scholarly journals Epitope-Dependent Avidity Thresholds for Cytotoxic T-Lymphocyte Clearance of Virus-Infected Cells

2007 ◽  
Vol 81 (10) ◽  
pp. 4973-4980 ◽  
Author(s):  
Michael S. Bennett ◽  
Hwee L. Ng ◽  
Mirabelle Dagarag ◽  
Ayub Ali ◽  
Otto O. Yang
Keyword(s):  
Infected Cell ◽  
Viral Infections ◽  
Cytotoxic T Lymphocyte ◽  
Cell Killing ◽  
Target Cells ◽  
Functional Avidity ◽  
Viral Epitope ◽  
Infected Cells ◽  
Relationship Of ◽  
The Relationship

ABSTRACT Cytotoxic T lymphocytes (CTLs) are crucial for immune control of viral infections. “Functional avidity,” defined by the sensitizing dose of exogenously added epitope yielding half-maximal CTL triggering against uninfected target cells (SD50), has been utilized extensively as a measure of antiviral efficiency. However, CTLs recognize infected cells via endogenously produced epitopes, and the relationship of SD50 to antiviral activity has never been directly revealed. We elucidate this relationship by comparing CTL killing of cells infected with panels of epitope-variant viruses to the corresponding SD50 for the variant epitopes. This reveals a steeply sigmoid relationship between avidity and infected cell killing, with avidity thresholds (defined as the SD50 required for CTL to achieve 50% efficiency of infected cell killing [KE50]), below which infected cell killing rapidly drops to none and above which killing efficiency rapidly plateaus. Three CTL clones recognizing the same viral epitope show the same KE50 despite differential recognition of individual epitope variants, while CTLs recognizing another epitope show a 10-fold-higher KE50, demonstrating epitope dependence of KE50. Finally, the ability of CTLs to suppress viral replication depends on the same threshold KE50. Thus, defining KE50 values is required to interpret the significance of functional avidity measurements and predict CTL efficacy against virus-infected cells in pathogenesis and vaccine studies.

scholarly journals EXPERIMENTALLY INDUCED CHANGES IN NASAL MUCOUS SECRETORY SYSTEMS AND THEIR EFFECT ON VIRUS INFECTION IN CHICKENS

1969 ◽  
Vol 130 (1) ◽  
pp. 121-140 ◽  
Author(s):  
Frederik B. Bang ◽  
Marie A. Foard
Keyword(s):  
Virulent Strain ◽  
Time Intervals ◽  
Sharp Drop ◽  
Ciliary Action ◽  
Infected Cells ◽  
Unanesthetized Animals ◽  
Induced Changes ◽  
Ciliated Epithelial Cells ◽  
Relationship Of ◽  
The Relationship

Chickens 3 wk old, inoculated intranasally with a mesogenic (moderately virulent) strain of Newcastle disease virus, developed necrotic lesions of the mucous acini, predominantly of the middle turbinates. The infection subsequently spread to involve much of the rest of the mucosa, including mucous and ciliated epithelial cells, and other acini. The early phase of adsorption of a virulent strain of the virus to the middle turbinates of chicks 5–21 days of age was studied by giving a standard inoculum intranasally to unanesthetized animals. Variation in amounts adsorbed by individual chickens was large, but was minimized by making measurements on pools of turbinates from three chicks at intervals of 1, 3, and 5 hr after exposure of the excised turbinates to antibody, by washing, and by trypsinization. The virus released from the cells into the trypsin was designated as adherent virus, and the infectious virus in the cells after destruction of the cells by water grinding, as cell virus. Paralysis of ciliary action by cocaine increased the number of infected cells in the turbinates about 10-fold at all three time intervals. Pilocarpine injection before virus inoculation caused a large increase in the amount of infected cells 1 hr after virus administration, but was followed by a sharp drop in infected cells by 3 or 5 hr. Pilocarpine given after the virus decreased the number of infected cells and changed the relationship of infected cells to adherent virus. Exposure of chicks to sustained or severe cold caused a similar but less marked effect. The drop in infected cells was restored to control values if chicks were returned to brooder temperatures. The marked drop of infected cells produced by pilocarpine and cold in living chicks, and in cultures of chicken trachea (previous study), is consonant with the idea that virus has been adsorbed on mucus granules in the mucous cells of the turbinates and then has been reexcreted, as unincorporated virus, into the moving mucous sheet. A series of accessory data support this interpretation.

