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1.
J Microbiol Biotechnol ; 29(12): 2006-2013, 2019 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-31581384

RESUMO

The isolation of respiratory viruses, especially from clinical specimens, often shows poor efficiency with classical cell culture methods. The lack of suitable methods to generate virus particles inhibits the development of diagnostic assays, treatments, and vaccines. We compared three inoculation methods, classical cell culture, the addition of a JAK2 inhibitor AZD1480, and centrifugation-enhanced inoculation (CEI), to replicate human respiratory syncytial virus (HRSV) and human metapneumovirus (HMPV). In addition, a combined method using AZD1480 treatment and CEI was used on throat swabs to verify that this method could increase virus isolation efficiency from human clinical specimens. Both CEI and AZD1480 treatment increased HRSV and HMPV genome replication. Also, the combined method using CEI and AZD1480 treatment enhanced virus proliferation synergistically. The combined method is particularly suited for the isolation of interferon-sensitive or slowly growing viruses from human clinical specimens.


Assuntos
Centrifugação/métodos , Pneumovirus/isolamento & purificação , Pirazóis/farmacologia , Pirimidinas/farmacologia , Cultura de Vírus/métodos , Humanos , Metapneumovirus/efeitos dos fármacos , Metapneumovirus/genética , Metapneumovirus/crescimento & desenvolvimento , Metapneumovirus/isolamento & purificação , Pneumovirus/efeitos dos fármacos , Pneumovirus/crescimento & desenvolvimento , Vírus Sincicial Respiratório Humano/efeitos dos fármacos , Vírus Sincicial Respiratório Humano/genética , Vírus Sincicial Respiratório Humano/crescimento & desenvolvimento , Vírus Sincicial Respiratório Humano/isolamento & purificação , Manejo de Espécimes , Replicação Viral
2.
BMC Vet Res ; 15(1): 300, 2019 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-31426794

RESUMO

BACKGROUND: Canine pneumovirus (CPV) is a pathogen that causes respiratory disease in dogs, and recent outbreaks in shelters in America and Europe have been reported. However, based on published data and documents, the identification of CPV and its variant in clinically symptomatic individual dogs in Thailand through Asia is limited. Therefore, the aims of this study were to determine the emergence of CPV and to consequently establish the genetic characterization and phylogenetic analysis of the CPV strains from 209 dogs showing respiratory distress in Thailand. RESULTS: This study identified and described the full-length CPV genome from three strains, designated herein as CPV_CP13 TH/2015, CPV_CP82 TH/2016 and CPV_SR1 TH/2016, that were isolated from six dogs out of 209 dogs (2.9%) with respiratory illness in Thailand. Phylogenetic analysis suggested that these three Thai CPV strains (CPV TH strains) belong to the CPV subgroup A and form a novel lineage; proposed as the Asian prototype. Specific mutations in the deduced amino acids of these CPV TH strains were found in the G/glycoprotein sequence, suggesting potential substitution sites for subtype classification. Results of intragenic recombination analysis revealed that CPV_CP82 TH/2016 is a recombinant strain, where the recombination event occurred in the L gene with the Italian prototype CPV Bari/100-12 as the putative major parent. Selective pressure analysis demonstrated that the majority of the nucleotides in the G/glycoprotein were under purifying selection with evidence of positive selection sites. CONCLUSIONS: This collective information on the CPV TH strains is the first evidence of CPV emergence with genetic characterization in Thailand and as first report in Asia, where homologous recombination acts as a potential force driving the genetic diversity and shaping the evolution of canine pneumovirus.


Assuntos
Doenças do Cão/virologia , Filogenia , Infecções por Pneumovirus/veterinária , Pneumovirus/classificação , Vírus Reordenados/genética , Infecções Respiratórias/veterinária , Sequência de Aminoácidos , Animais , Doenças do Cão/epidemiologia , Cães , Genoma Viral , Mutação , Pneumovirus/genética , Infecções por Pneumovirus/epidemiologia , Infecções por Pneumovirus/virologia , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/virologia , Tailândia/epidemiologia , Proteínas Virais/genética , Proteínas Virais/metabolismo
3.
mBio ; 10(3)2019 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-31088929

RESUMO

Paramyxoviruses and pneumoviruses have similar life cycles and share the respiratory tract as a point of entry. In comparative genome-scale siRNA screens with wild-type-derived measles, mumps, and respiratory syncytial viruses in A549 cells, a human lung adenocarcinoma cell line, we identified vesicular transport, RNA processing pathways, and translation as the top pathways required by all three viruses. As the top hit in the translation pathway, ABCE1, a member of the ATP-binding cassette transporters, was chosen for further study. We found that ABCE1 supports replication of all three viruses, confirming its importance for viruses of both families. More detailed characterization revealed that ABCE1 is specifically required for efficient viral but not general cellular protein synthesis, indicating that paramyxoviral and pneumoviral mRNAs exploit specific translation mechanisms. In addition to providing a novel overview of cellular proteins and pathways that impact these important pathogens, this study highlights the role of ABCE1 as a host factor required for efficient paramyxovirus and pneumovirus translation.IMPORTANCE The Paramyxoviridae and Pneumoviridae families include important human and animal pathogens. To identify common host factors, we performed genome-scale siRNA screens with wild-type-derived measles, mumps, and respiratory syncytial viruses in the same cell line. A comparative bioinformatics analysis yielded different members of the coatomer complex I, translation factors ABCE1 and eIF3A, and several RNA binding proteins as cellular proteins with proviral activity for all three viruses. A more detailed characterization of ABCE1 revealed its essential role for viral protein synthesis. Taken together, these data sets provide new insight into the interactions between paramyxoviruses and pneumoviruses and host cell proteins and constitute a starting point for the development of broadly effective antivirals.


