent reservoir host in natural conditions.
[So] Source:Parasit Vectors;10(1):210, 2017 Apr 27.
[Is] ISSN:1756-3305
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: In order to optimize net transmission success, parasites are hypothesized to evolve towards causing minimal damage to their reservoir host while obtaining high shedding rates. For many parasite species however this paradigm has not been tested, and conflicting results have been found regarding the effect of arenaviruses on their rodent host species. The rodent Mastomys natalensis is the natural reservoir host of several arenaviruses, including Lassa virus that is known to cause Lassa haemorrhagic fever in humans. Here, we examined the effect of three arenaviruses (Gairo, Morogoro and Lassa virus) on four parameters of wild-caught Mastomys natalensis: body mass, head-body length, sexual maturity and fertility. After correcting for the effect of age, we compared these parameters between arenavirus-positive (arenavirus RNA or antibody) and negative animals using data from different field studies in Guinea (Lassa virus) and Tanzania (Morogoro and Gairo viruses). RESULTS: Although the sample sizes of our studies (1297, 749 and 259 animals respectively) were large enough to statistically detect small differences in body conditions, we did not observe any adverse effects of these viruses on Mastomys natalensis. We did find that sexual maturity was significantly positively related with Lassa virus antibody presence until a certain age, and with Gairo virus antibody presence in general. Gairo virus antibody-positive animals were also significantly heavier and larger than antibody-free animals. CONCLUSION: Together, these results suggest that the pathogenicity of arenaviruses is not severe in M. natalensis, which is likely to be an adaptation of these viruses to optimize transmission success. They also suggest that sexual behaviour might increase the probability of M. natalensis to become infected with arenaviruses.
[Mh] Termos MeSH primário: Infecções por Arenaviridae/veterinária
Arenavirus/isolamento & purificação
Portador Sadio/veterinária
Vetores de Doenças
Murinae/fisiologia
Murinae/virologia
[Mh] Termos MeSH secundário: Animais
Infecções por Arenaviridae/patologia
Infecções por Arenaviridae/virologia
Portador Sadio/patologia
Portador Sadio/virologia
Guiné
Tanzânia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180109
[Lr] Data última revisão:
180109
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170429
[St] Status:MEDLINE
[do] DOI:10.1186/s13071-017-2146-0


  2 / 216 MEDLINE  
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[PMID]:28953976
[Au] Autor:Malmlov A; Seetahal J; Carrington C; Ramkisson V; Foster J; Miazgowicz KL; Quackenbush S; Rovnak J; Negrete O; Munster V; Schountz T
[Ad] Endereço:Arthropod-borne and Infectious Disease Laboratory, Department of Microbiology, Immunology and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, Colorado, United States of America.
[Ti] Título:Serological evidence of arenavirus circulation among fruit bats in Trinidad.
[So] Source:PLoS One;12(9):e0185308, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Tacaribe virus (TCRV) was isolated in the 1950s from artibeus bats captured on the island of Trinidad. The initial characterization of TCRV suggested that artibeus bats were natural reservoir hosts. However, nearly 60 years later experimental infections of Jamaican fruit bats (Artibeus jamaicensis) resulted in fatal disease or clearance, suggesting artibeus bats may not be a reservoir host. To further evaluate the TCRV reservoir host status of artibeus bats, we captured bats of six species in Trinidad for evidence of infection. Bats of all four fruigivorous species captured had antibodies to TCRV nucleocapsid, whereas none of the insectivore or nectarivore species did. Many flat-faced fruit-eating bats (A. planirostris) and great fruit-eating bats (A. literatus) were seropositive by ELISA and western blot to TCRV nucleocapsid antigen, as were two of four Seba's fruit bats (Carollia perspicillata) and two of three yellow-shouldered fruit bats (Sturnira lilium). Serum neutralization tests failed to detect neutralizing antibodies to TCRV from these bats. TCRV RNA was not detected in lung tissues or lung homogenates inoculated onto Vero cells. These data indicate that TCRV or a similar arenavirus continues to circulate among fruit bats of Trinidad but there was no evidence of persistent infection, suggesting artibeus bats are not reservoir hosts.
[Mh] Termos MeSH primário: Arenavirus/fisiologia
Quirópteros/sangue
Quirópteros/virologia
Testes Sorológicos
[Mh] Termos MeSH secundário: Animais
Arenavirus/isolamento & purificação
Geografia
Estudos Soroepidemiológicos
Trinidad e Tobago
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171016
[Lr] Data última revisão:
171016
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170928
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0185308


  3 / 216 MEDLINE  
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[PMID]:28777079
[Au] Autor:Yekwa E; Khourieh J; Canard B; Papageorgiou N; Ferron F
[Ad] Endereço:CNRS, AFMB UMR 7257, 13288 Marseille, France.
