Varying Inoculum Dose to Assess the Roles of the Immune Response and Target Cell Depletion by the Pathogen in Control of Acute Viral Infections

2020 ◽  
Vol 82 (3) ◽  
Author(s):  
James R. Moore ◽  
Hasan Ahmed ◽  
Balaji Manicassamy ◽  
Adolfo Garcia-Sastre ◽  
Andreas Handel ◽  
...  
Keyword(s):  
Immune Response ◽  
Target Cell ◽  
Viral Infections ◽  
Cell Depletion ◽  
Inoculum Dose

scholarly journals Mathematical Modeling of Within-Host, Untreated, Cytomegalovirus Infection Dynamics after Allogeneic Transplantation

Viruses ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2292
Author(s):  
Elizabeth R. Duke ◽  
Florencia A. T. Boshier ◽  
Michael Boeckh ◽  
Joshua T. Schiffer ◽  
E. Fabian Cardozo-Ojeda
Keyword(s):  
Mathematical Modeling ◽  
Immune Response ◽  
Target Cell ◽  
Hematopoietic Cell Transplantation ◽  
Viral Infections ◽  
Immune Cell ◽  
Controlled Trial ◽  
Antiviral Treatment ◽  
Serum Samples ◽  
Cell Compartments

Cytomegalovirus (CMV) causes significant morbidity and mortality in recipients of allogeneic hematopoietic cell transplantation (HCT). Whereas insights gained from mathematical modeling of other chronic viral infections such as HIV, hepatitis C, and herpes simplex virus-2 have aided in optimizing therapy, previous CMV modeling has been hindered by a lack of comprehensive quantitative PCR viral load data from untreated episodes of viremia in HCT recipients. We performed quantitative CMV DNA PCR on stored, frozen serum samples from the placebo group of participants in a historic randomized controlled trial of ganciclovir for the early treatment of CMV infection in bone marrow transplant recipients. We developed four main ordinary differential Equation mathematical models and used model selection theory to choose between 38 competing versions of these models. Models were fit using a population, nonlinear, mixed-effects approach. We found that CMV kinetics from untreated HCT recipients are highly variable. The models that recapitulated the observed patterns most parsimoniously included explicit, dynamic immune cell compartments and did not include dynamic target cell compartments, consistent with the large number of tissue and cell types that CMV infects. In addition, in our best-fitting models, viral clearance was extremely slow, suggesting severe impairment of the immune response after HCT. Parameters from our best model correlated well with participants’ clinical risk factors and outcomes from the trial, further validating our model. Our models suggest that CMV dynamics in HCT recipients are determined by host immune response rather than target cell limitation in the absence of antiviral treatment.

scholarly journals IgA Vasculitis: Etiology, Treatment, Biomarkers and Epigenetic Changes

2021 ◽  
Vol 22 (14) ◽  
pp. 7538
Author(s):  
Hitomi Sugino ◽  
Yu Sawada ◽  
Motonobu Nakamura
Keyword(s):  
Immune Response ◽  
Autoimmune Diseases ◽  
Organ Dysfunction ◽  
Human Body ◽  
Therapeutic Approach ◽  
Viral Infections ◽  
External Environment ◽  
Iga Vasculitis ◽  
Epigenetic Changes ◽  
Flexible Response

IgA, previously called Henoch-Schönlein vasculitis, is an essential immune component that drives the host immune response to the external environment. As IgA has the unique characteristic of a flexible response to broad types of microorganisms, it sometimes causes an autoreactive response in the host human body. IgA vasculitis and related organ dysfunction are representative IgA-mediated autoimmune diseases; bacterial and viral infections often trigger IgA vasculitis. Recent drug developments and the presence of COVID-19 have revealed that these agents can also trigger IgA vasculitis. These findings provide a novel understanding of the pathogenesis of IgA vasculitis. In this review, we focus on the characteristics of IgA and symptoms of IgA vasculitis and other organ dysfunction. We also mention the therapeutic approach, biomarkers, novel triggers for IgA vasculitis, and epigenetic modifications in patients with IgA vasculitis.

