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It is challenging to differentiate between central nervous system (CNS) virus infections and neurological autoimmune diseases in the emergency department. Considering their different pathogenesis, we assume they differ in neuropsychiatric symptoms and laboratory results. A total of 80 patients were included in this study, 50 with CNS virus infections and 30 with CNS autoimmune diseases, confirmed by a polymerase chain reaction (PCR) of cerebrospinal fluid (CSF). A binary logistic regression model and receiver operating characteristic (ROC) curve were employed to examine the discrimination between the two types of diseases based on neuropsychiatric symptoms and laboratory results. Compared to patients with neurological autoimmune diseases, patients with CNS virus infections had a higher incidence of abnormal behavior (p = 0.026) and abnormal sensation/thought (p = 0.029); higher total (p = 0.005), direct (p = 0.004), and indirect bilirubin (p = 0.004); and increased CSF cell (p = 0.01) and CSF white cell counts (p = 0.01). Patients with disturbance of consciousness and abnormal sensation/thought were 7.79-fold and 5.07-fold more likely to be diagnosed with CNS virus infections (OR = 7.79, p = 0.008; OR = 5.07, p = 0.032). Each unit increase in blood indirect bilirubin concentration and CSF white cell counts increased the risk of developing CNS virus infections by 1.25-fold and 1.01-fold (OR = 1.25, p = 0.016; OR = 1.01, p = 0.011). ROC analysis showed that the area under the curve was 88.0% (p < 0.001). Our study found that patients with CNS viral infections tend to have higher blood indirect bilirubin concentration, CSF leukocyte count, frequency of disorders of consciousness, and abnormal sensation and thought, which may help differentiate them from those with neurological autoimmune diseases. [ABSTRACT FROM AUTHOR]

Cell biologists have long sought the ability to observe intracellular structures in living cells without labels. This study presents procedures to adjust a commercially available apodized phase-contrast (APC) microscopy system for better visualizing the dynamic behaviors of various subcellular organelles in living cells. By harnessing the versatility of this technique to capture sequential images, we could observe morphological changes in cellular geometry after virus infection in real time without probes or invasive staining. The tune-up APC microscopy system is a highly efficient platform for simultaneously observing the dynamic behaviors of diverse subcellular structures with exceptional resolution.

It is challenging to differentiate between central nervous system (CNS) virus infections and neurological autoimmune diseases in the emergency department. Considering their different pathogenesis, we assume they differ in neuropsychiatric symptoms and laboratory results. A total of 80 patients were included in this study, 50 with CNS virus infections and 30 with CNS autoimmune diseases, confirmed by a polymerase chain reaction (PCR) of cerebrospinal fluid (CSF). A binary logistic regression model and receiver operating characteristic (ROC) curve were employed to examine the discrimination between the two types of diseases based on neuropsychiatric symptoms and laboratory results. Compared to patients with neurological autoimmune diseases, patients with CNS virus infections had a higher incidence of abnormal behavior (p = 0.026) and abnormal sensation/thought (p = 0.029); higher total (p = 0.005), direct (p = 0.004), and indirect bilirubin (p = 0.004); and increased CSF cell (p = 0.01) and CSF white cell counts (p = 0.01). Patients with disturbance of consciousness and abnormal sensation/thought were 7.79-fold and 5.07-fold more likely to be diagnosed with CNS virus infections (OR = 7.79, p = 0.008; OR = 5.07, p = 0.032). Each unit increase in blood indirect bilirubin concentration and CSF white cell counts increased the risk of developing CNS virus infections by 1.25-fold and 1.01-fold (OR = 1.25, p = 0.016; OR = 1.01, p = 0.011). ROC analysis showed that the area under the curve was 88.0% (p < 0.001). Our study found that patients with CNS viral infections tend to have higher blood indirect bilirubin concentration, CSF leukocyte count, frequency of disorders of consciousness, and abnormal sensation and thought, which may help differentiate them from those with neurological autoimmune diseases.

In bacteria, cCMP and cUMP have a key role in defense against infection with bacterial viruses. Bacteriophages encode phosphodiesterases (PDEs; 'nucleases'; Apyc1), which cleave cCMP/cUMP, counteracting this defense. We propose that PDEs are of broader biological relevance, including cCMP/cUMP-cleaving PDEs of eukaryotic viruses, which may constitute new drug targets. [ABSTRACT FROM AUTHOR]

Asthma is the most common chronic disease in children. Asthma is a heterogeneous disease characterized by variable, reversible airway obstruction and hyper-responsive airways. There is a high economic burden due to a child having poorly controlled asthma with one or more asthma exacerbations resulting in an emergency department visit or hospitalization in a year. Publications on diagnosis, treatment, and management of pediatric asthma are ongoing with over 2,549 papers published from January--November 2022. The intent of this paper is to summarize 8 key topics that have prompted discussions with local, regional, and national asthma experts due to a shift in clinical practice or lessons learned from the recent pandemic that may have future application. [ABSTRACT FROM AUTHOR]

