scholarly journals THE INFLUENCE OF CORTISONE ON EXPERIMENTAL VIRAL INFECTION

1966 ◽  
Vol 123 (5) ◽  
pp. 767-775 ◽  
Author(s):  
Michael W. Rytel ◽  
Edwin D. Kilbourne
Keyword(s):  
Viral Infection ◽  
Intravenous Injection ◽  
Marked Reduction ◽  
Interferon Response ◽  
Experimental Viral Infection

The administration, of 5.0 mg of cortisone 6 to 24 hr prior to the intravenous injection of mice with NDV was associated with a marked reduction in the interferon response as measured in serum and spleen. Reduced concentrations of interferon following cortisone pretreatment were demonstrable from 6 to 16 hr following injection of virus.

OBSERVATIONS ON THE RELATIONSHIP BETWEEN OXYTOCIN AND ADRENALINE IN MILK EJECTION IN THE SOW

1952 ◽  
Vol 8 (3) ◽  
pp. 238-241 ◽  
Author(s):  
R. BRAUDE ◽  
K. G. MITCHELL
Keyword(s):  
Intravenous Injection ◽  
Marked Reduction ◽  
Milk Ejection ◽  
The Relationship

The intravenous injection of adrenaline simultaneously with 1 i.u. of Pitocin in the sow caused a marked reduction in the amount of milk that is normally ejected following the injection of 1 i.u. of Pitocin alone. In each sow a plateau was reached with a dose of approximately 400 μg. of adrenaline, and an increase in the amount of adrenaline injected up to 2000 μg. did not cause any further reduction in the amount of milk ejected. The injection of 1000 μg. adrenaline, 62 to 90 secs, before the injection of 1 i.u. of Pitocin, completely inhibited the ejection of milk associated with the latter. In two out of three sows a definite, though small, ejection of milk occurred following the injection of either 400 or 1000μg. of adrenaline alone. The possible actions of adrenaline in these experiments are discussed.

scholarly journals Virus-inclusive single cell RNA sequencing reveals molecular signature predictive of progression to severe dengue infection

2018 ◽  
Author(s):  
Fabio Zanini ◽  
Makeda L. Robinson ◽  
Derek Croote ◽  
Malaya Kumar Sahoo ◽  
Ana Maria Sanz ◽  
...  
Keyword(s):  
B Cells ◽  
Viral Infection ◽  
Single Cell ◽  
Immune Activation ◽  
Dengue Infection ◽  
Predictive Biomarkers ◽  
Molecular Signature ◽  
Interferon Response ◽  
Severe Dengue ◽  
Specific Cell

AbstractDengue virus (DENV) infection can result in severe complications. Yet, the understanding of the molecular correlates of severity is limited, partly due to difficulties in defining the peripheral blood mononuclear cells (PBMCs) that are associated with DENV in vivo. Additionally, there are currently no biomarkers predictive of progression to severe dengue (SD). Bulk transcriptomics data are difficult to interpret because blood consists of multiple cell types that may react differently to infection. Here we applied virus-inclusive single cell RNA-seq approach (viscRNA-Seq) to profile transcriptomes of thousands of single PBMCs derived early in the course of disease from six dengue patients and four healthy controls, and to characterize distinct DENV-associated leukocytes. Multiple genes, particularly interferon response genes, were upregulated in a cell-specific manner prior to progression to SD. Expression of MX2 in naive B cells and CD163 in CD14+ CD16+ monocytes was predictive of SD. The majority of DENV-associated cells in the blood of two patients who progressed to SD were naive IgM B cells expressing the CD69 and CXCR4 receptors and antiviral genes, followed by monocytes. Bystander uninfected B cells also demonstrated immune activation, and plasmablasts from two patients exhibited antibody lineages with convergently hypermutated heavy chain sequences. Lastly, assembly of the DENV genome revealed diversity at unexpected genomic sites. This study presents a multi-faceted molecular elucidation of natural dengue infection in humans and proposes biomarkers for prediction of SD, with implications for profiling any tissue and viral infection, and for the development of a dengue prognostic assay.SignificanceA fraction of the 400 million people infected with dengue annually progresses to severe dengue (SD). Yet, there are currently no biomarkers to effectively predict disease progression. We profiled the landscape of host transcripts and viral RNA in thousands of single blood cells from dengue patients prior to progressing to SD. We discovered cell-type specific immune activation and candidate predictive biomarkers. We also revealed preferential virus association with specific cell populations, particularly naive B cells and monocytes. We then explored immune activation of bystander cells, clonality and somatic evolution of adaptive immune repertoires, and viral genomics. This multi-faceted approach could advance understanding of pathogenesis of any viral infection, map an atlas of infected cells and promote the development of prognostics.

