scholarly journals Broad Impact of Exchange Protein Directly Activated by cAMP 2 (EPAC2) on Respiratory Viral Infections

Viruses ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1179
Author(s):  
Eun-Jin Choi ◽  
Wenzhe Wu ◽  
Xiaoyan Cong ◽  
Ke Zhang ◽  
Jiaqi Luo ◽  
...  
Keyword(s):  
Therapeutic Target ◽  
Ebola Virus ◽  
Viral Infections ◽  
Rna Virus ◽  
Specific Inhibitor ◽  
New Family ◽  
Respiratory Viral Infections ◽  
Syncytial Virus ◽  
The Impact ◽  
Exchange Protein

The recently discovered exchange protein directly activated by cAMP (EPAC), compared with protein kinase A (PKA), is a fairly new family of cAMP effectors. Soon after the discovery, EPAC has shown its significance in many diseases including its emerging role in infectious diseases. In a recent study, we demonstrated that EPAC, but not PKA, is a promising therapeutic target to regulate respiratory syncytial virus (RSV) replication and its associated inflammation. In mammals, there are two isoforms of EPAC—EPAC1 and EPAC2. Unlike other viruses, including Middle East respiratory syndrome coronavirus (MERS-CoV) and Ebola virus, which use EPAC1 to regulate viral replication, RSV uses EPAC2 to control its replication and associated cytokine/chemokine responses. To determine whether EPAC2 protein has a broad impact on other respiratory viral infections, we used an EPAC2-specific inhibitor, MAY0132, to examine the functions of EPAC2 in human metapneumovirus (HMPV) and adenovirus (AdV) infections. HMPV is a negative-sense single-stranded RNA virus belonging to the family Pneumoviridae, which also includes RSV, while AdV is a double-stranded DNA virus. Treatment with an EPAC1-specific inhibitor was also included to investigate the impact of EPAC1 on these two viruses. We found that the replication of HMPV, AdV, and RSV and the viral-induced immune mediators are significantly impaired by MAY0132, while an EPAC1-specific inhibitor, CE3F4, does not impact or slightly impacts, demonstrating that EPAC2 could serve as a novel common therapeutic target to control these viruses, all of which do not have effective treatment and prevention strategies.

Universal Face Masking Reduces Respiratory Viral Infections Among Inpatient Very-Low-Birthweight Neonatal Infants

2020 ◽  
Vol 71 (11) ◽  
pp. 2958-2961 ◽  
Author(s):  
Wing Yee Tong ◽  
Chee Fu Yung ◽  
Lee Chern Chiew ◽  
Siong Beng Chew ◽  
Li Duan Ang ◽  
...  
Keyword(s):  
Low Birthweight ◽  
Viral Infections ◽  
Very Low Birthweight ◽  
Very Low Birthweight Infants ◽  
Respiratory Viral Infections ◽  
Step Down ◽  
Syncytial Virus ◽  
The Impact ◽  
Level 2 ◽  
Neonatal Infants

Abstract We reviewed the impact of a universal face masking policy on respiratory viral infections (RVIs) among admitted very-low-birthweight infants in our neonatal department. There was a significant decrease in RVI incidence, specifically in our step-down level 2 unit, with respiratory syncytial virus and parainfluenza virus being the most common viruses isolated.

scholarly journals Progress in Defining the Role of RSV in Allergy and Asthma: From Clinical Observations to Animal Models

2004 ◽  
Vol 11 (2) ◽  
pp. 113-119 ◽  
Author(s):  
W. V. Kalina ◽  
L. J. Gershwin
Keyword(s):  
Animal Models ◽  
Rna Virus ◽  
Allergic Sensitization ◽  
Upper Respiratory Tract ◽  
Young Infants ◽  
Wide Range ◽  
Similar Disease ◽  
Rsv Infection ◽  
Syncytial Virus ◽  
The Impact

