scholarly journals Exploring Cell Tropism as a Possible Contributor to Influenza Infection Severity

2021 ◽  
Author(s):  
Catherine A. A. Beauchemin ◽  
Hana M. Dobrovolny ◽  
Marc J. Baron ◽  
Ronald Gieschke ◽  
Brian E. Davies ◽  
...  
Keyword(s):  
Mathematical Model ◽  
Target Cell ◽  
Influenza A ◽  
Cell Model ◽  
Influenza Infection ◽  
Virus Production ◽  
Cell Types ◽  
Cell Receptor ◽  
Cell Tropism ◽  
Severe Influenza

Several mechanisms have been proposed to account for the marked increase in severity of human infections with avian compared to human influenza strains, including increased cytokine expression, poor immune response, and differences in target cell receptor affinity. Here, the potential effect of target cell tropism on disease severity is studied using a mathematical model for in-host influenza viral infection in a cell population consisting of two different cell types. The two cell types differ only in their susceptibility to infection and rate of virus production. We show the existence of a parameter regime which is characterized by high viral loads sustained long after the onset of infection. This finding suggests that differences in cell tropism between influenza strains could be sufficient to cause significant differences in viral titer profiles, similar to those observed in infections with certain strains of influenza A virus. The two target cell mathematical model offers good agreement with experimental data from severe influenza infections, as does the usual, single target cell model albeit with biologically unrealistic parameters. Both models predict that while neuraminidase inhibitors and adamantanes are only effective when administered early to treat an uncomplicated seasonal infection, they can be effective against more severe influenza infections even when administered late.

scholarly journals Exploring Cell Tropism as a Possible Contributor to Influenza Infection Severity

2021 ◽  
Author(s):  
Catherine A. A. Beauchemin ◽  
Hana M. Dobrovolny ◽  
Marc J. Baron ◽  
Ronald Gieschke ◽  
Brian E. Davies ◽  
...  
Keyword(s):  
Mathematical Model ◽  
Target Cell ◽  
Influenza A ◽  
Cell Model ◽  
Influenza Infection ◽  
Virus Production ◽  
Cell Types ◽  
Cell Receptor ◽  
Cell Tropism ◽  
Severe Influenza

Several mechanisms have been proposed to account for the marked increase in severity of human infections with avian compared to human influenza strains, including increased cytokine expression, poor immune response, and differences in target cell receptor affinity. Here, the potential effect of target cell tropism on disease severity is studied using a mathematical model for in-host influenza viral infection in a cell population consisting of two different cell types. The two cell types differ only in their susceptibility to infection and rate of virus production. We show the existence of a parameter regime which is characterized by high viral loads sustained long after the onset of infection. This finding suggests that differences in cell tropism between influenza strains could be sufficient to cause significant differences in viral titer profiles, similar to those observed in infections with certain strains of influenza A virus. The two target cell mathematical model offers good agreement with experimental data from severe influenza infections, as does the usual, single target cell model albeit with biologically unrealistic parameters. Both models predict that while neuraminidase inhibitors and adamantanes are only effective when administered early to treat an uncomplicated seasonal infection, they can be effective against more severe influenza infections even when administered late.

scholarly journals Differential Expression of Serum Exosome microRNAs and Cytokines in Influenza A and B Patients Collected in the 2016 and 2017 Influenza Seasons

Pathogens ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 149
Author(s):  
Sreekumar Othumpangat ◽  
William G. Lindsley ◽  
Donald H. Beezhold ◽  
Michael L. Kashon ◽  
Carmen N. Burrell ◽  
...  
Keyword(s):  
Healthy Volunteers ◽  
Influenza A ◽  
Influenza Infection ◽  
Cell Types ◽  
Airway Epithelial Cells ◽  
Differentially Expressed ◽  
Influenza B ◽  
Airway Epithelial ◽  
Monocyte Chemoattractant Protein 1 ◽  
Novel Approach

