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1.
Anal Bioanal Chem ; 412(28): 7685-7699, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32870351

RESUMO

Pathogen-host cell interactions play an important role in many human infectious and inflammatory diseases. Several pathogens, including Escherichia coli (E. coli), Mycobacterium tuberculosis (M. tb), and even the recent 2019 novel coronavirus (2019-nCoV), can cause serious breathing and brain disorders, tissue injury and inflammation, leading to high rates of mortality and resulting in great loss to human physical and mental health as well as the global economy. These infectious diseases exploit the microbial and host factors to induce serious inflammatory and immunological symptoms. Thus the development of anti-inflammatory drugs targeting bacterial/viral infection is an urgent need. In previous studies, YojI-IFNAR2, YojI-IL10RA, YojI-NRP1,YojI-SIGLEC7, and YojI-MC4R membrane-protein interactions were found to mediate E. coli invasion of the blood-brain barrier (BBB), which activated the downstream anti-inflammatory proteins NACHT, LRR and PYD domains-containing protein 2(NLRP2), using a proteomic chip conjugated with cell immunofluorescence labeling. However, the studies of pathogen (bacteria/virus)-host cell interactions mediated by membrane protein interactions did not extend their principles to broad biomedical applications such as 2019-nCoV infectious disease therapy. The first part of this feature article presents in-depth analysis of the cross-talk of cellular anti-inflammatory transduction signaling among interferon membrane protein receptor II (IFNAR2), interleukin-10 receptor subunit alpha (IL-10RA), NLRP2 and [Ca2+]-dependent phospholipase A2 (PLA2G5), based on experimental results and important published studies, which lays a theoretical foundation for the high-throughput construction of the cytokine and virion solution chip. The paper then moves on to the construction of the novel GPCR recombinant herpes virion chip and virion nano-oscillators for profiling membrane protein functions, which drove the idea of constructing the new recombinant virion and cytokine liquid chips for HTS of leading drugs. Due to the different structural properties of GPCR, IFNAR2, ACE2 and Spike of 2019-nCoV, their ligands will either bind the extracellular domain of IFNAR2/ACE2/Spike or the specific loops of the GPCR on the envelope of the recombinant herpes virions to induce dynamic charge distribution changes that lead to the variable electron transition for detection. Taken together, the combined overview of two of the most innovative and exciting developments in the immunoinflammatory field provides new insight into high-throughput construction of ultrasensitive cytokine and virion liquid chips for HTS of anti-inflammatory drugs or clinical diagnosis and treatment of inflammatory diseases including infectious diseases, acute or chronic inflammation (acute gouty arthritis or rheumatoid arthritis), cardiovascular disease, atheromatosis, diabetes, obesity, tissue injury and tumors. It has significant value in the prevention and treatment of these serious and painful diseases. Graphical abstract.


Assuntos
Anti-Inflamatórios/farmacologia , Antivirais/farmacologia , Ensaios de Triagem em Larga Escala/instrumentação , Dispositivos Lab-On-A-Chip , Testes de Sensibilidade Microbiana/instrumentação , Animais , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/imunologia , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/imunologia , Citocinas/imunologia , Descoberta de Drogas/instrumentação , Descoberta de Drogas/métodos , Desenho de Equipamento , Ensaios de Triagem em Larga Escala/métodos , Humanos , Testes de Sensibilidade Microbiana/métodos , Pandemias , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/imunologia , Bibliotecas de Moléculas Pequenas/farmacologia , Vírion/efeitos dos fármacos , Vírion/imunologia , Viroses/tratamento farmacológico , Viroses/imunologia
2.
Nutrients ; 12(9)2020 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-32967126

RESUMO

Viral infections have been a cause of mortality for several centuries and continue to endanger the lives of many, specifically of the younger population. Vitamin D has long been recognized as a crucial element to the skeletal system in the human body. Recent evidence has indicated that vitamin D also plays an essential role in the immune response against viral infections and suggested that vitamin D deficiency increases susceptibility to viral infections as well as the risk of recurrent infections. For instance, low serum vitamin D levels were linked to increased occurrence of high burdens viral diseases such as hepatitis, influenza, Covid-19, and AIDS. As immune cells in infected patients are responsive to the ameliorative effects of vitamin D, the beneficial effects of supplementing vitamin D-deficient individuals with an infectious disease may extend beyond the impact on bone and calcium homeostasis. Even though numerous studies have highlighted the effect of vitamin D on the immune cells, vitamin D's antiviral mechanism has not been fully established. This paper reviews the recent mechanisms by which vitamin D regulates the immune system, both innate and adaptive systems, and reflects on the link between serum vitamin D levels and viral infections.


