The IFNL4 Gene Is a Noncanonical Interferon Gene with a Unique but Evolutionarily Conserved Regulation

ABSTRACT Interferon lambda 4 (IFN-λ4) is a recently identified enigmatic member of the interferon (IFN) lambda family. Genetic data suggest that the IFNL4 gene acts in a proviral and anti-inflammatory manner in patients. However, the protein is indistinguishable in vitro from the other members of the interferon lambda family. We have investigated the gene regulation of IFNL4 in detail and found that it differs radically from that of canonical antiviral interferons. Being induced by viral infection is a defining characteristic of interferons, but viral infection or overexpression of members of the interferon regulatory factor (IRF) family of transcription factors only leads to a minute induction of IFNL4. This behavior is evolutionarily conserved and can be reversed by inserting a functional IRF3 binding site into the IFNL4 promoter. Thus, the regulation of the IFNL4 gene is radically different and might explain some of the atypical phenotypes associated with the IFNL4 gene in humans. IMPORTANCE Recent genetic evidence has highlighted how the IFNL4 gene acts in a counterintuitive manner, as patients with a nonfunctional IFNL4 gene exhibit increased clearance of hepatitis C virus (HCV) but also increased liver inflammation. This suggests that the IFNL4 gene acts in a proviral and anti-inflammatory manner. These surprising but quite clear genetic data have prompted an extensive examination of the basic characteristics of the IFNL4 gene and its gene product, interferon lambda 4 (IFN-λ4). We have investigated the expression of the IFNL4 gene and found it to be poorly induced by viral infections. A thorough investigation of the IFNL4 promoter revealed a highly conserved and functional promoter, but also one that lacks the defining characteristic of interferons (IFNs), i.e., the ability to be effectively induced by viral infections. We suggest that the unique function of the IFNL4 gene is related to its noncanonical transcriptional regulation.

Download Full-text

Principles of healing of virus-infected raspberry varieties by chemotherapy in vitro

Interdepartmental Thematic Scientific Collection of Plant Protection and Quarantine ◽

10.36495/1606-9773.2018.64.90-98 ◽

2018 ◽

pp. 90-98

Author(s):

T. Medvedeva ◽

T. Natalchuk ◽

K. Suprun ◽

I. Ryaba ◽

N. Triapitsyna

Keyword(s):

Viral Infection ◽

Plant Material ◽

Viral Infections ◽

Virus Concentration ◽

Material Production ◽

Prolonged Effect ◽

Hybrid Forms

Most of promising raspberry varieties need to be heal from complex viral infections. Development of the most standardized and universal plant healing methods — one of the actual tasks of biotechnology works for raspberries plant material production. The decrease of virus concentration in explants of some promising hybrid forms and varieties of raspberry affected by complex viral infection were analyzed with semi quantitative LIA method after explants treatment with ribavirin. Rated the therapeutic, toxic and prolonged effect of ribavirin for elimination of four viruses were evaluated. It was revealed universal peculiarities for chemotherapy of raspberries shoots using this virocide.

Download Full-text

Scutellaria baicalensis Ameliorates Acute Lung Injury by Suppressing Inflammation In Vitro and In Vivo

The American Journal of Chinese Medicine ◽

10.1142/s0192415x17500100 ◽

2017 ◽

Vol 45 (01) ◽

pp. 137-157 ◽

Cited By ~ 18

Author(s):

Jian-Jung Chen ◽

Chung-Chun Huang ◽

Heng-Yuan Chang ◽

Pei-Ying Li ◽

Yu-Chia Liang ◽

...

Keyword(s):

