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2.
Sheng Wu Gong Cheng Xue Bao ; 37(9): 3101-3107, 2021 Sep 25.
Artigo em Chinês | MEDLINE | ID: mdl-34622620

RESUMO

Viral myocarditis (VMC) is a disease characterized by inflammation of myocardial cells caused by viral infection. Since the pathogenesis mechanism of VMC has not been fully elucidated, the diagnosis and treatment of this disease remains extremely challenging. Non-coding RNAs (ncRNAs) are a class of RNAs that do not encode proteins. An increasing number of studies have shown that ncRNAs are involved in regulating the occurrence and development of VMC, thus providing potential new targets for the treatment and diagnosis of VMC. This review summarizes the possible roles of ncRNAs in the pathogenesis and diagnosis of VMC revealed recently.


Assuntos
Infecções por Coxsackievirus , Miocardite , Viroses , Enterovirus Humano B , Humanos , Inflamação , Miocardite/genética , Viroses/diagnóstico , Viroses/genética
3.
Front Cell Infect Microbiol ; 11: 725043, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34595133

RESUMO

Host cell metabolism is essential for the viral replication cycle and, therefore, for productive infection. Energy (ATP) is required for the receptor-mediated attachment of viral particles to susceptible cells and for their entry into the cytoplasm. Host cells must synthesize an array of biomolecules and engage in intracellular trafficking processes to enable viruses to complete their replication cycle. The tricarboxylic acid (TCA) cycle has a key role in ATP production as well as in the synthesis of the biomolecules needed for viral replication. The final assembly and budding process of enveloped viruses, for instance, require lipids, and the TCA cycle provides the precursor (citrate) for fatty acid synthesis (FAS). Viral infections may induce host inflammation and TCA cycle metabolic intermediates participate in this process, notably citrate and succinate. On the other hand, viral infections may promote the synthesis of itaconate from TCA cis-aconitate. Itaconate harbors anti-inflammatory, anti-oxidant, and anti-microbial properties. Fumarate is another TCA cycle intermediate with immunoregulatory properties, and its derivatives such as dimethyl fumarate (DMF) are therapeutic candidates for the contention of virus-induced hyper-inflammation and oxidative stress. The TCA cycle is at the core of viral infection and replication as well as viral pathogenesis and anti-viral immunity. This review highlights the role of the TCA cycle in viral infections and explores recent advances in the fast-moving field of virometabolism.


Assuntos
Viroses , Vírus , Ciclo do Ácido Cítrico , Humanos , Inflamação , Replicação Viral
6.
Clin Sci (Lond) ; 135(19): 2217-2242, 2021 10 14.
Artigo em Inglês | MEDLINE | ID: mdl-34623425

RESUMO

The ability of dendritic cells (DCs) to sense viral pathogens and orchestrate a proper immune response makes them one of the key players in antiviral immunity. Different DC subsets have complementing functions during viral infections, some specialize in antigen presentation and cross-presentation and others in the production of cytokines with antiviral activity, such as type I interferons. In this review, we summarize the latest updates concerning the role of DCs in viral infections, with particular focus on the complex interplay between DC subsets and severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Despite being initiated by a vast array of immune receptors, DC-mediated antiviral responses often converge towards the same endpoint, that is the production of proinflammatory cytokines and the activation of an adaptive immune response. Nonetheless, the inherent migratory properties of DCs make them a double-edged sword and often viral recognition by DCs results in further viral dissemination. Here we illustrate these various aspects of the antiviral functions of DCs and also provide a brief overview of novel antiviral vaccination strategies based on DCs targeting.


Assuntos
COVID-19/virologia , Células Dendríticas/virologia , Receptores de Reconhecimento de Padrão/imunologia , SARS-CoV-2/patogenicidade , Viroses/virologia , Citocinas/imunologia , Células Dendríticas/imunologia , Humanos , Viroses/imunologia
7.
BMC Genomics ; 22(1): 720, 2021 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-34610790