Assuntos
Fatores Imunológicos/uso terapêutico , Viroses/terapia , Deficiência de Vitamina D/terapia , Vitamina D/uso terapêutico , Vitaminas/uso terapêutico , Betacoronavirus , Infecções por Coronavirus/sangue , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/terapia , Suplementos Nutricionais , Humanos , Sistema Imunitário , Pandemias , Pneumonia Viral/sangue , Pneumonia Viral/imunologia , Pneumonia Viral/terapia , Viroses/imunologia , Viroses/virologia , Vitamina D/sangue , Deficiência de Vitamina D/imunologia , Deficiência de Vitamina D/virologia
3.
Int J Mol Sci ; 21(18)2020 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-32933166

RESUMO

The glycans on enveloped viruses are synthesized by host-cell machinery. Some of these glycans on zoonotic viruses of mammalian reservoirs are recognized by human natural antibodies that may protect against such viruses. These antibodies are produced mostly against carbohydrate antigens on gastrointestinal bacteria and fortuitously, they bind to carbohydrate antigens synthesized in other mammals, neutralize and destroy viruses presenting these antigens. Two such antibodies are: anti-Gal binding to α-gal epitopes synthesized in non-primate mammals, lemurs, and New World monkeys, and anti-N-glycolyl neuraminic acid (anti-Neu5Gc) binding to N-glycolyl-neuraminic acid (Neu5Gc) synthesized in apes, Old World monkeys, and many non-primate mammals. Anti-Gal appeared in Old World primates following accidental inactivation of the α1,3galactosyltransferase gene 20-30 million years ago. Anti-Neu5Gc appeared in hominins following the inactivation of the cytidine-monophosphate-N-acetyl-neuraminic acid hydroxylase gene, which led to the loss of Neu5Gc <6 million-years-ago. It is suggested that an epidemic of a lethal virus eliminated ancestral Old World-primates synthesizing α-gal epitopes, whereas few mutated offspring lacking α-gal epitopes and producing anti-Gal survived because anti-Gal destroyed viruses presenting α-gal epitopes, following replication in parental populations. Similarly, anti-Neu5Gc protected few mutated hominins lacking Neu5Gc in lethal virus epidemics that eliminated parental hominins synthesizing Neu5Gc. Since α-gal epitopes are presented on many zoonotic viruses it is suggested that vaccines elevating anti-Gal titers may be of protective significance in areas endemic for such zoonotic viruses. This protection would be during the non-primate mammal to human virus transmission, but not in subsequent human to human transmission where the virus presents human glycans. In addition, production of viral vaccines presenting multiple α-gal epitopes increases their immunogenicity because of effective anti-Gal-mediated targeting of vaccines to antigen presenting cells for extensive uptake of the vaccine by these cells.


Assuntos
Antígenos Virais/imunologia , Glicoproteínas/imunologia , Viroses/imunologia , Animais , Reações Antígeno-Anticorpo , Evolução Molecular , Galactosiltransferases/genética , Galactosiltransferases/metabolismo , Interações Hospedeiro-Patógeno/genética , Interações Hospedeiro-Patógeno/imunologia , Humanos , Primatas
4.
Viruses ; 12(9)2020 09 21.
Artigo em Inglês | MEDLINE | ID: mdl-32967229

RESUMO

As evidence has mounted that virus-infected cells, such as cancer cells, negatively regulate the function of T-cells via immune checkpoints, it has become increasingly clear that viral infections similarly exploit immune checkpoints as an immune system escape mechanism. Although immune checkpoint therapy has been successfully used in cancer treatment, numerous studies have suggested that such therapy may also be highly relevant for treating viral infection, especially chronic viral infections. However, it has not yet been applied in this manner. Here, we reviewed recent findings regarding immune checkpoints in viral infections, including COVID-19, and discussed the role of immune checkpoints in different viral infections, as well as the potential for applying immune checkpoint blockades as antiviral therapy.


