scholarly journals Attenuation of Influenza A Virus Disease Severity by Viral Coinfection in a Mouse Model

2018 ◽  
Vol 92 (23) ◽  
Author(s):  
Andres J. Gonzalez ◽  
Emmanuel C. Ijezie ◽  
Onesmo B. Balemba ◽  
Tanya A. Miura
Keyword(s):  
Mouse Model ◽  
Respiratory Tract ◽  
Disease Severity ◽  
Influenza A Virus ◽  
Influenza A ◽  
Viral Infections ◽  
Respiratory Viruses ◽  
Viral Pathogen ◽  
Viral Coinfection ◽  
Murine Coronavirus

ABSTRACTInfluenza viruses and rhinoviruses are responsible for a large number of acute respiratory viral infections in human populations and are detected as copathogens within hosts. Clinical and epidemiological studies suggest that coinfection by rhinovirus and influenza virus may reduce disease severity and that they may also interfere with each other’s spread within a host population. To determine how coinfection by these two unrelated respiratory viruses affects pathogenesis, we established a mouse model using a minor serogroup rhinovirus (rhinovirus strain 1B [RV1B]) and mouse-adapted influenza A virus (A/Puerto Rico/8/1934 [PR8]). Infection of mice with RV1B 2 days before PR8 reduced the severity of infection by a low or medium, but not high, dose of PR8. Disease attenuation was associated with an early inflammatory response in the lungs and enhanced clearance of PR8. However, coinfection by RV1B did not reduce PR8 viral loads early in infection or inhibit replication of PR8 within respiratory epithelia orin vitro. Inflammation in coinfected mice remained focal compared to diffuse inflammation and damage in the lungs of mice infected by PR8. The timing of RV1B coinfection was a critical determinant of protection, suggesting that sufficient time is needed to induce this response. Finally, disease attenuation was not unique to RV1B: dose-dependent coinfection by a murine coronavirus (mouse hepatitis virus strain 1 [MHV-1]) also reduced the severity of PR8 infection. Unlike RV1B, coinfection with MHV-1 reduced early PR8 replication, which was associated with upregulation of beta interferon (IFN-β) expression. This model is critical for understanding the mechanisms responsible for influenza disease attenuation during coinfection by unrelated respiratory viruses.IMPORTANCEViral infections in the respiratory tract can cause severe disease and are responsible for a majority of pediatric hospitalizations. Molecular diagnostics have revealed that approximately 20% of these patients are infected by more than one unrelated viral pathogen. To understand how viral coinfection affects disease severity, we inoculated mice with a mild viral pathogen (rhinovirus or murine coronavirus), followed 2 days later by a virulent viral pathogen (influenza A virus). This model demonstrated that rhinovirus can reduce the severity of influenza A virus, which corresponded with an early but controlled inflammatory response in the lungs and early clearance of influenza A virus. We further determined the dose and timing parameters that were important for effective disease attenuation and showed that influenza disease is also reduced by coinfection with a murine coronavirus. These findings demonstrate that coinfecting viruses can alter immune responses and pathogenesis in the respiratory tract.

scholarly journals Attenuation of influenza A virus disease severity by viral co-infection in a mouse model

2018 ◽  
Author(s):  
Andres J. Gonzalez ◽  
Emmanuel C. Ijezie ◽  
Onesmo B. Balemba ◽  
Tanya A. Miura
Keyword(s):  
Mouse Model ◽  
Disease Severity ◽  
Influenza A Virus ◽  
Influenza A ◽  
Virus Disease ◽  
Respiratory Viruses ◽  
Influenza Viruses ◽  
Human Populations ◽  
Critical Determinant

AbstractInfluenza viruses and rhinoviruses are responsible for a large number of acute respiratory viral infections in human populations and are detected as co-pathogens within hosts. Clinical and epidemiological studies suggest that co-infection by rhinovirus and influenza virus may reduce disease severity and that they may also interfere with each other’s spread within a host population. To determine how co-infection by these two unrelated respiratory viruses affects pathogenesis, we established a mouse model using a minor serogroup rhinovirus (RV1B) and mouse-adapted influenza A virus (PR8). Infection of mice with RV1B two days before PR8 reduced pathogenesis of mild to moderate, but not severe PR8 infections. Disease attenuation was associated with an early inflammatory response in the lungs and enhanced clearance of PR8. However, co-infection by RV1B did not reduce PR8 viral loads early in infection or inhibit replication of PR8 within respiratory epithelia orin vitro. Inflammation in co-infected mice remained focal, in comparison to diffuse inflammation and damage in the lungs of mice infected by PR8. These findings suggest that RV1B stimulates an early immune response that clears PR8 while limiting excessive pulmonary inflammation. The timing of RV1B co-infection was a critical determinant of protection, suggesting that sufficient time is needed to induce this response. Finally, disease attenuation was not unique to RV1B: co-infection by a murine coronavirus two days before PR8 also reduced disease severity. This model will be critical for understanding the mechanisms responsible for attenuation of influenza disease during co-infection by unrelated respiratory viruses.

