scholarly journals mTOR kinase is a therapeutic target for respiratory syncytial virus and coronaviruses

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
HoangDinh Huynh ◽  
Ruth Levitz ◽  
Rong Huang ◽  
Jeffrey S. Kahn
Keyword(s):  
Respiratory Syncytial Virus ◽  
Respiratory Tract ◽  
Protein Production ◽  
Viral Infections ◽  
Antiviral Treatment ◽  
Effective Means ◽  
Respiratory Pathogen ◽  
Progeny Virus ◽  
Upper Respiratory Tract ◽  
Syncytial Virus

AbstractTherapeutic interventions targeting viral infections remain a significant challenge for both the medical and scientific communities. While specific antiviral agents have shown success as therapeutics, viral resistance inevitably develops, making many of these approaches ineffective. This inescapable obstacle warrants alternative approaches, such as the targeting of host cellular factors. Respiratory syncytial virus (RSV), the major respiratory pathogen of infants and children worldwide, causes respiratory tract infection ranging from mild upper respiratory tract symptoms to severe life-threatening lower respiratory tract disease. Despite the fact that the molecular biology of the virus, which was originally discovered in 1956, is well described, there is no vaccine or effective antiviral treatment against RSV infection. Here, we demonstrate that targeting host factors, specifically, mTOR signaling, reduces RSV protein production and generation of infectious progeny virus. Further, we show that this approach can be generalizable as inhibition of mTOR kinases reduces coronavirus gene expression, mRNA transcription and protein production. Overall, defining virus replication-dependent host functions may be an effective means to combat viral infections, particularly in the absence of antiviral drugs.

scholarly journals MTOR Kinase is a Therapeutic Target for Respiratory Syncytial Virus and Coronaviruses

2021 ◽  
Author(s):  
HoangDinh Huynh ◽  
Ruth Levitz ◽  
Jeffrey Kahn
Keyword(s):  
Respiratory Syncytial Virus ◽  
Respiratory Tract ◽  
Protein Production ◽  
Viral Infections ◽  
Antiviral Treatment ◽  
Effective Means ◽  
Therapeutic Interventions ◽  
Respiratory Pathogen ◽  
Upper Respiratory Tract ◽  
Syncytial Virus

Abstract Therapeutic interventions targeting viral infections remain a significant challenge for both the medical and scientific communities. While specific antiviral agents have shown success as therapeutics, viral resistance inevitably develops making many of these approaches ineffective. This inescapable obstacle warrants alternative approaches, such as targeting host cellular factors. Respiratory syncytial virus (RSV), the major respiratory pathogen of infants and children worldwide, causes respiratory tract infection ranging from mild upper respiratory tract symptoms to severe life-threatening lower respiratory tract disease. Despite the fact that the molecular biology of the virus, which was originally discovered in 1956, is well described, there is no vaccine or effective antiviral treatment against RSV infection. Here, we demonstrate that targeting host factors, specifically, mTOR signaling, limits RSV protein production and viral replication. Further, we show that this approach is generalizable as inhibition of mTOR kinases reduces coronavirus gene expression, protein production and replication. Overall, defining virus replication-dependent host functions may be an effective means to combat viral infections, particular in the absence of antiviral drugs.

Respiratory viruses

2011 ◽  
pp. 208-211
Author(s):  
Dr Mark Harrison
Keyword(s):  
Respiratory Syncytial Virus ◽  
Respiratory Tract ◽  
Common Cold ◽  
Respiratory Viruses ◽  
Upper Respiratory Tract Infections ◽  
Upper Respiratory Tract ◽  
The Common ◽  
Upper Respiratory ◽  
Syncytial Virus ◽  
Tract Infections

15.1 Rhinovirus, 209 15.2 Influenza, 210 15.3 Parainfluenza, 211 15.4 Respiratory syncytial virus (RSV), 211 • There are more than 100 different serotypes of rhinovirus. • Rhinovirus is chiefly limited to upper respiratory tract infections and is the major cause of the common cold....

scholarly journals Prevalence of upper respiratory tract infections at a tertiary care hospital in the city of São Paulo

