Alpha-synuclein dynamics bridge Type-I Interferon response and SARS-CoV-2 replication in peripheral cells

BACKGROUND: Increasing evidence suggests a double-faceted role of alpha-synuclein (α-syn) following infection by a variety of viruses, including SARS-CoV-2. Although α-syn accumulation is known to contribute to cell toxicity and the development and/or exacerbation of neuropathological manifestations, it is also a key to sustaining anti-viral innate immunity. Consistently with α-syn aggregation as a hallmark of Parkinson's disease, most studies investigating the biological function of α-syn focused on neural cells, while reports on the role of α-syn in periphery are limited, especially in SARS-CoV-2 infection. RESULTS: Results herein obtained by real time qPCR, immunofluorescence and western blot indicate that α-syn upregulation in peripheral cells occurs as a Type-I Interferon (IFN)-related response against SARS-CoV-2 infection. Noteworthy, this effect mostly involves α-syn multimers, and the dynamic α-syn multimer:monomer ratio. Administration of excess α-syn monomers promoted SARS-CoV-2 replication along with downregulation of IFN-Stimulated Genes (ISGs) in epithelial lung cells, which was associated with reduced α-syn multimers and α-syn multimer:monomer ratio. These effects were prevented by combined administration of IFN-ß, which hindered virus replication and upregulated ISGs, meanwhile increasing both α-syn multimers and α-syn multimer:monomer ratio in the absence of cell toxicity. Finally, in endothelial cells displaying abortive SARS-CoV-2 replication, α-syn multimers, and multimer:monomer ratio were not reduced following exposure to the virus and exogenous α-syn, suggesting that only productive viral infection impairs α-syn multimerization and multimer:monomer equilibrium. CONCLUSIONS: Our study provides novel insights into the biology of α-syn, showing that its dynamic conformations are implicated in the innate immune response against SARS-CoV-2 infection in peripheral cells. In particular, our results suggest that promotion of non-toxic α-syn multimers likely occurs as a Type-I IFN-related biological response which partakes in the suppression of viral replication. Further studies are needed to replicate our findings in neuronal cells as well as animal models, and to ascertain the nature of such α-syn conformations.

Phylogenetic relationship between rabies virus (Lyssavirus rabies) variants from two different species / Relações filogenéticas do vírus da raiva (Lyssavirus rabies) em duas diferentes espécies / Relaciones filogenéticas del virus de la rabia (Lyssavirus rabies) en dos especies diferentes

Rabies is a fatal zoonotic disease that affects several mammals. Hematophagous bats are recognized hosts of the rabies virus, and their main food source is the blood of other mammals, particularly cattle. During feeding, bats transmit the virus to cattle, which are victims of the disease, contributing to economic losses and increasing the risk of infection for humans. Based on this affinity in the rabies cycle between bats and cattle, the objective of this study was to analyze the phylogenetic relationships of rabies virus samples in cattle and bats. The G gene of the rabies virus was chosen for this study because it is directly related to the infection process. Nucleotide sequences of the viral G gene were selected from GenBank for samples obtained from infected cattle and bats. Maximum parsimony analyses were conducted using the Molecular Evolutionary Genetics Analysis software. The Maxima Parsimony tree indicated a phylogenetic relationship between the G genes of both hosts, indicating that the virus evolved from bats to cattle. Analysis of parsimoniously informative sites revealed that the viral G gene carried specific mutations in each host. Knowledge of the evolutionary relationships between the rabies virus and its hosts is critical for identifying potential new hosts and the possible routes of infection for humans.

A Raiva é uma zoonose fatal que infecta várias espécies de mamíferos. Os morcegos hematófagos são reconhecidos como hospedeiros do vírus da Raiva e sua principal fonte de alimento é o sangue de outros mamíferos, especialmente os bovinos. Quando se alimentam, os morcegos transmitem o vírus para o bovino os quais são vítimas da doença, contribuindo para perdas econômicas e riscos de infecção para humanos. Baseado nesta afinidade do ciclo da Raiva entre morcegos e bovinos, o objetivo deste estudo foi analisar as relações filogenéticas de amostras do vírus da Raiva em ambos os hospedeiros, bovinos e morcegos. O gene G do vírus da Raiva foi escolhido para esta pesquisa porque ele está diretamente relacionado ao processo de infecção. Sequências de nucleotídeos do gene G viral foram selecionadas no GenBank a partir de amostras obtidas de bovinos e morcegos infectados. Análises de Máxima Parcimônia foram conduzidas utilizando o software Molecular Evolutionary Genetics Analysis. A árvore de Máxima Parcimônia indicou uma relação filogenética entre o gene G de ambos os hospedeiros, indicando que o vírus evoluiu dos morcegos para os bovinos. A análise dos sítios parcimoniosamente informativos revelou que o gene G viral apresentou mutações específicas em cada hospedeiro. O conhecimento sobre as relações evolutivas do vírus da Raiva e seus hospedeiros é crucial para identificar nos hospedeiros potenciais e novas rotas possíveis de infecção para humanos.

La rabia es una zoonosis fatal que infecta a varias especies de mamíferos. Los murciélagos hematófagos son reconocidos como huéspedes del virus de la rabia y su principal fuente de alimentación es la sangre de otros mamíferos, especialmente del ganado. Al alimentarse, los murciélagos transmiten el virus al ganado que es víctima de la enfermedad, contribuyendo a pérdidas económicas y riesgos de infección para los humanos. Basado en esta afinidad del ciclo de la rabia entre murciélagos y ganado, el objetivo de este estudio fue analizar las relaciones filogenéticas de las muestras de virus de la rabia tanto en huéspedes, ganado y murciélagos. El gen G del virus de la rabia fue elegido para esta investigación porque está directamente relacionado con el proceso de infección. Las secuencias de nucleótidos del gen G viral se seleccionaron en GenBank a partir de muestras obtenidas de bovinos y murciélagos infectados. Los análisis de parsimonia máxima se realizaron utilizando el software Molecular Evolutionary Genetics Analysis. El árbol de Máxima Parsimônia indicó una relación filogenética entre el gen G de ambos huéspedes, indicando que el virus evolucionó de murciélagos a bovinos. El análisis de los sitios parsimoniosamente informativos reveló que el gen G viral presentaba mutaciones específicas en cada huésped. El conocimiento sobre las relaciones evolutivas del virus de la rabia y sus huéspedes es crucial para identificar huéspedes potenciales y nuevas posibles rutas de infección para humanos.