scholarly journals Active Surveillance of Influenza A and Other Respiratory Viruses in Children with Influenza-like-illness in Two Seasons

2018 ◽  
Vol 11 (12) ◽  
pp. 944-949
Author(s):  
Saniye Girit ◽  
Ayşe Karaaslan ◽  
Serap Gençer ◽  
Emel Yılmaz ◽  
Yetkin Ayhan ◽  
...  
Keyword(s):  
Risk Factors ◽  
Influenza A Virus ◽  
Influenza A ◽  
Respiratory Viruses ◽  
Influenza B ◽  
Human Bocavirus ◽  
Hospitalized Children ◽  
Viral Pathogen ◽  
Influenza Like Illness ◽  
Chronic Lung Diseases

Introduction: The aim of this study was to asses the surveillance of influenza A/other respiratory viruses and risk factors in hospitalized children with the symptoms of influenza-like illness during two consecutive influenza seasons. Methodology: All children hospitalized with adiagnosis of influenza-like illness had been investigated for Influenza A and other respiratory antigens in pharengeal/nasopharyngeal secretions. Results: A total of 132 hospitalized children between December 2013-May 2014 and December 2014-May 2015 were enrolled in this study. At least one respiratory virus was found to be positive by RT-PCR in 78 (59%) patients, influenza A (H3N2) was detected in only 8 (6%) patients. In 54 (41%) patients samples no respiratory viral pathogen was detected and in 70 (53%) patients, one non- influenza A virus was detected. The respiratory viral pathogens detected in decreasing rates were:RSV (n = 46, 35%), HCoV (n = 10, 7.5%), adenovirüs (n = 7, 5%), rhinovirüs (n = 6, 4.5%), HMPV (n = 5, 4%), Influenza B (n = 4, 3%) ve human Bocavirus (n = 2, 1.5%). In 10 patients, coinfection was detected, however none was with H3N2. In the H3N2 (+) group, the following risk factors were identified: age older than three years (p < 0.05), asthma history (p < 0.05) and chronic lung diseases (p < 0.05). Conclusion: Influenza A virus was detected in 6% of hospitalized patients with influenza-like illness. Viruses other then Influenza, especially RSV, can cause similar symptoms compatible with Influenza-like-illness.

scholarly journals Complement Decay-Accelerating Factor is a modulator of influenza A virus lung immunopathology

2021 ◽  
Author(s):  
Nuno Brito Santos ◽  
Zoé Enderlin Vaz da Silva ◽  
Catarina Gomes ◽  
Celso A. Reis ◽  
Maria João Amorim
Keyword(s):  
Disease Severity ◽  
Influenza A Virus ◽  
Immune Cells ◽  
Complement Activation ◽  
Influenza A ◽  
Viral Infections ◽  
Decay Accelerating Factor ◽  
Viral Loads ◽  
Adaptive Immune ◽  
The Impact

