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1.
Int J Mol Sci ; 22(21)2021 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-34769038

RESUMO

Tetraspanins are transmembrane glycoproteins that have been shown increasing interest as host factors in infectious diseases. In particular, they were implicated in the pathogenesis of both non-enveloped (human papillomavirus (HPV)) and enveloped (human immunodeficiency virus (HIV), Zika, influenza A virus, (IAV), and coronavirus) viruses through multiple stages of infection, from the initial cell membrane attachment to the syncytium formation and viral particle release. However, the mechanisms by which different tetraspanins mediate their effects vary. This review aimed to compare and contrast the role of tetraspanins in the life cycles of HPV, HIV, Zika, IAV, and coronavirus viruses, which cause the most significant health and economic burdens to society. In doing so, a better understanding of the relative contribution of tetraspanins in virus infection will allow for a more targeted approach in the treatment of these diseases.


Assuntos
Interações Hospedeiro-Patógeno/fisiologia , Tetraspaninas/fisiologia , Viroses/metabolismo , Regulação Viral da Expressão Gênica , HIV-1/patogenicidade , Humanos , Vírus da Influenza A/patogenicidade , Papillomaviridae/patogenicidade , SARS-CoV-2/patogenicidade , Viroses/genética , Viroses/virologia , Internalização do Vírus , Zika virus/patogenicidade
2.
Int J Mol Sci ; 22(19)2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34638920

RESUMO

Glycan-lectin interactions play an essential role in different cellular processes. One of their main functions is involvement in the immune response to pathogens or inflammation. However, cancer cells and viruses have adapted to avail themselves of these interactions. By displaying specific glycosylation structures, they are able to bind to lectins, thus promoting pathogenesis. While glycan-lectin interactions promote tumor progression, metastasis, and/or chemoresistance in cancer, in viral infections they are important for viral entry, release, and/or immune escape. For several years now, a growing number of investigations have been devoted to clarifying the role of glycan-lectin interactions in cancer and viral infections. Various overviews have already summarized and highlighted their findings. In this review, we consider the interactions of the lectins MGL, DC-SIGN, selectins, and galectins in both cancer and viral infections together. A possible transfer of ways to target and disrupt them might lead to new therapeutic approaches in different pathological backgrounds.


Assuntos
Lectinas/metabolismo , Neoplasias/metabolismo , Polissacarídeos/metabolismo , Viroses/metabolismo , Animais , Moléculas de Adesão Celular/química , Moléculas de Adesão Celular/metabolismo , Galectinas/química , Galectinas/metabolismo , Humanos , Lectinas/química , Lectinas Tipo C/química , Lectinas Tipo C/metabolismo , Polissacarídeos/química , Ligação Proteica , Receptores de Superfície Celular/química , Receptores de Superfície Celular/metabolismo , Selectinas/química , Selectinas/metabolismo , Viroses/virologia
4.
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
5.
Int J Mol Sci ; 22(17)2021 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-34502274

RESUMO

Heat shock proteins (HSPs) are a large group of chaperones found in most eukaryotes and bacteria. They are responsible for the correct protein folding, protection of the cell against stressors, presenting immune and inflammatory cytokines; furthermore, they are important factors in regulating cell differentiation, survival and death. Although the biological function of HSPs is to maintain cell homeostasis, some of them can be used by viruses both to fold their proteins and increase the chances of survival in unfavorable host conditions. Folding viral proteins as well as replicating many different viruses are carried out by, among others, proteins from the HSP70 and HSP90 families. In some cases, the HSP70 family proteins directly interact with viral polymerase to enhance viral replication or they can facilitate the formation of a viral replication complex and/or maintain the stability of complex proteins. It is known that HSP90 is important for the expression of viral genes at both the transcriptional and the translational levels. Both of these HSPs can form a complex with HSP90 and, consequently, facilitate the entry of the virus into the cell. Current studies have shown the biological significance of HSPs in the course of infection SARS-CoV-2. A comprehensive understanding of chaperone use during viral infection will provide new insight into viral replication mechanisms and therapeutic potential. The aim of this study is to describe the molecular basis of HSP70 and HSP90 participation in some viral infections and the potential use of these proteins in antiviral therapy.