MicroRNAs (miRNAs) have remarkable stability and are key regulators of mRNA transcripts for several essential proteins required for the survival of cells and replication of the virus. Exosomes are thought to play an essential role in intercellular communications by transporting proteins and miRNAs, making them ideal in the search for biomarkers. Evidence suggests that miRNAs are involved in the regulation of influenza virus replication in many cell types. During the 2016 and 2017 influenza season, we collected blood samples from 54 patients infected with influenza and from 30 healthy volunteers to identify the potential role of circulating serum miRNAs and cytokines in influenza infection. Data comparing the exosomal miRNAs in patients with influenza B to healthy volunteers showed 76 miRNAs that were differentially expressed (p < 0.05). In contrast, 26 miRNAs were differentially expressed between patients with influenza A (p < 0.05) and the controls. Of these miRNAs, 11 were commonly expressed in both the influenza A and B patients. Interferon (IFN)-inducing protein 10 (IP-10), which is involved in IFN synthesis during influenza infection, showed the highest level of expression in both influenza A and B patients. Influenza A patients showed increased expression of IFNα, GM-CSF, interleukin (IL)-13, IL-17A, IL-1β, IL-6 and TNFα, while influenza B induced increased levels of EGF, G-CSF, IL-1α, MIP-1α, and TNF-β. In addition, hsa-miR-326, hsa-miR-15b-5p, hsa-miR-885, hsa-miR-122-5p, hsa-miR-133a-3p, and hsa-miR-150-5p showed high correlations to IL-6, IL-15, IL-17A, IL-1β, and monocyte chemoattractant protein-1 (MCP-1) with both strains of influenza. Next-generation sequencing studies of H1N1-infected human lung small airway epithelial cells also showed similar pattern of expression of miR-375-5p, miR-143-3p, 199a-3p, and miR-199a-5p compared to influenza A patients. In summary, this study provides insights into the miRNA profiling in both influenza A and B virus in circulation and a novel approach to identify the early infections through a combination of cytokines and miRNA expression.

IFITM3 rs12252 T>C polymorphism is associated with the risk of severe influenza: a meta-analysis

2015 ◽  
Vol 143 (14) ◽  
pp. 2975-2984 ◽  
Author(s):  
Y. XUAN ◽  
L. N. WANG ◽  
W. LI ◽  
H. R. ZI ◽  
Y. GUO ◽  
...  
Keyword(s):  
Influenza A ◽  
Web Of Science ◽  
Transmembrane Protein ◽  
Influenza Infection ◽  
Meta Analysis ◽  
Severe Illness ◽  
Severe Influenza ◽  
Increased Risk ◽  
Interferon Pathway ◽  
Comprehensive Literature Search

SUMMARYThe interferon-inducible transmembrane protein 3 (IFITM3), as one of the key genes involved in the interferon pathway, is critical for defending the host against influenza virus, and the rs12252 T>C variant in IFITM3 might be associated with susceptibility to severe influenza. Owing to contradictory and inconclusive results, we performed a meta-analysis to assess the association between rs12252 T>C polymorphism and severe influenza risk. A comprehensive literature search up to 1 August 2014 was conducted in EMBASE, Pubmed, Web of Science, VIP, Wanfang and CNKI databases. Four eligible studies with a total of 445 influenza patients and 3396 controls were included in this meta-analysis. Overall, our results demonstrated a significant association between the IFITM3 rs12252 T>C polymorphism and influenza risk [C vs. T: odds ratio (OR) 1·68, 95% confidence interval (CI) 1·32–2·13; CC vs. CT+TT: OR 2·38, 95% CI 1·52–3·73; CC+CT vs. TT: OR 1·62, 95% CI 1·18–2·22]. Stratification by ethnicity indicated that the variant C allele was associated with an 88% increased risk of influenza in Asians (C vs. T: OR 1·88, 95% CI 1·34–2·62). Moreover, subjects carrying the variant C allele had an increased risk of developing severe illness upon influenza infection (C vs. T: OR 2·70, 95% CI 1·86–3·94). However, no significant association was observed in patients with mild infection (C vs. T: OR 1·26, 95% CI 0·93–1·71). Our meta-analysis suggests that IFITM3 rs12252 T>C polymorphism is significantly associated with increased risk of severe influenza but not with the chance of initial virus infection.

scholarly journals CD8+ T cell recognition of an endogenously processed epitope is regulated primarily by residues within the epitope.