AbstractClearance of viral infections, such as SARS-CoV-2 and influenza A virus (IAV), must be fine-tuned to eliminate the pathogen without causing immunopathology. As such, an aggressive initial innate immune response favors the host in contrast to a detrimental prolonged inflammation. The complement pathway bridges innate and adaptive immune system and contributes to the response by directly clearing pathogens or infected cells, as well as recruiting proinflammatory immune cells and regulating inflammation. However, the impact of modulating complement activation in viral infections is still unclear. In this work, we targeted the complement decay-accelerating factor (DAF/CD55), a surface protein that protects cells from non-specific complement attack, and analyzed its role in IAV infections. We found that DAF modulates IAV infection in vivo, via an interplay with the antigenic viral proteins hemagglutinin (HA) and neuraminidase (NA), in a strain specific manner. Our results reveal that, contrary to what could be expected, DAF potentiates complement activation, increasing the recruitment of neutrophils, monocytes and T cells. We also show that viral NA acts on the heavily sialylated DAF and propose that it exacerbates complement activation, leading to lung immunopathology. Remarkably, this mechanism has no impact on viral loads but rather on the host resilience to infection and may have direct implications in zoonotic influenza transmissions.Author summaryExacerbated complement activation and immune deregulation are at the basis of several pathologies induced by respiratory viruses. Here, we report that complement decay-accelerating factor (DAF), which inhibits complement activation in healthy cells, increases disease severity upon Influenza A virus (IAV) infection. Remarkably, DAF interaction with IAV proteins, hemagglutinin (HA) and neuraminidase (NA), resulted in excessive complement activation and recruitment of innate and adaptive immune cells, without affecting viral loads. Furthermore, we observed that viral NA directly cleaves DAF and promotes complement activation, providing a possible link between IAV-DAF interaction and pathology. Therefore, our results unveil a novel pathway that could modulate disease severity, which may help to understand the increased pathogenicity of zoonotic and pandemic IAV infections.

scholarly journals Pattern of Respiratory Viruses among Pilgrims during 2019 Hajj Season Who Sought Healthcare Due to Severe Respiratory Symptoms

Pathogens ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 315
Author(s):  
Salma M. Alsayed ◽  
Thamir A. Alandijany ◽  
Sherif A. El-Kafrawy ◽  
Ahmed M. Hassan ◽  
Leena H. Bajrai ◽  
...  
Keyword(s):  
Respiratory Tract ◽  
Influenza A ◽  
Viral Infections ◽  
Single Case ◽  
Respiratory Viruses ◽  
Influenza B ◽  
Healthcare Facilities ◽  
Influenza A H1n1 ◽  
Hajj Season ◽  
Tract Infections

The aim of our study was to define the spectrum of viral infections in pilgrims with acute respiratory tract illnesses presenting to healthcare facilities around the holy places in Makkah, Saudi Arabia during the 2019 Hajj pilgrimage. During the five days of Hajj, a total of 185 pilgrims were enrolled in the study. Nasopharyngeal swabs (NPSs) of 126/185 patients (68.11%) tested positive for one or more respiratory viruses by PCR. Among the 126 pilgrims whose NPS were PCR positive: (a) there were 93/126 (74%) with a single virus infection, (b) 33/126 (26%) with coinfection with more than one virus (up to four viruses): of these, 25/33 cases had coinfection with two viruses; 6/33 were infected with three viruses, while the remaining 2/33 patients had infection with four viruses. Human rhinovirus (HRV) was the most common detected viruses with 53 cases (42.06%), followed by 27 (21.43%) cases of influenza A (H1N1), and 23 (18.25%) cases of influenza A other than H1N1. Twenty-five cases of CoV-229E (19.84%) were detected more than other coronavirus members (5 CoV-OC43 (3.97%), 4 CoV-HKU1 (3.17%), and 1 CoV-NL63 (0.79%)). PIV-3 was detected in 8 cases (6.35%). A single case (0.79%) of PIV-1 and PIV-4 were found. HMPV represented 5 (3.97%), RSV and influenza B 4 (3.17%) for each, and Parechovirus 1 (0.79%). Enterovirus, Bocavirus, and M. pneumoniae were not detected. Whether identification of viral nucleic acid represents nasopharyngeal carriage or specific causal etiology of RTI remains to be defined. Large controlled cohort studies (pre-Hajj, during Hajj, and post-Hajj) are required to define the carriage rates and the specific etiology and causal roles of specific individual viruses or combination of viruses in the pathogenesis of respiratory tract infections in pilgrims participating in the annual Hajj. Studies of the specific microbial etiology of respiratory track infections (RTIs) at mass gathering religious events remain a priority, especially in light of the novel SARS-CoV-2 pandemic.

scholarly journals Thapsigargin Is a Broad-Spectrum Inhibitor of Major Human Respiratory Viruses: Coronavirus, Respiratory Syncytial Virus and Influenza A Virus

Viruses ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 234
Author(s):  
Sarah Al-Beltagi ◽  
Cristian Alexandru Preda ◽  
Leah V. Goulding ◽  
Joe James ◽  
Juan Pu ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Respiratory Syncytial Virus ◽  
Influenza A Virus ◽  
Broad Spectrum ◽  
Influenza A ◽  
Respiratory Viruses ◽  
Influenza Viruses ◽  
Virus Challenge ◽  
2009 H1n1 ◽  
Syncytial Virus