Assuntos
Proteínas de Choque Térmico HSP70/metabolismo , Proteínas de Choque Térmico HSP90/metabolismo , Viroses/patologia , COVID-19/metabolismo , COVID-19/patologia , COVID-19/virologia , Vírus de DNA/fisiologia , Humanos , Isoformas de Proteínas/metabolismo , Vírus de RNA/fisiologia , SARS-CoV-2/isolamento & purificação , Viroses/metabolismo , Viroses/virologia
6.
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
7.
Biomed Res Int ; 2021: 9998420, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34527748

RESUMO

The global burden of viral infection, especially the current pandemics of SARS-CoV-2, HIV/AIDS, and hepatitis, is a very risky one. Additionally, HCV expresses the necessity for antiviral therapeutic elements. Venoms are known to contain an array of bioactive peptides that are commonly used in the treatment of various medical issues. Several peptides isolated from scorpion venom have recently been proven to possess an antiviral activity against several viral families. The aim of this review is to provide an up-to-date overview of scorpion antiviral peptides and to discuss their modes of action and potential biomedical application against different viruses.


Assuntos
Antivirais/química , Antivirais/farmacologia , Peptídeos/farmacologia , Venenos de Escorpião/química , Viroses/tratamento farmacológico , Animais , Coronavirus/efeitos dos fármacos , HIV-1/efeitos dos fármacos , Vírus de Hepatite/efeitos dos fármacos , Herpesvirus Humano 1/efeitos dos fármacos , Humanos , Vírus do Sarampo/efeitos dos fármacos , Peptídeos/química , Peptídeos/isolamento & purificação , Viroses/virologia
8.
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
9.
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
10.
Appl Environ Microbiol ; 87(22): e0121521, 2021 10 28.
Artigo em Inglês | MEDLINE | ID: mdl-34469200

RESUMO

Fomites can represent a reservoir for pathogens, which may be subsequently transferred from surfaces to skin. In this study, we aim to understand how different factors (including virus type, surface type, time since last hand wash, and direction of transfer) affect virus transfer rates, defined as the fraction of virus transferred, between fingerpads and fomites. To determine this, 360 transfer events were performed with 20 volunteers using Phi6 (a surrogate for enveloped viruses), MS2 (a surrogate for nonenveloped viruses), and three clean surfaces (stainless steel, painted wood, and plastic). Considering all transfer events (all surfaces and both transfer directions combined), the mean transfer rates of Phi6 and MS2 were 0.17 and 0.26, respectively. Transfer of MS2 was significantly higher than that of Phi6 (P < 0.05). Surface type was a significant factor that affected the transfer rate of Phi6: Phi6 is more easily transferred to and from stainless steel and plastic than to and from painted wood. Direction of transfer was a significant factor affecting MS2 transfer rates: MS2 is more easily transferred from surfaces to fingerpads than from fingerpads to surfaces. Data from these virus transfer events, and subsequent transfer rate distributions, provide information that can be used to refine quantitative microbial risk assessments. This study provides a large-scale data set of transfer events with a surrogate for enveloped viruses, which extends the reach of the study to the role of fomites in the transmission of human enveloped viruses like influenza and SARS-CoV-2. IMPORTANCE This study created a large-scale data set for the transfer of enveloped viruses between skin and surfaces. The data set produced by this study provides information on modeling the distribution of enveloped and nonenveloped virus transfer rates, which can aid in the implementation of risk assessment models in the future. Additionally, enveloped and nonenveloped viruses were applied to experimental surfaces in an equivalent matrix to avoid matrix effects, so results between different viral species can be directly compared without confounding effects of different matrices. Our results indicating how virus type, surface type, time since last hand wash, and direction of transfer affect virus transfer rates can be used in decision-making processes to lower the risk of viral infection from transmission through fomites.


