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1.
Reumatol. clín. (Barc.) ; 19(1): 49-52, Ene. 2023. tab
Artigo em Espanhol | IBECS | ID: ibc-214166

RESUMO

Antecedentes: La vacunación contra agentes infecciosos como influenza y neumococo está ampliamente recomendada para pacientes con artritis reumatoide, no se conoce la prevalencia de adherencia a estos programas de vacunación en México. Métodos: Se realizó un estudio descriptivo trasversal, por medio de aplicación de encuesta a pacientes adultos con diagnóstico de artritis reumatoide atendidos en un hospital de tercer nivel en la Ciudad de México. Resultados: Se incluyeron 227 pacientes, se encontró una prevalencia de vacunación contra influenza en 31,3% y contra neumococo en 17,6% de los pacientes, los principales motivos para el no cumplimiento del esquema de vacunación estuvieron en relación con el desconocimiento y a la recomendación por parte de los médicos de no hacerlo. Conclusiones: El cumplimiento de los esquemas de vacunación recomendados en la población estudiada es más bajo que los reportados en otras poblaciones. Las intervenciones más importantes para mejorar la cobertura deben ir encaminadas a la educación tanto de pacientes, como de personal médico.(AU)


Background: Vaccination against pathogens such as influenza or pneumococcus is widely recommended for patients with rheumatoid arthritis; the prevalence of adherence to these vaccination programmes in Mexico is not known. Methods: A cross-sectional descriptive study was carried out, through the application of a survey to adult patients with a diagnosis of rheumatoid arthritis treated in a tertiary hospital in Mexico City. Results: 227 patients were included, vaccination against influenza was found in 31.3% and against pneumococcus in 17.6% of patients, the main reasons for non-compliance with the vaccination schedule were related to ignorance and the recommendation by doctors not to do so. Conclusions: Compliance with the recommended vaccination schedules in the studied population is lower than those reported in other populations. The most important interventions to improve coverage should be aimed at educating both patients and medical personnel.(AU)


Assuntos
Humanos , Masculino , Feminino , Vacinação , Influenza Humana , Infecções Pneumocócicas/imunologia , Influenza Humana/imunologia , Artrite Reumatoide , Reumatologia , Doenças Reumáticas , Estudos Transversais , Epidemiologia Descritiva
2.
Nat Commun ; 13(1): 7864, 2022 12 21.
Artigo em Inglês | MEDLINE | ID: mdl-36543789

RESUMO

Contemporary influenza A H3N2 viruses circulating since 2016 have acquired a glycosylation site in the neuraminidase in close proximity to the enzymatic active site. Here, we investigate if this S245N glycosylation site, as a result of antigenic evolution, can impact binding and function of human monoclonal antibodies that target the conserved active site. While we find that a reduction in the inhibitory ability of neuraminidase active site binders is measurable, this class of broadly reactive monoclonal antibodies maintains protective efficacy in vivo.


Assuntos
Anticorpos Monoclonais , Vírus da Influenza A Subtipo H3N2 , Neuraminidase , Humanos , Anticorpos Monoclonais/química , Anticorpos Monoclonais/imunologia , Anticorpos Antivirais/química , Anticorpos Antivirais/metabolismo , Domínio Catalítico/imunologia , Domínio Catalítico/fisiologia , Glicosilação , Glicoproteínas de Hemaglutininação de Vírus da Influenza , Vírus da Influenza A , Vírus da Influenza A Subtipo H3N2/imunologia , Vírus da Influenza A Subtipo H3N2/metabolismo , Influenza Humana/imunologia , Influenza Humana/metabolismo , Neuraminidase/química , Neuraminidase/imunologia
3.
Curr Opin Immunol ; 78: 102252, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36215931

RESUMO

The outbreak of the COVID-19 pandemic one year after the centennial of the 1918 influenza pandemic reaffirms the catastrophic impact respiratory viruses can have on global health and economy. A key feature of SARS-CoV-2 and influenza A viruses (IAV) is their remarkable ability to suppress or dysregulate human immune responses. Here, we summarize the growing knowledge about the interplay of SARS-CoV-2 and antiviral innate immunity, with an emphasis on the regulation of type-I or -III interferon responses that are critically implicated in COVID-19 pathogenesis. Furthermore, we draw parallels to IAV infection and discuss shared innate immune sensing mechanisms and the respective viral countermeasures.