Lung Injury ◽

Viral Infections ◽

Inflammatory Diseases ◽

Water Extract ◽

Scutellaria Baicalensis ◽

Raw 264.7 Cells ◽

Necrosis Factor Alpha ◽

Anti Inflammatory

Scutellaria baicalensis has been widely used as both a dietary ingredient and traditional herbal medicine in Taiwan to treat inflammation, cancer, and bacterial and viral infections of the respiratory tract and gastrointestinal tract. This paper aims to investigate the in vitro and in vivo anti-inflammatory effects of S. baicalensis. In HPLC analysis, the fingerprint chromatogram of the water extract of S. baicalensis (WSB) was established. The anti-inflammatory effects of WSB were inverstigated using lipopolysaccharide (LPS)-stimulated mouse macrophage (RAW264.7) in vitro and LPS-induced lung injury in vivo. WSB attenuated the production of LPS-induced nitric oxide (NO), tumor necrosis factor-alpha (TNF-[Formula: see text], interleukin-[Formula: see text] (IL-1[Formula: see text], and IL-6 in vitro and in vivo. Pretreatment with WSB markedly reduced the LPS-induced histological alterations in lung tissues. Furthermore, WSB significantly reduced the number of total cells and the protein concentration levels in the BALF. WSB blocked protein expression of inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), phosphorylation of I[Formula: see text]B-[Formula: see text] protein and MAPKs in LPS-stimulated RAW 264.7 cells and LPS-induce lung injury was also blocked. This study suggests that WSB possesses anti-inflammatory effects in vitro and in vivo, and the results suggested that WSB may be a potential therapeutic candidate for the treatment of inflammatory diseases.

Download Full-text

Myxomavirus-Derived Serpin Prolongs Survival and Reduces Inflammation and Hemorrhage in an Unrelated Lethal Mouse Viral Infection

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.02594-12 ◽

2013 ◽

Vol 57 (9) ◽

pp. 4114-4127 ◽

Cited By ~ 21

Author(s):

Hao Chen ◽

Donghang Zheng ◽

Jeff Abbott ◽

Liying Liu ◽

Mee Y. Bartee ◽

...

Keyword(s):

Viral Infection ◽

Serine Proteases ◽

Viral Infections ◽

Inflammatory Responses ◽

Clotting Factor ◽

Factor X ◽

Virus Load ◽

Murine Gammaherpesvirus ◽

Wide Range ◽

Anti Inflammatory

ABSTRACTLethal viral infections produce widespread inflammation with vascular leak, clotting, and bleeding (disseminated intravascular coagulation [DIC]), organ failure, and high mortality. Serine proteases in clot-forming (thrombotic) and clot-dissolving (thrombolytic) cascades are activated by an inflammatory cytokine storm and also can induce systemic inflammation with loss of normalserineproteaseinhibitor (serpin) regulation. Myxomavirus secretes a potent anti-inflammatory serpin, Serp-1, that inhibits clotting factor X (fX) and thrombolytic tissue- and urokinase-type plasminogen activators (tPA and uPA) with anti-inflammatory activity in multiple animal models. Purified serpin significantly improved survival in a murine gammaherpesvirus 68 (MHV68) infection in gamma interferon receptor (IFN-γR) knockout mice, a model for lethal inflammatory vasculitis. Treatment of MHV68-infected mice with neuroserpin, a mammalian serpin that inhibits only tPA and uPA, was ineffective. Serp-1 reduced virus load, lung hemorrhage, and aortic, lung, and colon inflammation in MHV68-infected mice and also reduced virus load. Neuroserpin suppressed a wide range of immune spleen cell responses after MHV68 infection, while Serp-1 selectively increased CD11c+splenocytes (macrophage and dendritic cells) and reduced CD11b+tissue macrophages. Serp-1 altered gene expression for coagulation and inflammatory responses, whereas neuroserpin did not. Serp-1 treatment was assessed in a second viral infection, mouse-adapted Zaire ebolavirus in wild-type BALB/c mice, with improved survival and reduced tissue necrosis. In summary, treatment with this unique myxomavirus-derived serpin suppresses systemic serine protease and innate immune responses caused by unrelated lethal viral infections (both RNA and DNA viruses), providing a potential new therapeutic approach for treatment of lethal viral sepsis.

Download Full-text

Fucoidan and Lung Function: Value in Viral Infection

Marine Drugs ◽

10.3390/md19010004 ◽

2020 ◽

Vol 19 (1) ◽

pp. 4

Author(s):

J. Helen Fitton ◽

Ah Young Park ◽

Samuel S. Karpiniec ◽

Damien N. Stringer

Keyword(s):

