Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 11.084
Filtrar
1.
Elife ; 122023 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-36626205

RESUMO

Virus-based tumour vaccines offer many advantages compared to other antigen-delivering systems. They generate concerted innate and adaptive immune response, and robust CD8+ T cell responses. We engineered a non-replicating pseudotyped influenza virus (S-FLU) to deliver the well-known cancer testis antigen, NY-ESO-1 (NY-ESO-1 S-FLU). Intranasal or intramuscular immunization of NY-ESO-1 S-FLU virus in mice elicited a strong NY-ESO-1-specific CD8+ T cell response in lungs and spleen that resulted in the regression of NY-ESO-1-expressing lung tumour and subcutaneous tumour, respectively. Combined administration with anti-PD-1 antibody, NY-ESO-1 S-FLU virus augmented the tumour protection by reducing the tumour metastasis. We propose that the antigen delivery through S-FLU is highly efficient in inducing antigen-specific CD8+ T cell response and protection against tumour development in combination with PD-1 blockade.


Assuntos
Inibidores de Checkpoint Imunológico , Orthomyxoviridae , Masculino , Camundongos , Animais , Antígenos de Neoplasias , Proteínas de Membrana , Imunização , Anticorpos , Linfócitos T CD8-Positivos
2.
PLoS One ; 18(1): e0280811, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36662890

RESUMO

Manufactured influenza vaccines have to contain a defined amount of hemagglutinin (HA) antigen. Therefore, vaccine viruses with a high HA antigen yield (HAY) are preferable for manufacturing vaccines, particularly vaccines in response to a pandemic, when vaccines need to be rapidly produced. However, the viral properties associated with a high HAY have not yet been fully clarified. To identify the HAY-associated traits, we first propagated 26 H5 candidate vaccine viruses (CVVs) in eggs, which were previously developed based on genetic reassortment methods using master viruses, to determine their total protein yield (TPY), ratio of HA to total viral protein (%-HA content) and HAY. The results revealed that the HAY was correlated with the TPY but not with the %-HA content. We further found that altering the sequences of the 3' noncoding region of HA vRNA or replacing the master virus improved the HAYs and TPYs of the low-HAY CVVs to approximately double the values of the original CVVs but did not change the %-HA content, which a previous study suggested was associated with the HAY. Analyses based on real-time PCR assays and scanning electron microscopy revealed that the virus samples with an improved HAY contained more copies of the virus genome and viral particles than the original samples. The results suggest that an improvement in virus growth (i.e., an increase in the amount of viral particles) leads to an increase in the TPY and thus in the HAY, regardless of the %-HA content. The approximately twofold increase in the HAY shown in this study may not appear to represent a large improvement, but the impact will be significant given the millions of chicken eggs used to produce vaccines. These findings will be informative for developing high-HAY vaccine viruses.


Assuntos
Vacinas contra Influenza , Orthomyxoviridae , Animais , Hemaglutininas/genética , Glicoproteínas de Hemaglutininação de Vírus da Influenza , Galinhas , Anticorpos Antivirais
3.
Toxins (Basel) ; 15(1)2023 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-36668886

RESUMO

Aflatoxin B1 (AFB1), one of the most common environmental mycotoxin contaminations in food and feed, poses significant threats to human and animal health. Our previous study indicated that even non-toxic AFB1 concentrations could promote influenza virus replication and induce influenza virus-infected alveolar macrophages polarizing from M1 (immunostimulatory phenotype) to M2 (immunosuppressive phenotype) over time. However, whether AFB1 promotes influenza replication via modulating the polarization of alveolar macrophages is unknown. Here, we specifically depleted alveolar macrophages using clodronate-containing liposomes in swine influenza virus (SIV)-infected mice to explore the mechanism the promotion of SIV replication by AFB1. The results show that the depletion of alveolar macrophages significantly alleviated the AFB1-induced weight loss, inflammatory responses, and lung and immune organ damage of the SIV-infected mice after 14 days and greatly diminished the AFB1-promoted SIV replication. In contrast, the depletion of alveolar macrophages did not alleviate the AFB1-induced weight loss, and lung and immune organ damage of the SIV-infected mice after 28 days and slightly diminished the AFB1-promoted SIV replication. Collectively, the data indicate that alveolar macrophages play a crucial role the promotion of SIV infection by AFB1 in the early rather than late stage, and AFB1 can promote SIV replication by inducing alveolar macrophages to polarize towards M1 macrophages. This research provides novel targets for reducing the risk of AFB1-promoted influenza virus infection.