Assuntos
Transportadores de Cassetes de Ligação de ATP/genética , Interações entre Hospedeiro e Microrganismos/genética , Paramyxoviridae/patogenicidade , Pneumovirus/patogenicidade , Células A549 , Biologia Computacional , Expressão Gênica , Humanos , RNA Mensageiro , RNA Interferente Pequeno , Proteínas de Ligação a RNA/genética
4.
PLoS One ; 14(3): e0210102, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30840626

RESUMO

Pneumonia severity index (PSI) is an important scoring system that can assess the severity of community acquired pneumonia and determine admission status. However, there is a lack of research on whether this scoring system can be applied to viral community acquired pneumonia. The purpose of this study was to evaluate the usefulness of PSI in viral community acquired pneumonia. This retrospective cohort study included 1,434 adult patients (aged ≥18 years) who were admitted to the emergency department of a university hospital during 2013-2015 because of community-acquired pneumonia. Viral infections were diagnosed by multiplex PCR. Patients diagnosed with non-viral community-acquired pneumonia were included in the control group (N = 1,173). The main outcome was 30-day all-cause mortality. multivariate Cox regression analyses were performed to calculate the risk of death. Respiratory viruses were detected in 261 (18.2%) patients with community-acquired pneumonia. Two types of respiratory viruses were detected in 7 cases. Of the 254 cases detected with only one virus, 62 were influenza A, 18 were influenza B, 65 were rhinovirus, 35 were respiratory syncytial virus, 25 were metapneumovirus, 20 were parainfluenza, 17 were coronavirus, 7 were bocavirus, and 5 were adenovirus. Mortality was not significantly different between patients with respiratory virus and those without respiratory virus; the 30-day all-cause mortality rates were 20.3% and 22.4%, respectively (P = 0.45). Mortality rate increased with an increasing PSI score with or without respiratory viral infection. Pulmonary severity index was significantly associated with mortality adjusted for respiratory virus detection (hazard ratio = 1.024, 95% confidence interval = 1.020-1.028). Pneumonia severity index score is an important factor for assessing the prognosis of patients with community-acquired pneumonia, regardless of respiratory virus detection.


Assuntos
Infecções Comunitárias Adquiridas/mortalidade , Pneumonia Viral/mortalidade , Pneumovirus/patogenicidade , Infecções Respiratórias/mortalidade , Índice de Gravidade de Doença , Adolescente , Adulto , Idoso , Infecções Comunitárias Adquiridas/epidemiologia , Infecções Comunitárias Adquiridas/virologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pneumonia Viral/epidemiologia , Pneumonia Viral/virologia , Pneumovirus/classificação , Pneumovirus/isolamento & purificação , Prognóstico , República da Coreia/epidemiologia , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/virologia , Estudos Retrospectivos , Taxa de Sobrevida
5.
Virus Res ; 265: 68-73, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30844414

RESUMO

Pneumoviruses represent a major public health burden across the world. Respiratory syncytial virus (RSV) and human metapneumovirus (HMPV), two of the most recognizable pediatric infectious agents, belong to this family. These viruses are enveloped with a non-segmented negative-sense RNA genome, and their replication occurs in specialized cytosolic organelles named inclusion bodies (IB). The critical role of IBs in replication of pneumoviruses has begun to be elucidated, and our current understanding suggests they are highly dynamic structures. From IBs, newly synthesized nucleocapsids are transported to assembly sites, potentially via the actin cytoskeleton, to be incorporated into nascent virions. Released virions, which generally contain one genome, can then diffuse in the extracellular environment to target new cells and reinitiate the process of infection. This is a challenging business for virions, which must face several risks including the extracellular immune responses. In addition, several recent studies suggest that successful infection may be achieved more rapidly by multiple, rather than single, genomic copies being deposited into a target cell. Interestingly, recent data indicate that pneumoviruses have several mechanisms that permit their transmission en bloc, i.e. transmission of multiple genomes at the same time. These mechanisms include the well-studied syncytia formation as well as the newly described formation of long actin-based intercellular extensions. These not only permit en bloc viral transmission, but also bypass assembly of complete virions. In this review we describe several aspects of en bloc viral transmission and how these mechanisms are reshaping our understanding of pneumovirus replication, assembly and spread.