La función de las proteínas de choque térmico en las infecciones virales / The Role of Heat Shock Proteins in Viral Infections

Resumen Las proteínas de choque térmico se describieron como una respuesta intracelular al estrés calórico; sin embargo, al paso del tiempo, se observó que estas proteínas tienen múltiples funciones y que participan de manera relevante tanto en los procesos fisiológicos como patológicos. Las actividades que realizan las proteínas de choque térmico se relacionan con su localización, que puede ser intra o extracelular, al momento fisiológico y a las diferentes asociaciones estructurales, que pueden ser desde péptidos derivados de estas, hasta dímeros o multímeros. Con base en estas características funcionales, se les ha denominado proteínas multiempleo o "moonlighting proteins". En este artículo se describen algunas de las actividades de estas proteínas con relación al sistema inmunológico y las infecciones virales, en particular con los procesos inflamatorios.

Abstract Heat shock proteins (HSP) were first described as a cell response to heat stress. However, over time, it has become clear they have multiple functions inside and outside cells, and that they actively participate in different physiological and pathological processes. They perform functions related to their cellular location or physiological moment, which is why they have been called multi-use proteins or "moonlighting proteins". Furthermore, HSP activity is associated with different structural conformations, from peptides derived from them or as dimers or multimers, to mention a few. This article describes these functions and their relationship with the immune system, and their relationship with viral infection, particularly with inflammatory processes.

El enigma del coronavirus - De pandemia a endemia COVID-19 ¿Debemos seguir cuidándonos?

Pareciera que se están calmando las cosas con el SARS-Cov-2, pues ya no aparecen comunicaciones y notas diarias de hallazgos de nuevas variantes y subvariantes del virus, así como las modificaciones clínicas en sintomatología, hospitalizaciones, severidad y muertes por COVID-19. No conocemos cómo deberemos cuidarnos de sufrir la infección viral durante la inminente fase endémica de la enfermedad, conociendo los problemas de salud complejos del COVID prolongado si contraemos la virosis. En este artículo hacemos una descripción de las últimas mutaciones conocidas del coronavirus, cómo afectan ciertos órganos y sistemas, la ventaja de una mejor respuesta a la infección en personas con estilo de vida saludable, el rebote de la sintomatología, reinfecciones en la época de la vacuna, el COVID prolongado, el exceso de mortalidad de los médicos que atendieran las primeras olas sin vacuna, y algunas noticias y conocimientos sobre el COVID en la gestante y su feto y recién nacido, quedando la incógnita del futuro del neonato nacido de madre con COVID. En la endemia por COVID, ¿deberemos seguir protegiéndonos? ¿Cómo?

It seems that things are calming down with SARS-Cov-2, as there are no longer daily reports and notes of findings of new variants and subvariants of the virus, as well as clinical changes in symptomatology, hospitalizations, severity, and deaths due to COVID-19. We do not know how we should guard against viral infection during the impending endemic phase of the disease, knowing the complex health problems of prolonged COVID if we contract the virus. In this article we describe the latest known coronavirus mutations, how they affect certain organs and systems, the advantage of a better response to infection in people with healthy lifestyle, the rebound of symptomatology, reinfections at the time of the vaccine, prolonged COVID, excess mortality of physicians who attended the first waves without vaccine, and some news and knowledge about COVID in the pregnant woman and her fetus and newborn; the future of the newborn born to a mother with COVID remains unknown. In the COVID endemic, should we continue to protect ourselves? How?

Research progress in the role of E3 ubiquitin ligases in viral infection / 中华微生物学和免疫学杂志

Ubiquitination modifications are a kind of post-translational modifications of proteins widely found in eukaryotes and involved in a variety of biological activities. E3 ubiquitin ligases are an important component of the ubiquitin system, with the function of specific recognition of substrate proteins and mediation of different types of ubiquitination modifications. They can regulate the function and life time of substrate proteins. Recent studies have shown that E3 ubiquitin ligases are widely involved in the regulation of the host innate immune response and can directly or indirectly influence viral infection. Moreover, viruses are able to encode or hijack E3 ubiquitin ligases in their long-term evolution, allowing them to play an important role in viral infection and replication cycle. This paper reviewed the progress in the mechanisms of E3 ubiquitin ligases in innate immune responses and viral infection in recent years.

Progress in the function of nucleoporin 50 and its relationship with viral infection / 中华微生物学和免疫学杂志

Nucleoporin 50 (Nup50) is a component of nuclear basket in nuclear pore complex. It includes three main domains: N domain binding to importin α, F domain binding to importin β and R domain binding to Ran. The N domain has two importin α-binding segments. There are mainly two models for explaining the role of Nup50 in nuclear import: tri-stable switch and disassemble-recycle model. Nup50 not only participates in nuclear import, but also regulates genome organization and gene expression. In addition, Nup50 is involved in the process of viral infection and replication. There is some evidence that Nup50 is related to hepatitis B virus and human immunodeficiency virus 1 infections. However, there are few researches on the relationship between Nup50 and viral infection. This article summarized the progress in the function of Nup50 and its relationship with viral infection, aiming to provide new ideas for the following in-depth study.

Contribution of tobacco smoking to the risk of novel coronavirus infection and related mechanisms / 上海预防医学

The severe acute respiratory syndrome coronavirus 2 （SARS-CoV-2） and its variants are still globally spreading. Vaccines can reduce the mortality， but cannot eliminate the risk of infection. The identification and protection of the high-risk susceptible population remains of great importance for the prevention and control of SARS-CoV2 and other coronavirus infections. Smoking is an important risk factor for many respiratory diseases， and therefore may also influence the risk of SARS-CoV2 infection and the disease progression after infection. This study reviewed the epidemiological and mechanistic evidence supporting the relationship between tobacco exposure and SARS-CoV2 infection， summarized the contributing effects of tobacco exposure to the infection risk， disease severity， and mortality of COVID-19， and analyzed the molecular mechanisms by which cigarette smoking affects COVID-19 through regulating inflammatory microenvironment and gene expression.

