scholarly journals Persistent Airway Hyperresponsiveness Following Recovery from Infection with Pneumonia Virus of Mice

Viruses ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 728
Author(s):  
Ajinkya R. Limkar ◽  
Caroline M. Percopo ◽  
Jamie L. Redes ◽  
Kirk M. Druey ◽  
Helene F. Rosenberg
Keyword(s):  
Airway Hyperresponsiveness ◽  
Respiratory Virus ◽  
Infection Model ◽  
Post Inoculation ◽  
Virus Infections ◽  
Long Term Effects ◽  
Lung Dysfunction ◽  
Syncytial Virus ◽  
Underlying Mechanisms ◽  
Precision Cut Lung Slices

Respiratory virus infections can have long-term effects on lung function that persist even after the acute responses have resolved. Numerous studies have linked severe early childhood infection with respiratory syncytial virus (RSV) to the development of wheezing and asthma, although the underlying mechanisms connecting these observations remain unclear. Here, we examine airway hyperresponsiveness (AHR) that develops in wild-type mice after recovery from symptomatic but sublethal infection with the natural rodent pathogen, pneumonia virus of mice (PVM). We found that BALB/c mice respond to a limited inoculum of PVM with significant but reversible weight loss accompanied by virus replication, acute inflammation, and neutrophil recruitment to the airways. At day 21 post-inoculation, virus was no longer detected in the airways and the acute inflammatory response had largely resolved. However, and in contrast to most earlier studies using the PVM infection model, all mice survived the initial infection and all went on to develop serum anti-PVM IgG antibodies. Furthermore, using both invasive plethysmography and precision-cut lung slices, we found that these mice exhibited significant airway hyperresponsiveness at day 21 post-inoculation that persisted through day 45. Taken together, our findings extend an important and versatile respiratory virus infection model that can now be used to explore the role of virions and virion clearance as well as virus-induced inflammatory mediators and their signaling pathways in the development and persistence of post-viral AHR and lung dysfunction.

scholarly journals Authentic Modeling of Human Respiratory Virus Infection in Human Pluripotent Stem Cell-Derived Lung Organoids

mBio ◽  
2019 ◽  
Vol 10 (3) ◽  
Author(s):  
M. Porotto ◽  
M. Ferren ◽  
Y.-W. Chen ◽  
Y. Siu ◽  
N. Makhsous ◽  
...  
Keyword(s):  
Virus Infection ◽  
Viral Infection ◽  
Pluripotent Stem Cells ◽  
Respiratory Virus ◽  
Human Lung ◽  
Cultured Cells ◽  
Virus Infections ◽  
Distal Lung ◽  
Syncytial Virus ◽  
Respiratory Virus Infections

ABSTRACTInfectious viruses so precisely fit their hosts that the study of natural viral infection depends on host-specific mechanisms that affect viral infection. For human parainfluenza virus 3, a prevalent cause of lower respiratory tract disease in infants, circulating human viruses are genetically different from viruses grown in standard laboratory conditions; the surface glycoproteins that mediate host cell entry on circulating viruses are suited to the environment of the human lung and differ from those of viruses grown in cultured cells. Polarized human airway epithelium cultures have been used to represent the large, proximal airways of mature adult airways. Here we modeled respiratory virus infections that occur in children or infect the distal lung using lung organoids that represent the entire developing infant lung. These 3D lung organoids derived from human pluripotent stem cells contain mesoderm and pulmonary endoderm and develop into branching airway and alveolar structures. Whole-genome sequencing analysis of parainfluenza viruses replicating in the organoids showed maintenance of nucleotide identity, suggesting that no selective pressure is exerted on the virus in this tissue. Infection with parainfluenza virus led to viral shedding without morphological changes, while respiratory syncytial virus infection induced detachment and shedding of infected cells into the lung organoid lumens, reminiscent of parainfluenza and respiratory syncytial virus in human infant lungs. Measles virus infection, in contrast, induced syncytium formation. These human stem cell-derived lung organoids may serve as an authentic model for respiratory viral pathogenesis in the developing or infant lung, recapitulating respiratory viral infection in the host.IMPORTANCERespiratory viruses are among the first pathogens encountered by young children, and the significant impact of these viral infections on the developing lung is poorly understood. Circulating viruses are suited to the environment of the human lung and are different from those of viruses grown in cultured cells. We modeled respiratory virus infections that occur in children or infect the distal lung using lung organoids that represent the entire developing infant lung. These 3D lung organoids, derived from human pluripotent stem cells, develop into branching airway and alveolar structures and provide a tissue environment that maintains the authentic viral genome. The lung organoids can be genetically engineered prior to differentiation, thereby generating tissues bearing or lacking specific features that may be relevant to viral infection, a feature that may have utility for the study of host-pathogen interaction for a range of lung pathogens.