Assuntos
Influenza Humana , Infecções por Orthomyxoviridae , Orthomyxoviridae , Animais , Humanos , Camundongos , Macrófagos Alveolares , Aflatoxina B1/toxicidade , Redução de Peso
4.
Arch Virol ; 168(2): 53, 2023 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-36609722

RESUMO

The prevalence of coinfection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza virus among referred patients in Hamadan province, Iran, from November 2, 2021, to January 30, 2022, was evaluated. Samples were obtained from 14,116 individuals with COVID-19 symptoms and screened for SARS-CoV-2 and influenza viruses using a multiplex real-time PCR panel assay. Of these patients, 14.19%, 17.11%, and 1.35% were infected with influenza virus, SARS-CoV-2, and both viruses, respectively. The majority of the coinfected patients were female outpatients aged 19-60 years.


Assuntos
COVID-19 , Coinfecção , Influenza Humana , Orthomyxoviridae , Humanos , Feminino , Masculino , COVID-19/epidemiologia , SARS-CoV-2 , Coinfecção/epidemiologia , Pandemias , Orthomyxoviridae/genética
5.
Eur J Med Chem ; 247: 115035, 2023 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-36603507

RESUMO

Influenza is one of the leading causes of disease-related mortalities worldwide. Several strategies have been implemented during the past decades to hinder the replication cycle of influenza viruses, all of which have resulted in the emergence of resistant virus strains. The most recent example is baloxavir marboxil, where a single mutation in the active site of the target endonuclease domain of the RNA-dependent-RNA polymerase renders the recent FDA approved compound ∼1000-fold less effective. Raltegravir is a first-in-class HIV inhibitor that shows modest activity to the endonuclease. Here, we have used structure-guided approaches to create rationally designed derivative molecules that efficiently engage the endonuclease active site. The design strategy was driven by our previously published structures of endonuclease-substrate complexes, which allowed us to target functionally conserved residues and reduce the likelihood of resistance mutations. We succeeded in developing low nanomolar equipotent inhibitors of both wild-type and baloxavir-resistant endonuclease. We also developed macrocyclic versions of these inhibitors that engage the active site in the same manner as their 'open' counterparts but with reduced affinity. Structural analyses provide clear avenues for how to increase the affinity of these cyclic compounds.


Assuntos
Dibenzotiepinas , Inibidores de Integrase de HIV , Influenza Humana , Orthomyxoviridae , Humanos , RNA Polimerase Dependente de RNA , Piridonas/farmacologia , Piridonas/uso terapêutico , Influenza Humana/tratamento farmacológico , Dibenzotiepinas/farmacologia , Dibenzotiepinas/uso terapêutico , Endonucleases , Triazinas/farmacologia , Antivirais/farmacologia
6.
Viruses ; 15(1)2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36680284