Assuntos
Dedos/virologia , Fômites/virologia , Fenômenos Fisiológicos Virais , Bacteriófago phi 6/fisiologia , Bacteriófago phi 6/ultraestrutura , Fômites/classificação , Higiene das Mãos , Humanos , Levivirus/fisiologia , Levivirus/ultraestrutura , Envelope Viral/ultraestrutura , Viroses/transmissão , Viroses/virologia , Vírus/ultraestrutura
11.
Sci Rep ; 11(1): 17545, 2021 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-34475462

RESUMO

The importance of virus disease outbreaks and its prevention is of growing public concern but our understanding of virus transmission routes is limited by adequate sampling strategies. While conventional swabbing methods provide merely a microbial snapshot, an ideal sampling strategy would allow reliable collection of viral genomic data over longer time periods. This study has evaluated a new, paper-based sticker approach for collection of reliable viral genomic data over longer time periods up to 14 days and after implementation of different hygiene measures. In contrast to swabbing methods, which sample viral load present on a surface at a given time, the paper-based stickers are attached to the surface area of interest and collect viruses that would have otherwise been transferred onto that surface. The major advantage of one-side adhesive stickers is that they are permanently attachable to a variety of surfaces. Initial results demonstrate that stickers permit stable recovery characteristics, even at low virus titers. Stickers also allow reliable virus detection after implementation of routine hygiene measures and over longer periods up to 14 days. Overall, results for this new sticker approach for virus genomic data collection are encouraging, but further studies are required to confirm anticipated benefits over a range of virus types.


Assuntos
Viroses/virologia , Vírus/isolamento & purificação , DNA Viral/análise , DNA Viral/genética , Desinfecção , Humanos , Reação em Cadeia da Polimerase , Propriedades de Superfície , Viroses/epidemiologia , Viroses/prevenção & controle , Vírus/genética
12.
Int J Mol Sci ; 22(18)2021 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-34576241

RESUMO

Although it had been reported that Israeli acute paralysis virus (IAPV) can cause systemic infection in honey bees, little is known about how it establishes this infection and results in the typical symptoms, paralysis and trembling. Here, we used our previously constructed IAPV infectious clone to investigate viral loads in different tissues of honey bees and further identify the relation between tissue tropism and paralytic symptoms. Our results showed that tracheae showed a greater concentration of viral abundance than other tissues. The abundance of viral protein in the tracheae was positively associated with viral titers, and was further confirmed by immunological and ultrastructural evidence. Furthermore, higher viral loads in tracheae induced remarkable down-regulation of succinate dehydrogenase and cytochrome c oxidase genes, and progressed to causing respiratory failure of honey bees, resulting in the appearance of typical symptoms, paralysis and body trembling. Our results showed that paralysis symptoms or trembling was actually to mitigate tachypnea induced by IAPV infection due to the impairment of honey bee tracheae, and revealed a direct causal link between paralysis symptoms and tissue tropism. These findings provide new insights into the understanding of the underlying mechanism of paralysis symptoms of honey bees after viral infection and have implications for viral disease prevention and specific therapeutics in practice.


Assuntos
Dicistroviridae , Paralisia/fisiopatologia , Taquipneia/fisiopatologia , Viroses/fisiopatologia , Animais , Abelhas/virologia , Complexo IV da Cadeia de Transporte de Elétrons/metabolismo , Paralisia/virologia , Succinato Desidrogenase/metabolismo , Taquipneia/virologia , Traqueia/virologia , Carga Viral , Proteínas Virais , Viroses/virologia
13.
PLoS One ; 16(9): e0258002, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34591907