scholarly journals Trace Elements as Immunoregulators in SARS-CoV-2 and Other Viral Infections

2021 ◽  
Author(s):  
Karthick Dharmalingam ◽  
Amandeep Birdi ◽  
Sojit Tomo ◽  
Karli Sreenivasulu ◽  
Jaykaran Charan ◽  
...  
Keyword(s):  
Immune Response ◽  
Trace Elements ◽  
Viral Entry ◽  
Viral Infections ◽  
Inhibitory Effect ◽  
Antioxidants Activity ◽  
Host Immune Responses ◽  
Complex Interactions ◽  
Downstream Processes

AbstractNutritional deficiency is associated with impaired immunity and increased susceptibility to infections. The complex interactions of trace elements with the macromolecules trigger the effective immune response against the viral diseases. The outcome of various viral infections along with susceptibility is affected by trace elements such as zinc, selenium, iron, copper, etc. due to their immuno-modulatory effects. Available electronic databases have been comprehensively searched for articles published with full text available and with the key words “Trace elements”, “COVID-19”, “Viral Infections” and “Immune Response” (i.e. separately Zn, Se, Fe, Cu, Mn, Mo, Cr, Li, Ni, Co) appearing in the title and abstract. On the basis of available articles we have explored the role of trace elements in viral infections with special reference to COVID-19 and their interactions with the immune system. Zinc, selenium and other trace elements are vital to triggerTH1 cells and cytokine-mediated immune response for substantial production of proinflammatory cytokines. The antiviral activity of some trace elements is attributed to their inhibitory effect on viral entry, replication and other downstream processes. Trace elements having antioxidants activity not only regulate host immune responses, but also modify the viral genome. Adequate dietary intake of trace elements is essential for activation, development, differentiation and numerous functions.

scholarly journals 521. Similarities and Differences in Transcriptomic Host Response between SARS-CoV-2 and Other Viral Infections

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S326-S327
Author(s):  
Simone A Thair ◽  
Yudong He ◽  
Yehudit Hasin-Brumshtein ◽  
Suraj Sakaram ◽  
Rushika R Pandya ◽  
...  
Keyword(s):  
Immune Response ◽  
B Cells ◽  
Nk Cells ◽  
Pathway Analysis ◽  
Host Response ◽  
Viral Infections ◽  
Cell Types ◽  
Gene Signature ◽  
Gene Signatures ◽  
Similarities And Differences

Abstract Background COVID-19 is a pandemic caused by the SARS-CoV-2 virus that shares and differs in clinical characteristics of known viral infections. Methods We obtained RNAseq profiles of 62 prospectively enrolled COVID-19 patients and 24 healthy controls (HC). We collected 23 independent studies profiling 1,855 blood samples from patients covering six viruses (influenza, RSV, HRV, Ebola, Dengue and SARS-CoV-1). We studied host whole-blood transcriptomic responses in COVID-19 compared to non-COVID-19 viral infections to understand similarities and differences in host response. Gene signature threshold was absolute effect size ≥1, FDR ≤ 0.05%. Results Differential gene expression of COVID-19 vs HC are highly correlated with non-COVID-19 vs HC (r=0.74, p< 0.001). We discovered two gene signatures: COVID-19 vs HC (2002 genes) (COVIDsig) and non-COVID-19 vs HC (635 genes) (nonCOVIDsig). Pathway analysis of over-expressed signature genes in COVIDsig or nonCOVIDsig identified similar pathways including neutrophil activation, innate immune response, immune response to viral infection and cytokine production. Conversely, for under-expressed genes, pathways indicated repression of lymphocyte differentiation and activation (Fig1). Intersecting the two gene signatures found two genes significantly oppositely regulated (ACO1, ATL3). We derived a third gene signature using COCONUT to compare COVID-19 to non-COVID-19 viral infections (416 genes) (Fig2). Pathway analysis did not result in significant enrichment, suggesting identification of novel biology (Fig1). Statistical deconvolution of bulk transcriptomic data found M1 macrophages, plasmacytoid dendritic cells, CD14+ monocytes, CD4+ T cells and total B cells changed in the same direction across COVID-19 and non-COVID-19 infections. Cell types that increased in COVID-19 relative to non-COVID-19 were CD56bright NK cells, M2 macrophages and total NK cells. Those that decreased in non-COVID-19 relative to COVID-19 were CD56dim NK cells & memory B cells and eosinophils (Fig3). Figure 1 Figure 2 Figure 3 Conclusion The concordant and discordant responses mapped here provide a window to explore the pathophysiology of COVID-19 vs other viral infections and show clear differences in signaling pathways and cellularity as part of the host response to SARS-CoV-2. Disclosures Simone A. Thair, PhD, Inflammatix, Inc. (Employee, Shareholder) Yudong He, PhD, Inflammatix Inc. (Employee) Yehudit Hasin-Brumshtein, PhD, Inflammatix (Employee, Shareholder) Suraj Sakaram, MS in Biochemistry and Molecular Biology, Inflammatix (Employee, Other Financial or Material Support, stock options) Rushika R. Pandya, MS, Inflammatix Inc. (Employee, Shareholder) David C. Rawling, PhD, Inflammatix Inc. (Employee, Shareholder) Purvesh Khatri, PhD, Inflammatix Inc. (Shareholder) Timothy Sweeney, MD, PHD, Inflammatix, Inc. (Employee, Shareholder)