Innate Immunity ◽

Lung Function ◽

Viral Infection ◽

Animal Studies ◽

Viral Infections ◽

Short Review ◽

Lung Damage ◽

Acute Viral Infection ◽

Pulmonary Damage

Compromised lung function is a feature of both infection driven and non-infective pathologies. Viral infections—including the current pandemic strain SARS-CoV-2—that affect lung function can cause both acute and long-term chronic damage. SARS-CoV-2 infection suppresses innate immunity and promotes an inflammatory response. Targeting these aspects of SARS-CoV-2 is important as the pandemic affects greater proportions of the population. In clinical and animal studies, fucoidans have been shown to increase innate immunity and decrease inflammation. In addition, dietary fucoidan has been shown to attenuate pulmonary damage in a model of acute viral infection. Direct inhibition of SARS-CoV-2 in vitro has been described, but is not universal. This short review summarizes the current research on fucoidan with regard to viral lung infections and lung damage.

Download Full-text

Assessment of different ways of improving promising potato varieties and hybrids

Siberian Herald of Agricultural Science ◽

10.26898/0370-8799-2020-4-3 ◽

2020 ◽

Vol 50 (4) ◽

pp. 23-31

Author(s):

V. I. Kulikova ◽

V. P. Khodaeva ◽

N. A. Lapshinov

Keyword(s):

Viral Infection ◽

Apical Meristem ◽

Viral Infections ◽

Fungal Infections ◽

Axillary Buds ◽

Health Improvement ◽

New Variety ◽

Phases Of Development ◽

Regenerant Plants

The results of application of the apical meristem method for the selection of regenerant plants free of pathogens are presented. The study was carried out in laboratory and field conditions of Kemerovo region (2016–2019). The objects of research were a new variety of Pamyati Anoshkinoi and promising hybrids 6-14-11, 22103-10. The experiment on the health improvement of potatoes was carried out by the following methods: 1) the use of chemotherapy with the addition of virus inhibitors to the nutrient medium on the samples containing a viral infection in a latent form; 2) study of vegetative plants of different ages healthy from pathogens using apical and axillary buds as explants. Antiviral drugs and their concentrations were identified: virazole 0.01% + chitosan 0.05% + interferon 0.05% (a combination of drugs) and cycloferon 0.05%, completely suppressing viral infection SBK and MBK in the Pamyati Anoshkinoi variety and 22103-10 hybrid, and YBK in 6-14-11 hybrid. The use of these drugs makes it possible to obtain from 10 to 50% of viable meristems free from viral infections. Research into the improvement of vegetative plants of potato variety Pamyati Anoshkinoi and 22103-10 hybrid revealed phases of growth and development with less accumulation of viral and fungal infections – a period of plant regrowth of 15–20 cm and a phase of flowering. Isolation of the apical meristem from the apical and axillary buds of healthy vegetative plants in these phases of development has a positive effect on the survival of the meristems (3050%), and makes it possible to obtain from 30.0 to 43.3% of regenerant plants free from infections, which ensures a reliable yield in vitro material and reduces the period for obtaining healthy lines by 6.9 times.

Download Full-text

Intracellular Lipid Droplet Accumulation Occurs Early Following Viral Infection and Is Required for an Efficient Interferon Response

10.1101/2020.02.12.946749 ◽

2020 ◽

Author(s):

EA Monson ◽

KM Crosse ◽

M Duan ◽

W Chen ◽

RD O’Shea ◽

...

Keyword(s):

Viral Replication ◽

Viral Infection ◽

Molecular Mechanisms ◽

Viral Infections ◽

Interferon Response ◽

Type I ◽

Antiviral Immune Response ◽

Alternate Mechanism

SummaryLipid droplets (LDs) are increasingly recognized as critical organelles in signalling events, transient protein sequestration and inter-organelle interactions. However, the role LDs play in antiviral innate immune pathways remains unknown. Here we demonstrate that induction of LDs occurs as early as 2 hours post viral infection, is transient, and returns to basal levels by 72 hours. This phenomenon occurred following viral infections, both in vitro and in vivo. Virally driven LD induction was type-I interferon (IFN) independent, however, was dependent on EGFR engagement, offering an alternate mechanism of LD induction in comparison to our traditional understanding of their biogenesis. Additionally, LD induction corresponded with enhanced cellular type-I and -III IFN production in infected cells, with enhanced LD accumulation decreasing viral replication of both HSV-1 and Zika virus (ZIKV). Here, we demonstrate for the first time, that LDs play vital roles in facilitating the magnitude of the early antiviral immune response specifically through the enhanced modulation of IFN following viral infection, and control of viral replication. By identifying LDs as a critical signalling organelle, this data represents a paradigm shift in our understanding of the molecular mechanisms which coordinate an effective antiviral response.

