Mouse Models of Viral Infection: Influenza Infection in the Lung

2009 ◽  
pp. 299-318 ◽  
Author(s):  
Adele M. Mount ◽  
Gabrielle T. Belz
Keyword(s):  
Viral Infection ◽  
Mouse Models ◽  
Influenza Infection

scholarly journals Comparison of Type I Interferon Expression in Adult and Neonatal Mice during Respiratory Viral Infection

10.29007/ltkw ◽  
2019 ◽  
Author(s):  
Zifeng Liang
Keyword(s):  
Immune Response ◽  
Viral Infection ◽  
Mouse Models ◽  
Post Infection ◽  
Type I Interferon ◽  
Sendai Virus ◽  
Killer Cell ◽  
Type I ◽  
Respiratory Viral Infection ◽  
Neonatal Mice

The aim of this paper is to identify the difference of type I interferon expression in 2- day neonatal and six-to-eight-weeks adult mice infected by Sendai virus (SeV), a single- stranded RNA virus of the family Paramyxoviridae. Sendai virus mimics the influence of respiratory syncytial virus (RSV) on humans, but does not infect humans. Although RSV has a fatal impact on people across age groups, little is understood about this common virus and the disparity between neonatal and adult immune response to it. It has been suggested by past findings that Type I interferon mRNA is present in higher levels in adults than in neonates, however there is a greater amount of interferon proteins in neonates rather than adults. To test the hypothesis that neonates are more capable of interferon production and preventing the translation of viral protein, I observed mouse models of respiratory viral infection and determined the expression of IFN-α1, IFN-α2, IFN-α5, IFN-α6, IFN-α7, IFN-β in archived mouse lung tissue samples harvested on different days post-infection with quantitative real time PCR. Expression of Glyceraldehyde 3-phosphate dehydrogenase(GAPDH), a housekeeping gene expressed constitutively in all mouse models, was used as a positive control of the experiment. To determine the ideal concentration of primer used in qPCR, primer reconstitution, primer optimization, and gel electrophoresis were conducted in advance. In addition, technical replicates and biological replicates were used to reduce error and confirm results in qPCR. In accordance with previous discovery, I found an upward trend in adults’ interferon expression from post-infection day 1 to day 5, and levels off in day 7. In contrast, neonatal levels were much higher on day 1 and remained high over the course of infection. This explains how type I interferon expression is altered in neonates to help them clear the virus at the same efficiency as adults without causing inflammation. Future research on immune response differences in human infection should focus on the evaluation of interferon protein amounts, as well as the analysis of activation of molecules downstream of the type I interferon receptors, such as signal transducer and activator of transcription (STAT) protein family. It is also crucial to compare immune cells like macrophages and natural killer cell activity in adult and neonatal mice during viral infection.

scholarly journals Brugada-Like Electrocardiographic Changes during Influenza Infection

2003 ◽  
Vol 31 (3) ◽  
pp. 244-246 ◽  
Author(s):  
K Kusaka ◽  
J Yamakawa ◽  
K Kawaura ◽  
T Itoh ◽  
T Takahashi ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Virus Infection ◽  
Viral Infection ◽  
Brugada Syndrome ◽  
Influenza Infection ◽  
Influenza Virus Infection ◽  
Ecg Changes ◽  
Early Repolarization ◽  
Electrocardiographic Changes

We describe a 32-year-old man with electrocardiographic (ECG) changes consistent with Brugada syndrome and influenza virus infection. The ECG pattern changed after 1 week to one of early repolarization in V1 and V2. This case suggests an association between Brugada syndrome and viral infection.

scholarly journals Mouse Models of Viral Infection

2018 ◽  
pp. 395-414
Author(s):  
Kerry M. Empey ◽  
R. Stokes Peebles ◽  
William J. Janssen
Keyword(s):  
Viral Infection ◽  
Mouse Models

scholarly journals A Multiscale Multicellular Spatiotemporal Model of Local Influenza Infection and Immune Response

2021 ◽  
Author(s):  
T.J. Sego ◽  
Ericka D. Mochan ◽  
G. Bard Ermentrout ◽  
James A. Glazier
Keyword(s):  
Immune Response ◽  
Viral Infection ◽  
Viral Infections ◽  
Influenza Infection ◽  
Ode Model ◽  
Spatiotemporal Model ◽  
Spatially Resolved ◽  
Ode Models ◽  
Respiratory Viral Infections ◽  
Spatial Cell