Background and Objectives: Community-acquired respiratory virus (CARV) infections pose a serious risk for lung transplant recipients (LTR) as they are prone to severe complications. When the COVID-19 pandemic hit Switzerland in 2020, the government implemented hygiene measures for the general population. We investigated the impact of these measures on the transmission of CARV in lung transplant recipients in Switzerland. Materials and Methods: In this multicenter, retrospective study of lung transplant recipients, we investigated two time periods: the year before the COVID-19 pandemic (1 March 2019–29 February 2020) and the first year of the pandemic (1 March 2020–28 February 2021). Data were mainly collected from the Swiss Transplant Cohort Study (STCS) database. Descriptive statistics were used to analyze the results. Results: Data from 221 Swiss lung transplant cohort patients were evaluated. In the year before the COVID-19 pandemic, 157 infections were diagnosed compared to 71 infections in the first year of the pandemic (decline of 54%, p < 0.001). Influenza virus infections alone showed a remarkable decrease from 17 infections before COVID-19 to 2 infections after the beginning of the pandemic. No significant difference was found in testing behavior; 803 vs. 925 tests were obtained by two of the three centers during the respective periods. Conclusions: We observed a significant decline in CARV infections in the Swiss lung transplant cohort during the first year of the COVID-19 pandemic. These results suggest a relevant impact of hygiene measures when implemented in the population due to the COVID-19 pandemic on the incidence of CARV infections. [ABSTRACT FROM AUTHOR]

Abstract Aryl hydrocarbon receptor (AHR) is a ligand-dependent transcriptional factor widely expressed among immune, epithelial, endothelial and stromal cells in barrier tissues. It can be activated by small molecules provided by pollutants, microorganisms, food, and metabolism. It has been demonstrated that AHR plays an important role in modulating the response to many microbial pathogens, and the abnormal expression of AHR signaling pathways may disrupt endocrine, cause immunotoxicity, and even lead to the occurrence of cancer. Most humans are infected with at least one known human cancer virus. While the initial infection with these viruses does not cause major disease, the metabolic activity of infected cells changes, thus affecting the activation of oncogenic signaling pathways. In the past few years, lots of studies have shown that viral infections can affect disease progression by regulating the transmission of multiple signaling pathways. This review aims to discuss the potential effects of virus infections on AHR signaling pathways so that we may find a new strategy to minimize the adverse effects of the AHR pathway on diseases. Video Abstract

Aryl hydrocarbon receptor (AHR) is a ligand-dependent transcriptional factor widely expressed among immune, epithelial, endothelial and stromal cells in barrier tissues. It can be activated by small molecules provided by pollutants, microorganisms, food, and metabolism. It has been demonstrated that AHR plays an important role in modulating the response to many microbial pathogens, and the abnormal expression of AHR signaling pathways may disrupt endocrine, cause immunotoxicity, and even lead to the occurrence of cancer. Most humans are infected with at least one known human cancer virus. While the initial infection with these viruses does not cause major disease, the metabolic activity of infected cells changes, thus affecting the activation of oncogenic signaling pathways. In the past few years, lots of studies have shown that viral infections can affect disease progression by regulating the transmission of multiple signaling pathways. This review aims to discuss the potential effects of virus infections on AHR signaling pathways so that we may find a new strategy to minimize the adverse effects of the AHR pathway on diseases. E2r6Fp5q5n3CyhkqcFYxmE Video Abstract [ABSTRACT FROM AUTHOR]

Heparan sulfate proteoglycans (HSPGs) are a major constituent of the extracellular matrix (ECM) and are found to be implicated in viral infections, where they play a role in both cell entry and release for many viruses. The enzyme heparanase-1 is the only known endo-beta-D-glucuronidase capable of degrading heparan sulphate (HS) chains of HSPGs and is thus important for regulating ECM homeostasis. Heparanase-1 expression is tightly regulated as the uncontrolled cleavage of HS may result in abnormal cell activation and significant tissue damage. The overexpression of heparanase-1 correlates with pathological scenarios and is observed in different human malignancies, such as lymphoma, breast, colon, lung, and hepatocellular carcinomas. Interestingly, heparanase-1 has also been documented to be involved in numerous viral infections, e.g., HSV-1, HPV, DENV. Moreover, very recent reports have demonstrated a role of heparanase-1 in HCV and SARS-CoV-2 infections. Due to the undenied pro-carcinogenic role of heparanase-1, multiple inhibitors have been developed, some reaching phase II and III in clinical studies. However, the use of heparanase inhibitors as antivirals has not yet been proposed. If it can be assumed that heparanase-1 is implicated in numerous viral life cycles, its inhibition by specific heparanase-acting compounds should result in a blockage of viral infection. This review addresses the perspectives of using heparanase inhibitors, not only for cancer treatment, but also as antivirals. Eventually, the development of a novel class antivirals targeting a cellular protein could help to alleviate the resistance problems seen with some current antiretroviral therapies. [ABSTRACT FROM AUTHOR]

Background and Objectives: Community-acquired respiratory virus (CARV) infections pose a serious risk for lung transplant recipients (LTR) as they are prone to severe complications. When the COVID-19 pandemic hit Switzerland in 2020, the government implemented hygiene measures for the general population. We investigated the impact of these measures on the transmission of CARV in lung transplant recipients in Switzerland. Materials and Methods: In this multicenter, retrospective study of lung transplant recipients, we investigated two time periods: the year before the COVID-19 pandemic (1 March 2019–29 February 2020) and the first year of the pandemic (1 March 2020–28 February 2021). Data were mainly collected from the Swiss Transplant Cohort Study (STCS) database. Descriptive statistics were used to analyze the results. Results: Data from 221 Swiss lung transplant cohort patients were evaluated. In the year before the COVID-19 pandemic, 157 infections were diagnosed compared to 71 infections in the first year of the pandemic (decline of 54%, p < 0.001). Influenza virus infections alone showed a remarkable decrease from 17 infections before COVID-19 to 2 infections after the beginning of the pandemic. No significant difference was found in testing behavior; 803 vs. 925 tests were obtained by two of the three centers during the respective periods. Conclusions: We observed a significant decline in CARV infections in the Swiss lung transplant cohort during the first year of the COVID-19 pandemic. These results suggest a relevant impact of hygiene measures when implemented in the population due to the COVID-19 pandemic on the incidence of CARV infections.