2010 ◽  
Vol 8 (2) ◽  
pp. 197-199 ◽  
Author(s):  
Amilton Mouro ◽  
Luci Black Tabacow Hidal ◽  
Marines Dalla Valle Martino ◽  
Jacyr Pasternark
Keyword(s):  
Respiratory Syncytial Virus ◽  
Respiratory Tract ◽  
Tertiary Care Hospital ◽  
Tertiary Care ◽  
Sao Paulo ◽  
Care Hospital ◽  
Upper Respiratory Tract ◽  
Upper Respiratory ◽  
Syncytial Virus ◽  
The City

ABSTRACT Objective: To evaluate the prevalence of pathogens in the upper respiratory tract according to age at a tertiary care hospital in the city of São Paulo. Methods: A total of 6,144 biological material tests from upper respiratory airways were analyzed: 740 bacterial cultures, 726 virus screenings and 4,678 rapid tests for S. pyogenes. Results: The most frequently found etiological agent was respiratory syncytial virus (29.6%; 215/726). The main agents detected per age groups were: respiratory syncytial virus (25.34%; 184/726) in patients aged 28 days-3 years; S. pyogenes (9.5%; 70/740) in 3-12 year-old children; influenza virus (8.8%; 64/726) in adults (18-59 years). Conclusions: The etiologic agents of upper respiratory infections vary according to age and imply diverse clinical and therapeutic management.

Similar Cytokine Profiles in Response to Infection with Respiratory Syncytial Virus Type A and Type B in the Upper Respiratory Tract in Infants

Intervirology ◽  
2008 ◽  
Vol 51 (2) ◽  
pp. 112-115 ◽  
Author(s):  
Jesus F. Bermejo-Martin ◽  
Alberto Tenorio ◽  
Raul Ortiz de Lejarazu ◽  
Jose M. Eiros ◽  
Vanesa Matías ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Respiratory Tract ◽  
Virus Type ◽  
Type A ◽  
Upper Respiratory Tract ◽  
Type B ◽  
Cytokine Profiles ◽  
Upper Respiratory ◽  
Syncytial Virus

scholarly journals Acute upper respiratory tract viral illness and influenza immunization in homes for the elderly

1990 ◽  
Vol 105 (3) ◽  
pp. 609-618 ◽  
Author(s):  
K. G. Nicholson ◽  
D. J. Baker ◽  
A. Farquhar ◽  
D. Hurd ◽  
J. Kent ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Respiratory Tract ◽  
The Elderly ◽  
Upper Respiratory Tract ◽  
Medical Conditions ◽  
Influenza Immunization ◽  
Immunization Rates ◽  
Homes For The Elderly ◽  
Upper Respiratory ◽  
Syncytial Virus

SUMMARYOccupants of 482 long-stay and 33 short-stay beds in 11 Leicester City Council homes for the elderly were studied during a 30-week period from September 1988 to March 1989 to determine the incidence, aetiology, morbidity, and mortality of acute upper respiratory tract viral infections and the use of influenza vaccine.Influenza immunization rates by home ranged from 15·4 to 90% (mean 45%). There were no differences in the distribution of medical conditions by home. The highest immunization rates were seen in people with chest disease (77%), heart disease (60%), diabetes (56%), and those with three medical conditions (75%). There was an average of 0·7 upper respiratory episodes per bed per annum with a mortality of 3·4% (6/179). Half of all episodes were seen by a general medical practitioner and 81 of 90 (90%) referrals were prescribed antibiotics costing approximately £7.50 per patient. Lower respiratory tract complications developed during 45 (25%) of 179 episodes including 3 of 12 coronavirus infections, 3 of 9 respiratory syncytial virus infections, 2 of 4 adenovirus infections, 1 of 11 rhinovirus infections, but none of 5 influenza infections. Respiratory infections were caused mostly by pathogens other than influenza virus during the influenza period documented nationally. This highlights the role of coronaviruses, respiratory syncytial virus, and unidentified agents in the elderly, and questions the assumptions made in American estimates on the impact of influenza and the value of influenza vaccines.

scholarly journals In vivo comparison of a laboratory-adapted and clinical-isolate-based recombinant human respiratory syncytial virus

