scholarly journals Metabolic Modifications by Common Respiratory Viruses and Their Potential as New Antiviral Targets

Viruses ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2068
Author(s):  
Jens Kleinehr ◽  
Janine J. Wilden ◽  
Yvonne Boergeling ◽  
Stephan Ludwig ◽  
Eike R. Hrincius

Respiratory viruses are known to be the most frequent causative mediators of lung infections in humans, bearing significant impact on the host cell signaling machinery due to their host-dependency for efficient replication. Certain cellular functions are actively induced by respiratory viruses for their own benefit. This includes metabolic pathways such as glycolysis, fatty acid synthesis (FAS) and the tricarboxylic acid (TCA) cycle, among others, which are modified during viral infections. Here, we summarize the current knowledge of metabolic pathway modifications mediated by the acute respiratory viruses respiratory syncytial virus (RSV), rhinovirus (RV), influenza virus (IV), parainfluenza virus (PIV), coronavirus (CoV) and adenovirus (AdV), and highlight potential targets and compounds for therapeutic approaches.

2020 ◽  
Vol 59 (1) ◽  
pp. e02142-20
Author(s):  
Ahmed Babiker ◽  
Heath L. Bradley ◽  
Victoria D. Stittleburg ◽  
Jessica M. Ingersoll ◽  
Autum Key ◽  
...  

ABSTRACTBroad testing for respiratory viruses among persons under investigation (PUIs) for SARS-CoV-2 has been performed inconsistently, limiting our understanding of alternative viral infections and coinfections in these patients. RNA metagenomic next-generation sequencing (mNGS) offers an agnostic tool for the detection of both SARS-CoV-2 and other RNA respiratory viruses in PUIs. Here, we used RNA mNGS to assess the frequencies of alternative viral infections in SARS-CoV-2 RT-PCR-negative PUIs (n = 30) and viral coinfections in SARS-CoV-2 RT-PCR-positive PUIs (n = 45). mNGS identified all viruses detected by routine clinical testing (influenza A [n = 3], human metapneumovirus [n = 2], and human coronavirus OC43 [n = 2], and human coronavirus HKU1 [n = 1]). mNGS also identified both coinfections (1, 2.2%) and alternative viral infections (4, 13.3%) that were not detected by routine clinical workup (respiratory syncytial virus [n = 3], human metapneumovirus [n = 1], and human coronavirus NL63 [n = 1]). Among SARS-CoV-2 RT-PCR-positive PUIs, lower cycle threshold (CT) values correlated with greater SARS-CoV-2 read recovery by mNGS (R2, 0.65; P < 0.001). Our results suggest that current broad-spectrum molecular testing algorithms identify most respiratory viral infections among SARS-CoV-2 PUIs, when available and implemented consistently.


2020 ◽  
Vol 35 (1) ◽  
pp. 122-131
Author(s):  
Erick Yuen ◽  
David A. Gudis ◽  
Nicholas R. Rowan ◽  
Shaun A. Nguyen ◽  
Rodney J. Schlosser

Background Viral respiratory tract infections are associated with a significant burden of disease and represent one of the leading causes of mortality worldwide. The current Coronavirus Disease 2019 (COVID-19) pandemic highlights the devastating toll that respiratory viruses have on humanity and the desperate need to understand the biological characteristics that define them in order to develop efficacious treatments and vaccines. To date, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has infected nearly 600 times more people and resulted in 200 times more deaths relative to Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and Middle Eastern Respiratory Syndrome Coronavirus (MERS-CoV) combined. Objective Through this review, we aim to summarize the key characteristics of respiratory viruses that hold global significance, with a focus on SARS-CoV-2. Our goal is to disseminate our current knowledge of these infectious agents to otolaryngologists, in particular rhinologists, practicing in the COVID-19 era. Methods The general and clinical characteristics of selected respiratory viruses along with available viral treatments and vaccines are reviewed. Results There has been significant progress in our understanding of the epidemiology and pathogenesis of various respiratory viruses. However, despite the advancement in knowledge, efficacious vaccines and antiviral treatments remain elusive for most respiratory viruses. The dire need for these scientific discoveries is highlighted by the recent COVID-19 pandemic, which has prompted investigators worldwide to conduct clinical trials at an accelerated timeline in an effort to reduce the morbidity and mortality associated with SARS-CoV-2 infection. Rhinologists will continue to remain on the front-lines of pandemics associated with respiratory viruses. Conclusion In light of these unprecedented times, the need to understand the nuances of these viral respiratory pathogens, especially SARS-CoV-2, cannot be overemphasized. This knowledge base is of particular importance to otolaryngologists, whose expertise in the upper airway coincides with the anatomic tropism of these infectious agents.


