scholarly journals Sex differences in innate anti-viral immune responses to respiratory viruses and in their clinical outcomes in a birth cohort study

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Eteri Regis ◽  
Sara Fontanella ◽  
Lijing Lin ◽  
Rebecca Howard ◽  
Sadia Haider ◽  
...  
Keyword(s):  
Sex Differences ◽  
Immune Responses ◽  
Birth Cohort ◽  
Respiratory Virus ◽  
Respiratory Infections ◽  
Respiratory Viruses ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
Virus Infections ◽  
Respiratory Virus Infections

AbstractThe mechanisms explaining excess morbidity and mortality in respiratory infections among males are poorly understood. Innate immune responses are critical in protection against respiratory virus infections. We hypothesised that innate immune responses to respiratory viruses may be deficient in males. We stimulated peripheral blood mononuclear cells from 345 participants at age 16 years in a population-based birth cohort with three live respiratory viruses (rhinoviruses A16 and A1, and respiratory syncytial virus) and two viral mimics (R848 and CpG-A, to mimic responses to SARS-CoV-2) and investigated sex differences in interferon (IFN) responses. IFN-α responses to all viruses and stimuli were 1.34–2.06-fold lower in males than females (P = 0.018 −  < 0.001). IFN-β, IFN-γ and IFN-induced chemokines were also deficient in males across all stimuli/viruses. Healthcare records revealed 12.1% of males and 6.6% of females were hospitalized with respiratory infections in infancy (P = 0.017). In conclusion, impaired innate anti-viral immunity in males likely results in high male morbidity and mortality from respiratory virus infections.

scholarly journals COVID-19 mitigation strategies were associated with decreases in other respiratory virus infections

2021 ◽  
Author(s):  
Sinha Pranay ◽  
Katherine Reifler ◽  
Michael Rossi ◽  
Manish Sagar
Keyword(s):  
Respiratory Virus ◽  
Respiratory Infections ◽  
Respiratory Viruses ◽  
Mitigation Strategies ◽  
Virus Infections ◽  
Time Period ◽  
Viral Respiratory Infections ◽  
Respiratory Virus Infections ◽  
Viral Respiratory

Abstract Detection of diverse respiratory viruses in Boston was around 80% lower after practices were instituted to limit COVID-19 spread compared to the same time period during the previous five years. Continuing the strategies that lower COVID-19 dissemination may be useful in decreasing the incidence of other viral respiratory infections.

scholarly journals Sex differences in innate anti-viral immune responses to respiratory viruses

2020 ◽  
Author(s):  
Eteri Regis ◽  
Sara Fontanella ◽  
Lijing Lin ◽  
Rebecca Howard ◽  
Sadia Haider ◽  
...  
Keyword(s):  
Sex Differences ◽  
Immune Responses ◽  
Mononuclear Cells ◽  
Respiratory Viruses ◽  
Innate Immune ◽  
Morbidity And Mortality ◽  
High Morbidity ◽  
Innate Immune Responses ◽  
Peripheral Blood Mononuclear ◽  
Syncytial Virus

Males have excess morbidity and mortality from respiratory viral infections and especially so in COVID-19. The mechanisms explaining this excess in disease burden in males are unknown. Innate immune responses are likely critical in protection against a novel virus like SARS-CoV-2. We hypothesised that innate immune responses may be deficient in males relative to females. To test this we stimulated peripheral blood mononuclear cells (PBMCs) from participants in a population-based birth cohort with three respiratory viruses (rhinoviruses-RV-A16 and RV-A1, and respiratory syncytial virus-RSV) and two viral mimics (R848 and CpG-A, to mimic responses to SARS-CoV-2). We measured interferon (IFN) and IFN-induced chemokine responses and investigated sex differences in virus-induced responses. IFN-α, IFN-β and IFN-γ responses to RV-A16 were deficient in males compared to females, fold-inductions being 1.92-fold (P<0.001), 2.04-fold (P<0.001) and 1.77-fold (P=0.003) lower in males than females, respectively. Similar significant deficiencies in innate immune responses were observed in males for eleven other cytokine-stimulus pairs. Responses in males were greater than those in females in only one of 35 cytokine-stimulus pairs investigated. Review of healthcare records revealed that 12.1% of males but only 6.6% of females were admitted to hospital with respiratory infections in the first year of life (P=0.017). Impaired innate anti-viral immunity in males likely results in high morbidity and mortality from respiratory viruses including COVID-19. Males may preferentially benefit from therapies that boost innate anti-viral immune responses.

scholarly journals Novel Functions of IFI44L as a Feedback Regulator of Host Antiviral Responses

2019 ◽  
Vol 93 (21) ◽  
Author(s):  
Marta L. DeDiego ◽  
Luis Martinez-Sobrido ◽  
David J. Topham
Keyword(s):  
Immune Responses ◽  
Nuclear Factor Kappa B ◽  
Virus Production ◽  
Innate Immune ◽  
Type I ◽  
Nuclear Factor ◽  
Innate Immune Responses ◽  
Virus Infections ◽  
Nuclear Factor Kappa ◽  
Ifn Treatment