Respiratory syncytial virus (RSV), an RNA virus in the family Paramyxoviridae, causes respiratory disease in humans. A closely related bovine RSV is responsible for a remarkably similar disease syndrome in young cattle. Severe RSV disease is characterized by bronchiolitis. The impact of RSV on human health is demonstrated annually when infants are admitted to the hospital in large numbers. Nearly every child will have been infected with RSV by the age of 3 years. While the disease is most severe in young infants and elderly people, it can re-infect adults causing mild upper respiratory tract disease throughout life. In addition, there is growing evidence that RSV infection may also predispose some children to the development of asthma. This is based on the observation that children who wheeze with RSV-induced bronchiolitis are more likely to develop into allergic asthmatics. Recent studies describe attempts to create an RSV induced asthma model in mice and other species; these have shown some degree of success. Such reports of case studies and animal models have suggested a wide range of factors possibly contributing to RSV induced asthma, these include timing of RSV infection with respect to allergen exposure, prior allergic sensitization, environmental conditions, exposure to endotoxin, and the genetic background of the person or animal. Herein, we primarily focus on the influence of RSV infection and inhalation of extraneous substances (such as allergens or endotoxin) on development of allergic asthma.

scholarly journals Clinical and epidemiological Semiotics in the diagnosis of etiology of acute respiratory viral infections in adults

2016 ◽  
Vol 21 (5) ◽  
pp. 268-273
Author(s):  
Aleksandr F. Popov ◽  
S. L Kolpakov ◽  
A. I Simakova ◽  
K. A Dmitrenko
Keyword(s):  
Viral Infections ◽  
Adenovirus Infection ◽  
Recent Period ◽  
Primorsky Krai ◽  
Etiological Diagnosis ◽  
Pcr Method ◽  
Respiratory Viral Infections ◽  
Syncytial Virus ◽  
Specific Symptoms ◽  
The City

For etiological diagnosis of acute respiratory viral infections the improvement of clinical semiotics and searchfor epidemiological consistent patterns are advantageous. Aim the establishment of consistent patterns of the clinical picture of etiologically AIRS decoded by PCR method and validities of epidemiological signs in the Primorsky Krai in the recent period. The material of the study were medical history cases on 276 patients admitted to the infectious department of Primorye Regional Clinical Hospital №2 in the city of Vladivostok in 2014 with a diagnosis of AIRS. Results. In the etiological structure of patients there was dominated influenza (48.2%). Hereafter there were: rhinovirus infection (13.0%), parainfluenza (11.2%), metapneumovirus infection (9,8,5%), adenovirus infection (8.0%). The minimum share was presented by bocavirus (HBoV)) infection (5.16%) and the respiratory syncytial virus, (HRSV) infection (4.7%). There were established the most sensitive and specific symptoms of considered infections. There were revealed features of the seasonality and the age structure of the patients, affecting on the efficiency of diagnosis.

Mechanisms of Action of Ribavirin in Antiviral Therapies

2001 ◽  
Vol 12 (5) ◽  
pp. 261-272 ◽  
Author(s):  
Robert C Tam ◽  
Johnson YN Lau ◽  
Zhi Hong
Keyword(s):  
Hepatitis C ◽  
Viral Infections ◽  
Rna Virus ◽  
Lassa Fever ◽  
Biological Properties ◽  
Interferon Α ◽  
Hepatitis C Infection ◽  
Antiviral Activities ◽  
Syncytial Virus

Although ribavirin was originally synthesized over 30 years ago and has been used to treat viral infections as monotherapy (respiratory syncytial virus and Lassa fever virus) or with interferon-α (IFN-α) as combination therapy (hepatitis C virus), the precise mechanism of its therapeutic activities remains controversial. In this review we focus on two main biological properties of ribavirin: its indirect and direct antiviral activities (with particular emphasis on its efficacy against chronic hepatitis C infection). Each property could individually or collectively account for its clinical efficacy against viral infections. First, with emphasis on the evidence for indirect activities of ribavirin, we will review the clinical observations that suggest that the immunomodulatory properties of ribavirin can in part account for its antiviral activities in vivo. We will then describe the mode of ribavirin's direct antiviral activities. These direct activities can be ascribed to several possible mechanisms, including the recently described activity as an RNA mutagen, a property that may be important in driving a rapidly mutating RNA virus over the threshold to ‘error catastrophe′.