Assuntos
Fatores Imunológicos/imunologia , Viroses/imunologia , Vírus/imunologia , Animais , Antivirais/uso terapêutico , Doença Crônica , Humanos , Fatores Imunológicos/antagonistas & inibidores , Imunoterapia , Ativação Linfocitária/efeitos dos fármacos , Linfócitos T/imunologia , Linfócitos T/patologia , Viroses/terapia , Vírus/classificação
5.
Med Hypotheses ; 143: 110125, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32763657

RESUMO

The novel coronavirus (SARS-CoV-2) is primarily a respiratory pathogen and its clinical manifestations are dominated by respiratory symptoms, the most severe of which is acute respiratory distress syndrome (ARDS). However, COVID-19 is increasingly recognized to cause an overwhelming inflammatory response and cytokine storm leading to end organ damage. End organ damage to heart is one of the most severe complications of COVID-19 that increases the risk of death. We proposed a two-fold mechanism responsible for causing acute coronary events in patients with COVID-19 infection: Cytokine storm leading to rapid onset formation of new coronary plaques along with destabilization of pre-existing plaques and direct myocardial injury secondary to acute systemic viral infection. A well-coordinated immune response is the first line innate immunity against a viral infection. However, an uncoordinated response and hypersecretion of cytokines and chemokines lead to immune related damage to the human body. Human Coronavirus (HCoV) infection causes infiltration of inflammatory cells that cause excessive production of cytokines, proteases, coagulation factors, oxygen radicals and vasoactive molecules causing endothelial damage, disruption of fibrous cap and initiation of formation of thrombus. Systemic viral infections also cause vasoconstriction leading to narrowing of vascular lumen and stimulation of platelet activation via shear stress. The resultant cytokine storm causes secretion of hypercoagulable tissue factor without consequential increase in counter-regulatory pathways such as AT-III, activated protein C and plasminogen activator type 1. Lastly, influx of CD4+ T-cells in cardiac vasculature results in an increased production of cytokines that stimulate smooth muscle cells to migrate into the intima and generate collagen and other fibrous products leading to advancement of fatty streaks to advanced atherosclerotic lesions. Direct myocardial damage and cytokine storm leading to destabilization of pre-existing plaques and accelerated formation of new plaques are the two instigating mechanisms for acute coronary syndromes in COVID-19.


Assuntos
Síndrome Coronariana Aguda/etiologia , Betacoronavirus , Infecções por Coronavirus/complicações , Modelos Cardiovasculares , Pandemias , Pneumonia Viral/complicações , Síndrome Coronariana Aguda/fisiopatologia , Linfócitos T CD4-Positivos/imunologia , Quimiocinas/fisiologia , Doença da Artéria Coronariana/etiologia , Doença da Artéria Coronariana/fisiopatologia , Vasos Coronários/metabolismo , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/fisiopatologia , Síndrome da Liberação de Citocina/etiologia , Síndrome da Liberação de Citocina/fisiopatologia , Citocinas/fisiologia , Humanos , Imunidade Inata , Placa Aterosclerótica/etiologia , Placa Aterosclerótica/fisiopatologia , Ativação Plaquetária , Pneumonia Viral/imunologia , Pneumonia Viral/fisiopatologia , Vasoconstrição , Viroses/complicações , Viroses/imunologia
6.
J Immunother Cancer ; 8(2)2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32611687

RESUMO

The present review summarizes up-to-date evidence addressing the frequently discussed clinical controversies regarding the use of immune checkpoint inhibitors (ICIs) in cancer patients with viral infections, including AIDS, hepatitis B and C, progressive multifocal leukoencephalopathy, influenza, and COVID-19. In detail, we provide available information on (1) safety regarding the risk of new infections, (2) effects on the outcome of pre-existing infections, (3) whether immunosuppressive drugs used to treat ICI-related adverse events affect the risk of infection or virulence of pre-existing infections, (4) whether the use of vaccines in ICI-treated patients is considered safe, and (5) whether there are beneficial effects of ICIs that even qualify them as a therapeutic approach for these viral infections.