[Ti] Título:Activity inhibition and crystal polymorphism induced by active-site metal swapping.
[So] Source:Acta Crystallogr D Struct Biol;73(Pt 8):641-649, 2017 Aug 01.
[Is] ISSN:2059-7983
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The Arenaviridae family is one of the two RNA viral families that encode a 3'-5' exonuclease in their genome. An exonuclease domain is found in the Arenaviridae nucleoprotein and targets dsRNA specifically. This domain is directly involved in suppression of innate immunity in the host cell. Like most phosphate-processing enzymes, it requires a divalent metal ion such as Mg (or Mn ) as a cofactor to catalyse nucleotide-cleavage and nucleotide-transfer reactions. On the other hand, calcium (Ca ) inhibits this enzymatic activity, in spite of the fact that Mg and Ca present comparable binding affinities and biological availabilities. Here, the molecular and structural effects of the replacement of magnesium by calcium and its inhibition mechanism for phosphodiester cleavage, an essential reaction in the viral process of innate immunity suppression, are studied. Biochemical data and high-resolution structures of the Mopeia virus exonuclease domain complexed with each ion are reported for the first time. The consequences of the ion swap for the stability of the protein, the catalytic site and the functional role of a specific metal ion in enabling the catalytic cleavage of a dsRNA substrate are outlined.
[Mh] Termos MeSH primário: Arenavirus/química
Arenavirus/enzimologia
Exonucleases/química
Proteínas do Nucleocapsídeo/química
Nucleoproteínas/química
[Mh] Termos MeSH secundário: Infecções por Arenaviridae/virologia
Arenavirus/metabolismo
Sítios de Ligação
Cálcio/metabolismo
Domínio Catalítico
Cátions Bivalentes/metabolismo
Cristalização
Cristalografia por Raios X
Exonucleases/metabolismo
Magnésio/metabolismo
Manganês/metabolismo
Simulação de Acoplamento Molecular
Proteínas do Nucleocapsídeo/metabolismo
Nucleoproteínas/metabolismo
Domínios Proteicos
RNA Viral/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cations, Divalent); 0 (Nucleocapsid Proteins); 0 (Nucleoproteins); 0 (RNA, Viral); 42Z2K6ZL8P (Manganese); EC 3.1.- (Exonucleases); I38ZP9992A (Magnesium); SY7Q814VUP (Calcium)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170926
[Lr] Data última revisão:
170926
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170805
[St] Status:MEDLINE
[do] DOI:10.1107/S205979831700866X


  4 / 216 MEDLINE  
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[PMID]:28329945
[Au] Autor:Li K; Lin XD; Li MH; Wang MR; Sun XY; Zhang YZ
[Ad] Endereço:Department of Zoonoses, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China.
[Ti] Título:[Genomic analysis of Wenzhou virus in rodents from Zhejiang province].
[So] Source:Zhonghua Liu Xing Bing Xue Za Zhi;38(3):384-387, 2017 Mar 10.
[Is] ISSN:0254-6450
[Cp] País de publicação:China
[La] Idioma:chi
[Ab] Resumo:Arenavirus is a negative single-stranded RNA virus and an important human pathogen, mainly harbored and transmitted by rodents, causing severe diseases, including hemorrhagic fever and encephalitis. Following the discovery of a novel pathogenic arenavirus (Wenzhou virus, WENV), the prevalence of WENV in local small rodents was investigated. By using RT-PCR, WENV was screened in 48 and 156 rodents sampled from Wenzhou and Longquan, respectively. Consequently, WENV was detected in 5 (10.41%) rodents sampled from Wenzhou. However, no WENV was identified in all the rodents sampled from Longquan. Genetic analysis of complete genome sequences indicated that 4 of 5 virus strains were closely related to the known Wenzhou viruses with high homology. Especially, the L and S segments of Wencheng-Rn-288 strain shared homology of 87.5% and 91.6% with other viruses, respectively. They formed a distinct lineage, suggesting that this strain might be a novel variant of WENV. Our results indicate that WENV has a high prevalence and high genetic diversity among rodents in Wenzhou. As the respiratory disease caused by WENV has been detected in Cambodia, it is necessary to strengthen the surveillance for WENV in China.