RESUMO

BACKGROUND: Varroa destructor mites, and the numerous viruses they vector to their honey bee hosts, are among the most serious threats to honey bee populations, causing mortality and morbidity to both the individual honey bee and colony, the negative effects of which convey to the pollination services provided by honey bees worldwide. Here we use a combination of targeted assays and deep RNA sequencing to determine host and microbial changes in resistant and susceptible honey bee lineages. We focus on three study sets. The first involves field sampling of sympatric western bees, some derived from resistant stock and some from stock susceptible to mites. The second experiment contrasts three colonies more deeply, two from susceptible stock from the southeastern U.S. and one from mite-resistant bee stock from Eastern Texas. Finally, to decouple the effects of mites from those of the viruses they vector, we experimentally expose honey bees to DWV in the laboratory, measuring viral growth and host responses. RESULTS: We find strong differences between resistant and susceptible bees in terms of both viral loads and bee gene expression. Interestingly, lineages of bees with naturally low levels of the mite-vectored Deformed wing virus, also carried lower levels of viruses not vectored by mites. By mapping gene expression results against current ontologies and other studies, we describe the impacts of mite parasitism, as well as viruses on bee health against two genetic backgrounds. We identify numerous genes and processes seen in other studies of stress and disease in honey bee colonies, alongside novel genes and new patterns of expression. CONCLUSIONS: We provide evidence that honey bees surviving in the face of parasitic mites do so through their abilities to resist the presence of devastating viruses vectored by these mites. In all cases, the most divergence between stocks was seen when bees were exposed to live mites or viruses, suggesting that gene activation, rather than constitutive expression, is key for these interactions. By revealing responses to viral infection and mite parasitism in different lineages, our data identify candidate proteins for the evolution of mite tolerance and virus resistance.


Assuntos
Vírus de RNA , Varroidae , Viroses , Animais , Abelhas , Vírus de RNA/genética , Carga Viral
8.
JMIR Public Health Surveill ; 7(10): e32468, 2021 10 06.
Artigo em Inglês | MEDLINE | ID: mdl-34612841

RESUMO

BACKGROUND: Contact tracing in association with quarantine and isolation is an important public health tool to control outbreaks of infectious diseases. This strategy has been widely implemented during the current COVID-19 pandemic. The effectiveness of this nonpharmaceutical intervention is largely dependent on social interactions within the population and its combination with other interventions. Given the high transmissibility of SARS-CoV-2, short serial intervals, and asymptomatic transmission patterns, the effectiveness of contact tracing for this novel viral agent is largely unknown. OBJECTIVE: This study aims to identify and synthesize evidence regarding the effectiveness of contact tracing on infectious viral disease outcomes based on prior scientific literature. METHODS: An evidence-based review was conducted to identify studies from the PubMed database, including preprint medRxiv server content, related to the effectiveness of contact tracing in viral outbreaks. The search dates were from database inception to July 24, 2020. Outcomes of interest included measures of incidence, transmission, hospitalization, and mortality. RESULTS: Out of 159 unique records retrieved, 45 (28.3%) records were reviewed at the full-text level, and 24 (15.1%) records met all inclusion criteria. The studies included utilized mathematical modeling (n=14), observational (n=8), and systematic review (n=2) approaches. Only 2 studies considered digital contact tracing. Contact tracing was mostly evaluated in combination with other nonpharmaceutical interventions and/or pharmaceutical interventions. Although some degree of effectiveness in decreasing viral disease incidence, transmission, and resulting hospitalizations and mortality was observed, these results were highly dependent on epidemic severity (R0 value), number of contacts traced (including presymptomatic and asymptomatic cases), timeliness, duration, and compliance with combined interventions (eg, isolation, quarantine, and treatment). Contact tracing effectiveness was particularly limited by logistical challenges associated with increased outbreak size and speed of infection spread. CONCLUSIONS: Timely deployment of contact tracing strategically layered with other nonpharmaceutical interventions could be an effective public health tool for mitigating and suppressing infectious outbreaks by decreasing viral disease incidence, transmission, and resulting hospitalizations and mortality.