Assuntos
Imunossupressores/uso terapêutico , Neoplasias/complicações , Viroses/terapia , Betacoronavirus , Infecções por Coronavirus/complicações , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/terapia , Hepatite B/complicações , Hepatite B/tratamento farmacológico , Hepatite B/imunologia , Hepatite B/terapia , Hepatite C/complicações , Hepatite C/tratamento farmacológico , Hepatite C/imunologia , Hepatite C/terapia , Humanos , Influenza Humana/complicações , Influenza Humana/tratamento farmacológico , Influenza Humana/imunologia , Influenza Humana/terapia , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/imunologia , Pneumonia Viral/terapia , Viroses/complicações , Viroses/tratamento farmacológico , Viroses/imunologia
7.
Curr Res Transl Med ; 68(3): 105-110, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32616467

RESUMO

The relative ease of isolation of mesenchymal stem cells (MSCs) from different tissues coupled with their culture expansion in vitro and their differentiation capacity to mesodermal, endodermal and ectodermal lineages have made these cells attractive for a large number of therapeutic applications. In recent years, there has been remarkable progress in the utilization of MSCs in diverse clinical indications both in animal models and human clinical trials. However, the potential of MSCs to control or treat viral diseases is still in its infancy. In this study, we report quantitative data on the MSC-based clinical trials over the last ten years as they appear on the online database of clinical research studies from US National Institutes of Health. In particular, we provide comprehensive review of either completed or ongoing clinical trials using MSCs for virus-associated diseases focusing on HIV, hepatitis B virus and COVID-19 virus.


Assuntos
Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/fisiologia , Viroses/terapia , Fenômenos Fisiológicos Virais , Animais , Betacoronavirus/fisiologia , Técnicas de Cultura de Células , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/terapia , Infecções por Coronavirus/virologia , HIV/fisiologia , Vírus da Hepatite B/fisiologia , Humanos , Transplante de Células-Tronco Mesenquimais/métodos , Transplante de Células-Tronco Mesenquimais/tendências , Pandemias , Pneumonia Viral/imunologia , Pneumonia Viral/terapia , Pneumonia Viral/virologia , Viroses/epidemiologia , Viroses/imunologia , Vírus/patogenicidade
8.
Scand J Immunol ; 92(3): e12928, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32640050

RESUMO

Several enveloped viruses, particularly some RNA viruses, have high rates of mutation or replication, which can make them virulent pathogens in humans and other mammals. A proposed treatment could use synthesized proteins to mask pathogenic viral surface proteins to quickly induce an immune attack on specific enveloped viruses by using existing immune cells. One treatment could inject dual-protein ligand masks into patients' bloodstreams to mask pathogenic surface proteins used to infect mammalian cells. The mammalian immune system already uses an analogous, more complex structure called a pentraxin to neutralize some pathogens by connecting their surface proteins to immune cells. And several types of antiviral peptides have already experimentally demonstrated effectiveness in blocking various viral pathogen infections. These treatments offer advantages, especially for currently untreatable viral pathogens. Furthermore, using dual-protein ligands and the antigenic memory of some sub-populations of NK cells would also allow the creation of defacto vaccines based on a host's NK cells, instead of vaccines utilizing CD4 and CD8 α:ß T cells, which are limited by the requirement of MHC presentation of the target antigens to α:ß T cells. Targeted NK cell vaccines could attack host cells latently or actively infected by intracellular pathogens, even host cells having pathogen downregulated MHC antigen presentation. Eight postulates concerning the effects of pathogen mutation, or change in phenotype from genetic recombination or rearrangement, and replication rates on pathogen vs host dominance are also listed, which should be applicable to viral and non-viral pathogens.