AbstractRespiratory viral infections pose a serious public health concern, from mild seasonal influenza to pandemics like those of SARS-CoV-2. Spatiotemporal dynamics of viral infection impact nearly all aspects of the progression of a viral infection, like the dependence of viral replication rates on the type of cell and pathogen, the strength of the immune response and localization of infection. Mathematical modeling is often used to describe respiratory viral infections and the immune response to them using ordinary differential equation (ODE) models. However, ODE models neglect spatially-resolved biophysical mechanisms like lesion shape and the details of viral transport, and so cannot model spatial effects of a viral infection and immune response. In this work, we develop a multiscale, multicellular spatiotemporal model of influenza infection and immune response by combining non-spatial ODE modeling and spatial, cell-based modeling. We employ cellularization, a recently developed method for generating spatial, cell-based, stochastic models from non-spatial ODE models, to generate much of our model from a calibrated ODE model that describes infection, death and recovery of susceptible cells and innate and adaptive responses during influenza infection, and develop models of cell migration and other mechanisms not explicitly described by the ODE model. We determine new model parameters to generate agreement between the spatial and original ODE models under certain conditions, where simulation replicas using our model serve as microconfigurations of the ODE model, and compare results between the models to investigate the nature of viral exposure and impact of heterogeneous infection on the time-evolution of the viral infection. We found that using spatially homogeneous initial exposure conditions consistently with those employed during calibration of the ODE model generates far less severe infection, and that local exposure to virus must be multiple orders of magnitude greater than a uniformly applied exposure to all available susceptible cells. This strongly suggests a prominent role of localization of exposure in influenza A infection. We propose that the particularities of the microenvironment to which a virus is introduced plays a dominant role in disease onset and progression, and that spatially resolved models like ours may be important to better understand and more reliably predict future health states based on susceptibility of potential lesion sites using spatially resolved patient data of the state of an infection. We can readily integrate the immune response components of our model into other modeling and simulation frameworks of viral infection dynamics that do detailed modeling of other mechanisms like viral internalization and intracellular viral replication dynamics, which are not explicitly represented in the ODE model. We can also combine our model with available experimental data and modeling of exposure scenarios and spatiotemporal aspects of mechanisms like mucociliary clearance that are only implicitly described by the ODE model, which would significantly improve the ability of our model to present spatially resolved predictions about the progression of influenza infection and immune response.

scholarly journals Thymic stromal lymphopoietin limits primary and recall CD8+ T-cell anti-viral responses

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Risa Ebina-Shibuya ◽  
Erin E West ◽  
Rosanne Spolski ◽  
Peng Li ◽  
Jangsuk Oh ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Viral Infection ◽  
Cell Function ◽  
Influenza Infection ◽  
T Cell Responses ◽  
T Cell Response ◽  
Thymic Stromal Lymphopoietin ◽  
Direct Role ◽  
Cell Responses

Thymic stromal lymphopoietin (TSLP) is a cytokine that acts directly on CD4+ T cells and dendritic cells to promote progression of asthma, atopic dermatitis, and allergic inflammation. However, a direct role for TSLP in CD8+ T-cell primary responses remains controversial and its role in memory CD8+ T cell responses to secondary viral infection is unknown. Here, we investigate the role of TSLP in both primary and recall responses in mice using two different viral systems. Interestingly, TSLP limited the primary CD8+ T-cell response to influenza but did not affect T cell function nor significantly alter the number of memory CD8+ T cells generated after influenza infection. However, TSLP inhibited memory CD8+ T-cell responses to secondary viral infection with influenza or acute systemic LCMV infection. These data reveal a previously unappreciated role for TSLP on recall CD8+ T-cell responses in response to viral infection, findings with potential translational implications.

scholarly journals Selective dependence on IL-7 for antigen-specific CD8 T cell responses during airway influenza infection