Assuntos
COVID-19 , Influenza Humana , Interferons , SARS-CoV-2 , Humanos , COVID-19/imunologia , COVID-19/metabolismo , COVID-19/virologia , Imunidade Inata , Vírus da Influenza A/imunologia , Influenza Humana/imunologia , Influenza Humana/metabolismo , Influenza Humana/virologia , Interferons/imunologia , Pandemias , SARS-CoV-2/imunologia
4.
Virulence ; 13(1): 1558-1572, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36082929

RESUMO

Influenza A virus (IAV) infection poses a substantial challenge and causes high morbidity and mortality. Exacerbated pulmonary inflammatory responses are the major causes of extensive diffuse alveolar immunopathological damage. However, the relationship between the extent of cytokine storm, neutrophils/macrophages infiltration, and different IAV infection dose and time still needs to be further elucidated, and it is still unclear whether the signal transduction and transcriptional activator 1/3 (STAT1/3) signalling pathway plays a beneficial or detrimental role. Here, we established a mouse model of high- and low-dose pH1N1 infection. We found that pH1N1 infection induced robust and early pathological damage and cytokine storm in an infection dose- and time-dependent manner. High-dose pH1N1 infection induced massive and sustained recruitment of neutrophils as well as a higher ratio of M1:M2, which may contribute to severe lung immunopathological damage. pH1N1 infection activated dose- and time-dependent STAT1 and STAT3. Inhibition of STAT1 and/or STAT3 aggravated low-dose pH1N1 infection, induced lung damage, and decreased survival rate. Appropriate activation of STAT1/3 provided survival benefits and pathological improvement during low-dose pH1N1 infection. These results demonstrate that high-dose pH1N1 infection induces robust and sustained neutrophil infiltration, imbalanced macrophage polarization, excessive and earlier cytokine storm, and STAT1/3 activation, which are associated with pulmonary dysregulated proinflammatory responses and progress of acute lung injury. The severe innate immune responses may be the threshold at which protective functions give way to immunopathology, and assessing the magnitude of host innate immune responses is necessary in adjunctive immunomodulatory therapy for alleviating influenza-induced pneumonia.


Assuntos
Imunidade Inata , Vírus da Influenza A Subtipo H1N1 , Influenza Humana , Infecções por Orthomyxoviridae , Animais , Síndrome da Liberação de Citocina , Humanos , Vírus da Influenza A Subtipo H1N1/imunologia , Influenza Humana/imunologia , Pulmão/imunologia , Pulmão/patologia , Lesão Pulmonar/etiologia , Lesão Pulmonar/patologia , Camundongos , Fator de Transcrição STAT1/metabolismo , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais
5.
Front Immunol ; 13: 958801, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36091002

RESUMO

Fatal influenza (flu) virus infection often activates excessive inflammatory signals, leading to multi-organ failure and death, also referred to as cytokine storm. PPARγ (Peroxisome proliferator-activated receptor gamma) agonists are well-known candidates for cytokine storm modulation. The present study identified that influenza infection reduced PPARγ expression and decreased PPARγ transcription activity in human alveolar macrophages (AMs) from different donors. Treatment with PPARγ agonist Troglitazone ameliorated virus-induced proinflammatory cytokine secretion but did not interfere with the IFN-induced antiviral pathway in human AMs. In contrast, PPARγ antagonist and knockdown of PPARγ in human AMs further enhanced virus-stimulated proinflammatory response. In a mouse model of influenza infection, flu virus dose-dependently reduced PPARγ transcriptional activity and decreased expression of PPARγ. Moreover, PPARγ agonist troglitazone significantly reduced high doses of influenza infection-induced lung pathology. In addition, flu infection reduced PPARγ expression in all mouse macrophages, including AMs, interstitial macrophages, and bone-marrow-derived macrophages but not in alveolar epithelial cells. Our results indicate that the influenza virus specifically targets the PPARγ pathway in macrophages to cause acute injury to the lung.


Assuntos
Antivirais , Influenza Humana , Pulmão , Macrófagos , PPAR gama , Troglitazona , Lesão Pulmonar Aguda/tratamento farmacológico , Lesão Pulmonar Aguda/genética , Lesão Pulmonar Aguda/imunologia , Animais , Antivirais/imunologia , Antivirais/uso terapêutico , Síndrome da Liberação de Citocina/tratamento farmacológico , Síndrome da Liberação de Citocina/genética , Síndrome da Liberação de Citocina/imunologia , Humanos , Influenza Humana/tratamento farmacológico , Influenza Humana/genética , Influenza Humana/imunologia , Pulmão/imunologia , Macrófagos/imunologia , Camundongos , Orthomyxoviridae , Infecções por Orthomyxoviridae/tratamento farmacológico , Infecções por Orthomyxoviridae/genética , Infecções por Orthomyxoviridae/imunologia , Infecções por Orthomyxoviridae/virologia , PPAR gama/agonistas , PPAR gama/genética , PPAR gama/imunologia , Troglitazona/imunologia , Troglitazona/uso terapêutico
6.
Sheng Wu Gong Cheng Xue Bao ; 38(9): 3390-3405, 2022 Sep 25.
Artigo em Chinês | MEDLINE | ID: mdl-36151808