RESUMO

The emergence and spread of antiviral-resistant influenza viruses are of great concern. To minimize the public health risk, it is important to monitor antiviral susceptibilities of influenza viruses. Analyses of the antiviral susceptibilities of influenza A and B viruses have been conducted globally; however, those of influenza C and D viruses are limited. Here, we determined the susceptibilities of influenza C viruses representing all six lineages (C/Taylor, C/Yamagata, C/Sao Paulo, C/Aichi, C/Kanagawa, and C/Mississippi) and influenza D viruses representing four lineages (D/OK, D/660, D/Yama2016, and D/Yama2019) to RNA polymerase inhibitors (baloxavir and favipiravir) by using a focus reduction assay. All viruses tested were susceptible to both drugs. We then performed a genetic analysis to check for amino acid substitutions associated with baloxavir and favipiravir resistance and found that none of the viruses tested possessed these substitutions. Use of the focus reduction assay with the genotypic assay has proven valuable for monitoring the antiviral susceptibilities of influenza C and D viruses as well as influenza A and B viruses. Antiviral susceptibility monitoring of all influenza virus types should continue in order to assess the public health risks posed by these viruses.


Assuntos
Influenza Humana , Orthomyxoviridae , Humanos , Influenza Humana/tratamento farmacológico , Antivirais/farmacologia , Antivirais/uso terapêutico , Brasil , Farmacorresistência Viral/genética
7.
BMC Pediatr ; 23(1): 35, 2023 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-36681802

RESUMO

BACKGROUND: Anti-influenza treatment is important for children and is recommended in many countries. This study assessed safety, clinical, and virologic outcomes of baloxavir marboxil (baloxavir) treatment in children based on age and influenza virus type/subtype. METHODS: This was a post hoc pooled analysis of two open-label non-controlled studies of a single weight-based oral dose of baloxavir (day 1) in influenza virus-infected Japanese patients aged < 6 years (n = 56) and ≥ 6 to < 12 years (n = 81). Safety, time to illness alleviation (TTIA), time to resolution of fever (TTRF), recurrence of influenza illness symptoms and fever (after day 4), virus titer, and outcomes by polymerase acidic protein variants at position I38 (PA/I38X) were evaluated. RESULTS: Adverse events were reported in 39.0 and 39.5% of patients < 6 years and ≥ 6 to < 12 years, respectively. Median (95% confidence interval) TTIA was 43.2 (36.3-68.4) and 45.4 (38.9-61.0) hours, and TTRF was 32.2 (26.8-37.8) and 20.7 (19.2-23.8) hours, for patients < 6 years and ≥ 6 to < 12 years, respectively. Symptom and fever recurrence was more common in patients < 6 years with influenza B (54.5 and 50.0%, respectively) compared with older patients (0 and 25.0%, respectively). Virus titers declined (day 2) for both age groups. Transient virus titer increase and PA/I38X-variants were more common for patients < 6 years. CONCLUSIONS: The safety and effectiveness of single-dose baloxavir were observed in children across all age groups and influenza virus types. Higher rates of fever recurrence and transient virus titer increase were observed in children < 6 years. TRIAL REGISTRATION: Japan Pharmaceutical Information Center Clinical Trials Information JapicCTI-163,417 (registered 02 November 2016) and JapicCTI-173,811 (registered 15 December 2017).


Assuntos
Dibenzotiepinas , Influenza Humana , Orthomyxoviridae , Tiepinas , Criança , Humanos , Antivirais/efeitos adversos , Dibenzotiepinas/uso terapêutico , Febre/tratamento farmacológico , Influenza Humana/tratamento farmacológico , Japão , Oxazinas/efeitos adversos , Piridinas/efeitos adversos , Piridonas , Tiepinas/uso terapêutico , Tiepinas/efeitos adversos , Triazinas/efeitos adversos
8.
Cell Host Microbe ; 31(1): 146-157, 2023 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-36634620

RESUMO

Viruses that replicate in the human respiratory mucosa without infecting systemically, including influenza A, SARS-CoV-2, endemic coronaviruses, RSV, and many other "common cold" viruses, cause significant mortality and morbidity and are important public health concerns. Because these viruses generally do not elicit complete and durable protective immunity by themselves, they have not to date been effectively controlled by licensed or experimental vaccines. In this review, we examine challenges that have impeded development of effective mucosal respiratory vaccines, emphasizing that all of these viruses replicate extremely rapidly in the surface epithelium and are quickly transmitted to other hosts, within a narrow window of time before adaptive immune responses are fully marshaled. We discuss possible approaches to developing next-generation vaccines against these viruses, in consideration of several variables such as vaccine antigen configuration, dose and adjuventation, route and timing of vaccination, vaccine boosting, adjunctive therapies, and options for public health vaccination polices.