Exploration of the traditional medicinal plants is essential for drug discovery and development for various pharmacological targets. Various phytochemicals derived from medicinal plants were extensively studied for antiviral activity. This review aims to highlight the role of medicinal plants against viral infections that remains to be the leading cause of human death globally. Antiviral properties of phytoconstituents isolated from 45 plants were discussed for five different types of viral infections. The ability of the plants' active compounds with antiviral effects was highlighted as well as their mechanism of action, pharmacological studies, and toxicological data on a variety of cell lines. The experimental values, such as IC50, EC50, CC50, ED50, TD50, MIC100, and SI of the active compounds, were compiled and discussed to determine their potential. Among the plants mentioned, 11 plants showed the most promising medicinal plants against viral infections. Sambucus nigra and Clinacanthus nutans manifested antiviral activity against three different types of viral infections. Echinacea purpurea, Echinacea augustofolia, Echinacea pallida, Plantago major, Glycyrrhiza uralensis, Phyllanthus emblica, Camellia sinensis, and Cistus incanus exhibited antiviral activity against two different types of viral infections. Interestingly, Nicotiana benthamiana showed antiviral effects against mosquito-borne infections. The importance of phenolic acids, alkamides, alkylamides, glycyrrhizin, epicatechin gallate (ECG), epigallocatechin gallate (EGCG), epigallocatechin (EGC), protein-based plant-produced ZIKV Envelope (PzE), and anti-CHIKV monoclonal antibody was also reviewed. An exploratory approach to the published literature was conducted using a variety of books and online databases, including Scopus, Google Scholar, ScienceDirect, Web of Science, and PubMed Central, with the goal of obtaining, compiling, and reconstructing information on a variety of fundamental aspects, especially regarding medicinal plants. This evaluation gathered important information from all available library databases and Internet searches from 1992 to 2022. [ABSTRACT FROM AUTHOR]

In a virus pandemic context, buildings ventilation has been recognized as a solution for preventing transmission of the virus in aerosolized form. The impact of the widespread recommendation of window opening and sealing door on ventilation circuits needs to be considered with a multizone approach. We modeled the airflow distribution in a building where people are isolating in a pandemic context, including one infected person. We analyzed the impact of opening the window and sealing the door in the quarantine room on exposures and probability of infection for occupants of the flat and of adjacent flats. In order to study the sensitivity of the results, we tested three ventilation systems: balanced, exhaust‐only, and humidity‐based demand‐controlled, and several window‐ and door‐opening strategies. When the door of the quarantine room is sealed, we observe that opening the window in the quarantine room always results in increased exposure and probability of infection for at least one other occupant, including in neighbors' apartments. When all internal doors are opened, we observe moderate impacts, with rather an increase of exposure of the occupants of the same apartments and of their probability of infection, and a decrease for the occupants located in other apartments. Based on the analysis on the airflows distribution in this case study, we conclude that sealing the internal door has more influence than opening the window of the quarantine room, whatever the ventilation system. We observe that this widespread recommendation to open the window of a quarantine room and to seal the door is based on the consideration of a single zone model. We illustrate the importance of moving from such a single zone approach to a multizone approach for quantifying ventilation and airing impacts in multizone buildings as residences in order to prevent epidemics of viruses such as SARS‐CoV‐2. It highlights the need of air leakage databases. [ABSTRACT FROM AUTHOR]

• Preexisting alloreactivity may result from exposure to HLA proteins displayed on viral envelopes. • A new role of HLA molecules incorporated on viral envelope. • An advance in understanding the preexistence of alloreactivity. Despite significant advances in transplantation medicine, allograft rejection remains a major challenge in clinical practice. The preexistence of alloreactive lymphocytes is a primary cause of allograft rejection. The forthcoming challenges in clinical transplantation will involve the suppression or eradication of allospecific memory T cells. Viral infections and allograft rejection interact in multiple ways that can compromise the survival of transplanted organs. Evidence is currently accumulating on the incorporation of HLA antigens and other host cell plasma membrane molecules into the viral envelope. A consequence of the viral envelope displaying the HLA signature acquired from the plasma membrane of infected cells is that when virions are transmitted to the next host, the newly infected person became exposed to allogeneic molecules stimulating alloimmunity and generating memory to alloantigens. Thus, successive exposure to viral infections throughout life could potentially contribute to the development of alloimmunity and the generation of numerous clones of memory alloreactive lymphocytes. In this paper a novel hypothesis is developed on the potential role and mechanisms of alloresponse induced by human spread of enveloped viruses. As this hypothesis could aid in the knowledge of preexisting alloreactivity, additional research into the intricacies of virion-incorporated host cell proteins is necessary. A deeper understanding of this dynamic interaction will help promote advances in the long-term acceptance of transplants. [ABSTRACT FROM AUTHOR]