2021 ◽  
Vol 12 ◽  
Author(s):  
Barbara Gierlikowska ◽  
Albert Stachura ◽  
Wojciech Gierlikowski ◽  
Urszula Demkow

Neutrophils are crucial elements of innate immune system, which assure host defense via a range of effector functions, such as phagocytosis, degranulation, and NET formation. The latest literature clearly indicates that modulation of effector functions of neutrophils may affect the treatment efficacy. Pharmacological modulation may affect molecular mechanisms activating or suppressing phagocytosis, degranulation or NET formation. In this review, we describe the role of neutrophils in physiology and in the course of bacterial and viral infections, illustrating the versatility and plasticity of those cells. This review also focus on the action of plant extracts, plant-derived compounds and synthetic drugs on effector functions of neutrophils. These recent advances in the knowledge can help to devise novel therapeutic approaches via pharmacological modulation of the described processes.


2021 ◽  
Vol 42 (06) ◽  
pp. 759-770
Author(s):  
Tom D.Y. Reijnders ◽  
Alex R. Schuurman ◽  
Tom van der Poll

AbstractBiomedical research has long strived to improve our understanding of the immune response to respiratory viral infections, an effort that has become all the more important as we live through the consequences of a pandemic. The disease course of these infections is shaped in large part by the actions of various cells of the innate and adaptive immune systems. While these cells are crucial in clearing viral pathogens and establishing long-term immunity, their effector mechanisms may also escalate into excessive, tissue-destructive inflammation detrimental to the host. In this review, we describe the breadth of the immune response to infection with respiratory viruses such as influenza and respiratory syncytial virus. Throughout, we focus on the host rather than the pathogen and try to describe shared patterns in the host response to different viruses. We start with the local cells of the airways, onto the recruitment and activation of innate and adaptive immune cells, followed by the establishment of local and systemic memory cells key in protection against reinfection. We end by exploring how respiratory viral infections can predispose to bacterial superinfection.


1980 ◽  
Vol 1 (3) ◽  
pp. 165-182 ◽  
Author(s):  
William M. Valenti ◽  
Robert F. Betts ◽  
Caroline Breese Hall ◽  
Jerome F. Hruska ◽  
R. Gordon Douglas

AbstractThis article reviews the most likely mechanisms of transmission of the commonly encountered respiratory viruses (influenza, respiratory syncytial virus, parainfluenza, rhinovirus), herpesviruses, and hepatitis viruses, and presents the guidelines used currently for prevention and control that are in use at Strong Memorial Hospital.


Author(s):  
Lucy A Desmond ◽  
Melanie A Lloyd ◽  
Shelley A Ryan ◽  
Edward D Janus ◽  
Harin A Karunajeewa

