Academic literature on the topic 'Infections à cardiovirus'

ABSTRACT Cardioviruses cause enteric infections in mice and rats which when disseminated have been associated with myocarditis, type 1 diabetes, encephalitis, and multiple sclerosis-like symptoms. Cardioviruses have also been detected at lower frequencies in other mammals. The Cardiovirus genus within the Picornaviridae family is currently made up of two viral species, Theilovirus and Encephalomyocarditis virus. Until recently, only a single strain of cardioviruses (Vilyuisk virus within the Theilovirus species) associated with a geographically restricted and prevalent encephalitis-like condition had been reported to occur in humans. A second theilovirus-related cardiovirus (Saffold virus [SAFV]) was reported in 2007 and subsequently found in respiratory secretions from children with respiratory problems and in stools of both healthy and diarrheic children. Using viral metagenomics, we identified RNA fragments related to SAFV in the stools of Pakistani and Afghani children with nonpolio acute flaccid paralysis (AFP). We sequenced three near-full-length genomes, showing the presence of divergent strains of SAFV and preliminary evidence of a distant recombination event between the ancestors of the Theiler-like viruses of rats and those of human SAFV. Further VP1 sequencing showed the presence of five new SAFV genotypes, doubling the reported genetic diversity of human and animal theiloviruses combined. Both AFP patients and healthy children in Pakistan were found to be excreting SAFV at high frequencies of 9 and 12%, respectively. Further studies are needed to examine the roles of these highly common and diverse SAFV genotypes in nonpolio AFP and other human diseases.

ABSTRACTPicornaviruses induce dramatic rearrangements of endomembranes in the cells that they infect to produce dedicated platforms for viral replication. These structures, termed replication organelles (ROs), have been well characterized for theEnterovirusgenus of thePicornaviridae. However, it is unknown whether the diverse RO morphologies associated with enterovirus infection are conserved among other picornaviruses. Here, we use serial electron tomography at different stages of infection to assess the three-dimensional architecture of ROs induced by encephalomyocarditis virus (EMCV), a member of theCardiovirusgenus of the family of picornaviruses that is distantly related. Ultrastructural analyses revealed connections between early single-membrane EMCV ROs and the endoplasmic reticulum (ER), establishing the ER as a likely donor organelle for their formation. These early single-membrane ROs appear to transform into double-membrane vesicles (DMVs) as infection progresses. Both single- and double-membrane structures were found to support viral RNA synthesis, and progeny viruses accumulated in close proximity, suggesting a spatial association between RNA synthesis and virus assembly. Further, we explored the role of phosphatidylinositol 4-phosphate (PI4P), a critical host factor for both enterovirus and cardiovirus replication that has been recently found to expedite enterovirus RO formation rather than being strictly required. By exploiting an EMCV escape mutant, we found that low-PI4P conditions could also be overcome for the formation of cardiovirus ROs. Collectively, our data show that despite differences in the membrane source, there are striking similarities in the biogenesis, morphology, and transformation of cardiovirus and enterovirus ROs, which may well extend to other picornaviruses.IMPORTANCELike all positive-sense RNA viruses, picornaviruses induce the rearrangement of host cell membranes to form unique structures, or replication organelles (ROs), that support viral RNA synthesis. Here, we investigate the architecture and biogenesis of cardiovirus ROs and compare them with those induced by enteroviruses, members of the well-characterized picornavirus genusEnterovirus. The origins and dynamic morphologies of cardiovirus ROs are revealed using electron tomography, which points to the endoplasmic reticulum as the donor organelle usurped to produce single-membrane tubules and vesicles that transform into double-membrane vesicles. We show that PI4P, a critical lipid for cardiovirus and enterovirus replication, is not strictly required for the formation of cardiovirus ROs, as functional ROs with typical morphologies are formed under phosphatidylinositol 4-kinase type III alpha (PI4KA) inhibition in cells infected with an escape mutant. Our data show that the transformation from single-membrane structures to double-membrane vesicles is a conserved feature of cardiovirus and enterovirus infections that likely extends to other picornavirus genera.