scholarly journals A computational technique to estimate within-host productively infected cell lifetimes in emerging viral infections

2016 ◽  
Author(s):  
Soumya Banerjee
Keyword(s):  
Infected Cell ◽  
Viral Infections ◽  
Cell Types ◽  
Emerging Diseases ◽  
Computational Technique ◽  
Emerging Viruses ◽  
Novel Technique ◽  
Differential Equation Models ◽  
Infected Cells ◽  
Health Relevance

Emerging viruses cause a lot of fatalities as they jump to humans from other species. Here we develop a novel technique to computationally estimate an important parameter of within-host viral infection: the lifespan of infected cells. Our approach is general and can be applied to a large class of viruses and leverages experimental data from replicon studies. Current techniques have difficulties reliably estimating infected cell lifetimes due to issues of parameter identifiability and correlation of parameters. The infected cell lifetime is an important parameter that gives an estimate of the how fast virus levels will decline. Our method would also help determine if some infected cells are short-lived or have longer lifespans with the consequence that longer lived cells could be reservoirs of infection. This would give a mechanistic understanding of why particular cell types are reservoirs of infection. We apply our technique to West Nile virus (WNV), an emerging disease of public health relevance related to Zika virus. Our analysis suggests that the most abundant infectible cells are short-lived and could motivate therapy that targets these particular cells. Our approach is very general and can be combined with more traditional methods of using differential equation models to simulate viremia in hosts: the combination of these two techniques will likely yield results that may not be achievable using the models in isolation. This will be of great interest especially in modelling emerging diseases.

scholarly journals Evaluation of CD8 T cell killing models with computer simulations of 2-photon imaging experiments

2020 ◽  
Vol 16 (12) ◽  
pp. e1008428
Author(s):  
Ananya Rastogi ◽  
Philippe A. Robert ◽  
Stephan Halle ◽  
Michael Meyer-Hermann
Keyword(s):  
Cytotoxic T Lymphocyte ◽  
Three Dimensional ◽  
Critical Factor ◽  
Target Cells ◽  
Agent Based ◽  
Multiple Contacts ◽  
Infected Cells ◽  
New Interactions ◽  
Increased Susceptibility

In vivo imaging of cytotoxic T lymphocyte (CTL) killing activity revealed that infected cells have a higher observed probability of dying after multiple contacts with CTLs. We developed a three-dimensional agent-based model to discriminate different hypotheses about how infected cells get killed based on quantitative 2-photon in vivo observations. We compared a constant CTL killing probability with mechanisms of signal integration in CTL or infected cells. The most likely scenario implied increased susceptibility of infected cells with increasing number of CTL contacts where the total number of contacts was a critical factor. However, when allowing in silico T cells to initiate new interactions with apoptotic target cells (zombie contacts), a contact history independent killing mechanism was also in agreement with experimental datasets. The comparison of observed datasets to simulation results, revealed limitations in interpreting 2-photon data, and provided readouts to distinguish CTL killing models.