Download Full-text

High-Throughput Screening Platform for the Discovery of New Immunomodulator Molecules from Natural Product Extract Libraries

CrossRef Listing of Deleted DOIs ◽

10.1177/1087057116635517 ◽

2016 ◽

Vol 21 (6) ◽

pp. 567-578 ◽

Cited By ~ 6

Author(s):

José Pérez del Palacio ◽

Caridad Díaz ◽

Mercedes de la Cruz ◽

Frederick Annang ◽

Jesús Martín ◽

...

Keyword(s):

Neurodegenerative Diseases ◽

Natural Product ◽

High Throughput ◽

High Throughput Screening ◽

Viral Infections ◽

Inflammatory Diseases ◽

Immunomodulatory Activity ◽

Inflammatory Drugs ◽

Anti Inflammatory

It is widely accepted that central nervous system inflammation and systemic inflammation play a significant role in the progression of chronic neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease, neurotropic viral infections, stroke, paraneoplastic disorders, traumatic brain injury, and multiple sclerosis. Therefore, it seems reasonable to propose that the use of anti-inflammatory drugs might diminish the cumulative effects of inflammation. Indeed, some epidemiological studies suggest that sustained use of anti-inflammatory drugs may prevent or slow down the progression of neurodegenerative diseases. However, the anti-inflammatory drugs and biologics used clinically have the disadvantage of causing side effects and a high cost of treatment. Alternatively, natural products offer great potential for the identification and development of bioactive lead compounds into drugs for treating inflammatory diseases with an improved safety profile. In this work, we present a validated high-throughput screening approach in 96-well plate format for the discovery of new molecules with anti-inflammatory/immunomodulatory activity. The in vitro models are based on the quantitation of nitrite levels in RAW264.7 murine macrophages and interleukin-8 in Caco-2 cells. We have used this platform in a pilot project to screen a subset of 5976 noncytotoxic crude microbial extracts from the MEDINA microbial natural product collection. To our knowledge, this is the first report on an high-throughput screening of microbial natural product extracts for the discovery of immunomodulators.

Download Full-text

Efficacy of FDA-Approved Anti-Inflammatory Drugs Against Venezuelan Equine Encephalitis Virus Infection

Viruses ◽

10.3390/v11121151 ◽

2019 ◽

Vol 11 (12) ◽

pp. 1151 ◽

Cited By ~ 1

Author(s):

Kenneth Risner ◽

Aslaa Ahmed ◽

Allison Bakovic ◽

Stephanie Kortchak ◽

Nishank Bhalla ◽

...

Keyword(s):

Viral Infections ◽

Neurological Complications ◽

Venezuelan Equine Encephalitis Virus ◽

Encephalitis Virus ◽

Venezuelan Equine Encephalitis ◽

Equine Encephalitis Virus ◽

Inflammatory Drugs ◽

Anti Inflammatory ◽

Pre Treatment

Venezuelan equine encephalitis virus (VEEV) is a category B select agent pathogen that can be aerosolized. Infections in murine models and humans can advance to an encephalitic phenotype which may result in long-term neurological complications or death. No specific FDA-approved treatments or vaccines are available for the treatment or prevention of VEEV infection. Neurotropic viral infections have two damaging components: neuronal death caused by viral replication, and damage from the subsequent inflammatory response. Reducing the level of inflammation may lessen neurological tissue damage that often arises following VEEV infection. In this study, three commercially available anti-inflammatory drugs, Celecoxib, Rolipram, and Tofacitinib, were evaluated for antiviral activity in an astrocyte and a microglial model of VEEV infection. The inhibitors were tested against the vaccine strain VEEV TC-83, as well as the wild-type VEEV Trinidad donkey strain. Celecoxib, Tofacitinib, and Rolipram significantly decreased viral titers both after pre-treatment and post-treatment of infected cells. VEEV Trinidad Donkey (TrD) titers were reduced 6.45-fold in cells treated with 50 µM of Celecoxib, 2.45-fold when treated with 50 µM of Tofacitinib, and 1.81-fold when treated with 50 µM of Rolipram. Celecoxib was also shown to decrease inflammatory gene expression in the context of TC-83 infection. Overall, Celecoxib demonstrated potency as a countermeasure strategy that slowed VEEV infection and infection-induced inflammation in an in vitro model.