scholarly journals Differential Mucin Expression by Respiratory Syncytial Virus and Human Metapneumovirus Infection in Human Epithelial Cells

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Ma. Del Rocío Baños-Lara ◽  
Boyang Piao ◽  
Antonieta Guerrero-Plata
Keyword(s):  
Immune Response ◽  
Respiratory Syncytial Virus ◽  
Epithelial Cells ◽  
Viral Infections ◽  
Human Metapneumovirus ◽  
Human Epithelial Cells ◽  
Mucin Expression ◽  
Rsv Infection ◽  
Syncytial Virus ◽  
Tract Disease

Mucins (MUC) constitute an important component of the inflammatory and innate immune response. However, the expression of these molecules by respiratory viral infections is still largely unknown. Respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) are two close-related paramyxoviruses that can cause severe low respiratory tract disease in infants and young children worldwide. Currently, there is not vaccine available for neither virus. In this work, we explored the differential expression of MUC by RSV and hMPV in human epithelial cells. Our data indicate that the MUC expression by RSV and hMPV differs significantly, as we observed a stronger induction of MUC8, MUC15, MUC20, MUC21, and MUC22 by RSV infection while the expression of MUC1, MUC2, and MUC5B was dominated by the infection with hMPV. These results may contribute to the different immune response induced by these two respiratory viruses.

scholarly journals Deficient Immune Response to Viral Infections in Children Predicts Later Asthma Persistence

2018 ◽  
Vol 197 (5) ◽  
pp. 673-675 ◽  
Author(s):  
Simonetta Baraldo ◽  
Marco Contoli ◽  
Matteo Bonato ◽  
Deborah Snijders ◽  
Davide Biondini ◽  
...  
Keyword(s):  
Immune Response ◽  
Viral Infections

scholarly journals The Role of Micronutrients in Support of the Immune Response against Viral Infections

Nutrients ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 3198 ◽  
Author(s):  
Francesco Pecora ◽  
Federica Persico ◽  
Alberto Argentiero ◽  
Cosimo Neglia ◽  
Susanna Esposito
Keyword(s):  
Fatty Acids ◽  
Immune Response ◽  
Immune System ◽  
Viral Infections ◽  
Omega 3 Fatty Acids ◽  
Omega 3 ◽  
Optimal Function ◽  
The Impact