RNA granules are cytoplasmic, non-membranous ribonucleoprotein compartments that form ubiquitously and are often referred to as foci for post-transcriptional gene regulation. Recent research on RNA processing bodies (PB) and stress granules (SG) has shown wide implications of these cytoplasmic RNA granules and their components in suppression of RNA translation as host intracellular innate immunity against infecting viruses. Many RNA viruses either counteract or co-opt these RNA granules; however, many fundamental questions about DNA viruses with respect to their interaction with these two RNA granules remain elusive. Kaposi's sarcoma-associated herpesvirus (KSHV), a tumor-causing DNA virus, exhibits two distinct phases of infection and encodes ∼90 viral gene products during the lytic phase of infection compared to only a few (∼5) during the latent phase. Thus, productive KSHV infection relies heavily on the host cell translational machinery, which often links to the formation of PB and SG. One major question is how KSHV counteracts the hostile environment of RNA granules for its productive infection. Recent studies demonstrated that KSHV copes with the translational suppression by cellular RNA granules, PB and SG, by expressing ORF57, a viral RNA-binding protein, during KSHV lytic infection. ORF57 interacts with Ago2 and GW182, two major components of PB, and prevents the scaffolding activity of GW182 at the initial stage of PB formation in the infected cells. ORF57 also interacts with protein kinase R (PKR) and PKR-activating protein (PACT) to block PKR dimerization and kinase activation, and thus inhibits eIF2α phosphorylation and SG formation. The homologous immediate-early regulatory protein ICP27 of herpes simplex virus type 1 (HSV-1), but not the EB2 protein of Epstein-Barr virus (EBV), shares this conserved inhibitory function with KSHV ORF57 on PB and SG. Through KSHV ORF57 studies, we have learned much about how a DNA virus in the infected cells is equipped to evade host antiviral immunity for its replication and productive infection. KSHV ORF57 would be an excellent viral target for development of anti-KSHV-specific therapy. [ABSTRACT FROM AUTHOR]

RNA granules are cytoplasmic, non-membranous ribonucleoprotein compartments that form ubiquitously and are often referred to as foci for post-transcriptional gene regulation. Recent research on RNA processing bodies (PB) and stress granules (SG) has shown wide implications of these cytoplasmic RNA granules and their components in suppression of RNA translation as host intracellular innate immunity against infecting viruses. Many RNA viruses either counteract or co-opt these RNA granules; however, many fundamental questions about DNA viruses with respect to their interaction with these two RNA granules remain elusive. Kaposi’s sarcoma-associated herpesvirus (KSHV), a tumor-causing DNA virus, exhibits two distinct phases of infection and encodes ∼90 viral gene products during the lytic phase of infection compared to only a few (∼5) during the latent phase. Thus, productive KSHV infection relies heavily on the host cell translational machinery, which often links to the formation of PB and SG. One major question is how KSHV counteracts the hostile environment of RNA granules for its productive infection. Recent studies demonstrated that KSHV copes with the translational suppression by cellular RNA granules, PB and SG, by expressing ORF57, a viral RNA-binding protein, during KSHV lytic infection. ORF57 interacts with Ago2 and GW182, two major components of PB, and prevents the scaffolding activity of GW182 at the initial stage of PB formation in the infected cells. ORF57 also interacts with protein kinase R (PKR) and PKR-activating protein (PACT) to block PKR dimerization and kinase activation, and thus inhibits eIF2α phosphorylation and SG formation. The homologous immediate-early regulatory protein ICP27 of herpes simplex virus type 1 (HSV-1), but not the EB2 protein of Epstein-Barr virus (EBV), shares this conserved inhibitory function with KSHV ORF57 on PB and SG. Through KSHV ORF57 studies, we have learned much about how a DNA virus in the infected cells is equipped to evade host antiviral immunity for its replication and productive infection. KSHV ORF57 would be an excellent viral target for development of anti-KSHV-specific therapy.

Heparan sulfate proteoglycans (HSPGs) are a major constituent of the extracellular matrix (ECM) and are found to be implicated in viral infections, where they play a role in both cell entry and release for many viruses. The enzyme heparanase-1 is the only known endo-beta-D-glucuronidase capable of degrading heparan sulphate (HS) chains of HSPGs and is thus important for regulating ECM homeostasis. Heparanase-1 expression is tightly regulated as the uncontrolled cleavage of HS may result in abnormal cell activation and significant tissue damage. The overexpression of heparanase-1 correlates with pathological scenarios and is observed in different human malignancies, such as lymphoma, breast, colon, lung, and hepatocellular carcinomas. Interestingly, heparanase-1 has also been documented to be involved in numerous viral infections, e.g., HSV-1, HPV, DENV. Moreover, very recent reports have demonstrated a role of heparanase-1 in HCV and SARS-CoV-2 infections. Due to the undenied pro-carcinogenic role of heparanase-1, multiple inhibitors have been developed, some reaching phase II and III in clinical studies. However, the use of heparanase inhibitors as antivirals has not yet been proposed. If it can be assumed that heparanase-1 is implicated in numerous viral life cycles, its inhibition by specific heparanase-acting compounds should result in a blockage of viral infection. This review addresses the perspectives of using heparanase inhibitors, not only for cancer treatment, but also as antivirals. Eventually, the development of a novel class antivirals targeting a cellular protein could help to alleviate the resistance problems seen with some current antiretroviral therapies.