Assuntos
Infecções por Paramyxoviridae/transmissão , Pneumovirus/fisiologia , Montagem de Vírus , Animais , Linhagem Celular , Humanos , Metapneumovirus/genética , Metapneumovirus/fisiologia , Camundongos , Pneumovirus/genética , RNA Viral , Vírion/genética , Vírion/fisiologia , Replicação Viral
6.
Vet Res ; 49(1): 118, 2018 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-30518406

RESUMO

The presence of pneumoviruses in pigs is poorly documented. In this study, we used the published sequence of the nucleoprotein (N) of the recently identified Swine Orthopneumovirus (SOV) to express and purify SOV N as a recombinant protein in Escherichia coli. This protein was purified as nanorings and used to set up an enzyme-linked immunosorbent assay, which was used to analyse the presence of anti-pneumovirus N antibodies in swine sera. Sera collected from different pig farms in the West of France and from specific pathogen free piglets before colostrum uptake showed indirectly that a pneumovirus is circulating in pig populations with some variations between animals. Piglets before colostrum uptake were sero-negative for anti-pneumovirus antibodies while most of the other pigs showed positivity. Interestingly, in two farms presenting respiratory clinical signs and negative or under control for some common respiratory pathogens, pigs were detected positive for anti-pneumovirus antibodies. Globally, anti-pneumovirus N antibody concentrations were variable between and within farms. Further studies will aim to isolate the circulating virus and determine its potential pathogenicity. SOV could potentially become a new member of the porcine respiratory complex, important on its own or in association with other viral and bacterial micro-organisms.


Assuntos
Anticorpos Antivirais/sangue , Proteínas do Nucleocapsídeo/sangue , Infecções por Pneumovirus/veterinária , Pneumovirus/isolamento & purificação , Doenças dos Suínos/virologia , Animais , Colostro , Ensaio de Imunoadsorção Enzimática/veterinária , Escherichia coli/genética , França , Infecções por Pneumovirus/imunologia , Infecções por Pneumovirus/virologia , Proteínas Recombinantes/análise , Análise de Sequência de RNA/veterinária , Organismos Livres de Patógenos Específicos , Suínos , Doenças dos Suínos/imunologia
7.
Vet Microbiol ; 212: 31-38, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29173585

RESUMO

Canine infectious respiratory disease (CIRD) is a major cause of morbidity in dogs worldwide, and is associated with a number of new and emerging pathogens. In a large multi-centre European study the prevalences of four key emerging CIRD pathogens; canine respiratory coronavirus (CRCoV), canine pneumovirus (CnPnV), influenza A, and Mycoplasma cynos (M. cynos); were estimated, and risk factors for exposure, infection and clinical disease were investigated. CIRD affected 66% (381/572) of the dogs studied, including both pet and kennelled dogs. Disease occurrence and severity were significantly reduced in dogs vaccinated against classic CIRD agents, canine distemper virus (CDV), canine adenovirus 2 (CAV-2) and canine parainfluenza virus (CPIV), but substantial proportions (65.7%; 201/306) of vaccinated dogs remained affected. CRCoV and CnPnV were highly prevalent across the different dog populations, with overall seropositivity and detection rates of 47% and 7.7% for CRCoV, and 41.7% and 23.4% for CnPnV, respectively, and their presence was associated with increased occurrence and severity of clinical disease. Antibodies to CRCoV had a protective effect against CRCoV infection and more severe clinical signs of CIRD but antibodies to CnPnV did not. Involvement of M. cynos and influenza A in CIRD was less apparent. Despite 45% of dogs being seropositive for M. cynos, only 0.9% were PCR positive for M. cynos. Only 2.7% of dogs were seropositive for Influenza A, and none were positive by PCR.


Assuntos
Infecções por Coronavirus/veterinária , Doenças do Cão/epidemiologia , Infecções por Mycoplasma/veterinária , Infecções por Orthomyxoviridae/veterinária , Infecções por Pneumovirus/veterinária , Infecções Respiratórias/veterinária , Animais , Doenças Transmissíveis Emergentes/epidemiologia , Doenças Transmissíveis Emergentes/microbiologia , Doenças Transmissíveis Emergentes/veterinária , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/virologia , Coronavirus Canino/isolamento & purificação , Doenças do Cão/microbiologia , Cães , Monitoramento Epidemiológico , Europa (Continente)/epidemiologia , Vírus da Influenza A/isolamento & purificação , Mycoplasma/isolamento & purificação , Infecções por Mycoplasma/epidemiologia , Infecções por Mycoplasma/microbiologia , Infecções por Orthomyxoviridae/epidemiologia , Infecções por Orthomyxoviridae/virologia , Pneumovirus/isolamento & purificação , Infecções por Pneumovirus/epidemiologia , Infecções por Pneumovirus/virologia , Prevalência , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/virologia
8.
J Leukoc Biol ; 102(3): 905-913, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28619948

