6615 research outputs found
Sort by
Inflammaging in Endemic Areas for Infectious Diseases
No full textImmunosenescence is marked by a systemic process named inflammaging along with a series of defects in the immunological activity that results in poor responses to infectious agents and to vaccination. Inflammaging, a state of low-grade chronic inflammation, usually leads to chronic inflammatory diseases and frailty in the elderly. However, some elderly escape from frailty and reach advanced age free of the consequences of inflammaging. This process has been called immunological remodeling, and it is the hallmark of healthy aging as described in the studies of centenarians in Italy. The biological markers of healthy aging are still a matter of debate, and the studies on the topic have focused on inflammatory versus remodeling processes and molecules. The sub-clinical inflammatory status associated with aging might be a deleterious event for populations living in countries where chronic infectious diseases are not prevalent. Nevertheless, in other parts of the world where they are, two possibilities may occur. Inflammatory responses may have a protective effect against these infectious agents. At the same time, the long-term consequences of protective immune responses during chronic infections may result in accelerated immunosenescence in these individuals. Therefore, the biological markers of healthy aging can vary according to environmental, cultural, and geographical settings that reflect worldwide, and in a non-biased, non-westernized perspective, the changes that we experience regarding our contacts with microorganisms and the outcomes of such contacts. © Copyright © 2020 Batista, Calvo-Fortes, Silveira-Nunes, Camatta, Speziali, Turroni, Teixeira-Carvalho, Martins-Filho, Neretti, Maioli, Santos, Brigidi, Franceschi and Faria
The key roles of interferon lambda in human molecular defense against respiratory viral infections
No full textInterferons (IFN) are crucial for the innate immune response. Slightly more than two decades ago, a new type of IFN was discovered: the lambda IFN (type III IFN). Like other IFN, the type III IFN display antiviral activity against a wide variety of infections, they induce expression of antiviral, interferon-stimulated genes (MX1, OAS, IFITM1), and they have immuno-modulatory activities that shape adaptive immune responses. Unlike other IFN, the type III IFN signal through distinct receptors is limited to a few cell types, primarily mucosal epithelial cells. As a consequence of their greater and more durable production in nasal and respiratory tissues, they can determine the outcome of respiratory infections. This review is focused on the role of IFN-λ in the pathogenesis of respiratory viral infections, with influenza as a prime example. The influenza virus is a major public health problem, causing up to half a million lethal infections annually. Moreover, the virus has been the cause of four pandemics over the last century. Although IFN-λ are increasingly being tested in antiviral therapy, they can have a negative influence on epithelial tissue recovery and increase the risk of secondary bacterial infections. Therefore, IFN-λ expression deserves increased scrutiny as a key factor in the host immune response to infection. © 2020 by the authors. Licensee MDPI, Basel, Switzerland
Generation and characterization of universal live-attenuated influenza vaccine candidates containing multiple M2e epitopes
No full textInfluenza viruses constantly evolve, reducing the overall protective effect of routine vaccination campaigns. Many different strategies are being explored to design universal influenza vaccines capable of protecting against evolutionary diverged viruses. The ectodomain of influenza A M2e protein (M2e) is among the most promising targets for universal vaccine design. Here, we generated two recombinant live attenuated influenza vaccines (LAIVs) expressing additional four M2e tandem repeats (4M2e) from the N-terminus of the viral hemagglutinin (HA) protein, in an attempt to enhance the M2e-mediated cross-protection. The recombinant H1N1+4M2e and H3N2+4M2e viruses retained growth characteristics attributable to traditional LAIV viruses and induced robust influenza-specific antibody responses in BALB/c mice, although M2e-specific antibodies were raised only after two-dose vaccination with LAIV+4M2e viruses. Mice immunized with either LAIV or LAIV+4M2e viruses were fully protected against a panel of heterologous influenza challenge viruses suggesting that antibody and cell-mediated immunity contributed to the protection. The protective role of the M2e-specific antibody was seen in passive serum transfer experiments, where enhancement in the survival rates between classical LAIV and chimeric H3N2+4M2e LAIV was demonstrated for H3N2 and H5N1 heterologous challenge viruses. Overall, the results of our study suggest that M2e-specific antibodies induced by recombinant LAIV+4M2e in addition to cellular immunity by LAIV play an important role in conferring protection against heterologous viruses. © 2020 by the authors. Licensee MDPI, Basel, Switzerland
Psychiatric face of COVID-19
No full textThe Coronavirus Disease 2019 (COVID-19) represents a severe multiorgan pathology which, besides cardio-respiratory manifestations, affects the function of the central nervous system (CNS). The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), similarly to other coronaviruses demonstrate neurotropism; the viral infection of the brain stem may complicate the course of the disease through damaging central cardio-respiratory control. The systemic inflammation as well as neuroinflammatory changes are associated with massive increase of the brain pro-inflammatory molecules, neuroglial reactivity, altered neurochemical landscape and pathological remodelling of neuronal networks. These organic changes, emerging in concert with environmental stress caused by experiences of intensive therapy wards, pandemic fears and social restrictions, promote neuropsychiatric pathologies including major depressive disorder, bipolar disorder (BD), various psychoses, obsessive-compulsive disorder and post-traumatic stress disorder. The neuropsychiatric sequelae of COVID-19 represent serious clinical challenge that has to be considered for future complex therapies. © 2020, The Author(s)