Respiratory syncytial virus (RSV) can cause severe lower respiratory tract infections. Understanding why some individuals get more serious disease may help with diagnosis and treatment. One possible risk factor underlying severe disease is bacterial exposure before RSV infection. Bacterial exposure has been associated with increased respiratory viral-induced disease severity but the mechanism remains unknown. Respiratory bacterial infections or exposure to their pathogen associated molecular patterns (PAMPs) trigger innate immune inflammation, characterised by neutrophil and inflammatory monocyte recruitment and the production of inflammatory cytokines. We hypothesise that these changes to the lung environment alter the immune response and disease severity during subsequent RSV infection. To test this, we intranasally exposed mice to LPS, LTA or Acinetobacter baumannii (an airway bacterial pathogen) before RSV infection and observed an early induction of disease, measured by weight loss, at days 1-3 after infection. Neutrophils or inflammatory monocytes were not responsible for driving this exacerbated weight loss. Instead, exacerbated disease was associated with increased IL-1α and TNF-α, which orchestrated the recruitment of innate immune cells into the lung. This study shows that exposure to bacterial PAMPs prior to RSV infection increases the expression of IL-1α and TNF-α, which dysregulate the immune response resulting in exacerbated disease., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Cell biologists have long sought the ability to observe intracellular structures in living cells without labels. This study presents procedures to adjust a commercially available apodized phase-contrast (APC) microscopy system for better visualizing the dynamic behaviors of various subcellular organelles in living cells. By harnessing the versatility of this technique to capture sequential images, we could observe morphological changes in cellular geometry after virus infection in real time without probes or invasive staining. The tune-up APC microscopy system is a highly efficient platform for simultaneously observing the dynamic behaviors of diverse subcellular structures with exceptional resolution.

Coronavirus disease 2019 (COVID-19), which has high incidence rates with rapid rate of transmission, is a pandemic that spread across the world, resulting in more than 3,000,000 deaths globally. Currently, several drugs have been used for the clinical treatment of COVID-19, such as antivirals (radecivir, baritinib), monoclonal antibodies (tocilizumab), and glucocorticoids (dexamethasone). Accumulating evidence indicates that long noncoding RNAs (lncRNAs) are essential regulators of virus infections and antiviral immune responses including biological processes that are involved in the regulation of COVID-19 and subsequent disease states. Upon viral infections, cellular lncRNAs directly regulate viral genes and influence viral replication and pathology through virus-mediated changes in the host transcriptome. Additionally, several host lncRNAs could help the occurrence of viral immune escape by inhibiting type I interferons (IFN-1), while others could up-regulate IFN-1 production to play an antiviral role. Consequently, understanding the expression and function of lncRNAs during severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection will provide insights into the development of lncRNA-based methods. In this review, we summarized the current findings of lncRNAs in the regulation of the strong inflammatory response, immune dysfunction and thrombosis induced by SARS-CoV-2 infection, discussed the underlying mechanisms, and highlighted the therapeutic challenges of COVID-19 treatment and its future research directions.

Coronavirus disease 2019 (COVID-19), which has high incidence rates with rapid rate of transmission, is a pandemic that spread across the world, resulting in more than 3,000,000 deaths globally. Currently, several drugs have been used for the clinical treatment of COVID-19, such as antivirals (radecivir, baritinib), monoclonal antibodies (tocilizumab), and glucocorticoids (dexamethasone). Accumulating evidence indicates that long noncoding RNAs (lncRNAs) are essential regulators of virus infections and antiviral immune responses including biological processes that are involved in the regulation of COVID-19 and subsequent disease states. Upon viral infections, cellular lncRNAs directly regulate viral genes and influence viral replication and pathology through virus-mediated changes in the host transcriptome. Additionally, several host lncRNAs could help the occurrence of viral immune escape by inhibiting type I interferons (IFN-1), while others could up-regulate IFN-1 production to play an antiviral role. Consequently, understanding the expression and function of lncRNAs during severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection will provide insights into the development of lncRNA-based methods. In this review, we summarized the current findings of lncRNAs in the regulation of the strong inflammatory response, immune dysfunction and thrombosis induced by SARS-CoV-2 infection, discussed the underlying mechanisms, and highlighted the therapeutic challenges of COVID-19 treatment and its future research directions. [ABSTRACT FROM AUTHOR]

Pandemic virus infections pose a major public health threat globally. Much efforts have been devoted to suppress the virus, including vaccine prevention, autoimmunity enhancement, and anti-virus drugs treatment. Among these strategies, development of novel and improved vaccine technologies attracts broad attention as they can nip the virus outbreak in the bud and avoid the appearance of public health emergency. However, current influenza vaccines only provide protection against homologous viruses. Therefore, chemical technologies are being employed for the development of new and improved vaccine, such as chitosan, plant polysaccharides and virus-like particles. In addition, recently, Wang et al. offered a promising means to develop universal viral vaccine through biomimetic nanoparticles and heterosubtypic protection could be achieved. These strategies with multidisciplinary collaboration are promising to make conceptual and technological advances of modern vaccinology to address pandemic virus infections.