RESUMO

Administration of immunobiotic Lactobacillus plantarum (Lp) directly to the respiratory mucosa promotes cross-protection against lethal pneumovirus infection via B-cell-independent mechanisms. In this study, we examined Lp-mediated cross protection in Rag1-/- mice which cannot clear virus from lung tissue. Although Lp was initially protective, Rag1-/- mice ultimately succumbed to a delayed lethal outcome associated with local production of the proinflammatory cytokines CCL1, -2, and -7, granulocyte recruitment, and ongoing virus replication. By contrast, CD8null mice, which are fully capable of clearing virus, are protected by Lp with no delayed lethal outcome, granulocyte recruitment to the airways, or induction of CCL7. Repeated administration of Lp to virus-infected Rag1-/- mice had no impact on delayed mortality. Moreover, administration of Lp to the respiratory mucosa resulted in no induction of IFN-α or -ß in Rag1-/- or wild-type mice, and IFN-abR gene deletion had no impact on Lp-mediated protection. Overall, our findings indicate that although Lp administered to the respiratory tract has substantial impact on lethal virus-induced inflammation in situ, endogenous virus clearance mechanisms are needed to promote sustained protection. Our results suggest that a larger understanding of the mechanisms and mediators that limit acute virus-induced inflammation may yield new and useful therapeutic modalities.


Assuntos
Proteínas de Homeodomínio/genética , Lactobacillus plantarum , Infecções por Pneumovirus/imunologia , Infecções por Pneumovirus/terapia , Pneumovirus/imunologia , Animais , Quimiocinas CC/genética , Quimiocinas CC/imunologia , Camundongos , Camundongos Knockout , Infecções por Pneumovirus/genética
9.
Virus Res ; 234: 87-102, 2017 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-28104450

RESUMO

The paramyxo- and pneumoviruses are members of the order Mononegavirales, a group of viruses with non-segmented, negative strand RNA genomes. The polymerases of these viruses are multi-functional complexes, capable of transcribing subgenomic capped and polyadenylated mRNAs and replicating the genome. Although there is no native structure available for any complete paramyxo- or pneumovirus polymerase, functional and structural studies of a fragment of a pneumovirus polymerase protein and mutation analyses and resistance profiling of small-molecule inhibitors have generated a wealth of mechanistic information. This review integrates these data with the structure of a related polymerase, identifying similarities, differences, gaps in knowledge, and avenues for antiviral drug development.


Assuntos
Paramyxoviridae/enzimologia , Pneumovirus/enzimologia , RNA Replicase/metabolismo , Análise Mutacional de DNA , Farmacorresistência Viral , Mutação de Sentido Incorreto , Pneumovirus/fisiologia , RNA Replicase/genética , Transcrição Genética , Replicação Viral
10.
Antiviral Res ; 132: 131-40, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27312104

RESUMO

Pattern recognition receptors (PRRs) engage microbial components in the lung, although their role in providing primary host defense against respiratory virus infection is not fully understood. We have previously shown that Gram-positive Lactobacillus plantarum (Lp) administered to the respiratory tract promotes full and sustained protection in response to an otherwise lethal mouse pneumovirus (PVM) infection, a robust example of heterologous immunity. While Lp engages PRRs TLR2 and NOD2 in ex vivo signaling assays, we found that Lp-mediated protection was unimpaired in single gene-deleted TLR2(-/-) and NOD2(-/-) mice. Here we demonstrate substantial loss of Lp-mediated protection in a double gene-deleted NOD2(-/-)TLR2(-/-) strain. Furthermore, we demonstrate protection against PVM infection by administration of the bi-functional NOD2-TLR2 agonist, CL-429. The bi-functional NOD2-TLR2 ligand CL-429 not only suppresses virus-induced inflammation, it is significantly more effective at preventing lethal infection than equivalent amounts of mono-molecular TLR2 and NOD2 agonists. Interestingly, and in contrast to biochemical NOD2 and/or TLR2 agonists, Lp remained capable of eliciting primary proinflammatory responses from NOD2(-/-)TLR2(-/-) mice in vivo and from alveolar macrophages challenged ex vivo. Taken together, we conclude that coordinate engagement of NOD2 and TLR2 constitutes a key step in the genesis of Lp-mediated protection from a lethal respiratory virus infection, and represents a critical target for modulation of virus-induced inflammatory pathology.