1992 ◽  
Vol 176 (5) ◽  
pp. 1335-1341 ◽  
Author(s):  
Y S Hahn ◽  
C S Hahn ◽  
V L Braciale ◽  
T J Braciale ◽  
C M Rice
Keyword(s):  
T Cell ◽  
Target Cell ◽  
Influenza A ◽  
Expression System ◽  
Cell Receptor ◽  
Class I ◽  
Antigenic Peptides ◽  
Peptide Fragments ◽  
Class I Mhc ◽  
Mhc Molecules

Cytotoxic T lymphocytes (CTL) recognize short antigenic peptides associated with cell surface class I major histocompatibility complex (MHC) molecules. This association presumably occurs between newly synthesized class I MHC molecules and peptide fragments in a pre-Golgi compartment. Little is known about the factors that regulate the formation of these antigenic peptide fragments within the cell. To examine the role of residues within a core epitope and in the flanking sequences for the generation and presentation of the newly synthesized peptide fragment recognized by CD8+ CTL, we have mutagenized the coding sequence for the CTL epitope spanning residues 202-221 in the influenza A/Japan/57 hemagglutinin (HA). In this study over 60 substitution mutations in the epitope were tested for their effects on target cell sensitization using a cytoplasmic viral expression system. The HA202-221 site contains two overlapping subsites defined by CTL clones 11-1 and 40-2. Mutations in HA residues 204-213 or residues 210-219 often abolished target cell lysis by CTL clones 11-1 and 40-2, respectively. Although residues outside the core epitope did not usually affect the ability to be lysed by CTL clones, substitution of a Gly residue for Val-214 abolished lysis by clone 11-1. These data suggest that residues within a site that affect MHC binding and T cell receptor recognition appear to play the predominant role in dictating the formation of the antigenic complex recognized by CD8+ CTL, and therefore the antigenicity of the protein antigen presented to CD8+ T cells. Most alterations in residues flanking the endogenously expressed epitope do not appreciably affect the generation and recognition of the site.

scholarly journals Replication kinetic, cell tropism and associated immune responses in SARS-CoV-2 and H5N1 virus infected human iPSC derived neural models

2021 ◽  
Author(s):  
Lisa Bauer ◽  
Bas Lendemeijer ◽  
Lonneke Leijten ◽  
Carmen W. E. Embregts ◽  
Barry Rockx ◽  
...  
Keyword(s):  
Immune Responses ◽  
Influenza A ◽  
H5n1 Virus ◽  
Cell Types ◽  
Neurological Complications ◽  
Olfactory Nerve ◽  
Cell Tropism ◽  
Replication Kinetic ◽  
H5n1 Influenza ◽  
Induced Pluripotent

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is associated with a wide variety of neurological complications. Even though SARS-CoV-2 is rarely detected in the central nervous system (CNS) or cerebrospinal fluid, evidence is accumulating that SARS-CoV-2 might enter the CNS via the olfactory nerve. However, what happens after SARS-CoV-2 enters the CNS is poorly understood. Therefore, we investigated the replication kinetics, cell tropism, and associated immune responses of SARS-CoV-2 infection in different types of neural cultures derived from human induced pluripotent stem cells (hiPSCs). SARS-CoV-2 was compared to the neurotropic and highly pathogenic H5N1 influenza A virus. SARS-CoV-2 infected a minority of individual mature neurons, without subsequent virus replication and spread, despite ACE2, TMPRSS2 and NPR1 expression in all cultures. However, this sparse infection did result in the production of type-III-interferons and IL-8. In contrast, H5N1 virus replicated and spread very efficiently in all cell types in all cultures. Taken together, our findings support the hypothesis that neurological complications might result from local immune responses triggered by virus invasion, rather than abundant SARS-CoV-2 replication in the CNS.

scholarly journals Hemagglutinin-specific cytotoxic T-cell response during influenza infection.