Effects of neutrophil extracellular traps during human respiratory syncytial virus infection in vitro / Efeitos das redes extracelulares dos neutrófilos durante a infecção in vitro pelo vírus sincicial respiratório

The human respiratory syncytial virus (hRSV) is the most common cause of severe lower respiratory tract diseases in young children worldwide, leading to a high number of hospitalizations and significant expenditures for health systems. Neutrophils are massively recruited to the lung tissue of patients with acute respiratory diseases. At the infection site, they release neutrophil extracellular traps (NETs) that can capture and/or inactivate different types of microorganisms, including viruses. Evidence has shown that the accumulation of NETs results in direct cytotoxic effects on endothelial and epithelial cells. Neutrophils stimulated by the hRSV-F protein generate NETs that are able to capture hRSV particles, thus reducing their transmission. However, the massive production of NETs obstructs the airways and increases disease severity. Therefore, further knowledge about the effects of NETs during hRSV infections is essential for the development of new specific and effective treatments. This study evaluated the effects of NETs on the previous or posterior contact with hRSV-infected Hep-2 cells. Hep-2 cells were infected with different hRSV multiplicity of infection (MOI 0.5 or 1.0), either before or after incubation with NETs (0.5–16 μg/mL). Infected and untreated cells showed decreased cellular viability and intense staining with trypan blue, which was accompanied by the formation of many large syncytia. Previous contact between NETs and cells did not result in a protective effect. Cells in monolayers showed a reduced number and area of syncytia, but cell death was similar in infected and non-treated cells. The addition of NETs to infected tissues maintained a similar virus-induced cell death rate and an increased syncytial area, indicating cytotoxic and deleterious damages. Our results corroborate previously reported findings that NETs contribute to the immunopathology developed by patients infected with hRSV.

O vírus sincicial respiratório humano (hRSV) é a causa mais comum de doenças graves do trato respiratório inferior em crianças pequenas em todo o mundo, resultando em grande número de hospitalizações e gastos significativos para os sistemas de saúde. Neutrófilos são recrutados em massa para o tecido pulmonar de pacientes com doenças respiratórias agudas. No local da infecção, eles liberam armadilhas extracelulares de neutrófilos (NETs) que podem capturar e/ou inativar diferentes tipos de microrganismos, incluindo vírus. Evidências demonstraram que o acúmulo de NETs resulta em efeitos citotóxicos diretos nas células endoteliais e epiteliais. Os neutrófilos estimulados pela proteína F do vírus sincicial respiratório (hRSV-F) geram NETs que são capazes de capturar partículas virais, reduzindo assim sua transmissão. No entanto, a produção maciça de NETs obstrui as vias aéreas e aumenta a gravidade da doença. Assim, um maior conhecimento sobre os efeitos das NETs durante as infecções por hRSV é essencial para o desenvolvimento de novos tratamentos específicos e eficazes. Este estudo avaliou os efeitos das NETs no contato prévio ou posterior à infecção de células Hep-2 com hRSV. As células Hep-2 foram infectadas com diferentes quantidades de hRSV (multiplicidade de infecção ou MOI 0,5 ou 1,0), antes ou após a incubação com NETs (0,5–16 μg/mL). Células infectadas e não tratadas mostraram redução da viabilidade celular e intensa coloração com azul de tripano, que foi acompanhada pela formação de sincícios numerosos e grandes. O contato prévio entre as NETs e as células não resultou em efeito protetor. As células em monocamadas mostraram um número e área de sincícios reduzidos, mas a morte celular foi semelhante àquela apresentada por células infectadas e não tratadas. A adição de NETs aos tecidos infectados manteve taxa de morte celular e formação de sincícios [...].

Effects of neutrophil extracellular traps during human respiratory syncytial virus infection in vitro

Abstract The human respiratory syncytial virus (hRSV) is the most common cause of severe lower respiratory tract diseases in young children worldwide, leading to a high number of hospitalizations and significant expenditures for health systems. Neutrophils are massively recruited to the lung tissue of patients with acute respiratory diseases. At the infection site, they release neutrophil extracellular traps (NETs) that can capture and/or inactivate different types of microorganisms, including viruses. Evidence has shown that the accumulation of NETs results in direct cytotoxic effects on endothelial and epithelial cells. Neutrophils stimulated by the hRSV-F protein generate NETs that are able to capture hRSV particles, thus reducing their transmission. However, the massive production of NETs obstructs the airways and increases disease severity. Therefore, further knowledge about the effects of NETs during hRSV infections is essential for the development of new specific and effective treatments. This study evaluated the effects of NETs on the previous or posterior contact with hRSV-infected Hep-2 cells. Hep-2 cells were infected with different hRSV multiplicity of infection (MOI 0.5 or 1.0), either before or after incubation with NETs (0.516 g/mL). Infected and untreated cells showed decreased cellular viability and intense staining with trypan blue, which was accompanied by the formation of many large syncytia. Previous contact between NETs and cells did not result in a protective effect. Cells in monolayers showed a reduced number and area of syncytia, but cell death was similar in infected and non-treated cells. The addition of NETs to infected tissues maintained a similar virus-induced cell death rate and an increased syncytial area, indicating cytotoxic and deleterious damages. Our results corroborate previously reported findings that NETs contribute to the immunopathology developed by patients infected with hRSV.