Assuntos
Imunomodulação , Proteína Adaptadora de Sinalização NOD2/metabolismo , Infecções por Pneumovirus/imunologia , Infecções por Pneumovirus/metabolismo , Pneumovirus/imunologia , Transdução de Sinais , Receptor 2 Toll-Like/metabolismo , Animais , Citocinas/metabolismo , Mediadores da Inflamação/metabolismo , Lactobacillus plantarum/imunologia , Ligantes , Pulmão/imunologia , Pulmão/metabolismo , Pulmão/patologia , Pulmão/virologia , Macrófagos Alveolares/imunologia , Macrófagos Alveolares/metabolismo , Camundongos , Camundongos Knockout , Vírus da Pneumonia Murina/imunologia , Proteína Adaptadora de Sinalização NOD2/genética , Infecções por Pneumovirus/mortalidade , Infecções por Pneumovirus/virologia , Receptores de Reconhecimento de Padrão/metabolismo , Receptor 2 Toll-Like/genética , Carga Viral
11.
Immunol Lett ; 172: 106-12, 2016 04.
Artigo em Inglês | MEDLINE | ID: mdl-26916143

RESUMO

The SV-40-transformed MH-S cell line maintains some, but not all, features of primary alveolar macrophages (AMs) from BALB/c mice. We show here that MH-S cells produce inflammatory cytokines IL-6 and CXCL10 in response to challenge with Gram-positive Lactobacillus reuteri, and to TLR2 and NOD2 ligands Pam3CSK4 and MDP, respectively. In contrast, although wild-type AMs are infected in vivo by pneumonia virus of mice (PVM), no virus replication was detected in MH-S cells. Interestingly, the surface immunophenotype of MH-S cells (CD11c(+)Siglec F(-)) differs from that of wild-type AMs (CD11c(+) Siglec F(+)) and is similar to that of immature AMs isolated from granulocyte macrophage-colony stimulating factor (GM-CSF) gene-deleted mice; AMs from GM-CSF(-/-) mice also support PVM replication. However, MH-S cells do not express the GM-CSF receptor alpha chain (CD116) and do not respond to GM-CSF. Due to these unusual features, MH-S cells should be used with caution as experimental models of AMs.


Assuntos
Lactobacillus reuteri/imunologia , Macrófagos Alveolares/virologia , Infecções por Pneumovirus/imunologia , Pneumovirus/fisiologia , Animais , Linhagem Celular Transformada , Quimiocina CXCL10/metabolismo , Fator Estimulador de Colônias de Granulócitos e Macrófagos/genética , Interleucina-6/metabolismo , Lipopeptídeos/imunologia , Macrófagos Alveolares/patologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Knockout , Receptor 2 Toll-Like/metabolismo , Replicação Viral
12.
PLoS One ; 10(4): e0123755, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25893441

RESUMO

This study aimed to determine the role of influenza-like illness (ILI) surveillance conducted on Leyte Island, the Philippines, including involvement of other respiratory viruses, from 2010 to 2013. ILI surveillance was conducted from January 2010 to March 2013 with 3 sentinel sites located in Tacloban city, Palo and Tanauan of Leyte Island. ILI was defined as fever ≥38°C or feverish feeling and either cough or running nose in a patient of any age. Influenza virus and other 5 respiratory viruses were searched. A total of 5,550 ILI cases visited the 3 sites and specimens were collected from 2,031 (36.6%) cases. Among the cases sampled, 1,637 (75.6%) were children aged <5 years. 874 (43.0%) cases were positive for at least one of the respiratory viruses tested. Influenza virus and respiratory syncytial virus (RSV) were predominantly detected (both were 25.7%) followed by human rhinovirus (HRV) (17.5%). The age distributions were significantly different between those who were positive for influenza, HRV, and RSV. ILI cases were reported throughout the year and influenza virus was co-detected with those viruses on approximately half of the weeks of study period (RSV in 60.5% and HRV 47.4%). In terms of clinical manifestations, only the rates of headache and sore throat were significantly higher in influenza positive cases than cases positive to other viruses. In conclusion, syndromic ILI surveillance in this area is difficult to detect the start of influenza epidemic without laboratory confirmation which requires huge resources. Age was an important factor that affected positive rates of influenza and other respiratory viruses. Involvement of older age children may be useful to detect influenza more effectively.


Assuntos
Influenza Humana/epidemiologia , Influenza Humana/virologia , Ilhas/epidemiologia , Orthomyxoviridae/fisiologia , Pneumovirus/fisiologia , Vigilância da População , Adolescente , Adulto , Criança , Pré-Escolar , Demografia , Feminino , Geografia , Humanos , Lactente , Recém-Nascido , Masculino , Filipinas/epidemiologia , Adulto Jovem
13.
Clin Vaccine Immunol ; 22(5): 477-83, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25716232