scholarly journals Respiratory Viral Infection Alters the Gut Microbiota by Inducing Inappetence

mBio ◽  
2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Helen T. Groves ◽  
Sophie L. Higham ◽  
Miriam F. Moffatt ◽  
Michael J. Cox ◽  
John S. Tregoning
Keyword(s):  
Weight Loss ◽  
Gut Microbiota ◽  
Viral Infection ◽  
Gut Microbiome ◽  
Viral Infections ◽  
Lung Infection ◽  
Significant Shift ◽  
Rsv Infection ◽  
Respiratory Viral Infections ◽  
The Impact

ABSTRACT Respiratory viral infections are extremely common, but their impacts on the composition and function of the gut microbiota are poorly understood. We previously observed a significant change in the gut microbiota after viral lung infection. Here, we show that weight loss during respiratory syncytial virus (RSV) or influenza virus infection was due to decreased food consumption, and that the fasting of mice altered gut microbiota composition independently of infection. While the acute phase tumor necrosis factor alpha (TNF-α) response drove early weight loss and inappetence during RSV infection, this was not sufficient to induce changes in the gut microbiota. However, the depletion of CD8+ cells increased food intake and prevented weight loss, resulting in a reversal of the gut microbiota changes normally observed during RSV infection. Viral infection also led to changes in the fecal gut metabolome, with a significant shift in lipid metabolism. Sphingolipids, polyunsaturated fatty acids (PUFAs), and the short-chain fatty acid (SCFA) valerate were all increased in abundance in the fecal metabolome following RSV infection. Whether this and the impact of infection-induced anorexia on the gut microbiota are part of a protective anti-inflammatory response during respiratory viral infections remains to be determined. IMPORTANCE The gut microbiota has an important role in health and disease: gut bacteria can generate metabolites that alter the function of immune cells systemically. Understanding the factors that can lead to changes in the gut microbiome may help to inform therapeutic interventions. This is the first study to systematically dissect the pathway of events from viral lung infection to changes in gut microbiota. We show that the cellular immune response to viral lung infection induces inappetence, which in turn alters the gut microbiome and metabolome. Strikingly, there was an increase in lipids that have been associated with the resolution of disease. This opens up new paths of investigation: first, what is the (presumably secreted) factor made by the T cells that can induce inappetence? Second, is inappetence an adaptation that accelerates recovery from infection, and if so, does the microbiome play a role in this?

scholarly journals Macrolide Therapy in Respiratory Viral Infections

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Jin-Young Min ◽  
Yong Ju Jang
Keyword(s):  
Influenza Virus ◽  
Viral Infection ◽  
Viral Infections ◽  
Wide Spectrum ◽  
Influenza Virus Infection ◽  
Respiratory Viral Infection ◽  
Rsv Infection ◽  
Respiratory Viral Infections ◽  
Syncytial Virus ◽  
Viral Titers

Background. Macrolides have received considerable attention for their anti-inflammatory and immunomodulatory actions beyond the antibacterial effect. These two properties may ensure some efficacy in a wide spectrum of respiratory viral infections. We aimed to summarize the properties of macrolides and their efficacy in a range of respiratory viral infection.Methods. A search of electronic journal articles through PubMed was performed using combinations of the following keywords including macrolides and respiratory viral infection.Results. Bothin vitroandin vivostudies have provided evidence of their efficacy in respiratory viral infections including rhinovirus (RV), respiratory syncytial virus (RSV), and influenza virus. Much data showed that macrolides reduced viral titers of RV ICAM-1, which is the receptor for RV, and RV infection-induced cytokines including IL-1β, IL-6, IL-8, and TNF-α. Macrolides also reduced the release of proinflammatory cytokines which were induced by RSV infection, viral titers, RNA of RSV replication, and the susceptibility to RSV infection partly through the reduced expression of activated RhoA which is an RSV receptor. Similar effects of macrolides on the influenza virus infection and augmentation of the IL-12 by macrolides which is essential in reducing virus yield were revealed.Conclusion. This paper provides an overview on the properties of macrolides and their efficacy in various respiratory diseases.