Resumo O vírus sincicial respiratório humano (hRSV) é a causa mais comum de doenças graves do trato respiratório inferior em crianças pequenas em todo o mundo, resultando em grande número de hospitalizações e gastos significativos para os sistemas de saúde. Neutrófilos são recrutados em massa para o tecido pulmonar de pacientes com doenças respiratórias agudas. No local da infecção, eles liberam armadilhas extracelulares de neutrófilos (NETs) que podem capturar e/ou inativar diferentes tipos de microrganismos, incluindo vírus. Evidências demonstraram que o acúmulo de NETs resulta em efeitos citotóxicos diretos nas células endoteliais e epiteliais. Os neutrófilos estimulados pela proteína F do vírus sincicial respiratório (hRSV-F) geram NETs que são capazes de capturar partículas virais, reduzindo assim sua transmissão. No entanto, a produção maciça de NETs obstrui as vias aéreas e aumenta a gravidade da doença. Assim, um maior conhecimento sobre os efeitos das NETs durante as infecções por hRSV é essencial para o desenvolvimento de novos tratamentos específicos e eficazes. Este estudo avaliou os efeitos das NETs no contato prévio ou posterior à infecção de células Hep-2 com hRSV. As células Hep-2 foram infectadas com diferentes quantidades de hRSV (multiplicidade de infecção ou MOI 0,5 ou 1,0), antes ou após a incubação com NETs (0,516 g/mL). Células infectadas e não tratadas mostraram redução da viabilidade celular e intensa coloração com azul de tripano, que foi acompanhada pela formação de sincícios numerosos e grandes. O contato prévio entre as NETs e as células não resultou em efeito protetor. As células em monocamadas mostraram um número e área de sincícios reduzidos, mas a morte celular foi semelhante àquela apresentada por células infectadas e não tratadas. A adição de NETs aos tecidos infectados manteve taxa de morte celular e formação de sincícios semelhantes àqueles induzidos pelo vírus em células não tratadas, indicando danos citotóxicos e deletérios. Nossos resultados corroboram achados relatados anteriormente de que as NETs contribuem para a imunopatologia desenvolvida por pacientes infectados com hRSV.

Knowledge, attitude and practices regarding dengue and its vector among medical practitioners in Malakand region, Pakistan

Abstract Dengue fever (DF) is increasingly recognized as one of the worlds major mosquito borne diseases and causes significant morbidity and mortality in tropical and subtropical countries. Dengue fever is endemic in most part of Pakistan and continues to be a public health concern. Knowledge, attitude and practices can play an important role in management of the disease. Current study was aimed to determine the level of knowledge, attitude and practices regarding dengue fever among health practitioners, to study the level of knowledge and attitude with preventive practices for dengue fever. A cross sectional study was carried out in medical practitioners of the four districts of Malakand region during October to November 2019. A pre-structured questionnaire was used to collect data from medical practitioners. Data was analyzed using Graph Pad version 5. Significant value was considered when less than 0.05 (at 95% confidence of interval). The results revealed that most of participants have seen dengue vector (62%), the media being the most quoted source of information. Nearly 81.2% participants were aware from transmission of dengue fever is by mosquito bite. Practices based upon preventive measures were found to be predominantly focused towards prevention of mosquito bites rather than elimination of breeding places. Although the knowledge regarding DF and mosquito control measure was quite high among the medical practitioners but this knowledge was not put into practice. Further studies are required to aware the people about dengue and its vector in order to get prevention and control.

Resumo A dengue (DF) é cada vez mais reconhecida como uma das principais doenças transmitidas por mosquitos do mundo e causa significativa morbidade e mortalidade em países tropicais e subtropicais. A dengue é endêmica na maior parte do Paquistão e continua a ser um problema de saúde pública. Conhecimento, atitude e práticas podem desempenhar papel importante no manejo da doença. O presente estudo teve como objetivo determinar o nível de conhecimento, atitude e práticas em relação à dengue entre os profissionais de saúde, para estudar o nível de conhecimento e atitude com as práticas preventivas da dengue. Um estudo transversal foi realizado com médicos dos quatro distritos da região de Malakand de outubro a novembro de 2019. Um questionário pré-estruturado foi usado para coletar dados de médicos. Os dados foram analisados no Graph Pad versão 5. Valor significativo foi considerado quando menor que 0,05 (com intervalo de confiança de 95%). Os resultados revelaram que a maioria dos participantes já viu o vetor da dengue (62%), sendo a mídia a fonte de informação mais citada. Quase 81,2% dos participantes sabiam que a transmissão da dengue é por picada de mosquito. Constatou-se que as práticas baseadas em medidas preventivas se concentravam predominantemente na prevenção de picadas de mosquitos, e não na eliminação de criadouros. Embora o conhecimento sobre DF e medidas de controle de mosquitos fosse bastante elevado entre os médicos, esse conhecimento não foi colocado em prática. Mais estudos são necessários para conscientizar a população sobre a dengue e seu vetor, a fim de se obter prevenção e controle.

Manifestação atípica do herpes zóster em boca: relato de caso / Atypical manifestation of herpes zoster in the mouth: case report / Manifestación atípica de herpes zoster en boca: reporte de caso

O herpes-zóster é uma infecção viral causada pela reativação do vírus da varicela-zóster (VZV) sendo os ramos do nervo trigêmeo afetados em até 20% dos casos. Apresenta-se comumente com dor em queimação e caracteristicamente, o zoster se manifesta como uma erupção vesicular unilateral que aparece na face, cabeça, tronco e até mesmo nas extremidades, variando de lesão leve e de rápida cicatrização à lesões graves e extensas com duração de semanas. Embora se reconheça que o zoster pode ocorrer sem exantema, classicamente apresenta-se como dermátomo unilateral, doloroso e/ou pruriginoso. A terapia fotodinâmica antimicrobiana (aPDT) tem sido indicada como uma modalidade promissora no tratamento de potenciais lesões infecciosas. Neste trabalho será relatado o caso clínico de um paciente diagnosticado com herpes zóster com manifestação atípica e que recebeu tratamento medicamentoso convencional associado à aPDT.