Assuntos
Controle de Doenças Transmissíveis/métodos , Busca de Comunicante , Viroses/prevenção & controle , COVID-19/prevenção & controle , Humanos
9.
FEBS J ; 288(17): 5071-5088, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34490733

RESUMO

While there is undeniable evidence to link endosomal acid-base homeostasis to viral pathogenesis, the lack of druggable molecular targets has hindered translation from bench to bedside. The recent identification of variants in the interferon-inducible endosomal Na+ /H+ exchanger 9 associated with severe coronavirus disease-19 (COVID-19) has brought a shift in the way we envision aberrant endosomal acidification. Is it linked to an increased susceptibility to viral infection or a propensity to develop critical illness? This review summarizes the genetic and cellular evidence linking endosomal Na+ /H+ exchangers and viral diseases to suggest how they can act as a broad-spectrum modulator of viral infection and downstream pathophysiology. The review also presents novel insights supporting the complex role of endosomal acid-base homeostasis in viral pathogenesis and discusses the potential causes for negative outcomes of clinical trials utilizing alkalinizing drugs as therapies for COVID-19. These findings lead to a pathogenic model of viral disease that predicts that nonspecific targeting of endosomal pH might fail, even if administered early on, and suggests that endosomal Na+ /H+ exchangers may regulate key host antiviral defence mechanisms and mediators that act to drive inflammatory organ injury.


Assuntos
COVID-19/terapia , SARS-CoV-2/patogenicidade , Trocadores de Sódio-Hidrogênio/genética , Viroses/terapia , COVID-19/genética , COVID-19/virologia , Endossomos/genética , Endossomos/virologia , Humanos , Prótons , Trocadores de Sódio-Hidrogênio/antagonistas & inibidores , Viroses/genética , Viroses/virologia
10.
Oncology ; 99(10): 641-651, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34515171

RESUMO

AIM: Atezolizumab plus bevacizumab (atezo + bev) shows a good overall survival (OS) in advanced hepatocellular carcinoma (HCC) patients. However, the OS of patients with nonviral infection is quite worse than that in those with viral infection. The present study investigated the efficacy and safety of lenvatinib in patients with nonviral infection, who were unlikely to obtain benefit from atezo + bev. METHODS: We conducted a multicenter retrospective study that included 139 advanced HCC patients treated with lenvatinib between March 2018 and September 2020. RESULTS: The median age was 72 years, and 116 patients (83.5%) were male. Based on the etiology of liver disease, 84 (60.4%) and 55 patients (39.6%) were assigned to the viral infection and nonviral infection groups, respectively. The significant extents in patient characteristics were not observed in both groups. The objective response rate per mRECIST and progression-free survival (PFS) did not differ significantly between the viral infection and nonviral infection groups (36.0 vs. 33.0%, p = 0.85; and 7.6 vs. 7.5 months, p = 0.94, respectively). The 1-year survival rates were 68.7% (95% confidence interval [CI] 57.7-79.7%) in the viral infection group and 59.5% (95% CI 45.2-73.8%) in the nonviral infection group. The viral infection group was not a significant factor associated with the PFS or OS in a multivariate analysis. CONCLUSIONS: Lenvatinib shows no significant difference in response between patients with and without viral infection. Treatment strategies based on the etiology of liver disease may lead to good clinical outcome.


Assuntos
Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/microbiologia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/microbiologia , Compostos de Fenilureia/uso terapêutico , Quinolinas/uso terapêutico , Idoso , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/virologia , Feminino , Humanos , Imunoterapia , Infecções/diagnóstico , Neoplasias Hepáticas/virologia , Masculino , Compostos de Fenilureia/efeitos adversos , Intervalo Livre de Progressão , Quinolinas/efeitos adversos , Estudos Retrospectivos , Viroses/diagnóstico
11.
Rinsho Ketsueki ; 62(8): 1334-1342, 2021.
Artigo em Japonês | MEDLINE | ID: mdl-34497224

RESUMO

Viral infections are one of the leading causes of death in hematopoietic cell transplantation (HCT) and are a problem that should be resolved. For post-HCT viral infections, reduction of antiviral treatment or immunosuppressive drug dose is generally performed; however, the effect of antiviral drug is sometimes limited, and reduction of immunosuppressive treatment might worsen the graft-versus-host disease. Therefore, appropriate infection preventive measures and early diagnosis and therapeutic intervention for viral infections are important. In addition, virus-specific T-cell (VST) therapy is attracting attention as a new treatment method for intractable and refractory post-HCT viral infections. Various methods have been developed to establish VSTs, from a single- to multiple-virus targeting and from related- to third-party-derived donors. Its safety and efficacy have already been reported in clinical trials, and thereby, it is expected to be established as one of the important treatments for post-HCT viral infections.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Viroses , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Linfócitos T , Transplante Homólogo , Viroses/terapia
12.
Biomed Res Int ; 2021: 5313832, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34485513