Exploration of the traditional medicinal plants is essential for drug discovery and development for various pharmacological targets. Various phytochemicals derived from medicinal plants were extensively studied for antiviral activity. This review aims to highlight the role of medicinal plants against viral infections that remains to be the leading cause of human death globally. Antiviral properties of phytoconstituents isolated from 45 plants were discussed for five different types of viral infections. The ability of the plants’ active compounds with antiviral effects was highlighted as well as their mechanism of action, pharmacological studies, and toxicological data on a variety of cell lines. The experimental values, such as IC50, EC50, CC50, ED50, TD50, MIC100, and SI of the active compounds, were compiled and discussed to determine their potential. Among the plants mentioned, 11 plants showed the most promising medicinal plants against viral infections. Sambucus nigra and Clinacanthus nutans manifested antiviral activity against three different types of viral infections. Echinacea purpurea, Echinacea augustofolia, Echinacea pallida, Plantago major, Glycyrrhiza uralensis, Phyllanthus emblica, Camellia sinensis, and Cistus incanus exhibited antiviral activity against two different types of viral infections. Interestingly, Nicotiana benthamiana showed antiviral effects against mosquito-borne infections. The importance of phenolic acids, alkamides, alkylamides, glycyrrhizin, epicatechin gallate (ECG), epigallocatechin gallate (EGCG), epigallocatechin (EGC), protein-based plant-produced ZIKV Envelope (PzE), and anti-CHIKV monoclonal antibody was also reviewed. An exploratory approach to the published literature was conducted using a variety of books and online databases, including Scopus, Google Scholar, ScienceDirect, Web of Science, and PubMed Central, with the goal of obtaining, compiling, and reconstructing information on a variety of fundamental aspects, especially regarding medicinal plants. This evaluation gathered important information from all available library databases and Internet searches from 1992 to 2022.

Immunosenescence is a process associated with aging that leads to dysregulation of cells of innate and adaptive immunity, which may become dysfunctional. Consequently, older adults show increased severity of viral and bacterial infections and impaired responses to vaccinations. A better understanding of the process of immunosenescence will aid the development of novel strategies to boost the immune system in older adults. In this review, we focus on major alterations of the immune system triggered by aging, and address the effect of chronic viral infections, effectiveness of vaccination of older adults and strategies to improve immune function in this vulnerable age group.

Immunosenescence is a process associated with aging that leads to dysregulation of cells of innate and adaptive immunity, which may become dysfunctional. Consequently, older adults show increased severity of viral and bacterial infections and impaired responses to vaccinations. A better understanding of the process of immunosenescence will aid the development of novel strategies to boost the immune system in older adults. In this review, we focus on major alterations of the immune system triggered by aging, and address the effect of chronic viral infections, effectiveness of vaccination of older adults and strategies to improve immune function in this vulnerable age group. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID-19) has caused a global pandemic associated with substantial morbidity and mortality. Nasopharyngeal swabs and sputum samples are generally collected for serial viral load screening of respiratory contagions, but temporal profiles of these samples are not completely clear in patients with COVID-19. We performed an observational cohort study at Renmin Hospital of Wuhan University, which involved 31 patients with confirmed COVID-19 with or without underlying diseases. We obtained samples from each patient, and serial viral load was measured by real-time quantitative polymerase chain reaction. We found that the viral load in the sputum was inclined to be higher than samples obtained from the nasopharyngeal swab at disease presentation. Moreover, the viral load in the sputum decreased more slowly over time than in the nasopharyngeal group as the disease progressed. Interestingly, even when samples in the nasopharyngeal swab turned negative, it was commonly observed that patients with underlying diseases, especially hypertension and diabetes, remained positive for COVID-19 and required a longer period for the sputum samples to turn negative. These combined findings emphasize the importance of tracking sputum samples even in patients with negative tests from nasopharyngeal swabs, especially for those with underlying conditions. In conclusion, this work reinforces the importance of sputum samples for SARS-CoV-2 detection to minimize transmission of COVID-19 within the community. [ABSTRACT FROM AUTHOR]

Background: Data on the development of Covid‐19 among people with intellectual disabilities (IDs) are scarce and it is uncertain to what extent general population data applies to people with ID. To give an indication of possible implications, this study investigated excess mortality patterns during a previous influenza epidemic. Methods: Using Dutch population and mortality registers, a historical cohort study was designed to compare mortality during the 2017–2018 influenza epidemic with mortality in the same period in the three previous years. People with ID were identified by entitlements to residential ID‐care services as retrieved from a national database. Results: Data covered the entire adult Dutch population (12.6 million; GenPop), of which 91 064 individuals were identified with an ID. During the influenza epidemic, mortality among people with ID increased almost three times as much than in the GenPop (15.2% vs. 5.4%), and more among male individuals with ID (+19.5%) than among female individuals with ID (+10.6%), as compared with baseline. In both cohorts, comparable increases in mortality within older age groups and due to respiratory causes were seen. Particularly in the ID‐cohort, excess deaths also occurred in younger age groups, due to endocrine diseases and ID‐specific causes. Conclusions: During the 2017–2018 influenza epidemic, excess mortality among people with ID was three times higher than in the general Dutch population, appeared more often at young age and with a broader range of underlying causes. These findings suggest that a pandemic may disproportionally affect people with ID while population data may not immediately raise warnings. Early detection of diverging patterns and faster implementation of tailored strategies therefore require collection of good quality data. [ABSTRACT FROM AUTHOR]

Quiescent long-term hematopoietic stem cells (LT-HSCs) are efficiently activated by type I interferon (IFN-I). However, this effect remains poorly investigated in the context of IFN-I-inducing virus infections. Here we report that both vesicular stomatitis virus (VSV) and murine cytomegalovirus (MCMV) infection induce LT-HSC activation that substantially differs from the effects triggered upon injection of synthetic IFN-I-inducing agents. In both infections, inflammatory responses had to exceed local thresholds within the bone marrow to confer LT-HSC cell cycle entry, and IFN-I receptor triggering was not critical for this activation. After resolution of acute MCMV infection, LT-HSCs returned to phenotypic quiescence. However, non-acute MCMV infection induced a sustained inflammatory milieu within the bone marrow that was associated with long-lasting impairment of LT-HSC function. In conclusion, our results show that systemic virus infections fundamentally affect LT-HSCs and that also non-acute inflammatory stimuli in bone marrow donors can affect the reconstitution potential of bone marrow transplants.