Assuntos
COVID-19 , Vacinas contra Influenza , Influenza Humana , Orthomyxoviridae , Humanos , COVID-19/prevenção & controle , SARS-CoV-2/genética , Anticorpos Antivirais
9.
Int J Mol Sci ; 24(2)2023 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-36674746

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the COVID-19 pandemic, whereas the influenza A virus (IAV) causes seasonal epidemics and occasional pandemics. Both viruses lead to widespread infection and death. SARS-CoV-2 and the influenza virus are RNA viruses. The SARS-CoV-2 genome is an approximately 30 kb, positive sense, 5' capped single-stranded RNA molecule. The influenza A virus genome possesses eight single-stranded negative-sense segments. The RNA secondary structure in the untranslated and coding regions is crucial in the viral replication cycle. The secondary structure within the RNA of SARS-CoV-2 and the influenza virus has been intensively studied. Because the whole of the SARS-CoV-2 and influenza virus replication cycles are dependent on RNA with no DNA intermediate, the RNA is a natural and promising target for the development of inhibitors. There are a lot of RNA-targeting strategies for regulating pathogenic RNA, such as small interfering RNA for RNA interference, antisense oligonucleotides, catalytic nucleic acids, and small molecules. In this review, we summarized the knowledge about the inhibition of SARS-CoV-2 and influenza A virus propagation by targeting their RNA secondary structure.


Assuntos
COVID-19 , Vírus da Influenza A , Orthomyxoviridae , Humanos , SARS-CoV-2 , Vírus da Influenza A/genética , Motivos de Nucleotídeos , Pandemias , RNA , RNA Viral/genética , RNA Viral/química
11.
Int J Biol Macromol ; 226: 885-899, 2023 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-36521707

RESUMO

Despite the availability of prevention and treatment strategies and advancing immunization approaches, the influenza virus remains a global threat that continues to plague humanity with unpredictable pandemics. Due to the unusual genetic variability and segmented genome, the reassortment between different strains of influenza is facilitated and the viruses continuously evolve and adapt to the host cell's immunity. This underlies the seasonal vaccine mismatches that decrease the vaccine efficacy and increase the risk of outbreaks. Thus, the development of a universal vaccine covering all the influenza A and B strains would reduce the pervasiveness of the influenza virus. In the current study, a potentially universal influenza multi-epitope vaccine was designed based on the experimentally tested conserved T cell and B cell epitopes of hemagglutinin (HA), neuraminidase (NA), nucleoprotein (NP), and matrix-2 proton channel (M2) of the virus. The immune simulation and molecular docking of the vaccine construct with TLR2, TLR3, and TLR4 elicited the favorable immunogenicity of the vaccine and the formation of stable complexes, respectively. Ultimately, based on the immunoinformatics analysis, the universal mRNA multi-epitope vaccine designed in this study might have a protection potential against the various subtypes of influenza A and B.