RESUMO

Detecting viruses, which have significant impact on health and the economy, is essential for controlling and combating viral infections. In recent years there has been a focus towards simpler and faster detection methods, specifically through the use of electronic-based detection at the point-of-care. Point-of-care sensors play a particularly important role in the detection of viruses. Tests can be performed in the field or in resource limited regions in a simple manner and short time frame, allowing for rapid treatment. Electronic based detection allows for speed and quantitative detection not otherwise possible at the point-of-care. Such approaches are largely based upon voltammetry, electrochemical impedance spectroscopy, field effect transistors, and similar electrical techniques. Here, we systematically review electronic and electrochemical point-of-care sensors for the detection of human viral pathogens. Using the reported limits of detection and assay times we compare approaches both by detection method and by the target analyte of interest. Compared to recent scoping and narrative reviews, this systematic review which follows established best practice for evidence synthesis adds substantial new evidence on 1) performance and 2) limitations, needed for sensor uptake in the clinical arena. 104 relevant studies were identified by conducting a search of current literature using 7 databases, only including original research articles detecting human viruses and reporting a limit of detection. Detection units were converted to nanomolars where possible in order to compare performance across devices. This approach allows us to identify field effect transistors as having the fastest median response time, and as being the most sensitive, some achieving single-molecule detection. In general, we found that antigens are the quickest targets to detect. We also observe however, that reports are highly variable in their chosen metrics of interest. We suggest that this lack of systematisation across studies may be a major bottleneck in sensor development and translation. Where appropriate, we use the findings of the systematic review to give recommendations for best reporting practice.


Assuntos
Sistemas Automatizados de Assistência Junto ao Leito , Viroses/diagnóstico , Eletrônica , Humanos , Viroses/virologia
14.
Int J Mol Sci ; 22(17)2021 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-34502533

RESUMO

Various intrinsic and extrinsic factors can interfere with the process of protein folding, resulting in protein aggregates. Usually, cells prevent the formation of aggregates or degrade them to prevent the cytotoxic effects they may cause. However, during viral infection, the formation of aggregates may serve as a cellular defense mechanism. On the other hand, some viruses are able to exploit the process of aggregate formation and removal to promote their replication or evade the immune response. This review article summarizes the process of cellular protein aggregation and gives examples of how different viruses exploit it. Particular emphasis is placed on the ribonucleotide reductases of herpesviruses and how their additional non-canonical functions in viral immune evasion are closely linked to protein aggregation.


Assuntos
Evasão da Resposta Imune/imunologia , Agregados Proteicos , Agregação Patológica de Proteínas/imunologia , Viroses/imunologia , Vírus/imunologia , Herpesviridae/imunologia , Herpesviridae/fisiologia , Infecções por Herpesviridae/imunologia , Infecções por Herpesviridae/metabolismo , Infecções por Herpesviridae/virologia , Interações Hospedeiro-Patógeno/imunologia , Humanos , Agregação Patológica de Proteínas/metabolismo , Agregação Patológica de Proteínas/virologia , Ribonucleotídeo Redutases/imunologia , Ribonucleotídeo Redutases/metabolismo , Viroses/metabolismo , Viroses/virologia
15.
Front Immunol ; 12: 667889, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34512622

RESUMO

Type 1 diabetes (T1D) is the most common paediatric endocrine disease, and its frequency has been found to increase worldwide. Similar to all conditions associated with poorly regulated glucose metabolism, T1D carries an increased risk of infection. Consequently, careful compliance by T1D children with schedules officially approved for child immunization is strongly recommended. However, because patients with T1D show persistent and profound limitations in immune function, vaccines may evoke a less efficient immune response, with corresponding lower protection. Moreover, T1D is an autoimmune condition that develops in genetically susceptible individuals and some data regarding T1D triggering factors appear to indicate that infections, mainly those due to viruses, play a major role. Accordingly, the use of viral live attenuated vaccines is being debated. In this narrative review, we discussed the most effective and safe use of vaccines in patients at risk of or with overt T1D. Literature analysis showed that several problems related to the use of vaccines in children with T1D have not been completely resolved. There are few studies regarding the immunogenicity and efficacy of vaccines in T1D children, and the need for different immunization schedules has not been precisely established. Fortunately, the previous presumed relationship between vaccine administration and T1D appears to have been debunked, though some doubts regarding rotavirus vaccines remain. Further studies are needed to completely resolve the problems related to vaccine administration in T1D patients. In the meantime, the use of vaccines remains extensively recommended in children with this disease.