RESUMO

Influenza B virus (IBV) is more likely to cause complications than influenza A virus (IAV) and even causes higher disease burden than IAV in a certain season, but IBV has received less attention. In order to analyze the genetic evolution characteristics of the clinical strain IBV (B/Guangxi-Jiangzhou/1352/2018), we constructed genetic evolution trees and analyzed the homology and different amino acids of hemagglutinin and neuraminidase referring to the vaccine strains recommended by World Health Organization (WHO). We found that strain B/Guangxi-Jiangzhou/1352/2018 was free of interlineage reassortment and poorly matched with the vaccine strain B/Colorado/06/2017 of the same year. We also determined the median lethal dose (LD50) and the pathogenicity of strain B/Guangxi-Jiangzhou/1352/2018 in mice. The results showed that the LD50 was 105.9 TCID50 (median tissue culture infective dose), the IBV titer in the lungs reached peak 1 d post infection and the mRNA level of the most of inflammatory cytokines in the lungs reached peak 12 h post infection. The alveoli in the lungs were severely damaged and a large number of inflammatory cells were infiltrated post infection. The study demonstrated that the clinical strain IBV (B/Guangxi-Jiangzhou/1352/2018) could infect mice and induce typical lung inflammation. This will facilitate the research on the pathogenesis and transmission mechanism of IBV, and provide an ideal animal model for evaluation of new vaccines, antiviral and anti-inflammatory drug.


Assuntos
Vírus da Influenza B , Influenza Humana , Aminoácidos/genética , Animais , Antivirais/farmacologia , China , Citocinas/metabolismo , Hemaglutininas/metabolismo , Humanos , Vírus da Influenza B/genética , Vírus da Influenza B/patogenicidade , Influenza Humana/imunologia , Influenza Humana/virologia , Camundongos , Neuraminidase/genética , Infecções por Orthomyxoviridae/imunologia , Infecções por Orthomyxoviridae/virologia , Filogenia , RNA Mensageiro/metabolismo , Virulência/genética
7.
J Exp Med ; 219(11)2022 11 07.
Artigo em Inglês | MEDLINE | ID: mdl-36112363

RESUMO

Autoantibodies neutralizing type I interferons (IFNs) can underlie critical COVID-19 pneumonia and yellow fever vaccine disease. We report here on 13 patients harboring autoantibodies neutralizing IFN-α2 alone (five patients) or with IFN-ω (eight patients) from a cohort of 279 patients (4.7%) aged 6-73 yr with critical influenza pneumonia. Nine and four patients had antibodies neutralizing high and low concentrations, respectively, of IFN-α2, and six and two patients had antibodies neutralizing high and low concentrations, respectively, of IFN-ω. The patients' autoantibodies increased influenza A virus replication in both A549 cells and reconstituted human airway epithelia. The prevalence of these antibodies was significantly higher than that in the general population for patients <70 yr of age (5.7 vs. 1.1%, P = 2.2 × 10-5), but not >70 yr of age (3.1 vs. 4.4%, P = 0.68). The risk of critical influenza was highest in patients with antibodies neutralizing high concentrations of both IFN-α2 and IFN-ω (OR = 11.7, P = 1.3 × 10-5), especially those <70 yr old (OR = 139.9, P = 3.1 × 10-10). We also identified 10 patients in additional influenza patient cohorts. Autoantibodies neutralizing type I IFNs account for ∼5% of cases of life-threatening influenza pneumonia in patients <70 yr old.


Assuntos
Autoanticorpos , Influenza Humana , Interferon Tipo I , Pneumonia , COVID-19/complicações , COVID-19/imunologia , Humanos , Influenza Humana/complicações , Influenza Humana/imunologia , Interferon Tipo I/imunologia , Interferon Tipo I/metabolismo , Pneumonia/complicações , Pneumonia/imunologia , Vacina contra Febre Amarela/efeitos adversos
8.
Proc Natl Acad Sci U S A ; 119(37): e2210321119, 2022 09 13.
Artigo em Inglês | MEDLINE | ID: mdl-36001732

RESUMO

Long noncoding RNAs (lncRNAs) have emerged as critical regulators of gene expression, yet their contribution to immune regulation in humans remains poorly understood. Here, we report that the primate-specific lncRNA CHROMR is induced by influenza A virus and SARS-CoV-2 infection and coordinates the expression of interferon-stimulated genes (ISGs) that execute antiviral responses. CHROMR depletion in human macrophages reduces histone acetylation at regulatory regions of ISG loci and attenuates ISG expression in response to microbial stimuli. Mechanistically, we show that CHROMR sequesters the interferon regulatory factor (IRF)-2-dependent transcriptional corepressor IRF2BP2, thereby licensing IRF-dependent signaling and transcription of the ISG network. Consequently, CHROMR expression is essential to restrict viral infection of macrophages. Our findings identify CHROMR as a key arbitrator of antiviral innate immune signaling in humans.