Deletion of BST2 Cytoplasmic and Transmembrane N-Terminal Domains Results in SARS-CoV, SARS-CoV-2, and Influenza Virus Production Suppression in a Vero Cell Line
No full textSARS-CoV-2, which emerged in Wuhan (China), has become a great worldwide problem in 2020 and has led to more than 1,000,000 deaths worldwide. Many laboratories are searching for ways to fight this pandemic. We studied the action of the cellular antiviral protein tetherin, which is encoded by the BST2 gene. We deleted the transmembrane domain-encoding part of the gene in the Vero cell line. The transmembrane domain is a target for virus-antagonizing proteins. We showed a decrease in SARS-CoV-2 in cells with deleted transmembrane BST2 domains compared to the initial Vero cell line. Similar results were obtained for SARS-CoV and avian influenza virus. This finding may help the development of antiviral therapies competitively targeting the transmembrane domain of tetherin with viral-antagonizing proteins. © Copyright © 2020 Dolskiy, Bodnev, Nazarenko, Smirnova, Pyankova, Matveeva, Grishchenko, Tregubchak, Pyankov, Ryzhikov, Gavrilova, Maksyutov and Yudkin
Possible prospects for using modern magnesium preparations for increasing stress resistance during COVID-19 pandemic
No full textIntroduction: The relevance of the issue of increasing stress resistance is due to a significant deterioration in the mental health of the population caused by the special conditions of the disease control and prevention during the COVID-19 pandemic. Recently, the decisive role in the severity of clinico-physiological manifestations of maladjustment to stress is assigned to magnesium ions. The aim of the work was to study the magnesium importance in the body coping mechanisms under stress for the pathogenetic substantiation of the magnesium correction in an unfavorable situation of disease control and prevention during the COVID-19 pandemic. Materials and methods: The theoretical basis of this scientific and analytical review was an analysis of modern Russian and foreign literature data posted on the electronic portals MEDLINE, PubMed-NCBI, Scientific Electronic Library eLIBRARY.RU, Google Academy, and CyberLeninka. Results and discussion: It was shown that the total magnesium level in the body plays the indicator role of the body functional reserves. Acute and chronic stresses significantly increase the magnesium consumption and cause a decrease in its body content. Magnesium deficiency is one of the main pathogenetic mechanisms of reducing stress resistance and adaptive body reserves. Arising during the COVID-19 pandemic, increased nervous and emotional tension, the lack of emotional comfort and balance can lead to the onset or deterioration of magnesium deficiency, which manifests itself in mental burnout and depletion of adaptive capacities. The inability to synthesize magnesium in the body necessitates including foodstuffs high in magnesium in the population diet during this period. The appointment of magnesium preparations is pathogenetically justified with moderate and severe magnesium deficiency. This therapy should take into account the major concomitant diseases, severity of magnesium deficiency, and a patient's age. Conclusion: magnesium correction, carried out during the COVID-19 pandemic, will contribute to increasing stress resistance, preventing mental diseases and improving the population's life quality. © 2020 Belgorod State National Research University. All rights reserved
Indications for Tracheal Intubation in Patients With Coronavirus Disease 2019 (COVID-19)
No full text
Conserved T-cell epitopes of respiratory syncytial virus (RSV) delivered by recombinant live attenuated influenza vaccine viruses efficiently induce RSV-specific lung-localized memory T cells and augment influenza-specific resident memory T-cell responses
No full textRespiratory syncytial virus (RSV) can cause recurrent infection in people because it does not stimulate a long-lived immunological memory. There is an urgent need to develop a safe and efficacious vaccine against RSV that would induce immunological memory without causing immunopathology following natural RSV infection. We have previously generated two recombinant live attenuated influenza vaccine (LAIV) viruses that encode immunodominant T-cell epitopes of RSV M2 protein in the neuraminidase or NS1 genes. These chimeric vaccines afforded protection against influenza and RSV infection in mice, without causing pulmonary eosinophilia or inflammatory RSV disease. The current study assessed the formation of influenza-specific and RSV-specific CD4 and CD8 T-cell responses in the lungs of mice, with special attention to the lung tissue-resident memory T cell subsets (TRM). The RSV epitopes did not affect influenza-specific CD4 effector memory T cell (Tem) levels in the lungs. The majority of these cells formed by LAIV or LAIV-RSV viruses had CD69+CD103- phenotype. Both LAIV+NA/RSV and LAIV+NS/RSV recombinant viruses induced significant levels of RSV M282 epitope-specific lung-localized CD8 Tem cells expressing both CD69 and CD103 TRM markers. Surprisingly, the CD69+CD103+ influenza-specific CD8 Tem responses were augmented by the addition of RSV epitopes, possibly as a result of the local microenvironment formed by the RSV-specific memory T cells differentiating to TRM in the lungs of mice immunized with LAIV-RSV chimeric viruses. This study provides evidence that LAIV vector-based vaccination can induce robust lung-localized T-cell immunity to the inserted T-cell epitope of a foreign pathogen, without altering the immunogenicity of the viral vector itself. © 2020 Elsevier B.V