Assuntos
Vacinas contra Influenza , Influenza Humana , Orthomyxoviridae , Humanos , Influenza Humana/epidemiologia , Influenza Humana/prevenção & controle , Epitopos/genética , Pandemias/prevenção & controle , Simulação de Acoplamento Molecular , Anticorpos Antivirais
12.
Vaccine ; 41(3): 787-794, 2023 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-36526501

RESUMO

Among inactivated influenza vaccines, the whole virus particle vaccine (WPV) elicits superior priming responses to split virus vaccine (SV) in efficiently inducing humoral and cellular immunity. However, there is concern for undesired adverse events such as fever for WPV due to its potent immunogenicity. Therefore, this study investigated the febrile response induced by subcutaneous injection with quadrivalent inactivated influenza vaccines of good manufacturing grade for pharmaceutical or investigational products in cynomolgus macaques. Body temperature was increased by 1 °C-2 °C for 6-12 h after WPV administration at the first vaccination but not at the second shot, whereas SV did not affect body temperature at both points. Given the potent priming ability of WPV, WPV-induced fever may be attributed to immune responses that uniquely occur during priming. Since WPV-induced fever was blunted by pretreatment with indomethacin (a cyclooxygenase inhibitor), the febrile response by WPV is considered to depend on the increase in prostaglandins synthesized by cyclooxygenase. In addition, WPV, but not SV, induced the elevation of type I interferons and monocyte chemotactic protein 1 in the plasma; these factors may be responsible for pyrogenicity caused by WPV, as they can increase prostaglandins in the brain. Notably, sufficient antibody responses were acquired by half the amount of WPV without causing fever, suggesting that excessive immune responses to trigger the febrile response is not required for acquired immunity induction. Thus, we propose that WPV with a reduced antigen dose should be evaluated for potential clinical usage, especially in naïve populations.


Assuntos
Vacinas contra Influenza , Influenza Humana , Orthomyxoviridae , Animais , Humanos , Influenza Humana/prevenção & controle , Macaca fascicularis , Febre/induzido quimicamente , Vacinas de Produtos Inativados , Prostaglandinas , Anticorpos Antivirais
13.
J Med Chem ; 66(1): 188-219, 2023 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-36521178

RESUMO

Influenza PAN inhibitors are of particular importance in current efforts to develop a new generation of antiviral drugs due to the growing emergence of highly pathogenic influenza viruses and the resistance to existing antiviral inhibitors. Herein, we design and synthesize a set of 1,3-cis-N-substituted-1,2,3,4-tetrahydroisoquinoline derivatives to enhance their potency by further exploiting the pockets 3 and 4 in the PAN endonuclease based on the hit d,l-laudanosoline. Particularly, the lead compound 35 exhibited potent and broad anti-influenza virus effects with EC50 values ranging from 0.43 to 1.12 µM in vitro and good inhibitory activity in a mouse model. Mechanistic studies demonstrated that 35 could bind tightly to the PAN endonuclease of RNA-dependent RNA polymerase, thus blocking the viral replication to exert antiviral activity. Overall, our study might establish the importance of 1,2,3,4-tetrahydroisoquinoline-6,7-diol-based derivatives for the development of novel PAN inhibitors of influenza viruses.


Assuntos
Influenza Humana , Orthomyxoviridae , Tetra-Hidroisoquinolinas , Animais , Camundongos , Humanos , Tetra-Hidroisoquinolinas/farmacologia , Antivirais/farmacologia , Antivirais/metabolismo , Endonucleases
14.
Influenza Other Respir Viruses ; 17(1): e13081, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36480419

RESUMO

BACKGROUND: Public health organizations have recommended various definitions of influenza-like illnesses under the assumption that the symptoms do not change during influenza virus infection. To explore the relationship between symptoms and influenza over time, we analyzed a dataset from an international multicenter prospective emergency department (ED)-based influenza-like illness cohort study. METHODS: We recruited patients in the US and Taiwan between 2015 and 2020 with: (1) flu-like symptoms (fever and cough, headache, or sore throat), (2) absence of any of the respiratory infection symptoms, or (3) positive laboratory test results for influenza from the current ED visit. We evaluated the association between the symptoms and influenza virus infection on different days of illness. The association was evaluated among different subgroups, including different study countries, influenza subtypes, and only patients with influenza. RESULTS: Among the 2471 recruited patients, 45.7% tested positive for influenza virus. Cough was the most predictive symptom throughout the week (odds ratios [OR]: 7.08-11.15). In general, all symptoms were more predictive during the first 2 days (OR: 1.55-10.28). Upper respiratory symptoms, such as sore throat and productive cough, and general symptoms, such as body ache and fatigue, were more predictive in the first half of the week (OR: 1.51-3.25). Lower respiratory symptoms, such as shortness of breath and wheezing, were more predictive in the second half of the week (OR: 1.52-2.52). Similar trends were observed for most symptoms in the different subgroups. CONCLUSIONS: The time course is an important factor to be considered when evaluating the symptoms of influenza virus infection.