scholarly journals Impact of the COVID-19 Pandemic on Cystic Fibrosis Pulmonary Exacerbations

2020 ◽  
Vol 3 ◽  
Author(s):  
Shreya Patel ◽  
Misty Thompson ◽  
James Slaven ◽  
Clement Ren
Keyword(s):  
Chart Review ◽  
Viral Infections ◽  
Retrospective Chart Review ◽  
Time Interval ◽  
Study Cohort ◽  
School Closures ◽  
Respiratory Viral Infections ◽  
Potential Impact ◽  
Pulmonary Exacerbations ◽  
The Impact

​Background and Hypothesis       CF pulmonary exacerbations (PEx) are episodes of decline in respiratory function that can be triggered by a variety of mechanisms, including respiratory viral infections.  The COVID-19 pandemic resulted in school closures and home isolation policies and a potential reduction in exposure to other respiratory viruses.  The goal of this project is to study the impact of the COVID-19 pandemic on CF PEx at the Riley Hospital for Children. We hypothesize that the incidence of PEx will be lower during the period of the COVID-19 lockdown from March 1 to May 15 in 2020 compared to the same time interval in 2019.      Methods  We performed a retrospective chart review of children with CF ages 2-12 (N=80) seen at Riley in 2019 and 2020 and collected data within the following timeframes: January 1 to March 15 2019 and 2020, and March 16 to May 15 2019 and 2020.  We collected data on baseline clinical features and details of each PEx event.  Data were analyzed with parametric and non-parametric descriptive statistic tests as appropriate; significance was set at P≤0.05.     Results       The percent of PEx events in the study cohort was significantly lower in 2020 compared to 2019 for January 1 to March 15 (56% vs 42%, P=0.0116) and March 16 to May 15 (35% vs 14%, P<0.0001).  The percent of in-person PEx events was significantly lower during March 16 to May 15 in 2020 compared to 2019 (15% vs 1%, P=0.0066)    Conclusions and Potential Impact        COVID-19 restrictions were associated with a decrease PEx events.  We speculate that this reflects a reduced exposure to respiratory viral infections in general. The decrease in in-person PEx events may reflect a shift towards telehealth during the COVID-19 restrictions.  These results provide a foundation for further research into triggers and prevention of CF PEx.   

scholarly journals A Polyamide Inhibits Replication of Vesicular Stomatitis Virus by Targeting RNA in the Nucleocapsid

2018 ◽  
Vol 92 (8) ◽  
pp. e00146-18 ◽  
Author(s):  
Ryan H. Gumpper ◽  
Weike Li ◽  
Carlos H. Castañeda ◽  
M. José Scuderi ◽  
James K. Bashkin ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Vesicular Stomatitis Virus ◽  
Ebola Virus ◽  
Rna Viruses ◽  
Rna Virus ◽  
Viral Rna ◽  
Negative Strand ◽  
Double Stranded Dna ◽  
Vesicular Stomatitis ◽  
Syncytial Virus