Assuntos
COVID-19 , Proteínas de Ligação a DNA , Imunidade Inata , Vírus da Influenza A , Influenza Humana , RNA Longo não Codificante , SARS-CoV-2 , Fatores de Transcrição , COVID-19/genética , COVID-19/imunologia , Proteínas de Ligação a DNA/metabolismo , Humanos , Imunidade Inata/genética , Vírus da Influenza A/imunologia , Influenza Humana/genética , Influenza Humana/imunologia , Fatores Reguladores de Interferon/genética , Fatores Reguladores de Interferon/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/fisiologia , SARS-CoV-2/imunologia , Fatores de Transcrição/metabolismo
9.
J Virol ; 96(16): e0097122, 2022 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-35916512

RESUMO

The continuous antigenic variation of influenza A viruses remains a major hurdle for vaccine selection; however, the molecular determinants and mechanisms of antigenic change remain largely unknown. In this study, two escape mutants were generated by serial passages of the Eurasian avian-like H1N1 swine influenza virus (EA H1N1 SIV) A/swine/Henan/11/2005 (HeN11) in the presence of two neutralizing monoclonal antibodies (mAbs) against the hemagglutinin (HA) protein, which were designated HeN11-2B6-P5 and HeN11-4C7-P8, respectively. The HeN11-2B6-P5 mutant simultaneously harbored the N190D and I230M substitutions in HA, whereas HeN11-4C7-P8 harbored the M269R substitution in HA (H3 numbering). The effects of each of these substitutions on viral antigenicity were determined by measuring the neutralization and hemagglutination inhibition (HI) titers with mAbs and polyclonal sera raised against the representative viruses. The results indicate that residues 190 and 269 are key determinants of viral antigenic variation. In particular, the N190D mutation had the greatest antigenic impact, as determined by the HI assay. Further studies showed that both HeN11-2B6-P5 and HeN11-4C7-P8 maintained the receptor-binding specificity of the parent virus, although the single mutation N190D decreased the binding affinity for the human-type receptor. The replicative ability in vitro of HeN11-2B6-P5 was increased, whereas that of HeN11-4C7-P8 was decreased. These findings extend our understanding of the antigenic evolution of influenza viruses under immune pressure and provide insights into the functional effects of amino acid substitutions near the receptor-binding site and the interplay among receptor binding, viral replication, and antigenic drift. IMPORTANCE The antigenic changes that occur continually in the evolution of influenza A viruses remain a great challenge for the effective control of disease outbreaks. Here, we identified three amino acid substitutions (at positions 190, 230, and 269) in the HA of EA H1N1 SIVs that determine viral antigenicity and result in escape from neutralizing monoclonal antibodies. All three of these substitutions have emerged in nature. Of note, residues 190 and 230 have synergistic effects on receptor binding and antigenicity. Our findings provide a better understanding of the functional effects of amino acid substitutions in HA and their consequences for the antigenic drift of influenza viruses.


Assuntos
Glicoproteínas de Hemaglutininação de Vírus da Influenza/genética , Evasão da Resposta Imune , Vírus da Influenza A Subtipo H1N1 , Animais , Anticorpos Monoclonais , Anticorpos Neutralizantes/genética , Anticorpos Antivirais , Deriva e Deslocamento Antigênicos , Antígenos Virais/genética , Hemaglutininas , Humanos , Vírus da Influenza A Subtipo H1N1/genética , Influenza Humana/imunologia , Influenza Humana/virologia , Mutação , Suínos
10.
J Virol ; 96(16): e0089622, 2022 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-35916534

RESUMO

Among circulating influenza viruses in humans, H3N2 viruses typically evolve faster than other subtypes and have caused disease in millions of people since emerging in 1968. Computationally optimized broadly reactive antigen (COBRA) technology is one strategy to broaden vaccine-elicited antibody responses among influenza subtypes. In this study, we determined the structural integrity of an H3N2 COBRA hemagglutinin (HA), TJ5, and we probed the antigenic profile of several H3N2 COBRA HAs by assessing recognition of these immunogens by human B cells from seasonally vaccinated human subjects. Of three recently described COBRA H3 HA antigens (TJ5, NG2, and J4), we determined that TJ5 and J4 HA proteins recognize pre-existing B cells more effectively than NG2 HA and a wild-type Hong Kong/4801/2014 protein. We also isolated a panel of 12 H3 HA-specific human monoclonal antibodies (MAbs) and identified that most MAbs recognize both wild-type and COBRA HA proteins and have functional activity against a broad panel of H3N2 viruses. Most MAbs target the receptor-binding site, and one MAb targets the HA stem. MAb TJ5-5 recognizes TJ5 and J4 COBRA HA proteins but has poor recognition of NG2 HA, similar to the global B-cell analysis. We determined a 3.4 Å structure via cryo-electron microscopy of Fab TJ5-5 complexed with the H3 COBRA TJ5, which revealed residues important to the differential binding. Overall, these studies determined that COBRA H3 HA proteins have correct antigenic and structural features, and the proteins are recognized by B cells and MAbs isolated from seasonally vaccinated humans. IMPORTANCE Vaccine development for circulating influenza viruses, particularly for the H3N2 subtype, remains challenging due to consistent antigenic drift. Computationally optimized broadly reactive antigen (COBRA) technology has proven effective for broadening influenza hemagglutinin (HA)-elicited antibody responses compared to wild-type immunogens. Here, we determined the structural features and antigenic profiles of H3 COBRA HA proteins. Two H3 COBRA HA proteins, TJ5 and J4, are better recognized by pre-existing B cells and monoclonal antibodies from the 2017 to 2018 vaccine season compared to COBRA NG2 and a wild-type A/Hong Kong/2014 HA protein. We determined a cryo-electron microscopy (cryo-EM) structure of one MAb that poorly recognizes NG2, MAb TJ5-5, in complex with the TJ5 COBRA HA protein and identified residues critical to MAb recognition. As NG2 is more effective than TJ5 for the recent Hong Kong/2019 virus, these data provide insights into the diminished effectiveness of influenza vaccines across vaccine seasons.