scholarly journals FluWatchers: Evaluation of a crowdsourced influenza-like illness surveillance application for Canadian influenza seasons 2015–2016 to 2018–2019

2021 ◽  
Vol 47 (09) ◽  
pp. 357-363
Author(s):  
Liza Lee ◽  
Mireille Desroches ◽  
Shamir Mukhi ◽  
Christina Bancej
Keyword(s):  
Respiratory Virus ◽  
Evaluation Criteria ◽  
Influenza Surveillance ◽  
Surveillance Program ◽  
Surveillance Systems ◽  
Virus Infections ◽  
Detection Rates ◽  
Influenza Like Illness ◽  
Syncytial Virus ◽  
Participatory Surveillance

Background: Sentinel influenza-like illness (ILI) surveillance is an essential component of a comprehensive influenza surveillance program. Community-based ILI surveillance systems that rely solely on sentinel healthcare practices omit important segments of the population, including those who do not seek medical care. Participatory surveillance, which relies on community participation in surveillance, may address some limitations of traditional ILI systems. Objective: We aimed to evaluate FluWatchers, a crowdsourced ILI application developed to complement and complete ILI surveillance in Canada. Methods: Using established frameworks for surveillance evaluations, we assessed the acceptability, reliability, accuracy and usefulness of the FluWatchers system 2015–2016, through 2018–2019. Evaluation indicators were compared against national surveillance indicators of ILI and of laboratory confirmed respiratory virus infections. Results: The acceptability of FluWatchers was demonstrated by growth of 50%–100% in season-over-season participation, and a consistent season-over-season retention of 80%. Reliability was greater for FluWatchers than for our traditional ILI system, although both systems had week-over-week fluctuations in the number of participants responding. FluWatchers’ ILI rates had moderate correlation with weekly influenza laboratory detection rates and other winter seasonal respiratory virus detections including respiratory syncytial virus and seasonal coronaviruses. Finally, FluWatchers has demonstrated its usefulness as a source of core FluWatch surveillance information and has the potential to fill data gaps in current programs for influenza surveillance and control. Conclusion: FluWatchers is an example of an innovative digital participatory surveillance program that was created to address limitations of traditional ILI surveillance in Canada. It fulfills the surveillance system evaluation criteria of acceptability, reliability, accuracy and usefulness.

scholarly journals Respiratory syncytial virus infection increases chlorine-induced airway hyperresponsiveness

2015 ◽  
Vol 309 (3) ◽  
pp. L205-L210 ◽  
Author(s):  
Weifeng Song ◽  
Zhihong Yu ◽  
Stephen F. Doran ◽  
Namasivayam Ambalavanan ◽  
Chad Steele ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Lung Injury ◽  
Airway Hyperresponsiveness ◽  
Neutrophil Infiltration ◽  
Lavage Fluid ◽  
Infection Model ◽  
Type 2 Cytokines ◽  
Rsv Infection ◽  
Syncytial Virus ◽  
First Time