ABSTRACT We describe a novel function for the interferon (IFN)-induced protein 44-like (IFI44L) gene in negatively modulating innate immune responses induced after virus infections. Furthermore, we show that decreasing IFI44L expression impairs virus production and that IFI44L expression negatively modulates the antiviral state induced by an analog of double-stranded RNA (dsRNA) or by IFN treatment. The mechanism likely involves the interaction of IFI44L with cellular FK506-binding protein 5 (FKBP5), which in turn interacts with kinases essential for type I and III IFN responses, such as inhibitor of nuclear factor kappa B (IκB) kinase alpha (IKKα), IKKβ, and IKKε. Consequently, binding of IFI44L to FKBP5 decreased interferon regulatory factor 3 (IRF-3)-mediated and nuclear factor kappa-B (NF-κB) inhibitor (IκBα)-mediated phosphorylation by IKKε and IKKβ, respectively. According to these results, IFI44L is a good target for treatment of diseases associated with excessive IFN levels and/or proinflammatory responses and for reduction of viral replication. IMPORTANCE Excessive innate immune responses can be deleterious for the host, and therefore, negative feedback is needed. Here, we describe a completely novel function for IFI44L in negatively modulating innate immune responses induced after virus infections. In addition, we show that decreasing IFI44L expression impairs virus production and that IFI44L expression negatively modulates the antiviral state induced by an analog of dsRNA or by IFN treatment. IFI44L binds to the cellular protein FKBP5, which in turn interacts with kinases essential for type I and III IFN induction and signaling, such as the kinases IKKα, IKKβ, and IKKε. IFI44L binding to FKBP5 decreased the phosphorylation of IRF-3 and IκBα mediated by IKKε and IKKβ, respectively, providing an explanation for the function of IFI44L in negatively modulating IFN responses. Therefore, IFI44L is a candidate target for reducing virus replication.

scholarly journals Altered Innate Immune Responses in Neutrophils from Patients with Well- and Suboptimally Controlled Asthma

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Francesca S. M. Tang ◽  
Gloria J. Foxley ◽  
Peter G. Gibson ◽  
Janette K. Burgess ◽  
Katherine J. Baines ◽  
...  
Keyword(s):  
Immune Responses ◽  
Respiratory Infections ◽  
Symptom Control ◽  
Innate Immune ◽  
Airflow Limitation ◽  
Poly I:C ◽  
Innate Immune Responses ◽  
Asthma Exacerbations ◽  
Blood Neutrophils ◽  
Refractory Asthma

Background. Respiratory infections are a major cause of asthma exacerbations where neutrophilic inflammation dominates and is associated with steroid refractory asthma. Structural airway cells in asthma differ from nonasthmatics; however it is unknown if neutrophils differ. We investigated neutrophil immune responses in patients who have good (AGood) and suboptimal (ASubopt) asthma symptom control.Methods. Peripheral blood neutrophils fromAGood(ACQ < 0.75,n=11),ASubopt(ACQ > 0.75,n=7), and healthy controls (HC) (n=9) were stimulated with bacterial (LPS (1 μg/mL), fMLF (100 nM)), and viral (imiquimod (3 μg/mL), R848 (1.5 μg/mL), and poly I:C (10 μg/mL)) surrogates or live rhinovirus (RV) 16 (MOI1). Cell-free supernatant was collected after 1 h for neutrophil elastase (NE) and matrix metalloproteinase- (MMP-) 9 measurements or after 24 h for CXCL8 release.Results. Constitutive NE was enhanced inAGoodneutrophils compared to HC. fMLF stimulated neutrophils fromASuboptbut notAGoodproduced 50% of HC levels. fMLF induced MMP-9 was impaired inASuboptandAGoodcompared to HC. fMLF stimulated CXCL8 but not MMP-9 was positively correlated with FEV1and FEV1/FVC.ASuboptandAGoodresponded similarly to other stimuli.Conclusions. Circulating neutrophils are different in asthma; however, this is likely to be related to airflow limitation rather than asthma control.

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 Toll-Like Receptor 4-Mediated Activation of p38 Mitogen-Activated Protein Kinase Is a Determinant of Respiratory Virus Entry and Tropism

2010 ◽  
Vol 84 (21) ◽  
pp. 11359-11373 ◽  
Author(s):  
David Marchant ◽  
Gurpreet K. Singhera ◽  
Soraya Utokaparch ◽  
Tillie L. Hackett ◽  
John H. Boyd ◽  
...  
Keyword(s):  
Influenza Virus ◽  
P38 Mapk ◽  
Respiratory Virus ◽  
Respiratory Viruses ◽  
Mitogen Activated Protein Kinase ◽  
Toll Like Receptor ◽  
Virus Infections ◽  
Toll Like Receptor 4 ◽  
Mitogen Activated Protein ◽  
Respiratory Virus Infections