THE RELATIONSHIP OF VIRAL INFECTIONS TO SUBSEQUENT ASTHMA

1981 ◽  
Vol 2 (1) ◽  
pp. 67-78
Author(s):  
CARL B. SHERTER ◽  
CHARLES A. POLNITSKY
Keyword(s):  
Viral Infections ◽  
Relationship Of ◽  
The Relationship

scholarly journals The Relationship of the Mechanisms of the Pathogenesis of Multiple Sclerosis and the Expression of Endogenous Retroviruses

Biology ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 464
Author(s):  
Vera R. Lezhnyova ◽  
Ekaterina V. Martynova ◽  
Timur I. Khaiboullin ◽  
Richard A. Urbanowicz ◽  
Svetlana F. Khaiboullina ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Viral Infections ◽  
Endogenous Retroviruses ◽  
Epigenetic Mechanisms ◽  
Humoral Factors ◽  
Human Endogenous Retroviruses ◽  
Relationship Of ◽  
The Relationship

Two human endogenous retroviruses of the HERV-W family can act as cofactors triggering multiple sclerosis (MS): MS-associated retrovirus (MSRV) and ERVWE1. Endogenous retroviral elements are believed to have integrated in our ancestors’ DNA millions of years ago. Their involvement in the pathogenesis of various diseases, including neurodegenerative pathologies, has been demonstrated. Numerous studies have shown a correlation between the deterioration of patients’ health and increased expression of endogenous retroviruses. The exact causes and mechanisms of endogenous retroviruses activation remains unknown, which hampers development of therapeutics. In this review, we will summarize the main characteristics of human endogenous W retroviruses and describe the putative mechanisms of activation, including epigenetic mechanisms, humoral factors as well as the role of the exogenous viral infections.

scholarly journals αEβ7 integrin interaction with E-cadherin promotes antitumor CTL activity by triggering lytic granule polarization and exocytosis

2007 ◽  
Vol 204 (3) ◽  
pp. 559-570 ◽  
Author(s):  
Audrey Le Floc'h ◽  
Abdelali Jalil ◽  
Isabelle Vergnon ◽  
Béatrice Le Maux Chansac ◽  
Vladimir Lazar ◽  
...  
Keyword(s):  
T Cell ◽  
Transforming Growth Factor ◽  
Cytotoxic T Lymphocyte ◽  
Tumor Infiltrating Lymphocytes ◽  
Cell Killing ◽  
Intercellular Adhesion Molecule ◽  
Target Cells ◽  
Autologous Tumor ◽  
Intercellular Adhesion Molecule 1 ◽  
E Cadherin

Various T cell adhesion molecules and their cognate receptors on target cells promote T cell receptor (TCR)–mediated cell killing. In this report, we demonstrate that the interaction of epithelial cell marker E-cadherin with integrin αE(CD103)β7, often expressed by tumor-infiltrating lymphocytes (TILs), plays a major role in effective tumor cell lysis. Indeed, we found that although tumor-specific CD103+ TIL-derived cytotoxic T lymphocyte (CTL) clones are able to kill E-cadherin+/intercellular adhesion molecule 1− autologous tumor cells, CD103− peripheral blood lymphocyte (PBL)-derived counterparts are inefficient. This cell killing is abrogated after treatment of the TIL clones with a blocking anti-CD103 monoclonal antibody or after targeting E-cadherin in the tumor using ribonucleic acid interference. Confocal microscopy analysis also demonstrated that αEβ7 is recruited at the immunological synapse and that its interaction with E-cadherin is required for cytolytic granule polarization and subsequent exocytosis. Moreover, we report that the CD103− profile, frequently observed in PBL-derived CTL clones and associated with poor cytotoxicity against the cognate tumor, is up-regulated upon TCR engagement and transforming growth factor β1 treatment, resulting in strong potentiation of antitumor lytic function. Thus, CD8+/CD103+ tumor-reactive T lymphocytes infiltrating epithelial tumors most likely play a major role in antitumor cytotoxic response through αEβ7–E-cadherin interactions.

scholarly journals On the Relationship of Viral Particles and Extracellular Vesicles: Implications for Viral Vector Technology