[Mh] Termos MeSH primário: Arenavirus/genética
Arenavirus/isolamento & purificação
Muridae/virologia
[Mh] Termos MeSH secundário: Animais
Arenavirus/classificação
Sequência de Bases
China
Genes Virais
Variação Genética
Genoma Viral
Genômica
Seres Humanos
Filogenia
Prevalência
Ratos
Roedores
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170904
[Lr] Data última revisão:
170904
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170323
[St] Status:MEDLINE
[do] DOI:10.3760/cma.j.issn.0254-6450.2017.03.022


  5 / 216 MEDLINE  
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[PMID]:28114434
[Au] Autor:Keller S; Hetzel U; Sironen T; Korzyukov Y; Vapalahti O; Kipar A; Hepojoki J
[Ad] Endereço:Institute of Veterinary Pathology, Vetsuisse Faculty, University of Zürich, Zürich, Switzerland.
[Ti] Título:Co-infecting Reptarenaviruses Can Be Vertically Transmitted in Boa Constrictor.
[So] Source:PLoS Pathog;13(1):e1006179, 2017 Jan.
[Is] ISSN:1553-7374
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Boid inclusion body disease (BIBD) is an often fatal disease affecting mainly constrictor snakes. BIBD has been associated with infection, and more recently with coinfection, by various reptarenavirus species (family Arenaviridae). Thus far BIBD has only been reported in captive snakes, and neither the incubation period nor the route of transmission are known. Herein we provide strong evidence that co-infecting reptarenavirus species can be vertically transmitted in Boa constrictor. In total we examined five B. constrictor clutches with offspring ranging in age from embryos over perinatal abortions to juveniles. The mother and/or father of each clutch were initially diagnosed with BIBD and/or reptarenavirus infection by detection of the pathognomonic inclusion bodies (IB) and/or reptarenaviral RNA. By applying next-generation sequencing and de novo sequence assembly we determined the "reptarenavirome" of each clutch, yielding several nearly complete L and S segments of multiple reptarenaviruses. We further confirmed vertical transmission of the co-infecting reptarenaviruses by species-specific RT-PCR from samples of parental animals and offspring. Curiously, not all offspring obtained the full parental "reptarenavirome". We extended our findings by an in vitro approach; cell cultures derived from embryonal samples rapidly developed IB and promoted replication of some or all parental viruses. In the tissues of embryos and perinatal abortions, viral antigen was sometimes detected, but IB were consistently seen only in the juvenile snakes from the age of 2 mo onwards. In addition to demonstrating vertical transmission of multiple species, our results also indicate that reptarenavirus infection induces BIBD over time in the offspring.
[Mh] Termos MeSH primário: Infecções por Arenaviridae/transmissão
Infecções por Arenaviridae/virologia
Arenavirus/genética
Boidae/virologia
[Mh] Termos MeSH secundário: Animais
Coinfecção
Sequenciamento de Nucleotídeos em Larga Escala
Imuno-Histoquímica
Corpos de Inclusão Viral
Transmissão Vertical de Doença Infecciosa
Filogenia
RNA Viral/análise
Reação em Cadeia da Polimerase Via Transcriptase Reversa
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (RNA, Viral)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170718
[Lr] Data última revisão:
170718
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170124
[St] Status:MEDLINE
[do] DOI:10.1371/journal.ppat.1006179


  6 / 216 MEDLINE  
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[PMID]:28076397
[Au] Autor:Gryseels S; Baird SJ; Borremans B; Makundi R; Leirs H; Goüy de Bellocq J
[Ad] Endereço:Evolutionary Ecology Group, Department of Biology, University of Antwerp, Antwerp, Belgium.
[Ti] Título:When Viruses Don't Go Viral: The Importance of Host Phylogeographic Structure in the Spatial Spread of Arenaviruses.
[So] Source:PLoS Pathog;13(1):e1006073, 2017 Jan.
[Is] ISSN:1553-7374
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Many emerging infections are RNA virus spillovers from animal reservoirs. Reservoir identification is necessary for predicting the geographic extent of infection risk, but rarely are taxonomic levels below the animal species considered as reservoir, and only key circumstances in nature and methodology allow intrinsic virus-host associations to be distinguished from simple geographic (co-)isolation. We sampled and genetically characterized in detail a contact zone of two subtaxa of the rodent Mastomys natalensis in Tanzania. We find two distinct arenaviruses, Gairo and Morogoro virus, each spatially confined to a single M. natalensis subtaxon, only co-occurring at the contact zone's centre. Inter-subtaxon hybridization at this centre and a continuum of quality habitat for M. natalensis show that both viruses have the ecological opportunity to spread into the other substaxon's range, but do not, strongly suggesting host-intrinsic barriers. Such barriers could explain why human cases of another M. natalensis-borne arenavirus, Lassa virus, are limited to West Africa.