The long-term control strategy of SARS-CoV-2 and other major respiratory viruses needs to include antivirals to treat acute infections, in addition to the judicious use of effective vaccines. Whilst COVID-19 vaccines are being rolled out for mass vaccination, the modest number of antivirals in use or development for any disease bears testament to the challenges of antiviral development. We recently showed that non-cytotoxic levels of thapsigargin (TG), an inhibitor of the sarcoplasmic/endoplasmic reticulum (ER) Ca2+ ATPase pump, induces a potent host innate immune antiviral response that blocks influenza A virus replication. Here we show that TG is also highly effective in blocking the replication of respiratory syncytial virus (RSV), common cold coronavirus OC43, SARS-CoV-2 and influenza A virus in immortalized or primary human cells. TG’s antiviral performance was significantly better than remdesivir and ribavirin in their respective inhibition of OC43 and RSV. Notably, TG was just as inhibitory to coronaviruses (OC43 and SARS-CoV-2) and influenza viruses (USSR H1N1 and pdm 2009 H1N1) in separate infections as in co-infections. Post-infection oral gavage of acid-stable TG protected mice against a lethal influenza virus challenge. Together with its ability to inhibit the different viruses before or during active infection, and with an antiviral duration of at least 48 h post-TG exposure, we propose that TG (or its derivatives) is a promising broad-spectrum inhibitor against SARS-CoV-2, OC43, RSV and influenza virus.

scholarly journals The Role of the Respiratory Microbiome and Viral Presence in Lower Respiratory Tract Infection Severity in the First Five Years of Life

2021 ◽  
Vol 9 (7) ◽  
pp. 1446
Author(s):  
Ivo Hoefnagels ◽  
Josephine van de Maat ◽  
Jeroen J.A. van Kampen ◽  
Annemarie van Rossum ◽  
Charlie Obihara ◽  
...  
Keyword(s):  
Respiratory Tract ◽  
Disease Severity ◽  
Lower Respiratory Tract ◽  
Influenza A ◽  
Pediatric Population ◽  
16S Rrna Gene Sequencing ◽  
Rrna Gene ◽  
Detection Rates ◽  
Tract Infections ◽  
Respiratory Microbiome

Lower respiratory tract infections (LRTIs) in children are common and, although often mild, a major cause of mortality and hospitalization. Recently, the respiratory microbiome has been associated with both susceptibility and severity of LRTI. In this current study, we combined respiratory microbiome, viral, and clinical data to find associations with the severity of LRTI. Nasopharyngeal aspirates of children aged one month to five years included in the STRAP study (Study to Reduce Antibiotic prescription in childhood Pneumonia), who presented at the emergency department (ED) with fever and cough or dyspnea, were sequenced with nanopore 16S-rRNA gene sequencing and subsequently analyzed with hierarchical clustering to identify respiratory microbiome profiles. Samples were also tested using a panel of 15 respiratory viruses and Mycoplasma pneumoniae, which were analyzed in two groups, according to their reported virulence. The primary outcome was hospitalization, as measure of disease severity. Nasopharyngeal samples were isolated from a total of 167 children. After quality filtering, microbiome results were available for 54 children and virology panels for 158 children. Six distinct genus-dominant microbiome profiles were identified, with Haemophilus-, Moraxella-, and Streptococcus-dominant profiles being the most prevalent. However, these profiles were not found to be significantly associated with hospitalization. At least one virus was detected in 139 (88%) children, of whom 32.4% had co-infections with multiple viruses. Viral co-infections were common for adenovirus, bocavirus, and enterovirus, and uncommon for human metapneumovirus (hMPV) and influenza A virus. The detection of enteroviruses was negatively associated with hospitalization. Virulence groups were not significantly associated with hospitalization. Our data underlines high detection rates and co-infection of viruses in children with respiratory symptoms and confirms the predominant presence of Haemophilus-, Streptococcus-, and Moraxella-dominant profiles in a symptomatic pediatric population at the ED. However, we could not assess significant associations between microbiome profiles and disease severity measures.

scholarly journals Increased Dietary Salt Intake Does Not Influence Influenza A Virus–Induced Disease Severity in Mice