Assuntos
Mutação , Viroses/virologia , Fenômenos Fisiológicos Virais , Replicação Viral , Vírus/genética , Antivirais/farmacologia , Antivirais/uso terapêutico , Interações Hospedeiro-Patógeno/imunologia , Humanos , Taxa de Mutação , Fenótipo , Recombinação Genética , Viroses/tratamento farmacológico , Viroses/imunologia , Vírus/efeitos dos fármacos , Vírus/imunologia
9.
Adv Exp Med Biol ; 1207: 425-432, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32671765

RESUMO

Autophagy plays an important role in the fight against viral infection, which can directly remove the virus, interact with the viral protein, and at the same time regulate the innate and adaptive immunity and promote virus clearance. The virus has also evolved autophagy, which evades, antagonizes and utilizes autophagy, and regulates autophagy pathways, affects autophagy maturation, changes autophagy small body environment or changes the body's immune response type to promote or inhibit autophagy. This chapter introduces the possible mechanisms of autophagy during pathogen infection such as human immunodeficiency virus and hepatitis virus, in order to provide new methods for the prevention and treatment of viral infection.


Assuntos
Autofagia , Viroses , Imunidade Adaptativa , Interações Hospedeiro-Patógeno/imunologia , Humanos , Imunidade Inata , Viroses/imunologia , Viroses/patologia
10.
Cardiovasc Pathol ; 49: 107260, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32683240

RESUMO

PURPOSE: to study the effect of immunosupressive therapy (IST) in the virus-negative and virus-positive patients with immune-mediated myocarditis. METHODS: in 60 patients (45 male, 46.7 ± 11.8 years, mean LV EDD, 6.7 ± 0.7 cm, EF 26.2 ± 9.1%) active/borderline myocarditis was verified by endomyocardial biopsy (n = 38), intraoperative biopsy (n = 10), examination of explanted heart (n = 3) and autopsy (n = 9). Indications for IST determined based on histological, immune activity. The follow-up was 19.0 [7.25; 40.25] months. RESULTS: The viral genome in the myocardium was detected in 32 patients (V+ group), incl. parvovirus B19 in 23. The anti-heart antibody level was equally high in the V+ and V- patients. Antiviral therapy was administered in 24 patients. IST (in 22 V+ and 24 V- patients) include steroids (n = 40), hydroxychloroquine (n = 20), azathioprine (n = 21). The significant decrease of LV EDD (6.7 ± 0.7 to 6.4 ± 0.8), PAP (48.9 ± 15.5 to 39.4 ± 11.5 mm Hg, р<0,01), increase of EF (26.5 ± 0.9 to 36.0 ± 10.8), and lower lethality (23.9% and 64.3%; RR 0.37, 95% CI 0.19-0.71), p<0.01, were found only in IST group. Significant improvement due to IST were achieved not only in V-, but also in V+ patients. CONCLUSIONS: IST in patients with immune-mediated lymphocytic myocarditis is effective and is associated with lower lethality both in virus-negative and virus-positive patients.


Assuntos
Antivirais/uso terapêutico , Autoanticorpos/sangue , Imunossupressores/uso terapêutico , Linfócitos/efeitos dos fármacos , Miocardite/tratamento farmacológico , Miocárdio/imunologia , Viroses/tratamento farmacológico , Vírus/efeitos dos fármacos , Adulto , Idoso , Biópsia , Feminino , Interações Hospedeiro-Patógeno , Humanos , Linfócitos/imunologia , Linfócitos/patologia , Linfócitos/virologia , Masculino , Pessoa de Meia-Idade , Miocardite/imunologia , Miocardite/patologia , Miocardite/virologia , Miocárdio/patologia , Resultado do Tratamento , Viroses/imunologia , Viroses/patologia , Viroses/virologia , Vírus/imunologia , Adulto Jovem
11.
Int J Mol Sci ; 21(11)2020 Jun 08.
Artigo em Inglês | MEDLINE | ID: covidwho-574726

RESUMO

Viruses use cell machinery to replicate their genome and produce viral proteins. For this reason, several intracellular factors, including the redox state, might directly or indirectly affect the progression and outcome of viral infection. In physiological conditions, the redox balance between oxidant and antioxidant species is maintained by enzymatic and non-enzymatic systems, and it finely regulates several cell functions. Different viruses break this equilibrium and induce an oxidative stress that in turn facilitates specific steps of the virus lifecycle and activates an inflammatory response. In this context, many studies highlighted the importance of redox-sensitive pathways as novel cell-based targets for therapies aimed at blocking both viral replication and virus-induced inflammation. In the review, we discuss the most recent findings in this field. In particular, we describe the effects of natural or synthetic redox-modulating molecules in inhibiting DNA or RNA virus replication as well as inflammatory pathways. The importance of the antioxidant transcription factor Nrf2 is also discussed. Most of the data reported here are on influenza virus infection. We believe that this approach could be usefully applied to fight other acute respiratory viral infections characterized by a strong inflammatory response, like COVID-19.