1977 ◽  
Vol 146 (3) ◽  
pp. 893-898 ◽  
Author(s):  
F A Ennis ◽  
W J Martin ◽  
M W Verbonitz
Keyword(s):  
T Cell ◽  
Target Cell ◽  
Cell Response ◽  
Influenza A ◽  
Influenza Infection ◽  
T Cell Response ◽  
Cytotoxic T Cell ◽  
Target Cells ◽  
Cervical Lymph Nodes ◽  
Cytotoxic Response

Specific cytotoxic thymus-derived (T) lymphocytes were detected in the cervical lymph nodes and spleen during influenza infection of mice. The cytotoxic T cells can distinguish target cells infected with different influenza A subtypes. Infection with parent viruses and their recombinant progeny possessing the hemagglutinin of one parent and the neuraminidase of the other demonstrated that significant cytotoxicity occurred only when the hemagglutinin of the immunizing viruses was the same as that of the virus used to infect the target cell. In addition to this specific cytotoxic response to the major surface antigen, a cross-reactive response could be detected when the relatively nonpermissive L cell was used as the target cell. These results indicate there is a specific cytotoxic T-cell response to the surface hemagglutinin, and a cross-reactive cytotoxic response, not directed to the hemagglutinin, during influenza infection. The cytotoxic T-cell response specific for the hemagglutinin antigen may play an important role in in vivo immunity to influenza.

scholarly journals Invasive pulmonary aspergillosisas a complication of severe influenza (case report)

2020 ◽  
Vol 12 (1) ◽  
pp. 96-103
Author(s):  
Yu. E. Melekhina ◽  
O. V. Shadrivova ◽  
E. V. Frolova ◽  
Yu. V. Borzova ◽  
E. V. Shagdileeva ◽  
...  
Keyword(s):  
Case Report ◽  
Influenza A ◽  
Clinical Case ◽  
Influenza Infection ◽  
Invasive Pulmonary Aspergillosis ◽  
Pulmonary Aspergillosis ◽  
Severe Influenza ◽  
Influenza A H1n1 ◽  
Influenza Case ◽  
Immunocompetent Patients

During  last  years  the  frequency  of  invasive  pulmonary aspergillosis  (IPA)  in  immunocompetent  patients  has  increased. Clinical case report of successful treatment invasive aspergillosis  with  influenza  A(H1N1)  presented  in  the  article. We analyzed the special literature of patients with IPA following influenza infection. The timely identification and treatment of these patients are necessary.

scholarly journals In-host Modelling of COVID-19 in Humans

2020 ◽  
Author(s):  
Esteban A. Hernandez-Vargas ◽  
Jorge X. Velasco-Hernandez
Keyword(s):  
Immune Responses ◽  
Target Cell ◽  
Viral Infections ◽  
Cell Model ◽  
Influenza Infection ◽  
Severe Disease ◽  
Reproductive Number ◽  
Infected Cells ◽  
Eclipse Phase ◽  
The Impact

ABSTRACTCOVID-19 pandemic has underlined the impact of emergent pathogens as a major threat for human health. The development of quantitative approaches to advance comprehension of the current outbreak is urgently needed to tackle this severe disease. In this work, several mathematical models are proposed to represent SARS-CoV-2 dynamics in infected patients. Considering different starting times of infection, parameters sets that represent infectivity of SARS-CoV-2 are computed and compared with other viral infections that can also cause pandemics.Based on the target cell model, SARS-CoV-2 infecting time between susceptible cells (mean of 30 days approximately) is much slower than those reported for Ebola (about 3 times slower) and influenza (60 times slower). The within-host reproductive number for SARS-CoV-2 is consistent to the values of influenza infection (1.7-5.35). The best model to fit the data was including immune responses, which suggest a slow cell response peaking between 5 to 10 days post onset of symptoms. The model with eclipse phase, time in a latent phase before becoming productively infected cells, was not supported. Interestingly, both, the target cell model and the model with immune responses, predict that virus may replicate very slowly in the first days after infection, and it could be below detection levels during the first 4 days post infection. A quantitative comprehension of SARS-CoV-2 dynamics and the estimation of standard parameters of viral infections is the key contribution of this pioneering work.