Herpes zoster is a viral infection caused by the reactivation of the varicella zoster virus (VZV), with the branches of the trigeminal nerve affected in up to 20% of cases. It commonly presents with burning pain and characteristically, zoster manifests as a unilateral vesicular eruption appearing on the face, head, trunk, and even the extremities, ranging from a mild, rapidly healing lesion to severe, extensive lesions lasting up to weeks. Although it is recognized that zoster can occur without rash, it classically presents as a unilateral, painful and/or pruritic dermatome. Antimicrobial photodynamic therapy (aPDT) has been indicated as a promising modality in the treatment of potential infectious lesions. In this work, the clinical case of a patient diagnosed with herpes zoster with atypical manifestation and who received conventional drug treatment associated with aPDT will be reported.

El herpes zóster es una infección vírica provocada por la reactivación del virus de la varicela zóster (VZV), con afectación de las ramas del nervio trigémino hasta en un 20% de los casos. Comúnmente se presenta con dolor ardiente y característicamente, el zoster se manifiesta como una erupción vesicular unilateral que aparece en la cara, la cabeza, el tronco e incluso las extremidades, que van desde una lesión leve que cura rápidamente hasta lesiones graves y extensas que duran semanas. Aunque se reconoce que el herpes zoster puede ocurrir sin exantema, clásicamente se presenta como un dermatoma unilateral, doloroso y/o pruriginoso. La terapia fotodinámica antimicrobiana (aPDT) se ha indicado como una modalidad prometedora en el tratamiento de posibles lesiones infecciosas. En este trabajo se reportará el caso clínico de un paciente diagnosticado de herpes zoster con manifestación atípica y que recibió tratamiento farmacológico convencional asociado a TFPa.

Tratamento de manifestação bucal exacerbada da doença de mão, pé e boca com apdt / Exacerbated oral manifestations of hand, foot and mouth disease: case report / Manifestaciones orales exacerbadas de la enfermedad de manos, pies y boca: reporte de un caso

Introdução: A doença da mão, pé e boca (DMPB) é uma infecção viral contagiosa que afeta principalmente crianças, mas também pode afetar adultos. É causada por diferentes tipos de enterovírus, sendo o CV-A16 e o EV-A71 os mais comuns. A transmissão ocorre pelo contato direto com fluidos corporais infectados ou por meio de objetos contaminados. Apresenta sintomas como febre, dor de garganta, falta de apetite e erupções cutâneas nas mãos, pés e boca. Embora a maioria dos casos seja leve e resolva- se espontaneamente, complicações graves, incluindo problemas neurológicos, podem ocorrer. O diagnóstico geralmente é clínico, com base nos sintomas e nas características das lesões. O tratamento é sintomático, com o uso de analgésicos e antitérmicos para aliviar a dor e a febre. No caso de lesões bucais graves a terapia fotodinâmica antimicrobiana (aPDT) em combinação com a fotobiomodulação com laser de baixa potência tem sido utilizada como uma abordagem promissora. A aPDT é capaz de eliminar microrganismos, incluindo vírus, independentemente de sua resistência aos antimicrobianos, e a fotobiomodulação auxilia na modulação da resposta inflamatória, alívio da dor e na cicatrização. Os lasers de baixa potência são a fonte de luz mais adequada para a fotoinativação viral, devido à sua interação precisa com o fotossensibilizante e a capacidade de fornecer a energia necessária para o efeito virucida. Metodologia: Relato de caso qualitativo e descritivo. Objetivo: Este relato de caso tem como objetivo descrever o tratamento de lesões bucais graves da DMPB combinando aPDT e fotobiomodulação com laser de baixa potência. Resultados: O tratamento mostrou resultados promissores no alívio dos sintomas e na melhora do quadro clínico. Conclusão: Mesmo em manifestações exacerbadas da doença de mão, pé e boca, podemos notar melhoras significativas nas lesões bucais após a aPDT com azul de metileno em combinação com a fotobiomodulação com laser de baixa potência.

Introduction: Hand, foot and mouth disease (HFMD) is a contagious viral infection that mainly affects children, but can also affect adults. It is caused by different types of enterovirus, with CV-A16 and EV-A71 being the most common. Transmission occurs through direct contact with infected body fluids or through contaminated objects. Symptoms include fever, sore throat, lack of appetite and rashes on the hands, feet and mouth. Although most cases are mild and resolve spontaneously, serious complications, including neurological problems, can occur. Diagnosis is usually clinical, based on the symptoms and characteristics of the lesions. Treatment is symptomatic, with the use of analgesics and antipyretics to relieve pain and fever. In the case of severe mouth lesions, antimicrobial photodynamic therapy (aPDT) in combination with low-power laser photobiomodulation has been used as a promising approach. aPDT is capable of eliminating microorganisms, including viruses, regardless of their resistance to antimicrobials, and photobiomodulation helps to modulate the inflammatory response, relieve pain and promote healing. Low-power lasers are the most suitable light source for viral photoinactivation, due to their precise interaction with the photosensitizer and their ability to provide the necessary energy for the virucidal effect. Methodology: Qualitative and descriptive case report. Objetive: This case report aims to describe the treatment of severe oral lesions of BPPD by combining aPDT and low-power laser photobiomodulation. Results: The treatment showed promising results in relieving symptoms and improving the clinical picture. Conclusion: Even in exacerbated manifestations of hand, foot and mouth disease, we can see significant improvements in mouth lesions after aPDT with methylene blue in combination with low-power laser photobiomodulation.