Assuntos
Glicoproteínas de Hemaglutininação de Vírus da Influenza/química , Vacinas contra Influenza , Influenza Humana , Anticorpos Monoclonais , Microscopia Crioeletrônica , Hemaglutininas , Humanos , Vírus da Influenza A Subtipo H3N2 , Vacinas contra Influenza/química , Influenza Humana/imunologia , Influenza Humana/virologia
11.
J Virol ; 96(15): e0076522, 2022 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-35862681

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza A virus (IAV) represent two highly transmissible airborne pathogens with pandemic capabilities. Although these viruses belong to separate virus families-SARS-CoV-2 is a member of the family Coronaviridae, while IAV is a member of the family Orthomyxoviridae-both have shown zoonotic potential, with significant animal reservoirs in species in close contact with humans. The two viruses are similar in their capacity to infect human airways, and coinfections resulting in significant morbidity and mortality have been documented. Here, we investigate the interaction between SARS-CoV-2 USA-WA1/2020 and influenza H1N1 A/California/04/2009 virus during coinfection. Competition assays in vitro were performed in susceptible cells that were either interferon type I/III (IFN-I/-III) nonresponsive or IFN-I/-III responsive, in addition to an in vivo golden hamster model. We find that SARS-CoV-2 infection does not interfere with IAV biology in vivo, regardless of timing between the infections. In contrast, we observe a significant loss of SARS-CoV-2 replication following IAV infection. The latter phenotype correlates with increased levels of IFN-I/-III and immune priming that interferes with the kinetics of SARS-CoV-2 replication. Together, these data suggest that cocirculation of SARS-CoV-2 and IAV is unlikely to result in increased severity of disease. IMPORTANCE The human population now has two circulating respiratory RNA viruses with high pandemic potential, namely, SARS-CoV-2 and influenza A virus. As both viruses infect the airways and can result in significant morbidity and mortality, it is imperative that we also understand the consequences of getting coinfected. Here, we demonstrate that the host response to influenza A virus uniquely interferes with SARS-CoV-2 biology although the inverse relationship is not evident. Overall, we find that the host response to both viruses is comparable to that to SARS-CoV-2 infection alone.


Assuntos
COVID-19 , Coinfecção , Apresentação Cruzada , Vírus da Influenza A Subtipo H1N1 , Influenza Humana , SARS-CoV-2 , Replicação Viral , Animais , COVID-19/imunologia , COVID-19/mortalidade , COVID-19/virologia , Coinfecção/imunologia , Coinfecção/virologia , Apresentação Cruzada/imunologia , Humanos , Vírus da Influenza A Subtipo H1N1/imunologia , Influenza Humana/imunologia , Influenza Humana/virologia , Interferons/imunologia , Mesocricetus/imunologia , Mesocricetus/virologia , SARS-CoV-2/crescimento & desenvolvimento , SARS-CoV-2/imunologia , Replicação Viral/imunologia
12.
J Virol ; 96(15): e0068922, 2022 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-35862698