RESUMO

Acute lower respiratory tract infections (ALRTI) are the leading cause of global childhood mortality, with human respiratory syncytial virus (hRSV) being a major cause of viral ALRTI in young children worldwide. In sub-Saharan Africa, many young children experience severe illnesses due to hRSV or Plasmodium infection. Although the incidence of malaria in this region has decreased in recent years, there remains a significant opportunity for coinfection. Recent data show that febrile young children infected with Plasmodium are often concurrently infected with respiratory viral pathogens but are less likely to suffer from pneumonia than are non-Plasmodium-infected children. Here, we hypothesized that blood-stage Plasmodium infection modulates pulmonary inflammatory responses to a viral pathogen but does not aid its control in the lung. To test this, we established a novel coinfection model in which mice were simultaneously infected with pneumovirus of mice (PVM) (to model hRSV) and blood-stage Plasmodium chabaudi chabaudi AS (PcAS) parasites. We found that PcAS infection was unaffected by coinfection with PVM. In contrast, PVM-associated weight loss, pulmonary cytokine responses, and immune cell recruitment to the airways were substantially reduced by coinfection with PcAS. Importantly, PcAS coinfection facilitated greater viral dissemination throughout the lung. Although Plasmodium coinfection induced low levels of systemic interleukin-10 (IL-10), this regulatory cytokine played no role in the modulation of lung inflammation or viral dissemination. Instead, we found that Plasmodium coinfection drove an early systemic beta interferon (IFN-ß) response. Therefore, we propose that blood-stage Plasmodium coinfection may exacerbate viral dissemination and impair inflammation in the lung by dysregulating type I IFN-dependent responses to respiratory viruses.


Assuntos
Bronquiolite Viral/imunologia , Coinfecção , Interferon beta/imunologia , Pulmão/virologia , Malária/imunologia , Infecções por Pneumovirus/imunologia , Pneumovirus/imunologia , Animais , Bronquiolite Viral/virologia , Modelos Animais de Doenças , Feminino , Inflamação/imunologia , Inflamação/parasitologia , Inflamação/virologia , Interferon beta/sangue , Interleucina-10/imunologia , Pulmão/imunologia , Malária/complicações , Plasmodium chabaudi , Pneumovirus/patogenicidade , Pneumovirus/fisiologia , Infecções por Pneumovirus/complicações , Vírus Sincicial Respiratório Humano/patogenicidade , Carga Viral , Perda de Peso
14.
J Immunol ; 193(8): 4072-82, 2014 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-25200951

RESUMO

Respiratory virus infections are often pathogenic, driving severe inflammatory responses. Most research has focused on localized effects of virus infection and inflammation. However, infection can induce broad-reaching, systemic changes that are only beginning to be characterized. In this study, we assessed the impact of acute pneumovirus infection in C57BL/6 mice on bone marrow hematopoiesis. We hypothesized that inflammatory cytokine production in the lung upregulates myeloid cell production in response to infection. We demonstrate a dramatic increase in the percentages of circulating myeloid cells, which is associated with pronounced elevations in inflammatory cytokines in serum (IFN-γ, IL-6, CCL2), bone (TNF-α), and lung tissue (TNF-α, IFN-γ, IL-6, CCL2, CCL3, G-CSF, osteopontin). Increased hematopoietic stem/progenitor cell percentages (Lineage(-)Sca-I(+)c-kit(+)) were also detected in the bone marrow. This increase was accompanied by an increase in the proportions of committed myeloid progenitors, as determined by colony-forming unit assays. However, no functional changes in hematopoietic stem cells occurred, as assessed by competitive bone marrow reconstitution. Systemic administration of neutralizing Abs to either TNF-α or IFN-γ blocked expansion of myeloid progenitors in the bone marrow and also limited virus clearance from the lung. These findings suggest that acute inflammatory cytokines drive production and differentiation of myeloid cells in the bone marrow by inducing differentiation of committed myeloid progenitors. Our findings provide insight into the mechanisms via which innate immune responses regulate myeloid cell progenitor numbers in response to acute respiratory virus infection.


Assuntos
Diferenciação Celular/imunologia , Citocinas/imunologia , Células Progenitoras Mieloides/citologia , Infecções por Pneumovirus/imunologia , Pneumovirus , Animais , Anticorpos Neutralizantes/administração & dosagem , Anticorpos Neutralizantes/imunologia , Células da Medula Óssea/citologia , Proliferação de Células , Citocinas/sangue , Hematopoese , Imunidade Inata , Inflamação/imunologia , Mediadores da Inflamação/imunologia , Interferon gama/imunologia , Pulmão/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fator de Necrose Tumoral alfa/imunologia
15.
J Immunol ; 192(11): 5265-72, 2014 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-24748495

RESUMO

We have shown previously that priming of respiratory mucosa with live Lactobacillus species promotes robust and prolonged survival from an otherwise lethal infection with pneumonia virus of mice, a property known as heterologous immunity. Lactobacillus priming results in a moderate reduction in virus recovery and a dramatic reduction in virus-induced proinflammatory cytokine production; the precise mechanisms underlying these findings remain to be elucidated. Because B cells have been shown to promote heterologous immunity against respiratory virus pathogens under similar conditions, in this study we explore the role of B cells in Lactobacillus-mediated protection against acute pneumovirus infection. We found that Lactobacillus-primed mice feature elevated levels of airway Igs IgG, IgA, and IgM and lung tissues with dense, B cell (B220(+))-enriched peribronchial and perivascular infiltrates with germinal centers consistent with descriptions of BALT. No B cells were detected in lung tissue of Lactobacillus-primed B cell deficient µMT mice or Jh mice, and Lactobacillus-primed µMT mice had no characteristic infiltrates or airway Igs. Nonetheless, we observed diminished virus recovery and profound suppression of virus-induced proinflammatory cytokines CCL2, IFN-γ, and CXCL10 in both wild-type and Lactobacillus-primed µMT mice. Furthermore, Lactobacillus plantarum-primed, B cell-deficient µMT and Jh mice were fully protected from an otherwise lethal pneumonia virus of mice infection, as were their respective wild-types. We conclude that B cells are dispensable for Lactobacillus-mediated heterologous immunity and were not crucial for promoting survival in response to an otherwise lethal pneumovirus infection.