ABSTRACTPolyamides have been shown to bind double-stranded DNA by complementing the curvature of the minor groove and forming various hydrogen bonds with DNA. Several polyamide molecules have been found to have potent antiviral activities against papillomavirus, a double-stranded DNA virus. By analogy, we reason that polyamides may also interact with the structured RNA bound in the nucleocapsid of a negative-strand RNA virus. Vesicular stomatitis virus (VSV) was selected as a prototype virus to test this possibility since its genomic RNA encapsidated in the nucleocapsid forms a structure resembling one strand of an A-form RNA duplex. One polyamide molecule, UMSL1011, was found to inhibit infection of VSV. To confirm that the polyamide targeted the nucleocapsid, a nucleocapsid-like particle (NLP) was incubated with UMSL1011. The encapsidated RNA in the polyamide-treated NLP was protected from thermo-release and digestion by RNase A. UMSL1011 also inhibits viral RNA synthesis in the intracellular activity assay for the viral RNA-dependent RNA polymerase. The crystal structure revealed that UMSL1011 binds the structured RNA in the nucleocapsid. The conclusion of our studies is that the RNA in the nucleocapsid is a viable antiviral target of polyamides. Since the RNA structure in the nucleocapsid is similar in all negative-strand RNA viruses, polyamides may be optimized to target the specific RNA genome of a negative-strand RNA virus, such as respiratory syncytial virus and Ebola virus.IMPORTANCENegative-strand RNA viruses (NSVs) include several life-threatening pathogens, such as rabies virus, respiratory syncytial virus, and Ebola virus. There are no effective antiviral drugs against these viruses. Polyamides offer an exceptional opportunity because they may be optimized to target each NSV. Our studies on vesicular stomatitis virus, an NSV, demonstrated that a polyamide molecule could specifically target the viral RNA in the nucleocapsid and inhibit viral growth. The target specificity of the polyamide molecule was proved by its inhibition of thermo-release and RNA nuclease digestion of the RNA bound in a model nucleocapsid, and a crystal structure of the polyamide inside the nucleocapsid. This encouraging observation provided the proof-of-concept rationale for designing polyamides as antiviral drugs against NSVs.

scholarly journals Exchange Proteins Directly Activated by cAMP and Their Roles in Respiratory Syncytial Virus Infection

2018 ◽  
Vol 92 (22) ◽  
Author(s):  
Eun-Jin Choi ◽  
Yuping Ren ◽  
Yu Chen ◽  
Shengxuan Liu ◽  
Wenzhe Wu ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Therapeutic Target ◽  
Molecular Mechanisms ◽  
Inflammatory Responses ◽  
Dominant Role ◽  
Specific Treatment ◽  
Specific Inhibitor ◽  
Public Health Problem ◽  
Specific Gene ◽  
Syncytial Virus

ABSTRACT Respiratory syncytial virus (RSV) is the leading cause of respiratory infection in young children and high-risk adults. However, a specific treatment for this viral infection is not currently available. In this study, we discovered that an exchange protein directly activated by cyclic AMP (EPAC) can serve as a potential therapeutic target for RSV. In both lower and upper epithelial cells, treatment with EPAC inhibitor (ESI-09), but not protein kinase A inhibitor (H89), significantly inhibits RSV replication and proinflammatory cytokine/chemokine induction. In addition, RSV-activated transcriptional factors belonging to the NF-κB and IRF families are also suppressed by ESI-09. Through isoform-specific gene knockdown, we found that EPAC2, but not EPAC1, plays a dominant role in controlling RSV replication and virus-induced host responses. Experiments using both EPAC2 knockout and EPAC2-specific inhibitor support such roles of EPAC2. Therefore, EPAC2 is a promising therapeutic target to regulate RSV replication and associated inflammation. IMPORTANCE RSV is a serious public health problem, as it is associated with bronchiolitis, pneumonia, and asthma exacerbations. Currently no effective treatment or vaccine is available, and many molecular mechanisms regarding RSV-induced lung disease are still significantly unknown. This project aims to elucidate an important and novel function of a protein, called EPAC2, in RSV replication and innate inflammatory responses. Our results should provide an important insight into the development of new pharmacologic strategies against RSV infection, thereby reducing RSV-associated morbidity and mortality.

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