scholarly journals Divergent Mast Cell Responses Modulate Antiviral Immunity During Influenza Virus Infection

2021 ◽  
Vol 11 ◽  
Author(s):  
Ashleigh R. Murphy-Schafer ◽  
Silke Paust
Keyword(s):  
Inflammatory Cytokines ◽  
Immune Cells ◽  
Tissue Damage ◽  
Influenza A ◽  
Secondary Infection ◽  
Influenza Infection ◽  
Influenza Virus Infection ◽  
Respiratory Pathogen ◽  
Severe Influenza ◽  
Adaptive Immune Cells

Influenza A virus (IAV) is a respiratory pathogen that infects millions of people each year. Both seasonal and pandemic strains of IAV are capable of causing severe respiratory disease with a high risk of respiratory failure and opportunistic secondary infection. A strong inflammatory cytokine response is a hallmark of severe IAV infection. The widespread tissue damage and edema in the lung during severe influenza is largely attributed to an overexuberant production of inflammatory cytokines and cell killing by resident and infiltrating leukocytes. Mast cells (MCs) are a sentinel hematopoietic cell type situated at mucosal sites, including the lung. Poised to react immediately upon detecting infection, MCs produce a vast array of immune modulating molecules, including inflammatory cytokines, chemokines, and proteases. As such, MCs have been implicated as a source of the immunopathology observed in severe influenza. However, a growing body of evidence indicates that MCs play an essential role not only in inducing an inflammatory response but in suppressing inflammation as well. MC-derived immune suppressive cytokines are essential to the resolution of a number of viral infections and other immune insults. Absence of MCs prolongs infection, exacerbates tissue damage, and contributes to dissemination of the pathogen to other tissues. Production of cytokines such as IL-10 and IL-6 by MCs is essential for mitigating the inflammation and tissue damage caused by innate and adaptive immune cells alike. The two opposing functions of MCs—one pro-inflammatory and one anti-inflammatory—distinguish MCs as master regulators of immunity at the site of infection. Amongst the first cells to respond to infection or injury, MCs persist for the duration of the infection, modulating the recruitment, activation, and eventual suppression of other immune cells. In this review, we will discuss the immune modulatory roles of MCs over the course of viral infection and propose that the immune suppressive mediators produced by MCs are vital to minimizing immunopathology during influenza infection.

scholarly journals Based on network pharmacology and molecular docking to explore the Traditional Chinese Medicine anti-influenza mechanisms:Chinese protocol for diagnosis and treatment of influenza.

2020 ◽  
Author(s):  
yifei Chen
Keyword(s):  
Molecular Docking ◽  
Influenza A ◽  
Influenza Infection ◽  
Diagnosis And Treatment ◽  
Network Pharmacology ◽  
Ppi Network ◽  
Active Components ◽  
Pharmacological Mechanism ◽  
Severe Influenza ◽  
Target Network

Background Explore the possible mechanism of anti-influenza virus, based on the study of the active components-drug-target network, Protein-Protein Interaction (PPI) network and molecular docking verification, we explored the potential action mechanism of TCM in Chinese protocol for diagnosis and treatment of influenza 2019. Methods Screening the active components and potential targets of 12 drugs in the scheme by using TCMSP database, and Obtaining the target of influenza by GeneCard, Durgbank, OMIM, TTD and PharmGkb databases. Then, constructed the “component-durg-target” network and PPI network were by Cytoscape3.8.0 software. Morethan, analyzed and the biological function and pathway, verified the molecular docking by AutoDock Vina software. Results The 12 drugs in the recommended scheme (XBCQ) for severe influenza contain 192 active components and involve 31 key antiviral targets, which may play an antiviral role through biological processes such as lipopolysaccharide, pathogen molecular reaction and regulate signaling pathway via the IL-17, influenza A, TNF, Toll-like receptors. Conclusion TCM play critical therapeutic roles through “multi-components, multi-targets and multi-pathways” mechanisms in influenza infection. The antiviral pharmacological mechanism of Xuanbai Chengqi decoction, which was analyzed by network pharmacology and molecular docking, provide a new idea for further exploring the diagnosis and treatment of severe influenza.

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