Granulocyte colony-stimulating factor (G-CSF), a growth factor for neutrophils, has been successfully used for stem cell mobilization and T cell immune tolerance induction. The establishment of G-CSF-primed unmanipulated haploidentical blood and marrow transplantation (The Beijing Protocol) has achieved outcomes for the treatment of acute leukemia, myelodysplastic syndrome, and severe aplastic anemia with haploidentical allografts comparable to those of human leukocyte antigen (HLA)-matched sibling donor transplantation. Currently, G-CSF-mobilized bone marrow and/or peripheral blood stem cell sources have been widely used in unmanipulated haploidentical transplant settings. In this review, we summarize the roles of G-CSF in inducing T cell immune tolerance. We discuss the recent advances in the Beijing Protocol, mainly focusing on strategies that have been used to improve transplant outcomes in cases of poor graft function, virus infections, and relapse. The application of G-CSF-primed allografts in other haploidentical modalities is also discussed.

Granulocyte colony-stimulating factor (G-CSF), a growth factor for neutrophils, has been successfully used for stem cell mobilization and T cell immune tolerance induction. The establishment of G-CSF-primed unmanipulated haploidentical blood and marrow transplantation (The Beijing Protocol) has achieved outcomes for the treatment of acute leukemia, myelodysplastic syndrome, and severe aplastic anemia with haploidentical allografts comparable to those of human leukocyte antigen (HLA)-matched sibling donor transplantation. Currently, G-CSF-mobilized bone marrow and/or peripheral blood stem cell sources have been widely used in unmanipulated haploidentical transplant settings. In this review, we summarize the roles of G-CSF in inducing T cell immune tolerance. We discuss the recent advances in the Beijing Protocol, mainly focusing on strategies that have been used to improve transplant outcomes in cases of poor graft function, virus infections, and relapse. The application of G-CSF-primed allografts in other haploidentical modalities is also discussed. [ABSTRACT FROM AUTHOR]

Background: Patients with pediatric cancer have a higher risk of morbidity and mortality because of respiratory viral infections than other patient populations. Objectives: To investigate the causative viruses of respiratory infections and their burden among patients with pediatric cancer in Lebanon. Study design: Nasopharyngeal swabs along with clinical and demographic data were collected from patients with pediatric cancer presenting febrile episodes with upper respiratory tract symptoms. Total nucleic acid was extracted from specimens followed by the real‐time PCR analysis targeting 14 respiratory viruses to estimate the frequency of infections. Results: We obtained 89 nasopharyngeal swabs from patients with pediatric cancer (mean age, 5.8 ± 4.2 years). Real‐time PCR confirmed viral infection in 77 swabs (86.5%). Among these, 151 respiratory viruses were detected. Several viruses cocirculated within the same period; respiratory syncytial virus (RSV) being the most common (45.45%), followed by parainfluenza virus (PIV; 26%), influenza type B (26%), human metapneumovirus (24.6%), and human coronavirus (HCoV; 24.6%). Coinfections were detected in 55% of the subjects, and most of them involved RSV with one or more other viruses. A strong correlation was found between PIV, Flu (influenza of any type), RSV, and HCoV with the incidence of coinfections. RSV was associated with lower respiratory tract infections, nasal congestion, bronchitis, and bacteremia. HCoV was associated with bronchiolitis; rhinovirus was associated with hospital admission. Conclusion: Patients with pediatric cancer have a high burden of respiratory viral infections and a high incidence of coinfections. Molecular diagnostics can improve management of febrile episodes and reduce antibiotic use. Highlights: Respiratory viruses are leading cause of ARTI in pediatric cancer patients.Coinfections are common among febrile pediatric cancer patients.RSV was the most common in mono‐ and coinfections among pediatric cancer patients.RSV, PIV, Flu, HCoV are associated with coinfections.Molecular diagnostics permit rapid and sensitive diagnostics and limit antibiotic abuse. [ABSTRACT FROM AUTHOR]

Summary: DOCK8 immunodeficiency syndrome (DIDS) is a progressive combined immunodeficiency that can be distinguished from other combined immunodeficiencies or hyperimmunoglobulinemia E syndromes in featuring (a) profound susceptibility to virus infections of the skin, with associated skin cancers, and (b) severe food allergies. The DOCK8 locus has many repetitive sequence elements that predispose to the generation of large germline deletions as well as recombination‐mediated somatic DNA repair. Residual DOCK8 protein contributes to the variable disease phenotype. The severe virus infections of the skin, and probably also VZV‐associated vasculopathy, reflect an important function of DOCK8, which is normally required to maintain lymphocyte shape integrity as the cells migrate through dense tissues. Loss of DOCK8 also causes immune deficits through other mechanisms including a milder generalized cell survival defect and skewing of T helper cell subsets. Recent work has uncovered the roles for DOCK8 in dendritic cell responses that can also help explain the virus susceptibility, as well as in regulatory T cells that might help explain autoimmunity in a minority of patients. Fortunately, hematopoietic stem cell transplantation cures the eczema and infection susceptibility of DIDS, but not necessarily the other disease manifestations including food allergies. [ABSTRACT FROM AUTHOR]