Exposure to chlorine (Cl2) damages airway and alveolar epithelia resulting in acute lung injury and reactive airway hyperresponsiveness (AHR) to methacholine. However, little is known about the effect of preexisting respiratory disease on Cl2-induced lung injury. By using a murine respiratory syncytial virus (RSV) infection model, we found that preexisting RSV infection increases Cl2 (187 ppm for 30 min)-induced lung inflammation and airway AHR at 24 h after exposure (5 days after infection). RSV infection and Cl2 exposure synergistically induced oxygen desaturation and neutrophil infiltration and increased MCP-1, MIP-1β, IL-10, IFN-γ, and RANTES concentrations in the bronchoalveolar lavage fluid (BALF). In contrast, levels of type 2 cytokines (i.e., IL-4, IL-5, IL-9, and IL-13) were not significantly affected by either RSV infection or Cl2 exposure. Cl2 exposure, but not RSV infection, induced AHR to methacholine challenge as measured by flexiVent. Moreover, preexisting RSV infection amplified BALF levels of hyaluronan (HA) and AHR. The Cl2-induced AHR was mitigated by treatment with inter-α-trypsin inhibitor antibody, which inhibits HA signaling, suggesting a mechanism of HA-mediated AHR from exacerbated oxidative injury. Our results show for the first time that preexisting RSV infection predisposes the lung to Cl2-induced injury. These data emphasize the necessity for further research on the effects of Cl2 in vulnerable populations and the development of appropriate treatments.

scholarly journals The Disappearance of Respiratory Viruses in Children during the COVID-19 Pandemic

2021 ◽  
Vol 18 (18) ◽  
pp. 9550
Author(s):  
Anna Chiara Vittucci ◽  
Livia Piccioni ◽  
Luana Coltella ◽  
Claudia Ciarlitto ◽  
Livia Antilici ◽  
...  
Keyword(s):  
Respiratory Virus ◽  
Respiratory Infections ◽  
Virus Transmission ◽  
Tertiary Hospital ◽  
Virus Infections ◽  
Epidemic Period ◽  
Syncytial Virus ◽  
Viral Respiratory Infections ◽  
Respiratory Virus Infections ◽  
The Impact

Background: Social distancing measures are used to reduce the spreading of COVID-19. The aim of this study was to assess the impact of local restrictions on the transmission of respiratory virus infections. Methods: we retrospectively analyzed the nasopharyngeal samples of all patients (0–18 years old) admitted with respiratory symptoms in a large Italian tertiary hospital during the last three seasons from 2018 to 2021. Results: A strong reduction in all viral respiratory infections was observed in the last season (2020–2021) compared to the two previous seasons (−79.69% and −80.66%, respectively). In particular, we found that during the epidemic period 2018–2019 and 2019–2020, the total number of Respiratory Syncytial Virus (RSV) cases was, respectively 726 and 689, while in the last season a total of five cases was detected. In the first months of 2018–2019 and 2019–2020, the total flu infections were 240 and 354, respectively, while in the last season we did not detect any influenza virus. As other viruses, the presence of Rhinovirus declined, but to a lesser extent: a total of 488 cases were assessed compared to the 1030 and 1165 cases of the two previous respective epidemic seasons. Conclusions: Public health interventions and distancing (including continuous use of face masks) settled to counter the pandemic spread of COVID-19 had a macroscopic impact on all respiratory virus transmission and related diseases, with a partial exception of Rhinovirus. The absence of viruses’ circulation could result in a lack of immunity and increased susceptibility to serious infections in the next seasons.

scholarly journals Respiratory Virus Infections in Adults with Hematologic Malignancies: A Prospective Study

2003 ◽  
Vol 36 (1) ◽  
pp. 1-8 ◽  
Author(s):  
Rodrigo Martino ◽  
Elena Rámila ◽  
Núria Rabella ◽  
José Manuel Muñoz ◽  
Mercé Peyret ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Tract Infection ◽  
Respiratory Tract ◽  
Respiratory Tract Infection ◽  
Respiratory Virus ◽  
Hematologic Malignancies ◽  
Respiratory Viruses ◽  
Virus Infections ◽  
Syncytial Virus ◽  
Respiratory Virus Infections