Assuntos
Antivirais/uso terapêutico , Oxirredução/efeitos dos fármacos , Viroses/tratamento farmacológico , Animais , Infecções por Coronavirus/tratamento farmacológico , Glutationa/metabolismo , Humanos , Inflamação/tratamento farmacológico , Influenza Humana/tratamento farmacológico , Viroses/imunologia , Viroses/patologia , Replicação Viral/efeitos dos fármacos
13.
Int J Mol Sci ; 21(11)2020 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-32521619

RESUMO

Viruses use cell machinery to replicate their genome and produce viral proteins. For this reason, several intracellular factors, including the redox state, might directly or indirectly affect the progression and outcome of viral infection. In physiological conditions, the redox balance between oxidant and antioxidant species is maintained by enzymatic and non-enzymatic systems, and it finely regulates several cell functions. Different viruses break this equilibrium and induce an oxidative stress that in turn facilitates specific steps of the virus lifecycle and activates an inflammatory response. In this context, many studies highlighted the importance of redox-sensitive pathways as novel cell-based targets for therapies aimed at blocking both viral replication and virus-induced inflammation. In the review, we discuss the most recent findings in this field. In particular, we describe the effects of natural or synthetic redox-modulating molecules in inhibiting DNA or RNA virus replication as well as inflammatory pathways. The importance of the antioxidant transcription factor Nrf2 is also discussed. Most of the data reported here are on influenza virus infection. We believe that this approach could be usefully applied to fight other acute respiratory viral infections characterized by a strong inflammatory response, like COVID-19.


Assuntos
Antivirais/uso terapêutico , Oxirredução/efeitos dos fármacos , Viroses/tratamento farmacológico , Animais , Infecções por Coronavirus/tratamento farmacológico , Glutationa/metabolismo , Humanos , Inflamação/tratamento farmacológico , Influenza Humana/tratamento farmacológico , Viroses/imunologia , Viroses/patologia , Replicação Viral/efeitos dos fármacos
14.
Proc Natl Acad Sci U S A ; 117(27): 15778-15788, 2020 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-32571931

RESUMO

RIG-I, MDA5, and LGP2 comprise the RIG-I-like receptors (RLRs). RIG-I and MDA5 are essential pathogen recognition receptors sensing viral infections while LGP2 has been described as both RLR cofactor and negative regulator. After sensing and binding to viral RNA, including double-stranded RNA (dsRNA), RIG-I and MDA5 undergo cytosol-to-membrane relocalization to bind and signal through the MAVS adaptor protein on intracellular membranes, thus directing downstream activation of IRF3 and innate immunity. Here, we report examination of the dynamic subcellular localization of all three RLRs within the intracellular response to dsRNA and RNA virus infection. Observations from high resolution biochemical fractionation and electron microscopy, coupled with analysis of protein interactions and IRF3 activation, show that, in resting cells, microsome but not mitochondrial fractions harbor the central components to initiate innate immune signaling. LGP2 interacts with MAVS in microsomes, blocking the RIG-I/MAVS interaction. Remarkably, in response to dsRNA treatment or RNA virus infection, LGP2 is rapidly released from MAVS and redistributed to mitochondria, temporally correlating with IRF3 activation. We reveal that IRF3 activation does not take place on mitochondria but instead occurs at endoplasmic reticulum (ER)-derived membranes. Our observations suggest ER-derived membranes as key RLR signaling platforms controlled through inhibitory actions of LGP2 binding to MAVS wherein LGP2 translocation to mitochondria releases MAVS inhibition to facilitate RLR-mediated signaling of innate immunity.