During infection by picornaviruses, the cellular environment is modified to favour virus replication. This includes the modification of specific host proteins, including the recently discovered viral proteinase cleavage of mRNA decay factor AU-rich binding factor 1 (AUF1). This cellular RNA-binding protein was shown previously to act as a restriction factor during poliovirus, rhinovirus and coxsackievirus infection. During infection by these viruses, AUF1 relocalizes to the cytoplasm and is cleaved by the viral 3C/3CD proteinase. In this study, we demonstrated that replication of encephalomyocarditis virus (EMCV), a picornavirus belonging to the genus Cardiovirus, is AUF1 independent. During EMCV infection, AUF1 relocalized to the cytoplasm; however, unlike what is seen during enterovirus infections, AUF1 was not cleaved to detectable levels, even at late times after infection. This suggests that AUF1 does not act broadly as an inhibitor of picornavirus infections but may instead act as a selective restriction factor targeting members of the genus Enterovirus.

ABSTRACT Cardioviruses (e.g., Theiler's murine encephalomyelitis virus [TMEV]) are members of the Picornaviridae family that cause myocarditis and encephalitis in rodents. Recently, several studies have identified human cardioviruses, including Saffold virus (SAFV) and a related virus named human TMEV-like cardiovirus (HTCV). At least eight cardiovirus genotypes are now recognized, with SAFV and most strains of HTCV belonging to genotypes 1 and 2, respectively; genotype 2 strains are the most common in the population. Although a genotype 3 cardiovirus has recently been cultured (SAFV-3), the genotype 1 and 2 cardioviruses have been difficult to propagate in vitro, hindering efforts to understand their seroprevalence and pathogenicity. Here we present the isolation and characterization of a genotype 2 human cardiovirus (HTCV-UC6). Notably, successful cultivation of HTCV-UC6 from stool required the addition of cytokine-blocking antibodies to interrupt downstream antiviral pathways. Unlike SAFV-3, HTCV-UC6 exhibited slow replication kinetics and demonstrated only a moderate cytopathic effect. Serologic assays revealed that 91% of U.S. adults carry antibodies to the genotype 2 cardioviruses, of which 80% generate neutralizing antibodies, in agreement with previous data showing that cardiovirus infection is widespread in humans. We also demonstrate an acute cardiovirus seroconversion event in a child with diarrhea and vomiting, thus reporting for the first time evidence linking cardiovirus infection to diarrheal disease in humans.

There have been a growing number of the outbreaks of human diseases with typical zoonotic infections, which have previously occurred exclusively in veterinary practice. Among them is monkeypox, whose first occurrence outside the African continent was registered in the USA in the spring of 2003. An important factor contributing to the penetration of infections into the human population is a close contact of people with fauna representatives in the context of intensively growing cities. Therefore, research into new zoonotic diseases, which are potentially dangerous to humans, seems to be critically important. Thus, retrospective studies carried out among the Peru population in 2009 revealed the cases of the encephalomyocarditis virus (EMCV) (Picornaviridae family, Cardiovirus genus) infection in people having suffered from acute febrile illness. A new virus strain belonging to the same genus was described during the infection outbreak among primates of the Sukhumi Monkey nursery (Republic of Abkhazia) in 1990–1999. This strain was also identified during the outbreak among the monkeys of the Primatological Centre in the Krasnodar Krai in 2012. In this review, we generalize the data available on the structure, virulence factors and distribution of EMCV.

Theiler’s murine encephalomyelitis virus (TMEV), a naturally occurring, enteric pathogen of mice is a Cardiovirus of the Picornaviridae family. Low neurovirulent TMEV strains such as BeAn cause a severe demyelinating disease in susceptible SJL mice following intracerebral infection. Furthermore, TMEV infections of C57BL/6 mice cause acute polioencephalitis initiating a process of epileptogenesis that results in spontaneous recurrent epileptic seizures in approximately 50% of affected mice. Moreover, C3H mice develop cardiac lesions after an intraperitoneal high-dose application of TMEV. Consequently, TMEV-induced diseases are widely used as animal models for multiple sclerosis, epilepsy, and myocarditis. The present review summarizes morphological lesions and pathogenic mechanisms triggered by TMEV with a special focus on the development of hippocampal degeneration and seizures in C57BL/6 mice as well as demyelination in the spinal cord in SJL mice. Furthermore, a detailed description of innate and adaptive immune responses is given. TMEV studies provide novel insights into the complexity of organ- and mouse strain-specific immunopathology and help to identify factors critical for virus persistence.