RESUMO

Background: Coinfections have a potential role in increased morbidity and mortality rates during pandemics. Our investigation is aimed at evaluating the viral coinfection prevalence in COVID-19 patients. Methods: We systematically searched scientific databases, including Medline, Scopus, WOS, and Embase, from December 1, 2019, to December 30, 2020. Preprint servers such as medRxiv were also scanned to find other related preprint papers. All types of studies evaluating the viral coinfection prevalence in COVID-19 patients were considered. We applied the random effects model to pool all of the related studies. Results: Thirty-three studies including 10484 patients were identified. The viral coinfection estimated pooled prevalence was 12.58%; 95% CI: 7.31 to 18.96). Blood viruses (pooled prevalence: 12.48%; 95% CI: 8.57 to 16.93) had the most frequent viral coinfection, and respiratory viruses (pooled prevalence: 4.32%; 95% CI: 2.78 to 6.15) had less frequent viral coinfection. The herpesvirus pooled prevalence was 11.71% (95% CI: 3.02 to 24.80). Also, the maximum and minimum of viral coinfection pooled prevalence were in AMRO and EMRO with 15.63% (95% CI: 3.78 to 33.31) and 7.05% (95% CI: 3.84 to 11.07), respectively. Conclusion: The lowest rate of coinfection belonged to respiratory viruses. Blood-borne viruses had the highest coinfection rate. Our results provide important data about the prevalence of blood-borne viruses among COVID-19 patients which can be critical when it comes to their treatment procedure.


Assuntos
COVID-19/epidemiologia , Coinfecção/epidemiologia , Coinfecção/virologia , Humanos , Pandemias/prevenção & controle , Prevalência , SARS-CoV-2/patogenicidade , Viroses/epidemiologia , Viroses/virologia , Vírus/patogenicidade
13.
JAMA Netw Open ; 4(9): e2124650, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34529066

RESUMO

Importance: Every year, respiratory viruses exact a heavy burden on Canadian hospitals during winter months. Generalizable seasonal patterns of respiratory virus transmission may estimate the evolution of SARS-CoV-2 or other emerging pathogens. Objective: To describe the annual and biennial variation in respiratory virus seasonality in a northern climate. Design, Setting, and Participants: This cohort study is an epidemiological assessment using population-based surveillance of patients with medically attended respiratory tract infection from 2005 through 2017 in Alberta, Canada. Incident cases of respiratory virus infection and infant respiratory syncytial virus (RSV) hospitalizations in Alberta were extracted from the Data Integration for Alberta Laboratories platform and Alberta Health Services Discharge Abstract Database, respectively. A deterministic susceptible-infected-recovered-susceptible mathematical model with seasonal forcing function was fitted to the data for each virus. The possible future seasonal course of SARS-CoV-2 in northern latitudes was modeled on the basis of these observations. The analysis was conducted between December 15, 2020, and February 10, 2021. Exposures: Seasonal respiratory pathogens. Main Outcomes and Measures: Incidence (temporal pattern) of respiratory virus infections and RSV hospitalizations. Results: A total of 37 719 incident infections with RSV, human metapneumovirus, or human coronaviruses 229E, NL63, OC43, or HKU1 among 35 375 patients (18 069 [51.1%] male; median [interquartile range], 1.29 [0.42-12.2] years) were documented. A susceptible-infected-recovered-susceptible model mirrored the epidemiological data, including a striking biennial variation with alternating severe and mild winter peaks. Qualitative description of the model and numerical simulations showed that strong seasonal contact rate and temporary immunity lasting 6 to 12 months were sufficient to explain biennial seasonality in these various respiratory viruses. The seasonality of 10 212 hospitalizations among children younger than 5 years with RSV was also explored. The median (interquartile range) rate of hospitalizations per 1000 live births was 18.6 (17.6-19.9) and 11.0 (10.4-11.7) in alternating even (severe) and odd (less-severe) seasons, respectively (P = .001). The hazard of admission was higher for children born in severe (even) seasons compared with those born in less-severe (odd) seasons (hazard ratio, 1.68; 95% CI, 1.61-1.75; P < .001). Conclusions and Relevance: In this modeling study of respiratory viruses in Alberta, Canada, the seasonality followed a pattern estimated by simple mathematical models, which may be informative for anticipating future waves of pandemic SARS-CoV-2.