Download Full-text

Mesenchymal Stromal Cells and Viral Infection

Stem Cells International ◽

10.1155/2015/860950 ◽

2015 ◽

Vol 2015 ◽

pp. 1-8 ◽

Cited By ~ 24

Author(s):

Maytawan Thanunchai ◽

Suradej Hongeng ◽

Arunee Thitithanyanont

Keyword(s):

Viral Infection ◽

Mesenchymal Stromal Cells ◽

Stromal Cells ◽

Immune Modulation ◽

Adult Stem Cells ◽

Viral Infections ◽

Ex Vivo ◽

Allogeneic Transplantation ◽

Viral Reactivation

Mesenchymal Stromal Cells (MSCs) are a subset of nonhematopoietic adult stem cells, readily isolated from various tissues and easily culture-expandedex vivo. Intensive studies of the immune modulation and tissue regeneration over the past few years have demonstrated the great potential of MSCs for the prevention and treatment of steroid-resistant acute graft-versus-host disease (GvHD), immune-related disorders, and viral diseases. In immunocompromised individuals, the immunomodulatory activities of MSCs have raised safety concerns regarding the greater risk of primary viral infection and viral reactivation, which is a major cause of mortality after allogeneic transplantation. Moreover, high susceptibilities of MSCs to viral infectionsin vitrocould reflect the destructive outcomes that might impair the clinical efficacy of MSCs infusion. However, the interplay between MSCs and virus is like a double-edge sword, and it also provides beneficial effects such as allowing the proliferation and function of antiviral specific effector cells instead of suppressing them, serving as an ideal tool for study of viral pathogenesis, and protecting hosts against viral challenge by using the antimicrobial activity. Here, we therefore review favorable and unfavorable consequences of MSCs and virus interaction with the highlight of safety and efficacy for applying MSCs as cell therapy.

Download Full-text

Transcriptome and Coronavirus: New Hope and Therapy

Biointerface Research in Applied Chemistry ◽

10.33263/briac112.95419552 ◽

2020 ◽

Vol 11 (2) ◽

pp. 9541-9552

Keyword(s):

Viral Infection ◽

Host Cell ◽

Genome Size ◽

Viral Entry ◽

Viral Infections ◽

Cell Transformation ◽

In Vitro Study ◽

Cell Protein ◽

Transformation Mechanism

Transcriptome refers to all RNA particles occur inside one cell or inside numerous cells in one organ. Coronaviruses are a family of correlated viruses that induce viral infection. In humans, coronaviruses induce respiratory viral infections that may be mild or dangerous. The coronavirus shape is large circular elements that have round tip outbreaks - the virus diameter particles=120 nm. The RNA viral genome occurs in coronavirus. The coronavirus genome size = 27-34 kilobases, and this size is the largest RNA genome size. The Life cycle of coronavirus includes viral entry, replication, and release. Coronavirus transmission was done through the connection of its protein with host cell receptors in a specific process. There are 4 types of coronavirus genus: (1) Alphacoronavirus, (2) Betacoronavirus, (3) Gammacoronavirus, and (4) Deltacoronavirus. Viral replication, immune evasion, and virion biogenesis correlated with host cell transformation mechanism. Viral molecular mechanism hijacks the host cell protein production mechanism. There is an important host factor (CPSF6) that connects with nuclear protein (NP1). The CPSF6 increases the nuclear production of NP1 in the same time, CPSF6 possesses an important role in the progress of capsid mRNAs inside the nucleus. In a viral infection, there is an increase in mRNA, myeloid differentiation 2-related lipid recognition protein (ML), and Niemann Pick-type C1 (NPC1) genes. Coronavirus is capable of replicating in in vitro study and causes lower transcriptomic variations before 12 h after viral infection. As infection progress, coronavirus causes a significant dysregulation of the host transcriptome greater than the SARS virus. In conclusion, future transcriptome studies are the basis for detecting coronavirus in the human host and for developing a specific preventive and therapeutic method for the virus.

Download Full-text