Assuntos
Proteína DEAD-box 58/genética , Helicase IFIH1 Induzida por Interferon/genética , RNA Helicases/genética , Viroses/imunologia , Proteína DEAD-box 58/imunologia , Humanos , Imunidade Inata/genética , Imunidade Inata/imunologia , Fator Regulador 3 de Interferon/genética , Helicase IFIH1 Induzida por Interferon/imunologia , Mitocôndrias/genética , Mitocôndrias/imunologia , RNA Helicases/imunologia , RNA de Cadeia Dupla/genética , RNA Viral/genética , RNA Viral/imunologia , Transdução de Sinais/genética , Transdução de Sinais/imunologia , Viroses/genética , Viroses/virologia
16.
Virus Res ; 286: 198036, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32492472

RESUMO

Interferon (IFN)-stimulated gene product 15 (ISG15) is a ubiquitin-like protein critical for the control of microbial infections. ISG15 appears to serve a wide variety of functions, which regulate multiple cellular responses contributing to the development of an antiviral state. ISG15 is a versatile molecule directly modulating both host and virus protein function which regulate many signaling pathways, including its own synthesis. Here we review the various roles ISG15 plays in the antiviral immune response, and examine the mechanisms by which viruses attempt to mitigate or exploit ISG15 activity.


Assuntos
Citocinas/metabolismo , Imunidade Inata/imunologia , Ubiquitinas/metabolismo , Viroses/imunologia , Replicação Viral/imunologia , Animais , Citocinas/genética , Humanos , Interferon Tipo I/imunologia , Macrófagos/imunologia , Camundongos , Neutrófilos/imunologia , Transdução de Sinais/genética , Transdução de Sinais/imunologia , Ubiquitinas/genética , Proteínas Virais/metabolismo , Internalização do Vírus
17.
Eur Respir J ; 56(4)2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32586885

RESUMO

Major epidemics, including some that qualify as pandemics, such as severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), HIV, influenza A (H1N1)pdm/09 and most recently COVID-19, affect the lung. Tuberculosis (TB) remains the top infectious disease killer, but apart from syndemic TB/HIV little is known regarding the interaction of viral epidemics and pandemics with TB. The aim of this consensus-based document is to describe the effects of viral infections resulting in epidemics and pandemics that affect the lung (MERS, SARS, HIV, influenza A (H1N1)pdm/09 and COVID-19) and their interactions with TB. A search of the scientific literature was performed. A writing committee of international experts including the European Centre for Disease Prevention and Control Public Health Emergency (ECDC PHE) team, the World Association for Infectious Diseases and Immunological Disorders (WAidid), the Global Tuberculosis Network (GTN), and members of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Study Group for Mycobacterial Infections (ESGMYC) was established. Consensus was achieved after multiple rounds of revisions between the writing committee and a larger expert group. A Delphi process involving the core group of authors (excluding the ECDC PHE team) identified the areas requiring review/consensus, followed by a second round to refine the definitive consensus elements. The epidemiology and immunology of these viral infections and their interactions with TB are discussed with implications for diagnosis, treatment and prevention of airborne infections (infection control, viral containment and workplace safety). This consensus document represents a rapid and comprehensive summary on what is known on the topic.


Assuntos
Infecções Respiratórias/epidemiologia , Tuberculose/epidemiologia , Viroses/epidemiologia , Vacina BCG/uso terapêutico , Betacoronavirus , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/imunologia , Epidemias , Infecções por HIV/diagnóstico , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Infecções por HIV/imunologia , Humanos , Vírus da Influenza A Subtipo H1N1 , Influenza Humana/diagnóstico , Influenza Humana/tratamento farmacológico , Influenza Humana/epidemiologia , Influenza Humana/imunologia , Pulmão/imunologia , Coronavírus da Síndrome Respiratória do Oriente Médio , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/epidemiologia , Pneumonia Viral/imunologia , Saúde Pública , Infecções Respiratórias/diagnóstico , Infecções Respiratórias/tratamento farmacológico , Infecções Respiratórias/imunologia , Síndrome Respiratória Aguda Grave/diagnóstico , Síndrome Respiratória Aguda Grave/tratamento farmacológico , Síndrome Respiratória Aguda Grave/epidemiologia , Síndrome Respiratória Aguda Grave/imunologia , Tuberculose/diagnóstico , Tuberculose/imunologia , Tuberculose/prevenção & controle , Viroses/diagnóstico , Viroses/tratamento farmacológico , Viroses/imunologia
18.
Artigo em Inglês | MEDLINE | ID: mdl-32450013