Assuntos
Influenza Humana , Orthomyxoviridae , Faringite , Humanos , Influenza Humana/diagnóstico , Influenza Humana/epidemiologia , Tosse , Estudos Prospectivos , Estudos de Coortes
15.
Nat Commun ; 13(1): 7336, 2022 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-36470871

RESUMO

To infect, enveloped viruses employ spike protein, spearheaded by its amphipathic fusion peptide (FP), that upon activation extends out from the viral surface to embed into the target cellular membrane. Here we report that synthesized influenza virus FPs are membrane active, generating pores in giant unilamellar vesicles (GUV), and thus potentially explain both influenza virus' hemolytic activity and the liposome poration seen in cryo-electron tomography. Experimentally, FPs are heterogeneously distributed on the GUV at the time of poration. Consistent with this heterogeneous distribution, molecular dynamics (MD) simulations of asymmetric bilayers with different numbers of FPs in one leaflet show FP aggregation. At the center of FP aggregates, a profound change in the membrane structure results in thinning, higher water permeability, and curvature. Ultimately, a hybrid bilayer nanodomain forms with one lipidic leaflet and one peptidic leaflet. Membrane elastic theory predicts a reduced barrier to water pore formation when even a dimer of FPs thins the membrane as above, and the FPs of that dimer tilt, to continue the leaflet bending initiated by the hydrophobic mismatch between the FP dimer and the surrounding lipid.


Assuntos
Influenza Humana , Orthomyxoviridae , Humanos , Orthomyxoviridae/metabolismo , Peptídeos , Lipossomas Unilamelares , Água/química , Bicamadas Lipídicas/química , Fusão de Membrana/fisiologia
16.
Zhongguo Zhong Yao Za Zhi ; 47(19): 5306-5315, 2022 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-36472038