ABSTRACT The Cardiovirus genus of the family Picornaviridae includes two distinct species, Encephalomyocarditis virus and Theilovirus. We now report the complete nucleotide sequences of three Theiler's murine encephalomyelitis virus (TMEV) strains (TO Yale, TOB15, and Vie 415HTR) and of Vilyuisk human encephalomyelitis virus (VHEV). This information, together with the recently reported sequences of divergent theiloviruses (Theiler's-like rat virus [TRV] and Saffold viruses 1 and 2 [SAFV-1 and SAFV-2]), enables an updated phylogenetic analysis as well as a reexamination of several gene products important in the pathogenesis of this emerging group of viruses. In the light of the known neurotropism of TMEV and the new human SAFV-1 and SAFV-2, the resulting data suggest the existence of theiloviruses that cause human central nervous system infections. Our phylogenetic analyses point to the classification of presently known theiloviruses into five types: TMEV, VHEV, TRV, SAFV-1, and SAFV-2.

ABSTRACT Although the ability of serum-neutralizing antibodies to protect against picornavirus infection is well established, the contribution of cell-mediated immunity to protection is uncertain. Using major histocompatibility complex class II-deficient (RHAβ−/−) mice, which are unable to mediate CD4+ T-lymphocyte-dependent humoral responses, we demonstrated antibody-independent protection against lethal encephalomyocarditis virus (EMCV) infection in the natural host. The majority of RHAβ−/− mice inoculated with 104 PFU of attenuated Mengo virus (vMC24) resolved infection and were resistant to lethal challenge with the highly virulent, serotypically identical cardiovirus, EMCV. Protection in these mice was in the absence of detectable serum-neutralizing antibodies. Depletion of CD8+T lymphocytes prior to lethal EMCV challenge ablated protection in vMC24-immunized RHAβ−/− mice. The CD8+ T-lymphocyte-dependent protection observed in vivo may, in part, be the result of cytotoxic T-lymphocyte (CTL) activity, as CD8+ T splenocytes exhibited in vitro cytolysis of EMCV-infected targets. The existence of virus-specific CD8+T-lymphocyte memory in these mice was demonstrated by increased expression of cell surface activation markers CD25, CD69, CD71, and CTLA-4 following antigen-specific reactivation in vitro. Although recall response in vMC24-immunized RHAβ−/− mice was intact and effectual shortly after immunization, protection abated over time, as only 3 of 10 vMC24-immunized RHAβ−/− mice survived when rechallenged 90 days later. The present study demonstrating CD8+ T-lymphocyte-dependent protection in the absence of serum-neutralizing antibodies, coupled with our previous results indicating that vMC24-specific CD4+ T lymphocytes confer protection against lethal EMCV in the absence of prophylactic antibodies, suggests the existence of nonhumoral protective mechanisms against picornavirus infections.

The family Picornaviridae is a large and diverse group of viruses that infect humans and animals. Picornaviruses are among the most common infections of humans and cause a wide spectrum of acute human disease. This study began as an investigation of acute flaccid paralysis (AFP) in a small area of eastern Bolivia, where surveillance had identified a persistently high AFP rate in children. Stools were collected and diagnostic studies ruled out poliovirus. We tested stool specimens from 51 AFP cases and 34 healthy household or community contacts collected during 2002–2003 using real-time and semi-nested reverse transcription polymerase chain reaction assays for enterovirus, parechovirus, cardiovirus, kobuvirus, salivirus and cosavirus. Anecdotal reports suggested a temporal association with neurological disease in domestic pigs, so six porcine stools were also collected and tested with the same set of assays, with the addition of an assay for porcine teschovirus. A total of 126 picornaviruses were detected in 73 of 85 human individuals, consisting of 53 different picornavirus types encompassing five genera (all except Kobuvirus). All six porcine stools contained porcine and/or human picornaviruses. No single virus, or combination of viruses, specifically correlated with AFP; however, the study revealed a surprising complexity of enteric picornaviruses in a single community.