2022 ◽  
Vol 12 (1) ◽  
Author(s):  
Abdalla Sheikh ◽  
Jennie Jackson ◽  
Hanjoo Brian Shim ◽  
Clement Yau ◽  
Jung Hee Seo ◽  
...  
Keyword(s):  
T Cells ◽  
Lymph Node ◽  
T Cell ◽  
Viral Infection ◽  
Cd8 T Cells ◽  
Mediastinal Lymph Node ◽  
Influenza Infection ◽  
Cd8 T Cell ◽  
Cell Responses ◽  
Deficient Mice

AbstractInterleukin-7 (IL-7) is a cytokine known for its importance in T cell development and survival. How IL-7 shapes CD8 T cell responses during an acute viral infection is less understood. We had previously shown that IL-7 signaling deficient mice have reduced accumulation of influenza-specific CD8 T cells following influenza infection. We sought to determine whether IL-7 affects early CD8 T cell expansion in the mediastinal lymph node and effector function in the lungs. Using IL-7Rα signaling deficient mice, we show that IL-7 is required for a normal sized mediastinal lymph node and the early clonal expansion of influenza-specific CD8 T cells therein. We show that IL-7 plays a cell-intrinsic role in the accumulation of NP366–374 and PA224–233-specific CD8 T cells in the lymph node. We also found that IL-7 shapes terminal differentiation, degranulation and cytokine production to a greater extent in PA224–233-specific than NP366–374-specific CD8 T cells. We further demonstrate that IL-7 is induced in the lung tissue by viral infection and we characterize multiple cellular sources that contribute to IL-7 production. Our findings on IL-7 and its effects on lower respiratory diseases will be important for expanding the utility of therapeutics that are currently available.

Severe respiratory viral infection induces procalcitonin in the absence of bacterial pneumonia

Thorax ◽  
2020 ◽  
Vol 75 (11) ◽  
pp. 974-981 ◽  
Author(s):  
Samir Gautam ◽  
Avi J Cohen ◽  
Yannick Stahl ◽  
Patricia Valda Toro ◽  
Grant M Young ◽  
...  
Keyword(s):  
Viral Infection ◽  
Disease Severity ◽  
Influenza Infection ◽  
Characteristic Curve ◽  
Severe Disease ◽  
Antibiotic Administration ◽  
Underlying Assumption ◽  
Cellular Models ◽  
Interferon Signalling ◽  
Bacterial Coinfection

IntroductionProcalcitonin expression is thought to be stimulated by bacteria and suppressed by viruses via interferon signalling. Consequently, during respiratory viral illness, clinicians often interpret elevated procalcitonin as evidence of bacterial coinfection, prompting antibiotic administration. We sought to evaluate the validity of this practice and the underlying assumption that viral infection inhibits procalcitonin synthesis.MethodsWe conducted a retrospective cohort study of patients hospitalised with pure viral infection (n=2075) versus bacterial coinfection (n=179). The ability of procalcitonin to distinguish these groups was assessed. In addition, procalcitonin and interferon gene expression were evaluated in murine and cellular models of influenza infection.ResultsPatients with bacterial coinfection had higher procalcitonin than those with pure viral infection, but also more severe disease and higher mortality (p<0.001). After matching for severity, the specificity of procalcitonin for bacterial coinfection dropped substantially, from 72% to 61%. In fact, receiver operating characteristic curve analysis showed that procalcitonin was a better indicator of multiple indices of severity (eg, organ failures and mortality) than of coinfection. Accordingly, patients with severe viral infection had elevated procalcitonin. In murine and cellular models of influenza infection, procalcitonin was also elevated despite bacteriologic sterility and correlated with markers of severity. Interferon signalling did not abrogate procalcitonin synthesis.DiscussionThese studies reveal that procalcitonin rises during pure viral infection in proportion to disease severity and is not suppressed by interferon signalling, in contrast to prior models of procalcitonin regulation. Applied clinically, our data suggest that procalcitonin represents a better indicator of disease severity than bacterial coinfection during viral respiratory infection.

scholarly journals Mouse Models of Influenza Infection with Circulating Strains to Test Seasonal Vaccine Efficacy

2018 ◽  
Vol 9 ◽  
Author(s):  
Helen T. Groves ◽  
Jacqueline U. McDonald ◽  
Pinky Langat ◽  
Ekaterina Kinnear ◽  
Paul Kellam ◽  
...  
Keyword(s):  
Mouse Models ◽  
Vaccine Efficacy ◽  
Influenza Infection