RESUMO

Based on Janus kinase 1/2-signal transducer and activator of transcription 1(JAK1/2-STAT1) signaling pathway, this study explored the immune mechanism of Maxing Shigan Decoction in alleviating the lung tissue and colon tissue damage in mice infected with influenza virus. The influenza virus infection was induced in mice by nasal drip of influenza virus. The normal group, model group, oseltamivir group, antiviral granule group, and Maxing Shigan Decoction group were designed. After intragastric administration of corresponding drugs or normal saline for 3 or 7 days, the body mass was measured, and lung index, spleen index, and thymus index were calculated. Based on hematoxylin-eosin(HE) staining, the pathological changes of lung tissue and colon tissue were observed. Enzyme-linked immunosorbent assay(ELISA) was used to detect serum levels of inflammatory factors interleukin-8(IL-8) and interferon-γ(IFN-γ), Western blot and real-time quantitative polymerase chain reaction(RT-qPCR) to determine the protein and mRNA levels of JAK1, JAK2, STAT1, interferon regulatory factor 9(IRF9), and IFN-γ in lung tissue and colon tissue. The results showed that after 3 and 7 days of administration, the body mass, spleen index, and thymus index were lower(P<0.05 or P<0.01), and the lung index was higher(P<0.01) in the model group than in the normal group. Moreover, the model group showed congestion, edema, and infiltration of a large number of lymphocytes and macrophages in the lung tissue, irregular structure of colon mucosa, ulceration and shedding of epithelial cells, and infiltration of a large number of inflammatory cells. The model group had higher levels of serum IFN-γ(P<0.01), higher protein and mRNA expression of JAK1, JAK2, STAT1, IRF9, IFN-γ in lung tissue(P<0.05 or P<0.01), higher level of JAK2 protein in colon tissue(P<0.01), and higher protein and mRNA levels of STAT1 and IRF9(P<0.05 or P<0.01) than the normal group. Compared with the model group, Maxing Shigan Decoction group had high body mass, spleen index, and thymus index(P<0.05 or P<0.01), low lung index(P<0.05 or P<0.01), and significant alleviation of pathological injury in lung and colon. Moreover, lower serum level of IFN-γ(P<0.05 or P<0.01), protein and mRNA levels of JAK1, JAK2, STAT1, IRF9, and IFN-γ in lung tissue(P<0.05 or P<0.01), JAK2 protein level in colon tissue(P<0.01), and protein and mRNA levels of STAT1 and IRF9(P<0.05 or P<0.01) were observed in the Maxing Shigan Decoction group than in the model group. After 3 days of administration, the level of serum IL-8 in the model group was significantly higher than that in the normal group(P<0.01), and the level in the Maxing Shigan Decoction group was significantly reduced(P<0.01). In conclusion, Maxing Shigan Decoction can significantly up-regulate body mass, spleen index, and thymus index, down-regulate lung index, reduce the levels of IL-8 and IFN-γ, and down-regulate protein and mRNA levels of JAK1, JAK2, STAT1, IRF9, and IFN-γ in lung tissue and protein and mRNA levels of JAK2, STAT1, and IRF9 in colon tissue, and alleviate pathological damage of lung tissue and colon tissue. The mechanism is the likelihood that it inhibits the activation of JAK1/2-STAT1 signaling pathway to alleviate the damage to lung and colon tissue damage.


Assuntos
Influenza Humana , Infecções por Orthomyxoviridae , Orthomyxoviridae , Camundongos , Animais , Humanos , Janus Quinase 1/genética , Fator de Transcrição STAT1/genética , Interleucina-8 , Transdução de Sinais , Interferon gama , Pulmão , RNA Mensageiro , Colo
17.
Viruses ; 14(12)2022 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-36560777

RESUMO

Defective interfering particles (DIPs) are particles containing defective viral genomes (DVGs) generated during viral replication. DIPs have been found in various RNA viruses, especially in influenza viruses. Evidence indicates that DIPs interfere with the replication and encapsulation of wild-type viruses, namely standard viruses (STVs) that contain full-length viral genomes. DIPs may also activate the innate immune response by stimulating interferon synthesis. In this review, the underlying generation mechanisms and characteristics of influenza virus DIPs are summarized. We also discuss the potential impact of DIPs on the immunogenicity of live attenuated influenza vaccines (LAIVs) and development of influenza vaccines based on NS1 gene-defective DIPs. Finally, we review the antiviral strategies based on influenza virus DIPs that have been used against both influenza virus and SARS-CoV-2. This review provides systematic insights into the theory and application of influenza virus DIPs.


Assuntos
COVID-19 , Vacinas contra Influenza , Orthomyxoviridae , Humanos , Antivirais , Vírus Defeituosos Interferentes , Vírus Defeituosos/fisiologia , SARS-CoV-2 , Orthomyxoviridae/genética , Replicação Viral/genética
18.
Biosensors (Basel) ; 12(12)2022 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-36551032

RESUMO

We demonstrate the possibility of applying surface-enhanced Raman spectroscopy (SERS) combined with machine learning technology to detect and differentiate influenza type A and B viruses in a buffer environment. The SERS spectra of the influenza viruses do not possess specific peaks that allow for their straight classification and detection. Machine learning technologies (particularly, the support vector machine method) enabled the differentiation of samples containing influenza A and B viruses using SERS with an accuracy of 93% at a concentration of 200 µg/mL. The minimum detectable concentration of the virus in the sample using the proposed approach was ~0.05 µg/mL of protein (according to the Lowry protein assay), and the detection accuracy of a sample with this pathogen concentration was 84%.