ABSTRACT Respiratory viruses exert a heavy toll of morbidity and mortality worldwide. Despite this burden there are few specific treatments available for respiratory virus infections. Since many viruses utilize host cell enzymatic machinery such as protein kinases for replication, we determined whether pharmacological inhibition of kinases could, in principle, be used as a broad antiviral strategy for common human respiratory virus infections. A panel of green fluorescent protein (GFP)-expressing recombinant respiratory viruses, including an isolate of H1N1 influenza virus (H1N1/Weiss/43), was used to represent a broad range of virus families responsible for common respiratory infections (Adenoviridae, Paramyxoviridae, Picornaviridae, and Orthomyxoviridae). Kinase inhibitors were screened in a high-throughput assay that detected virus infection in human airway epithelial cells (1HAEo-) using a fluorescent plate reader. Inhibition of p38 mitogen-activated protein kinase (MAPK) signaling was able to significantly inhibit replication by all viruses tested. Therefore, the pathways involved in virus-mediated p38 and extracellular signal-regulated kinase (ERK) MAPK activation were investigated using bronchial epithelial cells and primary fibroblasts derived from MyD88 knockout mouse lungs. Influenza virus, which activated p38 MAPK to approximately 10-fold-greater levels than did respiratory syncytial virus (RSV) in 1HAEo- cells, was internalized about 8-fold faster and more completely than RSV. We show for the first time that p38 MAPK is a determinant of virus infection that is dependent upon MyD88 expression and Toll-like receptor 4 (TLR4) ligation. Imaging of virus-TLR4 interactions showed significant clustering of TLR4 at the site of virus-cell interaction, triggering phosphorylation of downstream targets of p38 MAPK, suggesting the need for a signaling receptor to activate virus internalization.

scholarly journals Innate immune responses elicited by Sin Nombre virus or type I IFN agonists protect hamsters from lethal Andes virus infections

2018 ◽  
Vol 99 (10) ◽  
pp. 1359-1366 ◽  
Author(s):  
Rebecca L. Brocato ◽  
Victoria Wahl ◽  
Christopher D. Hammerbeck ◽  
Matthew D. Josleyn ◽  
Anita K. McElroy ◽  
...  
Keyword(s):  
Immune Responses ◽  
Innate Immune ◽  
Sin Nombre Virus ◽  
Type I ◽  
Type I Ifn ◽  
Innate Immune Responses ◽  
Virus Infections ◽  
Andes Virus

scholarly journals Conversion of Adenines to Inosines in RNA During Virus Infections Activates Innate Immune Responses

2010 ◽  
Vol 24 (S1) ◽  
Author(s):  
Jie‐Ying Liao ◽  
Chrissy Prater ◽  
Sheetal Thakur ◽  
Farhad Imani
Keyword(s):  
Immune Responses ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
Virus Infections

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.

Reduction in Rate of Nosocomial Respiratory Virus Infections in a Children’s Hospital Associated With Enhanced Isolation Precautions

2018 ◽  
Vol 39 (2) ◽  
pp. 152-156 ◽  
Author(s):  
Lorry G. Rubin ◽  
Nina Kohn ◽  
Susan Nullet ◽  
Margaret Hill
Keyword(s):  
Respiratory Virus ◽  
Viral Infections ◽  
Respiratory Infections ◽  
Medical Center ◽  
Tertiary Care ◽  
Virus Infections ◽  
Children's Hospital ◽  
Children’S Hospital ◽  
Respiratory Virus Infections ◽  
Hospital Days

OBJECTIVETo determine whether the use of enhanced isolation precautions (droplet and contact precautions) for inpatients with respiratory tract viral infections is associated with a reduction in rate of nosocomial viral respiratory infections.DESIGNQuasi-experimental study with the rate of nosocomial respiratory virus infection as the primary dependent variable and rate of nosocomialClostridium difficileinfection as a nonequivalent dependent variable comparator.SETTINGCohen Children’s Medical Center of NY, a tertiary-care children’s hospital attached to a large general hospital.INTERVENTIONDuring years 1 and 2 (July 2012 through June 2014), the Centers for Disease Control and Prevention/Healthcare Infection Control Practices Advisory Committee’s recommended isolation precautions for inpatients with selected respiratory virus infections were in effect. Enhanced isolation precautions were in effect during years 3 and 4 (July, 2014 through June, 2016), except for influenza, for which enhanced precautions were in effect during year 4 only.RESULTSDuring the period of enhanced isolation precautions, the rate of nosocomial respiratory virus infections with any of 4 virus categories decreased 39% from 0.827 per 1,000 hospital days prior to enhanced precautions to 0.508 per 1,000 hospital days (P<.0013). Excluding rhinovirus/enterovirus infections, the rates decreased 58% from 0.317 per 1,000 hospital days to 0.134 per 1,000 hospital days during enhanced precautions (P<.0014). During these periods, no significant change was detected in the rate of nosocomialC. difficileinfection.CONCLUSIONSEnhanced isolation precautions for inpatients with respiratory virus infections were associated with a reduction in the rate of nosocomial respiratory virus infections.Infect Control Hosp Epidemiol2018;39:152–156

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