2015 ◽  
Vol 28 (9) ◽  
pp. 532-537 ◽  
Author(s):  
Samuel Amoah ◽  
Weiping Cao ◽  
Priya Ranjan ◽  
Patricia Greer ◽  
Wun-Ju Shieh ◽  
...  
Keyword(s):  
Disease Severity ◽  
Influenza A Virus ◽  
Influenza A ◽  
Salt Intake ◽  
Dietary Salt ◽  
Dietary Salt Intake

scholarly journals Exogenous Activation of Invariant Natural Killer T Cells by α-Galactosylceramide Reduces Pneumococcal Outgrowth and Dissemination Postinfluenza

mBio ◽  
2016 ◽  
Vol 7 (6) ◽  
Author(s):  
Adeline Barthelemy ◽  
Stoyan Ivanov ◽  
Maya Hassane ◽  
Josette Fontaine ◽  
Béatrice Heurtault ◽  
...  
Keyword(s):  
Mouse Model ◽  
Influenza A Virus ◽  
Bacterial Pneumonia ◽  
Influenza A ◽  
Bacterial Infections ◽  
Pneumococcal Infection ◽  
Clinical Development ◽  
Inkt Cell ◽  
Inkt Cells ◽  
Invariant Natural Killer

ABSTRACT Influenza A virus infection can predispose to potentially devastating secondary bacterial infections. Invariant natural killer T (iNKT) cells are unconventional, lipid-reactive T lymphocytes that exert potent immunostimulatory functions. Using a mouse model of postinfluenza invasive secondary pneumococcal infection, we sought to establish whether α-galactosylceramide (α-GalCer [a potent iNKT cell agonist that is currently in clinical development]) could limit bacterial superinfection. Our results highlighted the presence of a critical time window during which α-GalCer treatment can trigger iNKT cell activation and influence resistance to postinfluenza secondary pneumococcal infection. Intranasal treatment with α-GalCer during the acute phase (on day 7) of influenza virus H3N2 and H1N1 infection failed to activate (gamma interferon [IFN-γ] and interleukin-17A [IL-17A]) iNKT cells; this effect was associated with a strongly reduced number of conventional CD103 + dendritic cells in the respiratory tract. In contrast, α-GalCer treatment during the early phase (on day 4) or during the resolution phase (day 14) of influenza was associated with lower pneumococcal outgrowth and dissemination. Less intense viral-bacterial pneumonia and a lower morbidity rate were observed in superinfected mice treated with both α-GalCer (day 14) and the corticosteroid dexamethasone. Our results open the way to alternative (nonantiviral/nonantibiotic) iNKT-cell-based approaches for limiting postinfluenza secondary bacterial infections. IMPORTANCE Despite the application of vaccination programs and antiviral drugs, influenza A virus (IAV) infection is responsible for widespread morbidity and mortality (500,000 deaths/year). Influenza infections can also result in sporadic pandemics that can be devastating: the 1918 pandemic led to the death of 50 million people. Severe bacterial infections are commonly associated with influenza and are significant contributors to the excess morbidity and mortality of influenza. Today’s treatments of secondary bacterial (pneumococcal) infections are still not effective enough, and antibiotic resistance is a major issue. Hence, there is an urgent need for novel therapies. In the present study, we set out to evaluate the efficacy of α-galactosylceramide (α-GalCer)—a potent agonist of invariant NKT cells that is currently in clinical development—in a mouse model of postinfluenza, highly invasive pneumococcal pneumonia. Our data indicate that treatment with α-GalCer reduces susceptibility to superinfections and, when combined with the corticosteroid dexamethasone, reduces viral-bacterial pneumonia.

Colorimetric detection of influenza A virus using antibody-functionalized gold nanoparticles

The Analyst ◽  
2015 ◽  
Vol 140 (12) ◽  
pp. 3989-3995 ◽  
Author(s):  
Yuanjian Liu ◽  
Linqun Zhang ◽  
Wei Wei ◽  
Hongyu Zhao ◽  
Zhenxian Zhou ◽  
...  
Keyword(s):  
Gold Nanoparticles ◽  
Influenza A Virus ◽  
Clinical Diagnosis ◽  
Specific Antibody ◽  
Influenza A ◽  
Colorimetric Detection ◽  
Viral Pathogen ◽  
Virus Surface ◽  
Functionalized Gold Nanoparticles

A colorimetric immunosensor for IAV based on AuNPs modified with mAb is developed. This assay depends on an ordered AuNPs structure covering the virus surface and can be applied to any viral pathogen by incorporating the appropriate pathogen-specific antibody, giving the proposed method a broad prospect in clinical diagnosis applications.

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