Assuntos
Diabetes Mellitus Tipo 1/imunologia , Vacinação , Vacinas Virais/administração & dosagem , Viroses/prevenção & controle , Diabetes Mellitus Tipo 1/epidemiologia , Humanos , Hospedeiro Imunocomprometido , Imunogenicidade da Vacina , Medição de Risco , Fatores de Risco , Vacinação/efeitos adversos , Vacinas Atenuadas/administração & dosagem , Vacinas Atenuadas/efeitos adversos , Vacinas Virais/efeitos adversos , Viroses/epidemiologia , Viroses/imunologia , Viroses/virologia
16.
PLoS One ; 16(9): e0256106, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34555028

RESUMO

Indiscriminate use of antibiotics to treat infections that are of viral origin contributes to unnecessary use which potentially may induce resistance in commensal bacteria. To counteract this a number of host gene transcriptional studies have been conducted to identify genes that are differently expressed during bacterial and viral infections in humans, and thus could be used as a tool to base decisions on the use of antibiotics. In this paper, we aimed to evaluate the potential of a selection of genes that have been considered biomarkers in humans, to differentially diagnose bacterial from viral infections in the pig. First porcine PBMC were induced with six toll-like receptor (TLR) agonists (FliC, LPS, ODN 2216, Pam3CSK4, poly I:C, R848) to mimic host gene expression induced by bacterial or viral pathogens, or exposed to heat-killed Actinobacillus pleuropneumoniae or a split influenza virus. Genes that were differentially expressed between bacterial and viral inducers were further evaluated on clinical material comprising eleven healthy pigs, and six pigs infected with A. pleuropneumoniae. This comprised three virally upregulated genes (IFI44L, MxA, RSAD2) and four bacterially upregulated genes (IL-1ß, IL-8, FAM89A, S100PBP). All six infected pigs could be differentially diagnosed to healthy pigs using a host gene transcription assay based on the geometric average of the bacterially induced genes IL-8 and S100PBP over that of the virally induced gene MxA.


Assuntos
Bactérias/classificação , Infecções Bacterianas/diagnóstico , Proteínas de Bactérias/metabolismo , Doenças dos Suínos/diagnóstico , Proteínas Virais/metabolismo , Viroses/diagnóstico , Vírus/classificação , Animais , Bactérias/isolamento & purificação , Infecções Bacterianas/genética , Infecções Bacterianas/microbiologia , Proteínas de Bactérias/genética , Bioensaio , Leucócitos Mononucleares/microbiologia , Leucócitos Mononucleares/patologia , Leucócitos Mononucleares/virologia , Suínos , Doenças dos Suínos/genética , Doenças dos Suínos/microbiologia , Doenças dos Suínos/virologia , Proteínas Virais/genética , Viroses/genética , Viroses/virologia , Vírus/isolamento & purificação
17.
Cells ; 10(9)2021 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-34571909

RESUMO

Pattern recognition receptors (PRRs) play a central role in the inflammation that ensues following microbial infection by their recognition of molecular patterns present in invading microorganisms but also following tissue damage by recognising molecules released during disease states. Such receptors are expressed in a variety of cells and in various compartments of these cells. PRR binding of molecular patterns results in an intracellular signalling cascade and the eventual activation of transcription factors and the release of cytokines, chemokines, and vasoactive molecules. PRRs and their accessory molecules are subject to tight regulation in these cells so as to not overreact or react in unnecessary circumstances. They are also key to reacting to infection and in stimulating the immune system when needed. Therefore, targeting PRRs offers a potential therapeutic approach for chronic inflammatory disease, infections and as vaccine adjuvants. In this review, the current knowledge on anti-viral PRRs and their signalling pathways is reviewed. Finally, compounds that target PRRs and that have been tested in clinical trials for chronic infections and as adjuvants in vaccine trials are discussed.