Introducción: La enfermedad de manos, pies y boca (EMPB) es una infección vírica contagiosa que afecta principalmente a los niños, aunque también puede afectar a los adultos. Está causada por diferentes tipos de enterovirus, siendo el CV-A16 y el EV-A71 los más comunes. La transmisión se produce por contacto directo con fluidos corporales infectados o a través de objetos contaminados. Los síntomas incluyen fiebre, dolor de garganta, falta de apetito y erupciones en manos, pies y boca. Aunque la mayoría de los casos son leves y se resuelven espontáneamente, pueden producirse complicaciones graves, incluidos problemas neurológicos. El diagnóstico suele ser clínico, basado en los síntomas y las características de las lesiones. El tratamiento es sintomático, con el uso de analgésicos y antipiréticos para aliviar el dolor y la fiebre. En el caso de lesiones bucales graves, la terapia fotodinámica antimicrobiana (aPDT) en combinación con la fotobiomodulación láser de baja potencia se ha utilizado como un enfoque prometedor. La aPDT es capaz de eliminar los microorganismos, incluidos los virus, independientemente de su resistencia a los antimicrobianos, y la fotobiomodulación ayuda a modular la respuesta inflamatoria, aliviar el dolor y favorecer la cicatrización. Los láseres de baja potencia son la fuente de luz más adecuada para la fotoinactivación viral, debido a su interacción precisa con el fotosensibilizador y a su capacidad para proporcionar la energía necesaria para el efecto virucida. Metodología: Caso clínico cualitativo y descriptivo. Objetivo: Este caso clínico pretende describir el tratamiento de lesiones orales severas de BPPD mediante la combinación de aPDT y fotobiomodulación con láser de baja potencia. Resultados: El tratamiento mostró resultados prometedores en el alivio de los síntomas y la mejora del cuadro clínico. Conclusión: Incluso en las manifestaciones exacerbadas de la enfermedad de manos, pies y boca, podemos observar mejoras significativas en las lesiones bucales tras la aPDT con azul de metileno en combinación con fotobiomodulación con láser de baja potencia.

Effects of neutrophil extracellular traps during human respiratory syncytial virus infection in vitro / Efeitos das redes extracelulares dos neutrófilos durante a infecção in vitro pelo vírus sincicial respiratório

Abstract The human respiratory syncytial virus (hRSV) is the most common cause of severe lower respiratory tract diseases in young children worldwide, leading to a high number of hospitalizations and significant expenditures for health systems. Neutrophils are massively recruited to the lung tissue of patients with acute respiratory diseases. At the infection site, they release neutrophil extracellular traps (NETs) that can capture and/or inactivate different types of microorganisms, including viruses. Evidence has shown that the accumulation of NETs results in direct cytotoxic effects on endothelial and epithelial cells. Neutrophils stimulated by the hRSV-F protein generate NETs that are able to capture hRSV particles, thus reducing their transmission. However, the massive production of NETs obstructs the airways and increases disease severity. Therefore, further knowledge about the effects of NETs during hRSV infections is essential for the development of new specific and effective treatments. This study evaluated the effects of NETs on the previous or posterior contact with hRSV-infected Hep-2 cells. Hep-2 cells were infected with different hRSV multiplicity of infection (MOI 0.5 or 1.0), either before or after incubation with NETs (0.5-16 μg/mL). Infected and untreated cells showed decreased cellular viability and intense staining with trypan blue, which was accompanied by the formation of many large syncytia. Previous contact between NETs and cells did not result in a protective effect. Cells in monolayers showed a reduced number and area of syncytia, but cell death was similar in infected and non-treated cells. The addition of NETs to infected tissues maintained a similar virus-induced cell death rate and an increased syncytial area, indicating cytotoxic and deleterious damages. Our results corroborate previously reported findings that NETs contribute to the immunopathology developed by patients infected with hRSV.

Resumo O vírus sincicial respiratório humano (hRSV) é a causa mais comum de doenças graves do trato respiratório inferior em crianças pequenas em todo o mundo, resultando em grande número de hospitalizações e gastos significativos para os sistemas de saúde. Neutrófilos são recrutados em massa para o tecido pulmonar de pacientes com doenças respiratórias agudas. No local da infecção, eles liberam armadilhas extracelulares de neutrófilos (NETs) que podem capturar e/ou inativar diferentes tipos de microrganismos, incluindo vírus. Evidências demonstraram que o acúmulo de NETs resulta em efeitos citotóxicos diretos nas células endoteliais e epiteliais. Os neutrófilos estimulados pela proteína F do vírus sincicial respiratório (hRSV-F) geram NETs que são capazes de capturar partículas virais, reduzindo assim sua transmissão. No entanto, a produção maciça de NETs obstrui as vias aéreas e aumenta a gravidade da doença. Assim, um maior conhecimento sobre os efeitos das NETs durante as infecções por hRSV é essencial para o desenvolvimento de novos tratamentos específicos e eficazes. Este estudo avaliou os efeitos das NETs no contato prévio ou posterior à infecção de células Hep-2 com hRSV. As células Hep-2 foram infectadas com diferentes quantidades de hRSV (multiplicidade de infecção ou MOI 0,5 ou 1,0), antes ou após a incubação com NETs (0,5-16 μg/mL). Células infectadas e não tratadas mostraram redução da viabilidade celular e intensa coloração com azul de tripano, que foi acompanhada pela formação de sincícios numerosos e grandes. O contato prévio entre as NETs e as células não resultou em efeito protetor. As células em monocamadas mostraram um número e área de sincícios reduzidos, mas a morte celular foi semelhante àquela apresentada por células infectadas e não tratadas. A adição de NETs aos tecidos infectados manteve taxa de morte celular e formação de sincícios semelhantes àqueles induzidos pelo vírus em células não tratadas, indicando danos citotóxicos e deletérios. Nossos resultados corroboram achados relatados anteriormente de que as NETs contribuem para a imunopatologia desenvolvida por pacientes infectados com hRSV.

El enigma del coronavirus - Reinfecciones por COVID-19, COVID prolongado - Vacunas bivalentes La gestante - Derechos humanos y Ética

Al finalizar el segundo año de la pandemia COVID-19, da la impresión que el coronavirus enigmático nos estuviera otorgando cierto respiro. Sin embargo, las cifras de infectados han iniciado un ascenso en el hemisferio norte, donde se aproxima un invierno fuerte, ya con nevadas. Pero también se observa este nuevo incremento en el hemisferio sur, como en el Perú, cuando estamos en primavera. El SARS-CoV-2 continúa diferenciándose en multitud de variantes y subvariantes, algunas de la cuales tienen mayor facilidad de evadir la inmunidad humana y aquella alcanzada con las vacunas de ARNm, y también podrían no responder a los tratamientos con anticuerpos monoclonales. La información clínica actual está orientada a la expectativa sobre si las vacunas existentes pudieran al menos minorizar las hospitalizaciones, el ingreso a cuidados intensivos y las muertes. Se sigue aprendiendo sobre los efectos clínicos de la infección por el SARS-CoV-2, la ocurrencia de reinfecciones y los daños físicos y mentales a largo plazo, buscándose la prevención de la infección, las reinfecciones y el COVID prolongado.