RESUMO

Vaccines targeting SARS-CoV-2 have been shown to be highly effective; however, the breadth against emerging variants and the longevity of protection remains unclear. Postimmunization boosting has been shown to be beneficial for disease protection, and as new variants continue to emerge, periodic (and perhaps annual) vaccination will likely be recommended. New seasonal influenza virus vaccines currently need to be developed every year due to continual antigenic drift, an undertaking made possible by a robust global vaccine production and distribution infrastructure. To create a seasonal combination vaccine targeting both influenza viruses and SARS-CoV-2 that is also amenable to frequent reformulation, we have developed an influenza A virus (IAV) genetic platform that allows the incorporation of an immunogenic domain of the SARS-CoV-2 spike (S) protein onto IAV particles. Vaccination with this combination vaccine elicited neutralizing antibodies and provided protection from lethal challenge with both pathogens in mice. This approach may allow the leveraging of established influenza vaccine infrastructure to generate a cost-effective and scalable seasonal vaccine solution for both influenza and coronaviruses. IMPORTANCE The rapid emergence of SARS-CoV-2 variants since the onset of the pandemic has highlighted the need for both periodic vaccination "boosts" and a platform that can be rapidly reformulated to manufacture new vaccines. In this work, we report an approach that can utilize current influenza vaccine manufacturing infrastructure to generate combination vaccines capable of protecting from both influenza virus- and SARS-CoV-2-induced disease. The production of a combined influenza/SARS-CoV-2 vaccine may represent a practical solution to boost immunity to these important respiratory viruses without the increased cost and administration burden of multiple independent vaccines.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Vírus da Influenza A , Vacinas contra Influenza , Infecções por Orthomyxoviridae , SARS-CoV-2 , Vacinas Combinadas , Vírion , Animais , Anticorpos Neutralizantes , Anticorpos Antivirais , COVID-19/imunologia , COVID-19/prevenção & controle , Vacinas contra COVID-19/administração & dosagem , Vacinas contra COVID-19/imunologia , Humanos , Vírus da Influenza A/imunologia , Vacinas contra Influenza/administração & dosagem , Vacinas contra Influenza/imunologia , Influenza Humana/imunologia , Influenza Humana/prevenção & controle , Camundongos , Infecções por Orthomyxoviridae/imunologia , Infecções por Orthomyxoviridae/prevenção & controle , SARS-CoV-2/classificação , SARS-CoV-2/imunologia , Vacinas Combinadas/administração & dosagem , Vacinas Combinadas/imunologia
13.
Eur J Pediatr ; 181(8): 3093-3101, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35705877

RESUMO

The exact immunological mechanisms of post infectious bronchiolitis obliterans (PIBO) in childhood are not fully known. It has been shown that the inflammasome and IL-18 pathway play important roles in the pathogenesis of lung fibrosis. We aimed to investigate the role of caspase-1, IL-18, and IL-18 components in PIBO. From January to May 2020, children with PIBO, children with history of influenza infection without PIBO, and healthy children were asked to participate in the study in three pediatric pulmonology centers. Serum caspase-1, IL-18, IL-18BP, IL-18R, and INF-γ levels were measured by ELISA and compared between the 3 groups. There were 21 children in the PIBO group, 16 children in the influenza group, and 39 children in the healthy control group. No differences in terms of age and gender between the 3 groups were found. IL-18 and IL-18BP levels were higher in the healthy control group (p = 0.018, p = 0.005, respectively). IL-18R was higher in the PIBO group (p = 0.001) and caspase-1 was higher in the PIBO and influenza group than the healthy control group (p = 0.002). IFN-γ levels did not differ between the 3 groups. IL-18BP/IL-18 was higher in the influenza group than the PIBO group and the healthy control group (p = 0.003). CONCLUSIONS: Caspase-1 level was increased in patients with PIBO which suggests that inflammasome activation may have a role in fibrosis; however, IL-18 level was found to be low. Mediators other than IL-18 may be involved in the inflammatory pathway in PIBO. Further immunological studies investigating inflammasome pathway are needed for PIBO with chronic inflammation. WHAT IS KNOWN: • Post infectious bronchiolitis obliterans (PIBO) is a rare, severe chronic lung disease during childhood which is associated with inflammation and fibrosis which lead to partial or complete luminal obstruction especially in small airways. • The exact immunological mechanisms of PIBO in childhood are not fully known. WHAT IS NEW: • Inflammasome activation persists even years after acute infection and may play a role in fibrosis in PIBO. • Mediators other than IL-18 may be involved in these inflammatory pathway.


Assuntos
Bronquiolite Obliterante , Caspase 1 , Interleucina-18 , Bronquiolite Obliterante/sangue , Bronquiolite Obliterante/etiologia , Bronquiolite Obliterante/genética , Bronquiolite Obliterante/imunologia , Estudos de Casos e Controles , Caspase 1/sangue , Caspase 1/genética , Caspase 1/imunologia , Criança , Fibrose/sangue , Fibrose/genética , Fibrose/imunologia , Humanos , Inflamassomos/imunologia , Inflamação/sangue , Inflamação/genética , Inflamação/imunologia , Influenza Humana/sangue , Influenza Humana/complicações , Influenza Humana/genética , Influenza Humana/imunologia , Peptídeos e Proteínas de Sinalização Intercelular/sangue , Peptídeos e Proteínas de Sinalização Intercelular/genética , Peptídeos e Proteínas de Sinalização Intercelular/imunologia , Interleucina-18/sangue , Interleucina-18/genética , Interleucina-18/imunologia
14.
J Exp Med ; 219(6)2022 06 06.
Artigo em Inglês | MEDLINE | ID: mdl-35486090

RESUMO

In this issue of JEM, Bastard et al. (2022. J. Exp. Med.https://doi.org/10.1084/jem.20220028) show that a loss-of-function IFNAR1 allele is common in western Polynesians, while Duncan et al. (2022. J. Exp. Med.https://doi.org/10.1084/jem.20212427) report that a loss-of-function IFNAR2 allele is common in Inuits. Homozygotes lack type I IFN immunity but are selectively vulnerable to influenza, COVID-19 pneumonia, and complications of live-attenuated viral vaccines.