Background Community-Acquired Pneumonia (CAP) is one of the highest health burden conditions in Australia. Disease notifications and other data from routine diagnosis suffers from selection bias that may misrepresent the true contribution of various aetiological agents. However existing Australian prospective studies of CAP aetiology have either under-represented elderly patients, not utilised Polymerase Chain Reaction (PCR) diagnostics or been limited to winter months. We therefore sought to re-evaluate CAP aetiology by systematically applying multiplex PCR in a representative cohort of mostly elderly patients hospitalised in Melbourne during non-winter months and compare diagnostic results with those obtained under usual conditions of care. Methods Seventy two CAP inpatients were prospectively enrolled over 2 ten-week blocks during non-winter months in Melbourne in 2016-17. Nasopharyngeal and oropharyngeal swabs were obtained at admission and analysed by multiplex-PCR for 7 respiratory viruses and 5 atypical bacteria. Results Median age was 74 (interquartile range 67-80) years, with 38 (52.8%) males and 34 (47.2%) females. PCR was positive in 24 (33.3%), including 12 Picornavirus (50.5% of those with a virus), 4 RSV (16.7%) and 4 influenza A (16.7%). CAP-Sym questionnaire responses were similar in those with and without viral infections. Most (80%) pathogens detected by the study, including all 8 cases of influenza and RSV, were not otherwise detected by treating clinicians during hospital admission. Conclusion One third of patients admitted with CAP during non-winter months had PCR-detectable respiratory viral infections, including many cases of influenza and RSV that were missed by existing routine clinical diagnostic processes. Keywords: Lower Respiratory Tract Infection (LRTI), Community-Acquired Pneumonia (CAP) Polymerase Chain Reaction (PCR), Influenza, Respiratory Syncytial Virus


2016 ◽  
Vol 7 (2) ◽  
pp. ar.2016.7.0157 ◽  
Author(s):  
Hirokuni Otsuka ◽  
Hiroyuki Tsukagoshi ◽  
Hirokazu Kimura ◽  
Ikuo Takanashi ◽  
Kimihiro Okubo

Background Respiratory virus infections are involved in asthma exacerbations. However, there are no reports of the relationship between respiratory virus infections and Japanese cedar pollinosis. Objective We studied the relationship between respiratory viral infection and the appearance of preseasonal symptoms and the severity of seasonal symptoms in Japanese cedar pollinosis. Methods In 36 patients with asthma and with no symptoms (PreAsyP) and 54 patients with asthma and with symptoms (PreSyP) before the cedar pollen shedding commenced (preseason), and 37 patients with mild-to-moderate severity (InMild/Mod) and 45 patients with severe to extreme severity (InSev/Ext) after cedar shedding commenced (in season), the occurrence of respiratory viruses and nasal smear cytology were examined. Results In total, seven infections with respiratory viruses were detected among the subjects. Human rhinovirus (HRV) C infection was detected in one subject in each of the PreAsyP and PreSyP groups, and one HRVA infection occurred in the InMild/Mod group. In the InSev/Ext group, one HRVA, one HRVC, one respiratory syncytial virus, and one human metapneumovirus were detected. There was no significant difference in the rate of detection of viral infections between the PreAsyP and the PreSyP groups (p = 0.077), and between the InMild/Mod group and the InSev/Ext group (p = 0.24, Wilcoxon rank sum test). When cells types in nasal smears were identified and their abundance examined, the rate of neutrophilia in the subjects in the PreSyP group was 54%, which was statistically higher (p < 0.01) than the subjects in the PreAsyP group (25%). Interestingly, in the subjects in the InSev/Ext group, the proportion of eosinophils (40%) was larger (p < 0.05) than in the subjects in the InMild/Mod group (19%). Conclusion These results provided no evidence that respiratory virus infections contributed to preseasonal symptoms and severity in season of Japanese cedar pollinosis. Nasal neutrophilia was related to preseasonal symptoms, whereas nasal eosinophilia was related to severity of symptoms during the pollen season.