scholarly journals The Trans-zoonotic Virome interface: Measures to balance, control and treat epidemics

2020 ◽  
Vol 4 (1) ◽  
pp. 020-027
Author(s):  
Nikhra Vinod
Keyword(s):  
Immune Response ◽  
Viral Load ◽  
Immune System ◽  
Viral Infection ◽  
Antiviral Therapy ◽  
Viral Infections ◽  
Habitat Destruction ◽  
Interferon Response ◽  
Viral Diseases ◽  
Intracellular Parasites

The global virome: The viruses have a global distribution, phylogenetic diversity and host specificity. They are obligate intracellular parasites with single- or double-stranded DNA or RNA genomes, and afflict bacteria, plants, animals and human population. The viral infection begins when surface proteins bind to receptor proteins on the host cell surface, followed by internalisation, replication and lysis. Further, trans-species interactions of viruses with bacteria, small eukaryotes and host are associated with various zoonotic viral diseases and disease progression. Virome interface and transmission: The cross-species transmission from their natural reservoir, usually mammalian or avian, hosts to infect human-being is a rare probability, but occurs leading to the zoonotic human viral infection. The factors like increased human settlements and encroachments, expanded travel and trade networks, altered wildlife and livestock practices, modernised and mass-farming practices, compromised ecosystems and habitat destruction, and global climate change have impact on the interactions between virome and its hosts and other species and act as drivers of trans-species viral spill-over and human transmission. Zoonotic viral diseases and epidemics: The zoonotic viruses have caused various deadly pandemics in human history. They can be further characterized as either newly emerging or re-emerging infectious diseases, caused by pathogens that historically have infected the same host species, but continue to appear in new locations or in drug-resistant forms, or reappear after apparent control or elimination. The prevalence of zoonoses underlines importance of the animal–human–ecosystem interface in disease transmission. The present COVID-19 infection has certain distinct features which suppress the host immune response and promote the disease potential. Treatment for epidemics like covid-19: It appears that certain nutraceuticals may provide relief in clinical symptoms to patients infected with encapsulated RNA viruses such as influenza and coronavirus. These nutraceuticals appear to reduce the inflammation in the lungs and help to boost type 1 interferon response to these viral infections. The human intestinal microbiota acting in tandem with the host’s defence and immune system, is vital for homeostasis and preservation of health. The integrity and balanced activity of the gut microbes is responsible for the protection from disease states including viral infections. Certain probiotics may help in improving the sensitivity and effectivity of immune system against viral infections. Currently, antiviral therapy is available only for a limited number of zoonotic viral infections. Because viruses are intracellular parasites, antiviral drugs are not able to deactivate or destroy the virus but can reduce the viral load by inhibiting replication and facilitating the host’s innate immune mechanisms to neutralize the virus. Conclusion: Lessons from recent viral epidemics - Considering that certain nutraceuticals have demonstrated antiviral effects in both clinical and animal studies, further studies are required to establish their therapeutic efficacy. The components of nutraceuticals such as luteolin, apigenin, quercetin and chlorogenic acid may be useful for developing a combo-therapy. The use of probiotics to enhance immunity and immune response against viral infections is a novel possibility. The available antiviral therapy is inefficient in deactivating or destroying the infecting viruses, may help in reducing the viral load by inhibiting replication. The novel efficient antiviral agents are being explored.

scholarly journals NSUN2-mediated m5C methylation of IRF3 mRNA negatively regulates type I interferon responses

2021 ◽  
Author(s):  
Hongyun Wang ◽  
Lu Zhang ◽  
Cong Zeng ◽  
Jiangpeng Feng ◽  
Yu Zhou ◽  
...  
Keyword(s):  
Viral Infection ◽  
Type I Interferon ◽  
Sendai Virus ◽  
Negative Regulator ◽  
Interferon Response ◽  
Rna Modification ◽  
Type I ◽  
Mrna Levels ◽  
Interferon Responses

5-Methylcytosine (m5C) is a widespread post-transcriptional RNA modification and is reported to be involved in manifold cellular responses and biological processes through regulating RNA metabolism. However, its regulatory role in antiviral innate immunity has not yet been elucidated. Here, we report that NSUN2, a typical m5C methyltransferase, can negatively regulate type I interferon responses during viral infection. NSUN2 specifically mediates m5C methylation of IRF3 mRNA and accelerates its degradation, resulting in low levels of IRF3 and downstream IFN-β production. Knockout or knockdown of NSUN2 could enhance type I interferon responses and downstream ISG expression after viral infection in vitro. And in vivo, the antiviral innate responses is more dramatically enhanced in Nsun2+/− mice than in Nsun2+/+ mice. Four highly m5C methylated cytosines in IRF3 mRNA were identified, and their mutation could enhance the cellular IRF3 mRNA levels. Moreover, infection with Sendai virus (SeV), vesicular stomatitis virus (VSV), herpes simplex virus 1 (HSV-1), Zika virus (ZIKV), or especially SARS-CoV-2 resulted in a reduction in endogenous levels of NSUN2. Together, our findings reveal that NSUN2 serves as a negative regulator of interferon response by accelerating the fast turnover of IRF3 mRNA, while endogenous NSUN2 levels decrease after viral infection to boost antiviral responses for the effective elimination of viruses. Our results suggest a paradigm of innate antiviral immune responses ingeniously involving NSUN2-mediated m5C modification.