Assuntos
Receptor de Interferon alfa e beta , Alelos , COVID-19/genética , COVID-19/imunologia , Humanos , Influenza Humana/genética , Influenza Humana/imunologia , Polinésia , Receptor de Interferon alfa e beta/genética
15.
BMC Infect Dis ; 22(1): 343, 2022 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-35382755

RESUMO

BACKGROUND: Pneumonia is a common complication of influenza and closely related to mortality in influenza patients. The present study examines cytokines as predictors of the prognosis of influenza-associated pneumonia. METHODS: This study included 101 inpatients with influenza (64 pneumonia and 37 non-pneumonia patients). 48 cytokines were detected in the serum samples of the patients and the clinical characteristics were analyzed. The correlation between them was analyzed to identify predictive biomarkers for the prognosis of influenza-associated pneumonia. RESULTS: Seventeen patients had poor prognosis and developed pneumonia. Among patients with influenza-associated pneumonia, the levels of 8 cytokines were significantly higher in those who had a poor prognosis: interleukin-6 (IL-6), interferon-γ (IFN-γ), granulocyte colony-stimulating factor (G-CSF), monocyte colony-stimulating factor (M-CSF), monocyte chemoattractant protein-1 (MCP-1), monocyte chemoattractant protein-3, Interleukin-2 receptor subunit alpha and Hepatocyte growth factor. Correlation analysis showed that the IL-6, G-CSF, M-CSF, IFN-γ, and MCP-1 levels had positive correlations with the severity of pneumonia. IL-6 and G-CSF showed a strong and positive correlation with poor prognosis in influenza-associated pneumonia patients. The combined effect of the two cytokines resulted in the largest area (0.926) under the receiver-operating characteristic curve. CONCLUSION: The results indicate that the probability of poor prognosis in influenza patients with pneumonia is significantly increased. IL-6, G-CSF, M-CSF, IFN-γ, and MCP-1 levels had a positive correlation with the severity of pneumonia. Importantly, IL-6 and G-CSF were identified as significant predictors of the severity of influenza-associated pneumonia.


Assuntos
Fator Estimulador de Colônias de Granulócitos , Influenza Humana , Interleucina-6 , Pneumonia Viral , Citocinas/sangue , Fator Estimulador de Colônias de Granulócitos/sangue , Humanos , Influenza Humana/complicações , Influenza Humana/imunologia , Interleucina-6/sangue , Pneumonia Viral/diagnóstico , Pneumonia Viral/imunologia , Prognóstico
16.
Nat Commun ; 13(1): 1928, 2022 04 08.
Artigo em Inglês | MEDLINE | ID: mdl-35396513

RESUMO

Mechanical breathing motions have a fundamental function in lung development and disease, but little is known about how they contribute to host innate immunity. Here we use a human lung alveolus chip that experiences cyclic breathing-like deformations to investigate whether physical forces influence innate immune responses to viral infection. Influenza H3N2 infection of mechanically active chips induces a cascade of host responses including increased lung permeability, apoptosis, cell regeneration, cytokines production, and recruitment of circulating immune cells. Comparison with static chips reveals that breathing motions suppress viral replication by activating protective innate immune responses in epithelial and endothelial cells, which are mediated in part through activation of the mechanosensitive ion channel TRPV4 and signaling via receptor for advanced glycation end products (RAGE). RAGE inhibitors suppress cytokines induction, while TRPV4 inhibition attenuates both inflammation and viral burden, in infected chips with breathing motions. Therefore, TRPV4 and RAGE may serve as new targets for therapeutic intervention in patients infected with influenza and other potential pandemic viruses that cause life-threatening lung inflammation.