Viral infections are a leading cause of morbidity and mortality worldwide, and the importance of public health practices including handwashing and vaccinations in reducing their spread is well established. Furthermore, it is well known that proper nutrition can help support optimal immune function, reducing the impact of infections. Several vitamins and trace elements play an important role in supporting the cells of the immune system, thus increasing the resistance to infections. Other nutrients, such as omega-3 fatty acids, help sustain optimal function of the immune system. The main aim of this manuscript is to discuss of the potential role of micronutrients supplementation in supporting immunity, particularly against respiratory virus infections. Literature analysis showed that in vitro and observational studies, and clinical trials, highlight the important role of vitamins A, C, and D, omega-3 fatty acids, and zinc in modulating the immune response. Supplementation with vitamins, omega 3 fatty acids and zinc appears to be a safe and low-cost way to support optimal function of the immune system, with the potential to reduce the risk and consequences of infection, including viral respiratory infections. Supplementation should be in addition to a healthy diet and fall within recommended upper safety limits set by scientific expert bodies. Therefore, implementing an optimal nutrition, with micronutrients and omega-3 fatty acids supplementation, might be a cost-effective, underestimated strategy to help reduce the burden of infectious diseases worldwide, including coronavirus disease 2019 (COVID-19).

scholarly journals Epigenetic dysregulation of ACE2 and interferon-regulated genes might suggest increased COVID-19 susceptibility and severity in lupus patients

2020 ◽  
Author(s):  
Amr H. Sawalha ◽  
Ming Zhao ◽  
Patrick Coit ◽  
Qianjin Lu
Keyword(s):  
Oxidative Stress ◽  
Immune Response ◽  
Viral Entry ◽  
Viral Infections ◽  
Severe Disease ◽  
Disease Course ◽  
Vicious Cycle ◽  
Respiratory Complications ◽  
Disease Remission ◽  
Functional Receptor

SummaryInfection caused by SARS-CoV-2 can result in severe respiratory complications and death. Patients with a compromised immune system are expected to be more susceptible to a severe disease course. In this report we suggest that patients with systemic lupus erythematous might be especially prone to severe COVID-19 independent of their immunosuppressed state from lupus treatment. Specially, we provide evidence in lupus to suggest hypomethylation and overexpression of ACE2, which is located on the X chromosome and encodes a functional receptor for the SARS-CoV-2 spike glycoprotein. Oxidative stress induced by viral infections exacerbates the DNA methylation defect in lupus, possibly resulting in further ACE2 hypomethylation and enhanced viremia. In addition, demethylation of interferon-regulated genes, NFκB, and key cytokine genes in lupus patients might exacerbate the immune response to SARS-CoV-2 and increase the likelihood of cytokine storm. These arguments suggest that inherent epigenetic dysregulation in lupus might facilitate viral entry, viremia, and an excessive immune response to SARS-CoV-2. Further, maintaining disease remission in lupus patients is critical to prevent a vicious cycle of demethylation and increased oxidative stress, which will exacerbate susceptibility to SARS-CoV-2 infection during the current pandemic. Epigenetic control of the ACE2 gene might be a target for prevention and therapy in COVID-19.

scholarly journals Directed attenuation to enhance vaccine immunity

2021 ◽  
Vol 17 (2) ◽  
pp. e1008602
Author(s):  
Rustom Antia ◽  
Hasan Ahmed ◽  
James J. Bull
Keyword(s):  
Immune Response ◽  
Genetic Engineering ◽  
Adaptive Immunity ◽  
Immune Evasion ◽  
Viral Infections ◽  
Wild Type Virus ◽  
Type Virus ◽  
Wild Type ◽  
Innate And Adaptive Immunity ◽  
Live Attenuated Vaccines

Many viral infections can be prevented by immunizing with live, attenuated vaccines. Early methods of attenuation were hit-and-miss, now much improved by genetic engineering. However, even current methods operate on the principle of genetic harm, reducing the virus’s ability to grow. Reduced viral growth has the undesired side-effect of reducing the host immune response below that of infection with wild-type. Might some methods of attenuation instead lead to an increased immune response? We use mathematical models of the dynamics of virus with innate and adaptive immunity to explore the tradeoff between attenuation of virus pathology and immunity. We find that modification of some virus immune-evasion pathways can indeed reduce pathology yet enhance immunity. Thus, attenuated vaccines can, in principle, be directed to be safe yet create better immunity than is elicited by the wild-type virus.

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