Assuntos
Infecções Respiratórias/virologia , Estações do Ano , Viroses/diagnóstico , Alberta/epidemiologia , Estudos de Coortes , Hospitalização/estatística & dados numéricos , Humanos , Incidência , Infecções Respiratórias/epidemiologia , Estatísticas não Paramétricas , Viroses/epidemiologia
14.
PLoS One ; 16(9): e0257512, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34529745

RESUMO

Reinfection and multiple viral strains are among the latest challenges in the current COVID-19 pandemic. In contrast, epidemic models often consider a single strain and perennial immunity. To bridge this gap, we present a new epidemic model that simultaneously considers multiple viral strains and reinfection due to waning immunity. The model is general, applies to any viral disease and includes an optimal control formulation to seek a trade-off between the societal and economic costs of mitigation. We validate the model, with and without mitigation, in the light of the COVID-19 epidemic in England and in the state of Amazonas, Brazil. The model can derive optimal mitigation strategies for any number of viral strains, whilst also evaluating the effect of distinct mitigation costs on the infection levels. The results show that relaxations in the mitigation measures cause a rapid increase in the number of cases, and therefore demand more restrictive measures in the future.


Assuntos
Algoritmos , COVID-19/prevenção & controle , Modelos Teóricos , Viroses/prevenção & controle , Brasil/epidemiologia , COVID-19/epidemiologia , COVID-19/virologia , Simulação por Computador , Inglaterra/epidemiologia , Epidemias/prevenção & controle , Humanos , SARS-CoV-2/fisiologia , Viroses/epidemiologia , Viroses/virologia
15.
Viruses ; 13(9)2021 09 13.
Artigo em Inglês | MEDLINE | ID: mdl-34578396

RESUMO

We introduce an explicit function that describes virus-load curves on a patient-specific level. This function is based on simple and intuitive model parameters. It allows virus load analysis of acute viral infections without solving a full virus load dynamic model. We validate our model on data from mice influenza A, human rhinovirus data, human influenza A data, and monkey and human SARS-CoV-2 data. We find wide distributions for the model parameters, reflecting large variability in the disease outcomes between individuals. Further, we compare the virus load function to an established target model of virus dynamics, and we provide a new way to estimate the exponential growth rates of the corresponding infection phases. The virus load function, the target model, and the exponential approximations show excellent fits for the data considered. Our virus-load function offers a new way to analyze patient-specific virus load data, and it can be used as input for higher level models for the physiological effects of a virus infection, for models of tissue damage, and to estimate patient risks.


Assuntos
Carga Viral , Viroses/epidemiologia , Viroses/etiologia , Doença Aguda , Algoritmos , Animais , Variação Biológica da População , COVID-19/epidemiologia , COVID-19/virologia , Humanos , Influenza Humana/epidemiologia , Influenza Humana/virologia , Macaca mulatta , Camundongos , Modelos Teóricos , Rhinovirus , SARS-CoV-2
16.
Viruses ; 13(9)2021 09 13.
Artigo em Inglês | MEDLINE | ID: mdl-34578399

RESUMO

Over the decades, the world has witnessed diverse virus associated pandemics. The significant inhibitory effects of marine sulfated polysaccharides against SARS-CoV-2 shows its therapeutic potential in future biomedical applications and drug development. Algal polysaccharides exhibited significant role in antimicrobial, antitumor, antioxidative, antiviral, anticoagulant, antihepatotoxic and immunomodulating activities. Owing to their health benefits, the sulfated polysaccharides from marine algae are a great deal of interest globally. Algal polysaccharides such as agar, alginate, carrageenans, porphyran, fucoidan, laminaran and ulvans are investigated for their nutraceutical potential at different stages of infection processes, structural diversity, complexity and mechanism of action. In this review, we focus on the recent antiviral studies of the marine algae-based polysaccharides and their potential towards antiviral medicines.