Abstract During a 2-year period, 157 consecutive episodes of respiratory virus infections that occurred in 130 patients with upper or lower respiratory tract infection were analyzed for respiratory viruses. A respiratory virus was identified in 75 episodes (48%), and several viruses were found in 13 episodes: there were a total of 56 influenza A virus infections, 14 respiratory syncytial virus infections, 8 adenovirus infections, 8 infections with parainfluenza virus types 1 or 3, and 7 enterovirus infections. On multivariate analysis, the only variable that predicted progression to pneumonia in patients with an upper respiratory tract infection was the presence of respiratory syncytial virus, whereas lymphocytopenia had a nonsignificant trend. Also, among the 38 patients who had pneumonia at any time during the episode, both respiratory syncytial virus and lymphocytopenia were commonly found. For both epidemiological and therapeutic considerations, frequent screening for respiratory viruses should be incorporated into the routine diagnostic study of patients with hematologic malignancies.

scholarly journals Impact of respiratory virus infection in patients with chronic chest disease

1993 ◽  
Vol 111 (2) ◽  
pp. 337-346 ◽  
Author(s):  
M. J. Wiselka ◽  
J. Kent ◽  
J. B. Cookson ◽  
K. G. Nicholson
Keyword(s):  
Respiratory Tract ◽  
Lower Respiratory Tract ◽  
Respiratory Virus ◽  
Virus Infections ◽  
Duration Of Illness ◽  
Chest Disease ◽  
Study Team ◽  
Syncytial Virus ◽  
Viral Diagnosis ◽  
Index Cases

SummaryThis study investigated the morbidity associated with respiratory virus infections in patients with well-documented chest disease, and the risk of transmission between close contacts. Patients informed the study team if they were exposed to a family member or colleague with a cold. Patients and symptomatic index cases recorded respiratory symptoms during the study period. Acute nasopharyngeal swabs and paired sera were obtained for viral diagnosis.Twenty-five (43%) of 58 recorded exposures resulted in a symptomatic illness and 16 (28%) patients developed lower respiratory tract symptoms. Sixteen (64%) of the 25 symptomatic patients contacted their general practitioner, 14 (56%) received antibiotics and 4 (16%) were hospitalized. Mean duration of illness was 10·6 days in symptomatic patients and 5·7 days in their corresponding index cases (P < 0·005). Mean symptom scores were 100·6 in symptomatic patients and 62.2 in index cases (P < 0·01). Respiratory viruses were identified in 19 (33%) episodes. Rhinovirus, coronavirus and respiratory syncytial virus infections were all associated with lower respiratory tract exacerbations.Respiratory tract symptoms following exposure to a cold were comparatively severe in these patients with chronic chest disease. This group of patients might gain particular benefit from the introduction of effective vaccines or antiviral therapy.

scholarly journals Etiology and Clinical Characteristics of Single and Multiple Respiratory Virus Infections Diagnosed in Croatian Children in Two Respiratory Seasons

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Sunčanica Ljubin-Sternak ◽  
Tatjana Marijan ◽  
Irena Ivković-Jureković ◽  
Jasna Čepin-Bogović ◽  
Alenka Gagro ◽  
...  
Keyword(s):  
Respiratory Virus ◽  
Virus Detection ◽  
Influenza Viruses ◽  
Hospitalized Children ◽  
Virus Infections ◽  
Viral Etiology ◽  
Parainfluenza Viruses ◽  
Multiple Virus ◽  
Syncytial Virus ◽  
Respiratory Virus Infections

The aim of this study was to determine the causative agent of acute respiratory infection (ARI) in hospitalized children, as well as investigate the characteristics of ARIs with single and multiple virus detection in two respiratory seasons. In 2010 and 2015, nasopharyngeal and pharyngeal swabs from a total of 134 children, admitted to the hospital due to ARI, were tested using multiplex PCR. Viral etiology was established in 81.3% of the patients. Coinfection with two viruses was diagnosed in 27.6% of the patients, and concurrent detection of three or more viruses was diagnosed in 12.8% of the patients. The most commonly diagnosed virus in both seasons combined was respiratory syncytial virus (RSV) (28.6%), followed by parainfluenza viruses (PIVs) types 1–3 (18.4%), rhinovirus (HRV) (14.3%), human metapneumovirus (10.1%), adenovirus (AdV) (7.1%), influenza viruses types A and B (4.8%), and coronaviruses (4.2%). In 2015, additional pathogens were investigated with the following detection rate: enterovirus (13.2%), bocavirus (HBoV) (10.5%), PIV-4 (2.6%), and parechovirus (1.3%). There were no statistical differences between single and multiple virus infection regarding patients age, localization of infection, and severity of disease(P>0.05). AdV, HRV, HBoV, and PIVs were significantly more often detected in multiple virus infections compared to the other respiratory viruses(P<0.001).