2020 ◽  
Vol 101 (10) ◽  
pp. 1037-1046 ◽  
Author(s):  
Laurine C. Rijsbergen ◽  
Linda J. Rennick ◽  
Brigitta M. Laksono ◽  
Peter R.W.A. van Run ◽  
Thijs Kuiken ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Respiratory Tract ◽  
Clinical Isolate ◽  
Human Respiratory Syncytial Virus ◽  
Post Inoculation ◽  
Upper Respiratory Tract ◽  
Cotton Rats ◽  
Syncytial Virus ◽  
Rats And Mice

Human respiratory syncytial virus (HRSV) is the leading cause of severe respiratory tract disease in infants. Most HRSV infections remain restricted to the upper respiratory tract (URT), but in a small percentage of patients the infection spreads to the lower respiratory tract, resulting in bronchiolitis or pneumonia. We have a limited understanding of HRSV pathogenesis and what factors determine disease severity, partly due to the widespread use of tissue-culture-adapted viruses. Here, we studied early viral dissemination and tropism of HRSV in cotton rats, BALB/cJ mice and C57BL/6 mice. We used a novel recombinant (r) strain based on a subgroup A clinical isolate (A11) expressing EGFP [rHRSVA11EGFP(5)]. A recombinant laboratory-adapted HRSV strain [rHRSVA2EGFP(5)] was used as a direct comparison. Our results show that rHRSVA11EGFP(5) replicated to higher viral titres than laboratory-adapted rHRSVA2EGFP(5) in the URT of cotton rats and mice. HRSV-infected cells were detected as early as 2 days post-inoculation in both species in the nasal septa and lungs. Infection was predominantly present in ciliated epithelial cells in cotton rats and in the olfactory mucosa of mice. In our opinion, this study highlights that the choice of virus strain is important when studying HRSV pathogenesis in vivo and demonstrates that A11 is a representative clinical-based virus. Additionally, we show critical differences in tropism and inflammation when comparing HRSV infection of cotton rats and mice.

Serious Respiratory Tract Disease Caused by Respiratory Syncytial Virus: Prospects for Improved Therapy and Effective Immunization

PEDIATRICS ◽  
1992 ◽  
Vol 90 (1) ◽  
pp. 137-143
Author(s):  
Robert M. Chanock ◽  
Robert H. Parrott ◽  
Mark Connors ◽  
Peter L. Collins ◽  
Brian R. Murphy
Keyword(s):  
Respiratory Syncytial Virus ◽  
Respiratory Tract ◽  
Lower Respiratory Tract ◽  
Durable Resistance ◽  
Secretory Iga ◽  
Upper Respiratory Tract ◽  
Viral Pathogen ◽  
Rsv Infection ◽  
Upper Respiratory ◽  
Syncytial Virus

On this felicitous occasion we honor Dr Saul Krugman for his many contributions to the study and control of a wide variety of important pediatric viral diseases. In preparing our remarks we found it difficult to identify a major pediatric viral pathogen upon which Saul had not left his mark. One of the few that escaped, for reasons unknown, is respiratory syncytial virus (RSV). Since RSV is the major pediatric respiratory tract viral pathogen, we thought this agent might pique his interest. Those of us studying RSV need all the help we can receive from biomedical scientists of Saul's caliber. What follows is a summary of current efforts to develop improved therapy and effective immunoprophylaxis for this elusive respiratory tract viral pathogen. IMMUNITY TO RSV DISEASE The mechanisms by which the immune system protects the respiratory tract against RSV infection and disease are not completely understood. However, it is clear that infection (or reinfection) induces resistance in the upper respiratory tract that is neither complete nor long lasting.1,2 The situation is some-what more favorable in the lower respiratory tract, where infection (or reinfection) induces more substantial and more durable resistance to disease. As a consequence, cumulative immunity from multiple reinfections protects older children and adults against the more serious forms of disease involving the lower respiratory tract such as bronchiolitis and pneumonia. Resistance to RSV infection in the upper respiratory tract appears to be mediated primarily by local secretory IgA antibodies, which explains the transitory nature of immunity in this region.3

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