Orientador: Maria Silvia Viccari Gatti
Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Biologia
Made available in DSpace on 2018-08-03T22:33:53Z (GMT). No. of bitstreams: 1 Rodrigues_DanieleMasselli_M.pdf: 1852380 bytes, checksum: f83cb847eec2bcf31bf414b3bbf154ba (MD5) Previous issue date: 2004
Resumo: O vírus da encefalomielite murina de Theiler (TMEV) é um patógeno entérico de camundongos, pertencente ao gênero Cardiovirus da família Picornaviridae. O TMEV é um vírus não envelopado, icosaédrico, com 20 - 30 nm e genoma constituído de RNA fita simples com polaridade positiva. Os TMEV têm sido classificados em dois subgrupos, de acordo com sua atividade biológica após inoculação intracerebral. Cepas neurovirulentas (GDVII e FA) induzem uma encefalite aguda e fatal, enquanto aquelas de baixa virulência (TO, WW, DA e BeAn) persistem no sistema nervoso central, induzindo doença crônica, caracterizada por desmielinização. A infecção natural por TMEV tem sido demonstrada em colônias onvencionais de camundongos e, em sua maioria, a infecção é assintomática. Embora o TMEV seja descrito como um patógeno de camundongos, anticorpos para TMEV-GDVII têm sido detectados em soros de ratos provenientes de biotérios que mantêm colônias convencionais. A prevalência da infecção por TMEV-GDVII nestas colônias de ratos é alta, em torno de 54,6%. Assim, este trabalho teve por finalidade demonstrar, por métodos sorológicos e molecular, a infecção natural por TMEV em colônias de ratos. Soros destes animais foram analisados pela reação de imunofluorescência indireta e a presença de anticorpos anti-TMEV-GDVII foi detectada em 86,3% deles. Ao mesmo tempo, pelo teste de soroneutralização, 77,2% destes soros demonstraram anticorpos neutralizantes para TMEV-GDVII. Com o objetivo de isolar o vírus de ratos, sistemas ¿in vitro¿ e ¿in vivo¿ foram utilizados. Nove passagens sucessivas de amostras de suspensão intestinal foram feitas em células BHK-21 e não foi possível demonstrar efeito citopático. Sinais clínicos da infecção por TMEV em camundongos, ou seja, paralisia das patas posteriores e tremores, foram demonstrados em camundongos e ratos neonatos inoculados com suspensão intestinal de ratos soropositivos e com a cepa padrão de TMEV-GDVII. Os resultados da RT-PCR demonstraram a presença de RNA viral em amostras de cérebro de ratos inoculados com a suspensão intestinal, com TMEV-GDVII e nas amostras de fezes de ratos provenientes de diferentes biotérios convencionais. Os resultados demonstram que ratos se infectam naturalmente por TMEV e, embora hajam poucas descrições na literatura da interferência deste vírus em pesquisas biomédicas, a monitoração sanitária para TMEV em biotérios que mantêm colônias de ratos deve ser incluída
Abstract: Theiler¿s murine encephalomyelitis virus (TMEV) is an enteric pathogen of mice and belongs to the Cardiovirus genus in the family Picornaviridae. TMEV is a non-enveloped, icosaedric virus with 20 ¿ 30 nm size and it has an RNAss positive sense genome. TMEV has been divided in two subgroups on the basis of their biological activities after intracerebral inoculation. Neurovirulent strains (GDVII and FA) causes an acute and fatal encephalitis in mice and in contrast, low neurovirulent strains (DA, BeAn 8386, WW and TO) causes a persistent infection in the central nervous system and produce a chronic disease characterized by demyelination. TMEV infection with low neurovirulent strains has been used as an experimental model to help the studies on demyelination process induced by virus infection and to study diseases as Multiple Sclerosis. The natural infection by TMEV has been related in conventional colonies of mice and it¿s frequently asymptomatic. Although TMEV has been described as a pathogen of mice, antibodies against TMEV-GDVII has been detected in serum of rats reared in non-barrier colonies. Facing this, the purpose of the present study was to demonstrate the natural infection of TMEV in rat colonies through serological and molecular methods (RT-PCR). The rat serum were analysed by indirect immunofluorescence assay and antibodies against TMEV-GDVII were detected in 86,3% of the serum analysed. In the neutralization assay, 77,2% of the same serum showed neutralizing antibodies anti TMEVGDVII. To further isolate this rat virus, ¿in vitro¿ and ¿in vivo¿ systems were used. Nine blinded passages of the intestinal suspension were realized in BHK-21 cells, but no citopathic effect was identified. Clinical signs of TMEV infection in mice were characterized by flaccid paralisis of hind legs and tremor when newborn rats and mice were inoculated with intestinal suspension of seropositive rats and with the prototype strain of TMEV-GDVII. The RT-PCR results showed the RNA genome in the brain samples of rats and mice inoculated both with the intestinal suspension and the prototype strain. In the fecal samples, the RNA genome was also detected. In summary, rats can be naturally infected by TMEV and although there are a few examples in the literature of TMEV infection interference with biomedical researches, a health monitoring program for TMEV should be included in the rat colonies
Mestrado
Microbiologia
Genetica e Biologia Molecular