[Mh] Termos MeSH primário: Arenavirus/classificação
Arenavirus/metabolismo
Reservatórios de Doenças/virologia
Murinae/virologia
Doenças dos Roedores/virologia
[Mh] Termos MeSH secundário: Animais
Arenavirus/fisiologia
Seres Humanos
Febre Lassa/virologia
Vírus Lassa/fisiologia
Filogeografia
Especificidade da Espécie
Tanzânia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170718
[Lr] Data última revisão:
170718
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170112
[St] Status:MEDLINE
[do] DOI:10.1371/journal.ppat.1006073


  7 / 216 MEDLINE  
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[PMID]:27855284
[Au] Autor:Cheng BY; Nogales A; de la Torre JC; Martínez-Sobrido L
[Ad] Endereço:Department of Microbiology and Immunology, University of Rochester, 601 Elmwood Avenue, Rochester, NY 14642, USA.
[Ti] Título:Development of live-attenuated arenavirus vaccines based on codon deoptimization of the viral glycoprotein.
[So] Source:Virology;501:35-46, 2017 Jan 15.
[Is] ISSN:1096-0341
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Several arenaviruses, chiefly Lassa (LASV) in West Africa, cause hemorrhagic fever (HF) disease in humans and pose important public health problems in their endemic regions. To date, there are no FDA-approved arenavirus vaccines and current anti-arenaviral therapy is limited to the use of ribavirin that has very limited efficacy. In this work we document that a recombinant prototypic arenavirus lymphocytic choriomeningitis virus (LCMV) with a codon deoptimized (CD) surface glycoprotein (GP), rLCMV/CD, exhibited wild type (WT)-like growth properties in cultured cells despite barely detectable GP expression levels in rLCMV/CD-infected cells. Importantly, rLCMV/CD was highly attenuated in vivo but able to induce complete protection against a subsequent lethal challenge with rLCMV/WT. Our findings support the feasibility of implementing an arenavirus GP CD-based approach for the development of safe and effective live-attenuated vaccines (LAVs) to combat diseases caused by human pathogenic arenaviruses.
[Mh] Termos MeSH primário: Infecções por Arenaviridae/virologia
Arenavirus/genética
Códon/genética
Glicoproteínas/genética
Vacinas Atenuadas/genética
Proteínas Virais/genética
Vacinas Virais/genética
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Animais
Infecções por Arenaviridae/imunologia
Arenavirus/imunologia
Códon/imunologia
Glicoproteínas/administração & dosagem
Glicoproteínas/imunologia
Seres Humanos
Camundongos
Dados de Sequência Molecular
Vacinas Atenuadas/administração & dosagem
Vacinas Atenuadas/imunologia
Proteínas Virais/administração & dosagem
Proteínas Virais/imunologia
Vacinas Virais/administração & dosagem
Vacinas Virais/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Codon); 0 (Glycoproteins); 0 (Vaccines, Attenuated); 0 (Viral Proteins); 0 (Viral Vaccines)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170630
[Lr] Data última revisão:
170630
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161118
[St] Status:MEDLINE


  8 / 216 MEDLINE  
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[PMID]:27569560
[Au] Autor:Ireland DD; Tami C; Pedras-Vasconcelos J; Verthelyi D
[Ad] Endereço:Division of Biologics Review and Research-III, Office of Biotechnology, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD 20993, USA.
[Ti] Título:CD4 and CD8 T cells mediate distinct lethal meningoencephalitis in mice challenged with Tacaribe arenavirus.
[So] Source:Cell Mol Immunol;14(1):90-107, 2017 Jan.