scholarly journals Direct exposure to SARS-CoV-2 and cigarette smoke increases infection severity and alters the stem cell-derived airway repair response

2020 ◽  
Author(s):  
Arunima Purkayastha ◽  
Chandani Sen ◽  
Gustavo Garcia ◽  
Justin Langerman ◽  
Preethi Vijayaraj ◽  
...  
Keyword(s):  
Viral Infection ◽  
Cigarette Smoke ◽  
Smoke Exposure ◽  
Disease Spread ◽  
Interferon Response ◽  
Cigarette Smoke Exposure ◽  
Airway Epithelial ◽  
Airway Injury ◽  
Increased Risk ◽  
Airway Cells

SUMMARYMost demographic studies are now associating current smoking status with increased risk of severe COVID-19 and mortality from the disease but there remain many questions about how direct cigarette smoke exposure affects SARS-CoV-2 airway cell infection. We directly exposed mucociliary air-liquid interface (ALI) cultures derived from primary human nonsmoker airway basal stem cells (ABSCs) to short term cigarette smoke and infected them with live SARS-CoV-2. We found an increase in the number of infected airway cells after cigarette smoke exposure as well as an increased number of apoptotic cells. Cigarette smoke exposure alone caused airway injury that resulted in an increased number of ABSCs, which proliferate to repair the airway. But we found that acute SARS-CoV-2 infection or the combination of exposure to cigarette smoke and SARS-CoV-2 did not induce ABSC proliferation. We set out to examine the underlying mechanism governing the increased susceptibility of cigarette smoke exposed ALI to SARS-CoV-2 infection. Single cell profiling of the cultures showed that infected airway cells displayed a global reduction in gene expression across all airway cell types. Interestingly, interferon response genes were induced in SARS-CoV-2 infected airway epithelial cells in the ALI cultures but smoking exposure together with SARS-CoV-2 infection reduced the interferon response. Treatment of cigarette smoke-exposed ALI cultures with Interferon β-1 abrogated the viral infection, suggesting that the lack of interferon response in the cigarette smoke-exposed ALI cultures allows for more severe viral infection and cell death. In summary, our data show that acute smoke exposure allows for more severe proximal airway epithelial disease from SARS-CoV-2 by reducing the mucosal innate immune response and ABSC proliferation and has implications for disease spread and severity in people exposed to cigarette smoke.

MATERNAL VIRAL INFECTION DURING PREGNANCY PROGRAMS FETAL DEVELOPMENT AND INDUCES A DIFFERENTIAL TYPE 1 INTERFERON RESPONSE

2007 ◽  
Vol 77 (Suppl_1) ◽  
pp. 191-191
Author(s):  
Megan Shoemaker ◽  
Natalia Smirnova ◽  
Hana Van Campen ◽  
Helle Bielefeldt-Ohmann ◽  
Kathy Austin ◽  
...  
Keyword(s):  
Viral Infection ◽  
Fetal Development ◽  
Interferon Response ◽  
Type 1 Interferon ◽  
Differential Type

scholarly journals Parallels between the anti-Viral State and the Irradiated State

2020 ◽  
Author(s):  
Heather M McGee ◽  
Ariel E Marciscano ◽  
Allison M Campbell ◽  
Arta M Monjazeb ◽  
Susan M Kaech ◽  
...  
Keyword(s):  
Viral Infection ◽  
Sterile Inflammation ◽  
Interferon Response ◽  
Tumor Control ◽  
Type I ◽  
Immune Mediated ◽  
Pathogen Control ◽  
Viral Mimicry ◽  
Viral Responses ◽  
Tumor Dna

Abstract Improved understanding of host anti-viral defense and anti-tumor immunity have elucidated molecular pathways important to both processes. During viral infection, RNA or DNA in the host cell serve as danger signals that initiate anti-viral responses. Recent studies have elucidated similarities in signaling pathways activated by viruses and induced by tumor DNA released into the cytoplasm of irradiated tumor cells. The host defense to viral infection and the sterile inflammation provoked by radiotherapy both induce a type I interferon response that is necessary for pathogen control and immune-mediated tumor control, respectively. These findings have led to the hypothesis that radiotherapy employs a form of viral mimicry.

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