At the end of the second year of the COVID-19 pandemic, it seems that the enigmatic coronavirus is giving us some respite. However, the number of people infected has started to rise in the northern hemisphere, where a strong winter with snowfall is approaching. But this new increase is also observed in the southern hemisphere, as in Peru, when we are in spring. SARS-CoV-2 continues to differentiate into a multitude of variants and subvariants, some of which are more easily able to evade human immunity and that achieved with mRNA vaccines, and also may not respond to monoclonal antibody treatments. Current clinical information is oriented to the expectation that existing vaccines could at least reduce hospitalizations, intensive care admission and deaths. Learning about the clinical effects of SARS-CoV-2 infection, the occurrence of reinfection, and long-term physical and mental harm continues, with prevention of infection, reinfection, and prolonged COVID being sought.

Perfil epidemiológico dos pacientes infectados por COVID-19 em um município de pequeno porte no nordeste brasileiro / Epidemiological pattern of COVID-19 in a brazilian northeast small municipality

Introdução: A pandemia do Coronavírus 2 relacionado à Síndrome Respiratória Aguda Grave (SARS-CoV-2), causador da doença do coronavírus 2019 (COVID-19), que emergiu no final de 2019 em Wuhan, Província de Hubei, China é uma variação da família do Coronavírus que causa infecções respiratórias. Os primeiros Coronavírus humanos foram isolados pela primeira vez em 1937. Objetivo: caracterizar perfil epidemiológico de casos confirmados e manifestações clínicas causadas pelo COVID-19 em um município de pequeno porte no nordeste brasileiro. Metodologia: estudo epidemiológico, descritivo, quantitativo de 564 pacientes confirmados com a doença COVID-19 no município de Poções ­ Bahia. Os dados foram obtidos a partir da plataforma do notifica-SUS e com a análise de prontuários somente dos pacientes que foram a óbito, e presença de sinais/sintomas relacionados a doença causada pelo COVID-19 entre o período de 01 de junho de 2020 a 08 de agosto de 2020. Resultados: A faixa etária mais atingida pela doença do COVID-19 esteve compreendida na faixa etária entre 20 a 39 anos com 40,24% de casos confirmados. Na população de 03 a 19 anos, o número de casos foi inversamente proporcional, tendo menor número de contaminados pelo vírus, 8,48% de casos confirmados, assim, seguidos pelos baixos números de casos em bebês/lactantes com taxa de infecção de baixa de 1,95%. Dentre os pacientes diagnosticados com a referida doença, os principais sintomas relatados foram tosse seca (276 [48,9%]), febre (225 [39,89%]), cefaleia (163 [28,90%]), dor de garganta (152 [26,95%), dispneia (124 [21,98%]), mialgia (107 [18,97%]) e anosmia (101 [17,90%]). Dentre os sintomas apresentados, em (76 [12,94%]) dos pacientes possuíam queixa sintomática do sistema gastrointestinal, dos quais, os principais sinais e sintomas relatados por estes foram diarreia, náusea, vômitos, inapetência, dor abdominal e perda de peso. Dentre os pacientes que evoluíram para óbito no município, os sinais/sintomas presentes eram febre e tosse seca (10 [100%]), dispneia (08 [80%]), (08 [80%]) baixa saturação, (01 [10%]) diarreia e (01 [10%]) apresentou queixa de cefaleia. Ressalta-se que as presenças dos sinais/sintomas supracitados foram associadas nos pacientes que foram a óbito. Conclusão: Dentre os pacientes sintomáticos, a febre e tosse foi a queixa mais presente no estudo desde entre os pacientes com quadro leve da doença, aos com quadro grave. A manifestação gastrointestinal isolada também esteve presente na infecção pelo COVID ­ 19 em pacientes. Deste modo, como uma doença nova e com uma vasta sintomatologia, a infecção pelo novo coronavírus deve ser visualizada sempre como um possível diagnóstico diferencial. [au]

Introduction: The Coronavirus 2 pandemic related to Severe Acute Respiratory Syndrome (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), which emerged in late 2019 in Wuhan, Hubei Province, China is a variation of the Coronavirus family that causes respiratory infections. The first human Coronaviruses were isolated for the first time in 1937. Objective: to characterize the epidemiological profile of confirmed cases and clinical manifestations caused by COVID-19 in a small municipality in northeastern Brazil.Methodology: epidemiological, descriptive, quantitative study of 564 patients confirmed with COVID-19 disease in the city of Poções - Bahia. The data were obtained from the notifica-SUS platform and with the analysis of medical records only of patients who died with confirmation of the disease between the period from June 1, 2020 to 08/08/2020. Results: The age group most affected by the COVID-19 disease was between 20 and 39 years old, with 40.24% of confirmed cases. In the population aged 3 to 19 years, the number of cases was inversely proportional, with a lower number of infected with the virus, 8.48% of confirmed cases, thus, followed by the low numbers of cases in babies/infants with a low infection rate. of 1.95%. Among the patients diagnosed with the disease, the main symptoms reported were dry cough (276 [48.9%]), fever (225 [39.89%]), headache (163 [28.90%]), sore throat (152 [26.95%), dyspnea (124 [21.98%]), myalgia (107 [18.97%]) and anosmia (101 [17.90%]). Among the symptoms presented, (76 [12.94%]) of the patients had symptomatic complaints of the gastrointestinal system, of which, the main signs and symptoms reported by them were diarrhea, nausea, vomiting, inappetence, abdominal pain and weight loss. Among the patients who died in the municipality, the signs / symptoms present were fever and dry cough (10 [100%]), dyspnoea (08 [80%]), (08 [80%]) low saturation, (01 [ 10%]) diarrhea and (01 [10%]) complained of an important headache. It is noteworthy that the presence of the aforementioned symptoms was associates in patients who died. Conclusion: Among symptomatic patients, fever and cough was the most common complaint in the study since among patients with mild illness, those with severe symptoms. The isolated gastrointestinal manifestation was also present in COVID-19 infection in patients. Thus, as a new disease and with a wide range of symptoms, infection with the new coronavirus should always be viewed as a possible differential diagnosis. [au]