RESUMO

Because viruses still represent a significant threat to human and animal health worldwide, the development of effective weapons against viral infections remains a top priority for the biopharmaceutical industry. This article reviews the dietary and pharmaceutical applications of polysaccharides (PS), first of all chitosan, in the prevention and treatment of viral diseases, focusing more particularly on solid or gel micro/nanoparticulate systems. The intrinsic antiviral activity of PS and their immunostimulatory effects, implemented in animal and human diets, are first surveyed. Then the review discusses the potential of PS-based particles as carriers of antiviral drugs and vaccines, with emphasis on the adjuvant potency of PS in solid vaccine formulations. The gap between the abundance of academic studies in this area and the lack of actual antiviral formulations dispensed to human patients is underlined, notwithstanding a number of branded products on the market.


Assuntos
Adjuvantes Imunológicos/administração & dosagem , Sistemas de Liberação de Medicamentos/métodos , Polissacarídeos/administração & dosagem , Polissacarídeos/imunologia , Vacinas Virais/administração & dosagem , Vacinas Virais/imunologia , Viroses/prevenção & controle , Adjuvantes Imunológicos/farmacologia , Animais , Antivirais/administração & dosagem , Humanos , Polissacarídeos/farmacologia , Viroses/imunologia , Viroses/terapia
19.
Science ; 368(6491): 608-612, 2020 05 08.
Artigo em Inglês | MEDLINE | ID: mdl-32381717

RESUMO

Viral infections during pregnancy can have devastating consequences on pregnancy outcomes, fetal development, and maternal health. In this review, we examine fetal and maternal immune defense mechanisms that mediate resistance against viral infections and discuss the range of syndromes that ensue when such mechanisms fail, from fetal developmental defects to establishment of chronic infection. Further, we highlight the role of maternal immune activation, or uncontrolled inflammation triggered by viral infections during pregnancy, and its potential downstream pathological effects, including tissue damage and fetal demise. Insights into the respective contributions of direct viral toxicity versus fetal and maternal immune responses that underlie the pathogenesis of congenital disease will guide future treatment strategies.


Assuntos
Doenças Fetais/virologia , Feto/anormalidades , Troca Materno-Fetal/imunologia , Complicações Infecciosas na Gravidez/virologia , Viroses/imunologia , Feminino , Desenvolvimento Fetal/imunologia , Doenças Fetais/imunologia , Feto/imunologia , Feto/virologia , Humanos , Imunidade Inata , Gravidez , Resultado da Gravidez
20.
Nat Commun ; 11(1): 2611, 2020 05 26.
Artigo em Inglês | MEDLINE | ID: mdl-32457298

RESUMO

Chronic opioid usage not only causes addiction behavior through the central nervous system, but also modulates the peripheral immune system. However, how opioid impacts the immune system is still barely characterized systematically. In order to understand the immune modulatory effect of opioids in an unbiased way, here we perform single-cell RNA sequencing (scRNA-seq) of peripheral blood mononuclear cells from opioid-dependent individuals and controls to show that chronic opioid usage evokes widespread suppression of antiviral gene program in naive monocytes, as well as in multiple immune cell types upon stimulation with the pathogen component lipopolysaccharide. Furthermore, scRNA-seq reveals the same phenomenon after a short in vitro morphine treatment. These findings indicate that both acute and chronic opioid exposure may be harmful to our immune system by suppressing the antiviral gene program. Our results suggest that further characterization of the immune modulatory effects of opioid is critical to ensure the safety of clinical opioids.


Assuntos
Regulação da Expressão Gênica/imunologia , Imunidade Inata/genética , Transtornos Relacionados ao Uso de Opioides/imunologia , Viroses/imunologia , Adulto , Antivirais/farmacologia , Feminino , Perfilação da Expressão Gênica , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Interferons/farmacologia , Leucócitos Mononucleares , Lipopolissacarídeos/farmacologia , Masculino , Pessoa de Meia-Idade , Morfina/farmacologia , Análise de Célula Única , Adulto Jovem
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