[Is] ISSN:2042-0226
[Cp] País de publicação:China
[La] Idioma:eng
[Ab] Resumo:Neonates are at increased risk of viral encephalopathies that can result in neurological dysfunction, seizures, permanent disability and even death. The neurological damage results from the combined effect of the virus and the immune response it elicits, thus finding tools to facilitate viral clearance from central nervous system (CNS) while minimizing neuron damage remains a critical challenge. Neonatal mice inoculated intraperitoneally with Tacaribe virus (TCRV) develop seizures, hindlimb paralysis and death within 15 days of inoculation. TCRV localizes to the CNS within days of challenge, primarily infecting astrocytes in the cerebellum and brain stem. We show that infection leads to inflammation, T cell and monocyte infiltration into the cerebellar parenchyma, apoptosis of astrocytes, neuronal degeneration and loss of Purkinje cells. Infiltrating antigen-specific T cells fail to clear the virus but drive the disease, as T-cell-deficient CD3É› KO mice survive TCRV infection with minimal inflammation or clinical manifestations despite no difference in CNS viral loads in comparison with T-cell sufficient mice. CD8+ T cells drive the pathology, which even in the absence of CD4+ T-cell help, infiltrate the parenchyma and mediate the apoptotic loss of cerebellar astrocytes, neurodegeneration and loss of Purkinje cells resulting in loss of balance, paralysis and death. CD4+ T cells are also pathogenic inducing gliosis and inflammation in the cerebellum and cerebrum that are associated with wasting and death several weeks after CD4+ T-cell transfer. These data demonstrate distinct pathogenic effects of CD4+ and CD8+ T cells and identify them as possible therapeutic targets.
[Mh] Termos MeSH primário: Infecções por Arenaviridae/imunologia
Infecções por Arenaviridae/virologia
Arenavirus/fisiologia
Linfócitos T CD4-Positivos/imunologia
Linfócitos T CD8-Positivos/imunologia
Meningoencefalite/imunologia
Meningoencefalite/virologia
[Mh] Termos MeSH secundário: Animais
Animais Recém-Nascidos
Apoptose
Infecções por Arenaviridae/patologia
Astrócitos/patologia
Sistema Nervoso Central/patologia
Sistema Nervoso Central/virologia
Gliose/patologia
Meningoencefalite/patologia
Camundongos Endogâmicos C57BL
Camundongos Transgênicos
Microglia/patologia
Degeneração Neural/patologia
Neurônios/patologia
Células de Purkinje/patologia
Linfócitos T/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170713
[Lr] Data última revisão:
170713
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160830
[St] Status:MEDLINE
[do] DOI:10.1038/cmi.2016.41


  9 / 216 MEDLINE  
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[PMID]:27630230
[Au] Autor:Shao J; Liu X; Ly H; Liang Y
[Ad] Endereço:Department of Veterinary and Biomedical Sciences, University of Minnesota, Twin Cities, Minnesota, USA.
[Ti] Título:Characterization of the Glycoprotein Stable Signal Peptide in Mediating Pichinde Virus Replication and Virulence.
[So] Source:J Virol;90(22):10390-10397, 2016 Nov 15.
[Is] ISSN:1098-5514
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Arenaviruses can cause lethal hemorrhagic fevers in humans with few preventative and therapeutic measures. The arenaviral glycoprotein stable signal peptide (SSP) is unique among signal peptides in that it is an integral component of the mature glycoprotein complex (GPC) and plays important roles not only in GPC expression and processing but also in the membrane fusion process during viral entry. Using the Pichinde virus (PICV) reverse genetics system, we analyzed the effects of alanine substitutions at many conserved residues within the SSP on viral replication in cell culture and in a guinea pig infection model. Our data showed that the K33A, F49A, and C57A mutations abolished GPC-mediated cell entry and therefore could not allow for the generation of viable recombinant viruses, demonstrating that these residues are essential for the PICV life cycle. The G2A mutation caused a marked reduction of cell entry at the membrane fusion step, and while this mutant virus was viable, it was significantly attenuated in vitro and in vivo The N20A mutation also reduced membrane fusion activity and viral virulence in guinea pigs, but it did not significantly affect cell entry or viral growth in cell culture. Two other mutations (N37A and R55A) did not affect membrane fusion or viral growth in vitro but significantly reduced viral virulence in vivo Taken together, our data suggest that the GPC SSP plays an essential role in mediating viral entry and also contributes to viral virulence in vivo IMPORTANCE: Several arenaviruses, such as Lassa fever virus, can cause severe and lethal hemorrhagic fever diseases with high mortality and morbidity, and no FDA-approved vaccines or therapies are currently available. Viral entry into cells is mediated by arenavirus GPC that consists of an SSP, the receptor-binding GP1, and transmembrane GP2 protein subunits. Using a reverse genetics system of a prototypic arenavirus, Pichinde virus (PICV), we have shown for the first time in the context of virus infections of cell culture and of guinea pigs that the SSP plays an essential role in mediating the membrane fusion step as well as in other yet-to-be-determined processes during viral infection. Our study provides important insights into the biological roles of GPC SSP and implicates it as a good target for the development of antivirals against deadly human arenavirus pathogens.