Summary: Autoimmune Addison's disease (AAD), or primary adrenocortical insufficiency, is a classical organ‐specific autoimmune disease with 160 years of history. AAD is remarkably homogeneous with one major dominant self‐antigen, the cytochrome P450 21‐hydroxylase enzyme, which is targeted by both autoantibodies and autoreactive T cells. Like most autoimmune diseases, AAD is thought to be caused by an unfortunate combination of genetic and environmental factors. While the number of genetic associations with AAD is increasing, almost nothing is known about environmental factors. A major environmental factor commonly proposed for autoimmune diseases, based partly on experimental and clinical data and partly on shared pathways between anti‐viral immunity and autoimmunity, is viral infections. However, there are few reports associating viral infections to AAD, and it has proved difficult to establish which immunological processes that could link any viral infection with the initiation or progression of AAD. In this review, we will summarize the current knowledge on the underlying mechanisms of AAD and take a closer look on the potential involvement of viruses. Autoimmune Addison's disease is a classic organ‐specific autoimmune disease caused by a combination of genetic and environmental factors. Although many genetic risk factors have been identified, almost nothing is known about environmental risk factors. Here we review the potential role of viral infections as an environmental factor in the pathogenesis of autoimmune Addison's disease. [ABSTRACT FROM AUTHOR]

Hepatitis E virus produces an emerging health problem, knowledge about epidemiology of hepatitis E virus infections in the USA and Latin America is still limited. The wide-ranging clinical manifestations lead to an extensive underestimation of the global seroprevalence. Clinical and diagnostic accuracy are critical to improve patient management.

Background Autoimmune (type 1) diabetes (T1D) is a frequent chronic disease in children and adolescents globally. Gestational enterovirus (EV) infections have been associated with an increased risk for T1D in the offspring. We test the hypothesis that EV infections during the first trimester were associated with beta cell autoantibodies in mothers of children who developed islet autoantibodies before 7 years of age. Materials and methods Local registries were used to identify mothers to children born 2000–2007 who developed either beta cell autoantibodies or T1D during follow up. Serum samples from the first trimester were located in the Biobank. A total of 448 index mothers were identified and compared to 891 matched control mothers. EV-IgM was determined in a capture enzyme immunoassay. Beta cell autoantibodies were analyzed in standard radio binding assays. Results The frequency of EV-IgM in index mothers was 20% (89/448), which did not differ from the control mothers 20% (175/891) ( p  = 0.922). Index mothers had multiple beta cell autoantibodies more often than control mothers (p = 0.037). Beta cell autoantibodies were increased during the November–April winter months in index compared to control mothers (p = 0.022). The observed difference was possibly explained by the months of February-April (p = 0.014). Concomitant EV-IgM and beta cell autoantibodies tended to be more common among index compared to control mothers (p = 0.039). Conclusion EV-IgM during the first trimester may be associated with beta cell autoantibodies in mothers to children who developed either beta cell autoantibodies or T1D before 7 years of age. [ABSTRACT FROM AUTHOR]

Abstract. The attempts to decrease a toxic action of Freund complete adjuvant have led to development of new emulsion adjuvant compositions. More often they are based on metabolizable oil (squalene) with addition the Tween 80 (Polisorbate 80) as an emulsifier. The third component is an immunomodulator. Adjuvants, intended for prevention of virus infections, should include the immunomodulators polarizing the immune response to Th1. From this point of view adjuvant based on a colloidal solution prepared by means of the Tween 80 from polyprenyl phasphates of fir needles (Phosprenyl) can be rather perspective. The last one, as well as squalene, is constructed by isoprene links, but has them not 6, but 16 that essentially reduces its toxicity. The obtained data shows that Phosprenyl essentially enhances efficiency of vaccination in such virus infections as tick born encephalitis, bird flu, poliomyelitis and polarizes the immune response to Th1.

Summary Quiescent long-term hematopoietic stem cells (LT-HSCs) are efficiently activated by type I interferon (IFN-I). However, this effect remains poorly investigated in the context of IFN-I-inducing virus infections. Here we report that both vesicular stomatitis virus (VSV) and murine cytomegalovirus (MCMV) infection induce LT-HSC activation that substantially differs from the effects triggered upon injection of synthetic IFN-I-inducing agents. In both infections, inflammatory responses had to exceed local thresholds within the bone marrow to confer LT-HSC cell cycle entry, and IFN-I receptor triggering was not critical for this activation. After resolution of acute MCMV infection, LT-HSCs returned to phenotypic quiescence. However, non-acute MCMV infection induced a sustained inflammatory milieu within the bone marrow that was associated with long-lasting impairment of LT-HSC function. In conclusion, our results show that systemic virus infections fundamentally affect LT-HSCs and that also non-acute inflammatory stimuli in bone marrow donors can affect the reconstitution potential of bone marrow transplants. [ABSTRACT FROM AUTHOR]

The new adamantine derivative ethyl(3-ethyladamant-1-yl)carbamate was found to have high antiviral activity against herpes simplex virus and vaccinia viruses, as well as adenovirus (EC = 0.62, 5.15, and 48.5 μg/ml respectively). Activity against the herpesvirus was demonstrated in experiments in various cell cultures using different virus strains, including a variant resistant to acycloguanosine (ACG). Simultaneous application of ethyl(3-ethyladamant-1-yl)carbamate and ACG increased the inhibition of herpesvirus reproduction in cell cultures and decreased the mortality of laboratory animals with experimental herpesvirus neuroinfection as compared with the use of each substance alone. 3-Ethyladamant-1-yl)carbamate was a low-toxicity compound, did not inhibit DNAsynthesis in uninfected cell cultures, and its acute intragastric LD for white mice was 1831.8 mg/kg. [ABSTRACT FROM AUTHOR]