Assuntos
Antivirais/uso terapêutico , Receptores de Reconhecimento de Padrão/antagonistas & inibidores , Viroses/tratamento farmacológico , Vírus/efeitos dos fármacos , Animais , Humanos , Receptores de Reconhecimento de Padrão/imunologia , Viroses/imunologia , Viroses/virologia , Vírus/imunologia
18.
Cells ; 10(9)2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34571927

RESUMO

Histone deacetylases (HDACs) are vital epigenetic modifiers not only in regulating plant development but also in abiotic- and biotic-stress responses. Though to date, the functions of HD2C-an HD2-type HDAC-In plant development and abiotic stress have been intensively explored, its function in biotic stress remains unknown. In this study, we have identified HD2C as an interaction partner of the Cauliflower mosaic virus (CaMV) P6 protein. It functions as a positive regulator in defending against CaMV infection. The hd2c mutants show enhanced susceptibility to CaMV infection. In support, the accumulation of viral DNA, viral transcripts, and the deposition of histone acetylation on the viral minichromosomes are increased in hd2c mutants. P6 interferes with the interaction between HD2C and HDA6, and P6 overexpression lines have similar phenotypes with hd2c mutants. In further investigations, P6 overexpression lines, together with CaMV infection plants, are more sensitive to ABA and NaCl with a concomitant increasing expression of ABA/NaCl-regulated genes. Moreover, the global levels of histone acetylation are increased in P6 overexpression lines and CaMV infection plants. Collectively, our results suggest that P6 dysfunctions histone deacetylase HD2C by physical interaction to promote CaMV infection.


Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/virologia , Caulimovirus/isolamento & purificação , Proteínas de Ligação a DNA/metabolismo , Regulação da Expressão Gênica de Plantas , Histona Desacetilases/metabolismo , Folhas de Planta/virologia , Proteínas Virais/metabolismo , Viroses/virologia , Acetilação , Arabidopsis/genética , Arabidopsis/crescimento & desenvolvimento , Arabidopsis/metabolismo , Proteínas de Arabidopsis/química , Proteínas de Arabidopsis/genética , Caulimovirus/fisiologia , Proteínas de Ligação a DNA/genética , Histona Desacetilases/química , Histona Desacetilases/genética , Fenótipo , Folhas de Planta/genética , Folhas de Planta/crescimento & desenvolvimento , Folhas de Planta/metabolismo , Plantas Geneticamente Modificadas/genética , Plantas Geneticamente Modificadas/crescimento & desenvolvimento , Plantas Geneticamente Modificadas/metabolismo , Plantas Geneticamente Modificadas/virologia , Tabaco/genética , Tabaco/crescimento & desenvolvimento , Tabaco/metabolismo , Tabaco/virologia , Proteínas Virais/genética , Viroses/genética , Viroses/metabolismo
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.
Nutrients ; 13(7)2021 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-34371920

RESUMO

Nutraceuticals, including vitamin D, vitamin A, zinc, lactoferrin, polyphenols coenzyme Q, magnesium, and selenium, are implicated in the modulation of the complex molecular pathways involved in the immune response against viral pathogens. A common element of the activity of nutraceuticals is their ability to enhance the innate immune response against pathogens by acting on the major cellular subsets and inducing the release of pro-inflammatory cytokines and antimicrobial peptides. In some cases, this action is accompanied by a direct antimicrobial effect, as evidenced in the specific case of lactoferrin. Furthermore, nutraceuticals act through complex molecular mechanisms to minimize the damage caused by the activation of the immune system against pathogens, reducing the oxidative damage, influencing the antigen presentation, enhancing the differentiation and proliferation of regulatory T cells, driving the differentiation of lymphocyte subsets, and modulating the production of pro-inflammatory cytokines. In this paper, we review the main molecular mechanisms responsible for the immunomodulatory function of nutraceuticals, focusing on the most relevant aspects for the prevention and treatment of viral infections.


Assuntos
Antivirais/uso terapêutico , Suplementos Nutricionais , Sistema Imunitário/efeitos dos fármacos , Fatores Imunológicos/uso terapêutico , Viroses/tratamento farmacológico , Vírus/efeitos dos fármacos , Animais , Antivirais/efeitos adversos , Suplementos Nutricionais/efeitos adversos , Interações Hospedeiro-Patógeno , Humanos , Sistema Imunitário/imunologia , Sistema Imunitário/metabolismo , Sistema Imunitário/virologia , Fatores Imunológicos/efeitos adversos , Resultado do Tratamento , Viroses/imunologia , Viroses/metabolismo , Viroses/virologia , Vírus/imunologia , Vírus/patogenicidade
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