[Mh] Termos MeSH primário: Glicoproteínas/genética
Vírus Pichinde/genética
Sinais Direcionadores de Proteínas/genética
Virulência/genética
[Mh] Termos MeSH secundário: Células A549
Animais
Infecções por Arenaviridae/virologia
Arenavirus/genética
Linhagem Celular
Linhagem Celular Tumoral
Cercopithecus aethiops
Replicação do DNA/genética
Cobaias
Células HEK293
Seres Humanos
Fusão de Membrana/genética
Mutação/genética
Subunidades Proteicas/genética
Células Vero
Proteínas do Envelope Viral/genética
Internalização do Vírus
Replicação Viral/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Glycoproteins); 0 (Protein Sorting Signals); 0 (Protein Subunits); 0 (Viral Envelope Proteins)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170508
[Lr] Data última revisão:
170508
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160916
[St] Status:MEDLINE


  10 / 216 MEDLINE  
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[PMID]:27605671
[Au] Autor:Zhang LK; Xin QL; Zhu SL; Wan WW; Wang W; Xiao G
[Ad] Endereço:State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.
[Ti] Título:Activation of the RLR/MAVS Signaling Pathway by the L Protein of Mopeia Virus.
[So] Source:J Virol;90(22):10259-10270, 2016 Nov 15.
[Is] ISSN:1098-5514
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The family Arenaviridae includes several important human pathogens that can cause severe hemorrhagic fever and greatly threaten public health. As a major component of the innate immune system, the RLR/MAVS signaling pathway is involved in recognizing viral components and initiating antiviral activity. It has been reported that arenavirus infection can suppress the innate immune response, and NP and Z proteins of pathogenic arenaviruses can disrupt RLR/MAVS signaling, thus inhibiting production of type I interferon (IFN-I). However, recent studies have shown elevated IFN-I levels in certain arenavirus-infected cells. The mechanism by which arenavirus infection induces IFN-I responses remains unclear. In this study, we determined that the L polymerase (Lp) of Mopeia virus (MOPV), an Old World (OW) arenavirus, can activate the RLR/MAVS pathway and thus induce the production of IFN-I. This activation is associated with the RNA-dependent RNA polymerase activity of Lp. This study provides a foundation for further studies of interactions between arenaviruses and the innate immune system and for the elucidation of arenavirus pathogenesis. IMPORTANCE: Distinct innate immune responses are observed when hosts are infected with different arenaviruses. It has been widely accepted that NP and certain Z proteins of arenaviruses inhibit the RLR/MAVS signaling pathway. The viral components responsible for the activation of the RLR/MAVS signaling pathway remain to be determined. In the current study, we demonstrate for the first time that the Lp of MOPV, an OW arenavirus, can activate the RLR/MAVS signaling pathway and thus induce the production of IFN-I. Based on our results, we proposed that dynamic interactions exist among Lp-produced RNA, NP, and the RLR/MAVS signaling pathway, and the outcome of these interactions may determine the final IFN-I response pattern: elevated or reduced. Our study provides a possible explanation for how IFN-I can become activated during arenavirus infection and may help us gain insights into the interactions that form between different arenavirus components and the innate immune system.
[Mh] Termos MeSH primário: Proteínas Adaptadoras de Transdução de Sinal/metabolismo
Infecções por Arenaviridae/metabolismo
Arenavirus do Velho Mundo/metabolismo
Transdução de Sinais/fisiologia
Proteínas Virais/metabolismo
[Mh] Termos MeSH secundário: Animais
Infecções por Arenaviridae/imunologia
Infecções por Arenaviridae/virologia
Arenavirus/imunologia
Arenavirus/metabolismo
Arenavirus do Velho Mundo/imunologia
Linhagem Celular
Linhagem Celular Tumoral
Cercopithecus aethiops
RNA Polimerases Dirigidas por DNA/metabolismo
Células HEK293
Células HeLa
Interações Hospedeiro-Patógeno/imunologia
Interações Hospedeiro-Patógeno/fisiologia
Seres Humanos
Imunidade Inata/imunologia
Interferon Tipo I/metabolismo
Células Vero
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Adaptor Proteins, Signal Transducing); 0 (Interferon Type I); 0 (VISA protein, human); 0 (Viral Proteins); EC 2.7.7.6 (DNA-Directed RNA Polymerases)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170508
[Lr] Data última revisão:
170508
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160909
[St] Status:MEDLINE



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