Assuntos
Linfócitos B/imunologia , Lactobacillus/imunologia , Pulmão/imunologia , Infecções por Pneumovirus/imunologia , Pneumovirus/imunologia , Mucosa Respiratória/imunologia , Animais , Anticorpos Antibacterianos/genética , Anticorpos Antibacterianos/imunologia , Citocinas/genética , Citocinas/imunologia , Pulmão/patologia , Pulmão/virologia , Camundongos , Camundongos Endogâmicos BALB C , Pneumovirus/genética , Infecções por Pneumovirus/genética , Infecções por Pneumovirus/patologia , Mucosa Respiratória/patologia , Mucosa Respiratória/virologia
16.
PLoS One ; 9(1): e85220, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24400129

RESUMO

An outbreak of canine infectious respiratory disease (CIRD) associated to canine pneumovirus (CnPnV) infection is reported. The outbreak occurred in a shelter of the Apulia region and involved 37 out of 350 dogs that displayed cough and/or nasal discharge with no evidence of fever. The full-genomic characterisation showed that the causative agent (strain Bari/100-12) was closely related to CnPnVs that have been recently isolated in the USA, as well as to murine pneumovirus, which is responsible for respiratory disease in mice. The present study represents a useful contribution to the knowledge of the pathogenic potential of CnPnV and its association with CIRD in dogs. Further studies will elucidate the pathogenicity and epidemiology of this novel pneumovirus, thus addressing the eventual need for specific vaccines.


Assuntos
Doenças do Cão/epidemiologia , Doenças do Cão/virologia , Genoma Viral , Infecções por Pneumovirus/veterinária , Pneumovirus/genética , Animais , Sequência de Bases , Surtos de Doenças , Cães , Feminino , Ordem dos Genes , Itália/epidemiologia , Masculino , Dados de Sequência Molecular , Filogenia , Pneumovirus/classificação , Pneumovirus/isolamento & purificação , Alinhamento de Sequência
17.
Vet Pathol ; 51(2): 492-504, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24232191

RESUMO

Canine infectious respiratory disease is a common, worldwide disease syndrome of multifactorial etiology. This review presents a summary of 6 viruses (canine respiratory coronavirus, canine pneumovirus, canine influenza virus, pantropic canine coronavirus, canine bocavirus, and canine hepacivirus) and 2 bacteria (Streptococcus zooepidemicus and Mycoplasma cynos) that have been associated with respiratory disease in dogs. For some pathogens a causal role is clear, whereas for others, ongoing research aims to uncover their pathogenesis and contribution to this complex syndrome. Etiology, clinical disease, pathogenesis, and epidemiology are described for each pathogen, with an emphasis on recent discoveries or novel findings.


Assuntos
Doenças Transmissíveis Emergentes/veterinária , Surtos de Doenças/veterinária , Doenças do Cão/epidemiologia , Infecções Respiratórias/veterinária , Animais , Bocavirus/patogenicidade , Doenças Transmissíveis Emergentes/diagnóstico , Doenças Transmissíveis Emergentes/epidemiologia , Doenças Transmissíveis Emergentes/microbiologia , Coronavirus Canino/patogenicidade , Doenças do Cão/diagnóstico , Doenças do Cão/microbiologia , Cães , Hepacivirus/patogenicidade , Mycoplasma/patogenicidade , Orthomyxoviridae/patogenicidade , Pneumovirus/patogenicidade , Infecções Respiratórias/diagnóstico , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/microbiologia , Streptococcus equi/patogenicidade
18.
Vestn Ross Akad Med Nauk ; (6): 21-5, 2013.
Artigo em Russo | MEDLINE | ID: mdl-24340631

RESUMO

INTRODUCTION: ARI occupying the first place in the structure of total human morbidity. The aim of the study was to investigate the species diversity of the viruses causing AR among residents of the Novosibirsk region during epidemic season (October to April). MATERIALS AND METHODS: 164 nasopharyngeal swabs were collected and analyzed. Viral RNA/DNA, cDNA synthesis and PCR were carried out employing "RIBO-prep" "eReverta-L", "AmpliSens Influenza virus A/B-FL" and "AmpliSens ARI-screen-FL" kits (CRI of Epidemiology). RESULTS: Etiological agent of the disease was found in 69(43%) samples. Monoinfection was found in 58 (35%). In 14 (9%) samples were detected serogroup I coronaviruses, in 13 (8%) rhinoviruses, in 7 (4%) respiratory syncytial virus, in 6 (4%) parainfluenza virus type 1, in 5 (3%) parainfluenza virus type 3. Adenoviruses and bocavirus were identified in 3 (2%) samples. Parainfluenza virus type 2 and 4, metapneumovirus, serogroup Il coronaviruses (HKU1 and OC43) were presented in 2 (1%) samples. In 11 (7%) samples was found mixed infection. CONCLUSION: The majority of common colds were caused by serogroup I coronaviruses (NL63 and 229E), rhinoviruses and mixed infections. The peak of species variability of viruses caused acute respiratory infections was determined in age group of children 2-4 years old. In older age groups the species variability of analyzed viruses was decreased, rhinovirus infection becomes prevalent.