Viruses ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1238
Author(s):  
Christoph Metzner ◽  
Marianne Zaruba
Keyword(s):  
Extracellular Vesicles ◽  
Biomedical Applications ◽  
Viral Vectors ◽  
Viral Infections ◽  
Viral Vector ◽  
Extracellular Vesicle ◽  
Viral Particles ◽  
Gene Therapy Vectors ◽  
Relationship Of ◽  
The Relationship

Gene therapy vectors derived from different viral species have become a fixture in biomedicine, both for direct therapeutic intervention and as tools to facilitate cell-based therapies, such as chimeric antigen receptor-based immunotherapies. On the contrary, extracellular vesicles have only recently gained a massive increase in interest and, concomitantly, knowledge in the field has drastically risen. Viral infections and extracellular vesicle biology overlap in many ways, both with pro- and antiviral outcomes. In this review, we take a closer look at these interactions for the most prominent groups of viral vectors (Adenoviral, Adeno-associated and Retro/Lentiviral vectors) and the possible implications of these overlaps for viral vector technology and its biomedical applications.

scholarly journals Unraveling the Relationship of Asthma and COVID-19

2021 ◽  
Vol 11 (12) ◽  
pp. 1374
Author(s):  
Agamemnon Bakakos ◽  
Petros Bakakos ◽  
Nikoletta Rovina
Keyword(s):  
Molecular Mechanisms ◽  
Viral Infections ◽  
Asthma Severity ◽  
Current Evidence ◽  
Asthma Exacerbations ◽  
Inflammatory Phenotypes ◽  
Relationship Of ◽  
The Impact ◽  
The Relationship

Viral infections are one of the main causes of asthma exacerbations. During the COVID-19 era, concerns regarding the relationship of SARS-CoV2 with asthma have been raised. The concerns are both for COVID severity and asthma exacerbations. Many studies on COVID-19 epidemiology and comorbidities have assessed whether asthma represents a risk factor for SARS-CoV2 infection and/or more severe course of the disease. This review covers the current evidence on the prevalence of asthma in COVID-19 and its association with susceptibility to and severity of SARS-CoV2 infection. It will examine the possible role of underlying asthma severity in COVID-19 related outcomes as well as the molecular mechanisms involved in the co-existence of these entities. The possible role of asthma inflammatory phenotypes will also be evaluated. Finally, the impact of asthma comorbidities and the implications of asthma medication on COVID-19 will be addressed.

scholarly journals A computational technique to estimate within-host productively infected cell lifetimes in emerging viral infections

2017 ◽  
Author(s):  
Soumya Banerjee
Keyword(s):  
Infected Cell ◽  
Viral Infections ◽  
Cell Types ◽  
Emerging Diseases ◽  
Computational Technique ◽  
Emerging Viruses ◽  
Novel Technique ◽  
Differential Equation Models ◽  
Infected Cells ◽  
Health Relevance

Emerging viruses cause a lot of fatalities as they jump to humans from other species. Here we develop a novel technique to computationally estimate an important parameter of within-host viral infection: the lifespan of infected cells. Our approach is general and can be applied to a large class of viruses and leverages experimental data from replicon studies. Current techniques have difficulties reliably estimating infected cell lifetimes due to issues of parameter identifiability and correlation of parameters. The infected cell lifetime is an important parameter that gives an estimate of the how fast virus levels will decline. Our method would also help determine if some infected cells are short-lived or have longer lifespans with the consequence that longer lived cells could be reservoirs of infection. This would give a mechanistic understanding of why particular cell types are reservoirs of infection. We apply our technique to West Nile virus (WNV), an emerging disease of public health relevance related to Zika virus. Our analysis suggests that the most abundant infectible cells are short-lived and could motivate therapy that targets these particular cells. Our approach is very general and can be combined with more traditional methods of using differential equation models to simulate viremia in hosts: the combination of these two techniques will likely yield results that may not be achievable using the models in isolation. This will be of great interest especially in modelling emerging diseases.

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