Progress on the protective effect of heme oxygenase-1 in viral infection / 药学学报

Heme oxygenase-1 (HO-1) is a cytoprotective enzyme that catalyzes the conversion of heme to CO, biliverdin, and iron, which together protect cells from oxidative and inflammatory damage and play an important role in maintaining cell homeostasis. In recent years, HO-1 has also been found to have antiviral biological effects, and the induced expression of HO-1 inhibits the replication of various viruses such as hepatitis C virus, hepatitis B virus, human immunodeficiency virus, dengue virus, ebolavirus, influenza A virus, Zika virus, severe acute respiratory syndrome coronavirus 2, human respiratory syncytial virus, hepatitis A virus and enterovirus 71. The inhibitory effect of HO-1 on these viruses involves three mechanisms, including direct inhibition of virus replication by HO-1 and its downstream products, enhancement of type I interferon responses in host cell, and attenuation of inflammatory damage caused by viral infection. This review focuses on the recent advances in the antiviral effect of HO-1 and its mechanism, which is expected to provide evidence for HO-1 as a potential target for antiviral therapy.

Do cytomegalovirus infections affect the daratumumab treatment course in multiple myeloma patients? - Literature review

ABSTRACT Introduction Multiple myeloma is a progressive and incurable hematological disease characterized by disordered and clonal multiplication of plasmacytes in the bone marrow. The main clinical manifestations are caused by the presence of neoplastic cells in bone tissue, as well as the excessive production of immunoglobulins and normal humoral immunity suppression. Daratumumab is an anti-CD38 monoclonal antibody that has promising results in managing the multiple myeloma disease. Objective This study aimed to investigate the scientific evidence concerning the impact of the cytomegalovirus infections in the daratumumab treatment course in extensively pretreated multiple myeloma patients. Method To this end, an integrative literature review was performed in different databases, comprising a 5-year period. Results The studies analysis revealed that the cytomegalovirus infection reactivation can occur during the use of daratumumab in multiple myeloma patients previously treated, which led to treatment discontinuation, compromised the drug efficacy and favored the disease progression. Moreover, it was observed that even with prophylactic antiviral therapy there was an infection reactivation in some cases, as well as deaths, in more severe situations. Conclusion Thus, even considering that few reports on such a topic are available in the scientific literature, the present review showed that cytomegalovirus reactivation can impair daratumumab therapy, mainly in multiple myeloma patients heavily pretreated. In addition, this study could contribute as a tool for the clinical decision and management of adverse effects in medical practices, demonstrating the importance of patient monitoring for the possibility of cytomegalovirus reactivation in heavily pretreated myeloma patients.

Critical analysis on the use of cholecalciferol as a COVID-19 intervention: a narrative review

ABSTRACT BACKGROUND: The World Health Organization has declared that a pandemic situation exists in relation to the disease caused by the new coronavirus, COVID-19. So far, the absence of a vaccine against the new coronavirus has led people worldwide to seek various therapeutic alternatives, including use of cholecalciferol. DESIGN AND SETTING: Narrative review developed by a research group at a public university in Recife (PE), Brazil. METHODS: We searched the literature on the use of cholecalciferol for prevention or treatment of COVID-19, using the MEDLINE and LILACS databases, with the keywords "vitamin D", "cholecalciferol", "SARS-CoV-2", "COVID-19" and "coronavirus", from January 1, 2020, to June 10, 2020. Narrative reviews, cohort studies and ecological studies were selected. RESULTS: We retrieved 32 references, of which 8 were considered eligible for intensive review and critical analysis. These comprised five narrative reviews, two observational studies and one protocol proposal. Most of the studies selected reported positive effects from use of vitamin D for prevention or treatment of COVID-19. However, there was little quantitative data to assess the real impact of using this vitamin as an intervention against this disease. CONCLUSIONS: Current studies on vitamin D used for purposes other than bone health promotion cannot be taken as support to justify its use in a disease as recent as COVID-19. Studies of greater robustness, with higher levels of clinical evidence, need to be conducted. Rational use of this vitamin needs to be ensured, thereby minimizing the impacts on the patient and the public healthcare system.

Dual role of exosomes in viral infection: immune activation and immune escape / 中华微生物学和免疫学杂志

Exosomes are extracellular vesicles containing a variety of cell membrane molecules and related protein. They have been found to act as important intercellular messengers carrying functional RNAs, proteins and lipids that can induce phenotypic changes in recipient cells and promote cell activation or inhibition effect. In recent years, some studies have shown that exosomes can not only play an immune activation role to trigger antiviral immune response after viral infection, but also help to spread virus among cells, thus contributing to viral immune escape. Exosomes can either spread or limit an infection depending on the type of pathogen and the features of source cells, and can be studied as potential targets for development of antiviral drugs and vaccines. This review summarized the role of exosomes in viral infections with an emphasis on their potential contribution to pathogenesis.

Progress in the mechanism of deubiquitinating enzymes of ovarian tumor-associated protease (OTUs) family in viral infection / 中华微生物学和免疫学杂志

Ubiquitin is a widespread form of post-translational modification of proteins in cells, which plays an important role in regulating immune response, inflammatory response, cell connection, cell cycle, apoptosis, DNA damage repair and many other life processes. The ubiquitin modification of proteins is also reversible. Deubiquitinating enzymes regulate the life span or function of proteins through hydrolyzing polyubiquitin chains to deubiquitinate substrate proteins, thus playing a role in ubiquitin-mediated signal transduction pathways. Ovarian tumor-associated proteases (OTUs) belong to the cysteine family. It has been found that many members of the OTUs family are closely related to the regulation of viral infection. This paper reviewed the role and mechanism of OTUs in host antivirus response in recent years.