Abstract 13747: Targeting Urokinase-Type Plasminogen Activator (uPA) and the uPA Receptor, Reduces Vascular Inflammation and Lung Hemorrhage in Systemic Lupus and SARS CoV2 Infection in Mouse Models of Respiratory Distress Syndromes

Circulation ◽  
2021 ◽  
Vol 144 (Suppl_2) ◽  
Author(s):  
Liqiang Zhang ◽  
Jordan R Yaron ◽  
Lauren Schutz ◽  
Emily Aliskevich ◽  
Kyle Browder ◽  
...  
Keyword(s):  
Autoimmune Disease ◽  
Respiratory Distress ◽  
Viral Infection ◽  
Serine Protease ◽  
Mouse Models ◽  
Vascular Inflammation ◽  
Virus Titer ◽  
Alveolar Hemorrhage ◽  
Blue Staining ◽  
Lung Hemorrhage

Introduction: Acute respiratory distress syndromes with vascular inflammation and alveolar hemorrhage have high mortality and limited treatment. Autoimmune disease and severe viral infection cause vascular inflammation and hemorrhage. Serine protease coagulation pathways increase inflammatory cell activation and damage. Viruses have evolved highly effective immune modulating ser ine p roteinase in hibitors, serpins . Myxomavirus Serp-1 improves survival and reduces inflammation, vasculitis and lung hemorrhage in MHV68 gamma herpes infections (P < 0.01). Serp-1 also reduces Lupus alveolar hemorrhage (DAH) and proved safe and effective in a randomized, blinded, dose escalating trial in patients with coronary stent implant. Hypothesis: We hypothesize that treatment with PEGylated Serp-1 (PEGSerp-1) will reduce hemorrhage and inflammatory vasculitis in autoimmune and infectious lung disease. Methods: Pristane induced DAH and SARS-CoV-2 virus infections were treated with PEGSerp-1 in mouse models. Results: Serp-1 and PEGSerp-1 given daily IP for 14 days significantly reduced pristane induced DAH (N = 30 C57Bl/6 mice; P < 0.05) at 14 days follow up. PEGSerp-1 also reduced lung hemorrhage given for 7days treatment (N = 6 mice; P <0.01) or when given 7 days after pristane induction of DAH (N = 6 mice; P < 0.01). Macrophage invasion (P < 0.01), Prussian blue staining for hemosiderosis, C5b-9 complex deposition and soluble uPAR (suPAR) were significantly reduced with PEGSerp-1 treatment. PEGSerp-1 given daily after SARS-CoV-2 infection (48hrs, BALB/c mice, N = 16) also significantly reduced lung inflammation; decreased F4/80+ and iNOS+ macrophage staining (P < 0.02). Virus titer was also reduced in TMPRS2+ Vero cells (10μg/mL), and in SARS infected lungs. PEG Serp-1 homes to areas of pristane lung damage, but not normal lungs, indicating targeting of protease activation. No adverse effects were detected. Conclusion: Treatment for vascular inflammation and hemorrhage in severe autoimmune and virus induced respiratory distress syndromes is very limited. Targeting thrombolytic and inflammatory serine protease uPA/ uPAR complex activation provides a new therapeutic approach to severe respiratory distress in autoimmune disease and viral infection.

An infection model for severe COVID-19

2020 ◽  
Author(s):  
Ho P ◽  
Tan Chuen Wen ◽  
Jason Chay Wai Mun ◽  
Chandramouli Nagarajan ◽  
Ng Heng Joo
Keyword(s):  
Immune Response ◽  
Viral Infection ◽  
Influenza Infection ◽  
Infection Model ◽  
Viral Shedding ◽  
Acute Viral Infection ◽  
Work Done ◽  
Therapeutic Considerations

We wish to propose an infection model to address some of the unique and unusual features observed in COVID-19, eg. why were severe patients mounting more intense immune response compared to the mild cases, why did severe patients demonstrate higher and more protracted viral shedding when the immune response was greater, etc. In this exposition, we will first describe a generic acute viral infection framework based on work done mainly in influenza infection to understand the acute infective cycle, then contrast it with COVID-19 data to highlight main differences to construct a pathogenic model, and finally extrapolate to discuss applications in potential therapeutic considerations.

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