Assuntos
Antígenos de Neoplasias , Imunidade Inata , Influenza Humana , Proteínas Quinases Ativadas por Mitógeno , Canais de Cátion TRPV , Antígenos de Neoplasias/metabolismo , Citocinas , Células Endoteliais , Humanos , Vírus da Influenza A Subtipo H3N2 , Influenza Humana/imunologia , Pulmão , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Canais de Cátion TRPV/metabolismo
17.
Virol J ; 19(1): 39, 2022 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-35248104

RESUMO

BACKGROUND: Influenza A viruses (IAVs) are zoonotic, segmented negative-stranded RNA viruses. The rapid mutation of IAVs results in host immune response escape and antiviral drug and vaccine resistance. RUNX1 is a transcription factor that not only plays essential roles in hematopoiesis, but also functions as a regulator in inflammation. However, its role in the innate immunity to IAV infection has not been well studied. METHODS: To investigate the effects of RUNX1 on IAV infection and explore the mechanisms that RUNX1 uses during IAV infection. We infected the human alveolar epithelial cell line (A549) with influenza virus A/Puerto Rico/8/34 (H1N1) (PR8) and examined RUNX1 expression by Western blot and qRT-PCR. We also knocked down or overexpressed RUNX1 in A549 cells, then evaluated viral replication by Western blot, qRT-PCR, and viral titration. RESULTS: We found RUNX1 expression is induced by IAV H1N1 PR8 infection, but not by poly(I:C) treatment, in the human alveolar epithelial cell line A549. Knockdown of RUNX1 significantly inhibited IAV infection. Conversely, overexpression of RUNX1 efficiently promoted production of progeny viruses. Additionally, RUNX1 knockdown increased IFN-ß and ISGs production while RUNX1 overexpression compromised IFN-ß and ISGs production upon PR8 infection in A549 cells. We further showed that RUNX1 may attenuate the interferon signaling transduction by hampering the expression of IRF3 and STAT1 during IAV infection. CONCLUSIONS: Taken together, we found RUNX1 attenuates type I interferon signaling to facilitate IAV infection in A549 cells.


Assuntos
Subunidade alfa 2 de Fator de Ligação ao Core , Influenza Humana , Interferon Tipo I , Células A549 , Fatores de Restrição Antivirais , Subunidade alfa 2 de Fator de Ligação ao Core/genética , Interações Hospedeiro-Patógeno , Humanos , Imunidade Inata , Vírus da Influenza A Subtipo H1N1/metabolismo , Influenza Humana/imunologia , Interferon Tipo I/imunologia , Interferon beta/genética , Replicação Viral
19.
Cells ; 11(3)2022 01 30.
Artigo em Inglês | MEDLINE | ID: mdl-35159296

RESUMO

The global outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still ongoing, as is research on the molecular mechanisms underlying cellular infection by coronaviruses, with the hope of developing therapeutic agents against this pandemic. Other important respiratory viruses such as 2009 pandemic H1N1 and H7N9 avian influenza virus (AIV), influenza A viruses, are also responsible for a possible outbreak due to their respiratory susceptibility. However, the interaction of these viruses with host cells and the regulation of post-transcriptional genes remains unclear. In this study, we detected and analyzed the comparative transcriptome profiling of SARS-CoV-2, panH1N1 (A/California/07/2009), and H7N9 (A/Shanghai/1/2013) infected cells. The results showed that the commonly upregulated genes among the three groups were mainly involved in autophagy, pertussis, and tuberculosis, which indicated that autophagy plays an important role in viral pathogenicity. There are three groups of commonly downregulated genes involved in metabolic pathways. Notably, unlike panH1N1 and H7N9, SARS-CoV-2 infection can inhibit the m-TOR pathway and activate the p53 signaling pathway, which may be responsible for unique autophagy induction and cell apoptosis. Particularly, upregulated expression of IRF1 was found in SARS-CoV-2, panH1N1, and H7N9 infection. Further analysis showed SARS-CoV-2, panH1N1, and H7N9 infection-induced upregulation of lncRNA-34087.27 could serve as a competitive endogenous RNA to stabilize IRF1 mRNA by competitively binding with miR-302b-3p. This study provides new insights into the molecular mechanisms of influenza A virus and SARS-CoV-2 infection.


Assuntos
COVID-19/imunologia , Imunidade/imunologia , Vírus da Influenza A Subtipo H1N1/imunologia , Subtipo H7N9 do Vírus da Influenza A/imunologia , Influenza Humana/imunologia , RNA/imunologia , Transcriptoma/imunologia , Células A549 , Animais , COVID-19/genética , COVID-19/virologia , Células HEK293 , Interações Hospedeiro-Patógeno/imunologia , Humanos , Imunidade/genética , Vírus da Influenza A Subtipo H1N1/fisiologia , Subtipo H7N9 do Vírus da Influenza A/fisiologia , Influenza Humana/genética , Influenza Humana/virologia , Fator Regulador 1 de Interferon/genética , Fator Regulador 1 de Interferon/imunologia , Fator Regulador 1 de Interferon/metabolismo , MicroRNAs/genética , MicroRNAs/imunologia , MicroRNAs/metabolismo , Pandemias/prevenção & controle , RNA/genética , RNA/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/imunologia , RNA Longo não Codificante/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/imunologia , RNA Mensageiro/metabolismo , RNA-Seq/métodos , SARS-CoV-2/fisiologia , Transdução de Sinais/genética , Transdução de Sinais/imunologia , Transcriptoma/genética
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