2012 ◽  
Vol 54 (5) ◽  
pp. 249-255 ◽  
Author(s):  
Maria Carolina M. Albuquerque ◽  
Rafael B. Varella ◽  
Norma Santos

The frequency of viral pathogens causing respiratory infections in children in the cities of Rio de Janeiro and Teresópolis was investigated. Nasal swabs from children with acute respiratory illnesses were collected between March 2006 and October 2007. Specimens were tested for viral detection by conventional (RT)-PCR and/or real time PCR. Of the 205 nasal swabs tested, 64 (31.2%) were positive for at least one of the viral pathogens. Single infections were detected in 56 samples, 50 of those were caused by RNA viruses: 33 samples tested positive for rhinovirus, five for influenza A, five for metapneumovirus, four for coronavirus and, three for respiratory syncytial virus. For the DNA viruses, five samples were positive for bocavirus and one for adenovirus. Co-infections with these viruses were detected in eight samples. Our data demonstrate a high frequency of viral respiratory infections, emphasizing the need for a more accurate diagnosis particularly for the emerging respiratory viruses. The fact that the emerging respiratory viruses were present in 9.2% of the tested samples suggests that these viruses could be important respiratory pathogens in the country.


Thorax ◽  
2021 ◽  
pp. thoraxjnl-2021-216949
Author(s):  
Pontus Hedberg ◽  
John Karlsson Valik ◽  
Suzanne van der Werff ◽  
Hideyuki Tanushi ◽  
Ana Requena Mendez ◽  
...  

BackgroundAn understanding of differences in clinical phenotypes and outcomes COVID-19 compared with other respiratory viral infections is important to optimise the management of patients and plan healthcare. Herein we sought to investigate such differences in patients positive for SARS-CoV-2 compared with influenza, respiratory syncytial virus (RSV) and other respiratory viruses.MethodsWe performed a retrospective cohort study of hospitalised adults and children (≤15 years) who tested positive for SARS-CoV-2, influenza virus A/B, RSV, rhinovirus, enterovirus, parainfluenza viruses, metapneumovirus, seasonal coronaviruses, adenovirus or bocavirus in a respiratory sample at admission between 2011 and 2020.ResultsA total of 6321 adult (1721 SARS-CoV-2) and 6379 paediatric (101 SARS-CoV-2) healthcare episodes were included in the study. In adults, SARS-CoV-2 positivity was independently associated with younger age, male sex, overweight/obesity, diabetes and hypertension, tachypnoea as well as better haemodynamic measurements, white cell count, platelet count and creatinine values. Furthermore, SARS-CoV-2 was associated with higher 30-day mortality as compared with influenza (adjusted HR (aHR) 4.43, 95% CI 3.51 to 5.59), RSV (aHR 3.81, 95% CI 2.72 to 5.34) and other respiratory viruses (aHR 3.46, 95% CI 2.61 to 4.60), as well as higher 90-day mortality, ICU admission, ICU mortality and pulmonary embolism in adults. In children, patients with SARS-CoV-2 were older and had lower prevalence of chronic cardiac and respiratory diseases compared with other viruses.ConclusionsSARS-CoV-2 is associated with more severe outcomes compared with other respiratory viruses, and although associated with specific patient and clinical characteristics at admission, a substantial overlap precludes discrimination based on these characteristics.


Biomimetics ◽  
2021 ◽  
Vol 7 (1) ◽  
pp. 3
Author(s):  
Aya Harb ◽  
Mohammad Fakhreddine ◽  
Hassan Zaraket ◽  
Fatima A. Saleh

Respiratory viral infections, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), are among the most common illnesses and a leading cause of morbidity and mortality worldwide. Due to the severe effects on health, the need of new tools to study the pathogenesis of respiratory viruses as well as to test for new antiviral drugs and vaccines is urgent. In vitro culture model systems, such as three-dimensional (3D) cultures, are emerging as a desirable approach to understand the virus host interactions and to identify novel therapeutic agents. In the first part of the article, we address the various scaffold-free and scaffold-based 3D culture models such as hydrogels, bioreactors, spheroids and 3D bioprinting as well as present their properties and advantages over conventional 2D methods. Then, we review the 3D models that have been used to study the most common respiratory viruses including influenza, parainfluenza, respiratory syncytial virus (RSV) and coronaviruses. Herein, we also explain how 3D models have been applied to understand the novel SARS-CoV-2 infectivity and to develop potential therapies.


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