Assuntos
Antivirais/farmacologia , Organismos Aquáticos/química , Polissacarídeos/farmacologia , Alga Marinha/química , Viroses/epidemiologia , Alginatos/química , Alginatos/farmacologia , Antivirais/química , Glucanos/química , Glucanos/farmacologia , Humanos , Estrutura Molecular , Pandemias , Polissacarídeos/química , Viroses/tratamento farmacológico , Viroses/etiologia , Viroses/prevenção & controle
17.
Biochim Biophys Acta Mol Basis Dis ; 1867(12): 166264, 2021 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-34481867

RESUMO

The molecular evolution of life on earth along with changing environmental, conditions has rendered mankind susceptible to endemic and pandemic emerging infectious diseases. The effects of certain systemic viral and bacterial infections on morbidity and mortality are considered as examples of recent emerging infections. Here we will focus on three examples of infections that are important in pregnancy and early childhood: SARS-CoV-2 virus, Zika virus, and Mycoplasma species. The basic structural characteristics of these infectious agents will be examined, along with their general pathogenic mechanisms. Coronavirus infections, such as caused by the SARS-CoV-2 virus, likely evolved from zoonotic bat viruses to infect humans and cause a pandemic that has been the biggest challenge for humanity since the Spanish Flu pandemic of the early 20th century. In contrast, Zika Virus infections represent an expanding infectious threat in the context of global climate change. The relationship of these infections to pregnancy, the vertical transmission and neurological sequels make these viruses highly relevant to the topics of this special issue. Finally, mycoplasmal infections have been present before mankind evolved, but they were rarely identified as human pathogens until recently, and they are now recognized as important coinfections that are able to modify the course and prognosis of various infectious diseases and other chronic illnesses. The infectious processes caused by these intracellular microorganisms are examined as well as some general aspects of their pathogeneses, clinical presentations, and diagnoses. We will finally consider examples of treatments that have been used to reduce morbidity and mortality of these infections and discuss briefly the current status of vaccines, in particular, against the SARS-CoV-2 virus. It is important to understand some of the basic features of these emerging infectious diseases and the pathogens involved in order to better appreciate the contributions of this special issue on how infectious diseases can affect human pregnancy, fetuses and neonates.


Assuntos
Infecções Bacterianas/prevenção & controle , Doenças Transmissíveis/transmissão , Viroses/prevenção & controle , Infecções Bacterianas/história , Infecções Bacterianas/transmissão , COVID-19/metabolismo , COVID-19/prevenção & controle , Doenças Transmissíveis/virologia , Feminino , História do Século XIX , História do Século XX , História do Século XXI , Humanos , Recém-Nascido , Transmissão Vertical de Doenças Infecciosas/história , Mycoplasma/patogenicidade , Infecções por Mycoplasma/metabolismo , Infecções por Mycoplasma/prevenção & controle , Gravidez , Gestantes , SARS-CoV-2/patogenicidade , Viroses/história , Viroses/transmissão , Zika virus/patogenicidade , Infecção por Zika virus/metabolismo , Infecção por Zika virus/prevenção & controle
18.
BioDrugs ; 35(5): 505-515, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34499320

RESUMO

Vaccine-associated enhanced disease (VAED) is a serious barrier to attaining successful virus vaccines in human and veterinary medicine. VAED occurs as two different immunopathologies, antibody-dependent enhancement (ADE) and vaccine-associated hypersensitivity (VAH). ADE contributes to the pathology of disease caused by four dengue viruses (DENV) through control of the intensity of cellular infection. Products of virus-infected cells are toxic. A partially protective yellow fever chimeric tetravalent DENV vaccine sensitized seronegative children to ADE breakthrough infections. A live-attenuated tetravalent whole virus vaccine in phase III testing appears to avoid ADE by providing durable protection against the four DENV. VAH sensitization by viral vaccines occurred historically. Children given formalin-inactivated measles or respiratory syncytial virus (RSV) vaccines experienced severe disease during breakthrough infections. Tissue responses demonstrated that VAH not ADE caused these vaccine safety problems. Subsequently, measles was successfully and safely contained by a live-attenuated virus vaccine. The difficulty in formulating a safe and effective RSV vaccine is troublesome evidence that avoiding VAH is a major research challenge. VAH-like tissue responses were observed during breakthrough homologous virus infections in monkeys given severe acute respiratory syndrome (SARS) or Middle East respiratory syndrome (MERS) vaccines.