scholarly journals 1182. Clinical Outcomes of Hospital-Associated Respiratory Virus Infections

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S423-S424
Author(s):  
Joshua G Petrie ◽  
Adam S Lauring ◽  
Keith S Kaye
Keyword(s):  
Respiratory Syncytial Virus ◽  
Clinical Outcomes ◽  
Influenza A ◽  
Respiratory Virus ◽  
Diagnostic Testing ◽  
Direct Result ◽  
Molecular Diagnostic ◽  
Virus Infections ◽  
Syncytial Virus ◽  
Respiratory Virus Infections

Abstract Background Influenza and respiratory syncytial virus (RSV) are recognized as important causes of hospital-acquired infection. Increased use of multiplex molecular diagnostic testing is shedding light on the incidence of other hospital-associated respiratory virus infections (HA-RVI). However, the incidence and clinical impact of HA-RVI are not well understood. Methods We identified hospitalized patients admitted between July 1, 2017 and June 30, 2018 who were clinically tested to diagnose respiratory virus infections. HA-RVI were defined as respiratory virus positivity beginning more than 48 hours after hospital admission. The clinical outcomes of HA-RVI were compared with respiratory virus infections that were not considered hospital-associated (non-HA-RVI). Results Respiratory virus testing was performed on 4,690 individuals during 5,942 inpatient encounters. At least 1 virus was identified in 1,871 (31%) encounters, and 229 (12%) were defined as HA-RVI (median hours from admission to positivity [IQR]: 154 [79, 308]). Among the patients with a respiratory virus infection, 56% were adults, 52% were male, 77% were non-Hispanic white, and the median Charlson score was 2 (IQR: 1, (4); HA-RVI patients were more likely to be male (59% vs. 51%, P = 0.01) and had higher median Charlson scores (3 vs. 2, P < 0.001). All 14 respiratory viruses in the diagnostic panel were positive for at least one HA-RVI (Figure 1), but rhino/enterovirus (99), influenza A (27), human metapneumovirus (22) and respiratory syncytial virus (20) were most common. Compared with non-HA-RVI patients, those with HA-RVI had longer post-infection lengths of stay (median: 9 vs. 4 days, P < 0.001) and were more likely to die during hospitalization (odds ratio [95% confidence interval]: 3.4 [2.0, 5.7]) (Table 1). Conclusion A substantial number of HA-RVI were identified during the 2017–2018 respiratory virus season, and they were associated with a striking number of severe outcomes. More in depth analyses are required to determine whether severe outcomes are a direct result of HA-RVI or whether HA-RVI are more common in critically ill patients and serve as a marker for severe morbidity. A broader understanding of HA-RVI transmission and prevention strategies is needed. Disclosures All authors: No reported disclosures.

scholarly journals Are Respiratory Viruses Involved in Preseasonal Symptoms or Severity in Japanese Cedar Pollinosis?

2016 ◽  
Vol 7 (2) ◽  
pp. ar.2016.7.0157 ◽  
Author(s):  
Hirokuni Otsuka ◽  
Hiroyuki Tsukagoshi ◽  
Hirokazu Kimura ◽  
Ikuo Takanashi ◽  
Kimihiro Okubo
Keyword(s):  
Respiratory Virus ◽  
Viral Infections ◽  
Japanese Cedar ◽  
Respiratory Viruses ◽  
Virus Infections ◽  
Significant Difference ◽  
Syncytial Virus ◽  
Japanese Cedar Pollinosis ◽  
Respiratory Virus Infections ◽  
The Relationship

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.

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