Assuntos
Herpesvirus Cercopitecino 1 , Vírus da Influenza A , Influenza Humana , Orthomyxoviridae , Humanos , Análise Espectral Raman/métodos , Influenza Humana/diagnóstico
19.
Artigo em Inglês | MEDLINE | ID: mdl-36498009

RESUMO

Community-acquired infections (CAI) can affect the duration of care and mortality of patients. Therefore, we aimed to investigate these as well as factors influencing the length of hospital stay in patients with CAI due to enteric pathogens, influenza viruses and multidrug-resistant (MDR) bacteria. We obtained data on 531 patients with CAI from the medical databases of a Hungarian university hospital and analyzed their characteristics using a regression model. Patients with MDR bacterial infection had the highest mortality (26.24%) and they stayed significantly longer in the hospital than cases with other CAIs. Our results showed that infection by Clostridioides difficile (odds ratio (OR): 6.98, 95% confidence interval (CI): 1.03-47.48; p = 0.047), MDR Escherichia coli (OR: 7.64, 95% CI: 1.24-47.17; p = 0.029), MDR Klebsiella spp. (OR: 7.35, 95% CI: 1.15-47.07; p = 0.035) and hospitalization in the department of pulmonology (OR: 5.48, 95% CI: 1.38-21.76; p = 0.016) and surgery (OR: 4.19, 95% CI: 1.18-14.81; p = 0.026) significantly increased, whereas female sex (OR: 0.62, 95% CI: 0.40-0.97; p = 0.037) and hospitalization in the department of pediatrics (OR: 0.17, 95% CI: 0.04-0.64; p = 0.009) decreased the odds of staying in the hospital for more than 6 days. Our findings provide new information on the epidemiology of CAI and can contribute to the development of public health programs that decrease the burden of infections acquired in the community.


Assuntos
Infecções Comunitárias Adquiridas , Infecção Hospitalar , Orthomyxoviridae , Humanos , Feminino , Criança , Infecções Comunitárias Adquiridas/epidemiologia , Tempo de Internação , Estudos Transversais , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/microbiologia , Farmacorresistência Bacteriana Múltipla , Escherichia coli , Antibacterianos/uso terapêutico , Antibacterianos/farmacologia , Estudos Retrospectivos
20.
Virol J ; 19(1): 188, 2022 11 16.
Artigo em Inglês | MEDLINE | ID: mdl-36384638

RESUMO

INTRODUCTION: We investigated the performance of the cobas® 6800 system and cobas SARS-CoV-2 & Influenza A/B, a fully automated molecular testing system for influenza viruses and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This enabled an assay in a batch of 96 samples in approximately 3 h. METHODS: An assay was performed using the cobas SARS-CoV-2 & Influenza A/B on the cobas 6800 system for samples collected in four facilities between November 2019 and March 2020 in our previous study. The results were compared with those obtained using the reference methods. RESULTS: Of the 127 samples analyzed, the cobas SARS-CoV-2 & Influenza A/B detected influenza A virus in 75 samples, of which 73 were positive using the reference methods. No false negative results were observed. The overall positive and negative percent agreement for influenza A virus detection were 100.0% and 96.3%, respectively. There were no positive results for the influenza B virus or SARS-CoV-2. CONCLUSION: The cobas 6800 system and cobas SARS-CoV-2 & Influenza A/B showed high accuracy for influenza A virus detection and can be useful for clinical laboratories, especially those that routinely assay many samples.


Assuntos
COVID-19 , Influenza Humana , Orthomyxoviridae , Humanos , Influenza Humana/diagnóstico , SARS-CoV-2/genética , Técnicas de Diagnóstico Molecular
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...