Assuntos
Epidemias/estatística & dados numéricos , Pneumovirus/isolamento & purificação , Infecções Respiratórias/virologia , Doença Aguda , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Morbidade/tendências , Infecções Respiratórias/epidemiologia , Estudos Retrospectivos , Sibéria/epidemiologia , Adulto Jovem
19.
J Clin Microbiol ; 51(12): 4112-9, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24088858

RESUMO

Canine pneumovirus (CnPnV) was recently identified during a retrospective survey of kenneled dogs in the United States. In this study, archived samples from pet and kenneled dogs in the United Kingdom were screened for CnPnV to explore the relationship between exposure to CnPnV and the development of canine infectious respiratory disease (CIRD). Within the pet dog population, CnPnV-seropositive dogs were detected throughout the United Kingdom and Republic of Ireland, with an overall estimated seroprevalence of 50% (n = 314/625 dogs). In the kennel population, there was a significant increase in seroprevalence, from 26% (n = 56/215 dogs) on the day of entry to 93.5% (n = 201/215 dogs) after 21 days (P <0001). Dogs that were seronegative on entry but seroconverted while in the kennel were 4 times more likely to develop severe respiratory disease than those that did not seroconvert (P < 0.001), and dogs with preexisting antibodies to CnPnV on the day of entry were significantly less likely to develop respiratory disease than immunologically naive dogs (P < 0.001). CnPnV was detected in the tracheal tissues of 29/205 kenneled dogs. Detection was most frequent in dogs with mild to moderate respiratory signs and histopathological changes and in dogs housed for 8 to 14 days, which coincided with a significant increase in the risk of developing respiratory disease compared to the risk of those housed 1 to 7 days (P < 0.001). These findings demonstrate that CnPnV is present in the United Kingdom dog population; there is a strong association between exposure to CnPnV and CIRD in the kennel studied and a potential benefit in vaccinating against CnPnV as part of a wider disease prevention strategy.


Assuntos
Doenças do Cão/epidemiologia , Doenças do Cão/virologia , Infecções por Pneumovirus/veterinária , Pneumovirus/isolamento & purificação , Infecções Respiratórias/veterinária , Animais , Cães , Irlanda/epidemiologia , Animais de Estimação , Pneumovirus/imunologia , Infecções por Pneumovirus/epidemiologia , Infecções por Pneumovirus/virologia , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/virologia , Estudos Retrospectivos , Estudos Soroepidemiológicos , Traqueia/virologia , Reino Unido/epidemiologia
20.
Virology ; 443(2): 257-64, 2013 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-23763766

RESUMO

A previous report of a novel pneumovirus (PnV) isolated from the respiratory tract of a dog described its significant homology to the rodent pathogen, pneumonia virus of mice (PVM). The original PnV-Ane4 pathogen replicated in and could be re-isolated in infectious state from mouse lung but elicited minimal mortality compared to PVM strain J3666. Here we assess phylogeny and physiologic responses to 10 new PnV isolates. The G/glycoprotein sequences of all PnVs include elongated amino-termini when compared to the characterized PVMs, and suggest division into groups A and B. While we observed significant differences in cytokine production and neutrophil recruitment to the lungs of BALB/c mice in response to survival doses (50 TCID50 units) of representative group A (114378-10-29-KY-F) and group B (7968-11-OK) PnVs, we observed no evidence for positive selection (dN > dS) among the PnV/PnV, PVM/PnV or PVM/PVM G/glycoprotein or F/fusion protein sequence pairs.


Assuntos
Evolução Molecular , Inflamação/patologia , Infecções por Pneumovirus/patologia , Pneumovirus/classificação , Pneumovirus/patogenicidade , Sequência de Aminoácidos , Animais , Glicoproteínas/química , Glicoproteínas/genética , Glicoproteínas/metabolismo , Inflamação/imunologia , Inflamação/virologia , Pulmão/imunologia , Pulmão/patologia , Glicoproteínas de Membrana , Camundongos , Camundongos Endogâmicos BALB C , Dados de Sequência Molecular , Vírus da Pneumonia Murina/genética , Vírus da Pneumonia Murina/patogenicidade , Filogenia , Pneumovirus/genética , Infecções por Pneumovirus/virologia , Proteínas Virais/química , Proteínas Virais/genética , Proteínas Virais/metabolismo
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