Assuntos
Vacinas contra Dengue , Dengue , Viroses , Anticorpos Neutralizantes , Anticorpos Antivirais , Humanos , Proteínas do Envelope Viral
19.
Int J Mol Sci ; 22(18)2021 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-34575975

RESUMO

Several classes of immunomodulators are used for treating relapsing-remitting multiple sclerosis (RRMS). Most of these disease-modifying therapies, except teriflunomide, carry the risk of progressive multifocal leukoencephalopathy (PML), a severely debilitating, often fatal virus-induced demyelinating disease. Because teriflunomide has been shown to have antiviral activity against DNA viruses, we investigated whether treatment of cells with teriflunomide inhibits infection and spread of JC polyomavirus (JCPyV), the causative agent of PML. Treatment of choroid plexus epithelial cells and astrocytes with teriflunomide reduced JCPyV infection and spread. We also used droplet digital PCR to quantify JCPyV DNA associated with extracellular vesicles isolated from RRMS patients. We detected JCPyV DNA in all patients with confirmed PML diagnosis (n = 2), and in six natalizumab-treated (n = 12), two teriflunomide-treated (n = 7), and two nonimmunomodulated (n = 2) patients. Of the 21 patients, 12 (57%) had detectable JCPyV in either plasma or serum. CSF was uniformly negative for JCPyV. Isolation of extracellular vesicles did not increase the level of detection of JCPyV DNA versus bulk unprocessed biofluid. Overall, our study demonstrated an effect of teriflunomide inhibiting JCPyV infection and spread in glial and choroid plexus epithelial cells. Larger studies using patient samples are needed to correlate these in vitro findings with patient data.


Assuntos
Crotonatos/farmacologia , Vírus de DNA/efeitos dos fármacos , Hidroxibutiratos/farmacologia , Leucoencefalopatia Multifocal Progressiva/tratamento farmacológico , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Neuroglia/efeitos dos fármacos , Nitrilas/farmacologia , Toluidinas/farmacologia , Astrócitos/efeitos dos fármacos , Astrócitos/virologia , Linhagem Celular , Plexo Corióideo/efeitos dos fármacos , Plexo Corióideo/virologia , Vírus de DNA/patogenicidade , Doenças Desmielinizantes/tratamento farmacológico , Doenças Desmielinizantes/patologia , Doenças Desmielinizantes/virologia , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/virologia , Vesículas Extracelulares/efeitos dos fármacos , Vesículas Extracelulares/virologia , Humanos , Fatores Imunológicos/efeitos adversos , Fatores Imunológicos/uso terapêutico , Vírus JC/efeitos dos fármacos , Vírus JC/patogenicidade , Leucoencefalopatia Multifocal Progressiva/induzido quimicamente , Leucoencefalopatia Multifocal Progressiva/patologia , Leucoencefalopatia Multifocal Progressiva/virologia , Esclerose Múltipla Recidivante-Remitente/genética , Esclerose Múltipla Recidivante-Remitente/patologia , Esclerose Múltipla Recidivante-Remitente/virologia , Neuroglia/virologia , Viroses/tratamento farmacológico , Viroses/genética , Viroses/virologia
20.
Front Cell Infect Microbiol ; 11: 725392, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34485180

RESUMO

Previous studies have shown that DEAD (Glu-Asp-Ala-Glu)-box RNA helicases play important roles in viral infection, either as cytosolic sensors of pathogenic molecules or as essential host factors against viral infection. In the current study, we found that DDX6, an RNA helicase belonging to the DEAD-box family of helicase, exhibited anti-Enterovirus 71 activity through augmenting RIG-I-mediated type-I IFN response. Moreover, DDX6 binds viral RNA to form an RNA-protein complex to positively regulate the RIG-I-mediated interferon response; however, EV71 has evolved a strategy to antagonize the antiviral effect of DDX6 by proteolytic degradation of the molecule through its non-structural protein 2A, a virus-encoded protease.


Assuntos
Interferon Tipo I , Viroses , Proteína DEAD-box 58 , RNA Helicases DEAD-box , Humanos , Helicase IFIH1 Induzida por Interferon , Proteínas Proto-Oncogênicas , RNA Viral
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