Dans le but d'évaluer le risque de transmission de l'EMCV de l'animal, en particulier le porc, à l'homme, notamment lors de xénotransplantations, nous nous sommes intéressés aux facteurs susceptibles de favoriser ou de limiter cette transmission par l'étude de l'interaction du virus avec des cellules humaines. Des outils permettant la mise en évidence de la multiplication du virus aux différentes étapes de l'infection ont été développés. Notamment, pour le suivi de la synthèse des protéines, un virus recombinant exprimant l'EGFP a été créé. Celui-ci, était pathogène pour la souris, à l'instar du virus parental. L'EGFP a pu être détectée par autofluorescence in vitro dans les cellules infectées et in vivo sur des empreintes de cerveaux de souris. Le pouvoir infectieux de différentes souches virales sur des lignées et des cellules primaires humaines, reflétant le tropisme du virus chez l'animal, a été analysé. Les résultats montrent que l'infection des cellules dépend du type cellulaire et de la souche virale et que l'adsorption varie essentiellement en fonction des souches. Par comparaison des séquences de capside, des acides aminés jouant un rôle probable dans cette adsorption ont été mis en évidence. L'analyse des partenaires cellulaires impliqués dans l'attachement a permis de montrer que l'adsorption de la souche 1086C est dépendante des acides sialiques et que la lysine 231 de VP1 jouerait un rôle important dans cette liaison. Par ailleurs, l'adsorption de la souche B279/95 est indépendante des acides sialiques mais dépend des héparanes sulfates. Ceci suggère l'utilisation probable de co-récepteurs portant des héparanes sulfates ou des acides sialiques
In order to evaluate the transmission risk of EMCV, from animal, mainly pig, to human, especially during xenotransplantations, we were interested in factors likely to support or limit this transmission by studying the interaction of EMCV with human cells. Tools allowing the detection of the virus multiplication at the various stages of the infection were developed. In particular, for the follow-up of the proteins synthesis, a recombinant EMCV expressing EGFP was created. The recombinant virus was pathogenic for mouse like the parental virus. EGFP could be detected by autofluorescence in vitro in infected cells and in vivo on prints of mouse brains. The infectious power of various viral strains on human cell lines and primary cells, reflecting the tropism of the virus in animal, was analysed. The results indicated that the infection of the cells depends on the cellular type and the viral strain and that adsorption varies primarily according to the strains. By comparison of the sequences of capsid, amino acids playing a probable part in this adsorption were highlighted. The analysis of the cellular partners implied in the attachment made it possible to show that the adsorption of the strain 1086C is dependent on sialic acid and that lysine 231 of VP1 would play an important part in this connection. In addition, the adsorption of the B279/95 strain is independent of sialic acid but depends on heparanes sulfates. This suggests the probable use of co-receptors carrying heparane sulfates or sialic acids