scholarly journals NAD+-consuming enzymes in immune defense against viral infection

2021 ◽  
Vol 478 (23) ◽  
pp. 4071-4092
Author(s):  
Jialin Shang ◽  
Michael R. Smith ◽  
Ananya Anmangandla ◽  
Hening Lin
Keyword(s):  
Immune Responses ◽  
Broad Spectrum ◽  
Defense Mechanisms ◽  
Viral Infections ◽  
Antiviral Agents ◽  
Scientific Progress ◽  
Immune Defense ◽  
Past Century ◽  
Antiviral Immune Response ◽  
Antiviral Function

The COVID-19 pandemic reminds us that in spite of the scientific progress in the past century, there is a lack of general antiviral strategies. In analogy to broad-spectrum antibiotics as antibacterial agents, developing broad spectrum antiviral agents would buy us time for the development of vaccines and treatments for future viral infections. In addition to targeting viral factors, a possible strategy is to understand host immune defense mechanisms and develop methods to boost the antiviral immune response. Here we summarize the role of NAD+-consuming enzymes in the immune defense against viral infections, with the hope that a better understanding of this process could help to develop better antiviral therapeutics targeting these enzymes. These NAD+-consuming enzymes include PARPs, sirtuins, CD38, and SARM1. Among these, the antiviral function of PARPs is particularly important and will be a focus of this review. Interestingly, NAD+ biosynthetic enzymes are also implicated in immune responses. In addition, many viruses, including SARS-CoV-2 contain a macrodomain-containing protein (NSP3 in SARS-CoV-2), which serves to counteract the antiviral function of host PARPs. Therefore, NAD+ and NAD+-consuming enzymes play crucial roles in immune responses against viral infections and detailed mechanistic understandings in the future will likely facilitate the development of general antiviral strategies.

scholarly journals Regulation of Antiviral Immune Response by N6-Methyladenosine of mRNA

2021 ◽  
Vol 12 ◽  
Author(s):  
Baoxin Zhao ◽  
Weijie Wang ◽  
Yan Zhao ◽  
Hongxiu Qiao ◽  
Zhiyun Gao ◽  
...  
Keyword(s):  
Immune Responses ◽  
Viral Infection ◽  
Viral Infections ◽  
Immune Cell ◽  
Vital Role ◽  
Immune Defense ◽  
Interferon Response ◽  
Adaptive Immune Responses ◽  
Antiviral Immune Response ◽  
Adaptive Immune

Host innate and adaptive immune responses play a vital role in clearing infected viruses. Meanwhile, viruses also evolve a series of mechanisms to weaken the host immune responses and evade immune defense. Recently, N6-methyladenosine (m6A), the most prevalent mRNA modification, has been revealed to regulate multiple steps of RNA metabolism, such as mRNA splicing, localization, stabilization, and translation, thus participating in many biological phenomena, including viral infection. In the process of virus–host interaction, the m6A modification that presents on the virus RNA impedes capture by the pattern recognition receptors, and the m6A modification appearing on the host immune-related molecules regulate interferon response, immune cell differentiation, inflammatory cytokine production, and other immune responses induced by viral infection. This review summarizes the research advances about the regulatory role of m6A modification in the innate and adaptive immune responses during viral infections.

Contributions of maternal and fetal antiviral immunity in congenital disease

Science ◽  
2020 ◽  
Vol 368 (6491) ◽  
pp. 608-612 ◽  
Author(s):  
Laura J. Yockey ◽  
Carolina Lucas ◽  
Akiko Iwasaki
Keyword(s):  
Immune Responses ◽  
Defense Mechanisms ◽  
Viral Infections ◽  
Treatment Strategies ◽  
Immune Defense ◽  
Congenital Disease ◽  
Fetal Demise ◽  
Developmental Defects ◽  
Maternal Immune Activation

Viral infections during pregnancy can have devastating consequences on pregnancy outcomes, fetal development, and maternal health. In this review, we examine fetal and maternal immune defense mechanisms that mediate resistance against viral infections and discuss the range of syndromes that ensue when such mechanisms fail, from fetal developmental defects to establishment of chronic infection. Further, we highlight the role of maternal immune activation, or uncontrolled inflammation triggered by viral infections during pregnancy, and its potential downstream pathological effects, including tissue damage and fetal demise. Insights into the respective contributions of direct viral toxicity versus fetal and maternal immune responses that underlie the pathogenesis of congenital disease will guide future treatment strategies.

scholarly journals The Antiviral Potential of Probiotics—A Review on Scientific Outcomes

2021 ◽  
Vol 11 (18) ◽  
pp. 8687
Author(s):  
Periyanaina Kesika ◽  
Bhagavathi Sundaram Sivamaruthi ◽  
Subramanian Thangaleela ◽  
Chaiyavat Chaiyasut
Keyword(s):  
Innate Immunity ◽  
Immune Responses ◽  
Viral Infections ◽  
Antiviral Agents ◽  
Therapeutic Agents ◽  
Therapeutic Measures ◽  
Immunomodulatory Properties ◽  
Probiotic Mechanisms ◽  
Antimicrobial Metabolites ◽  
Research Studies

A rich repertoire of research studies on probiotics has been documented as one of the therapeutic agents or adjuvants for vaccines in treating viral infections. It is well known that the immunomodulatory properties of probiotics reduce the severity of viral infections. The efficacy of probiotics alone and combined boost up the host’s innate immunity, thereby developing a robust antiviral paradigm. As dietary and therapeutic measures, probiotics potentially work as an alternative for those who lack access to vaccines or antiviral drugs. Potential probiotic mechanisms include competing with pathogens for nutrients and colonization sites, producing antimicrobial metabolites and enhancing protective immune responses. The live probiotics can reach and colonize the host animals’ intestines then confer the health benefits by improving the host’s natural defence against viral infections. The research studies on probiotics suggest that they reduce the risk of viral infections, yet the innermost mechanisms are still unknown. The reason for scripting this review is to discuss the current developments in probiotic therapeutic measures and their probable insights into antiviral agents.

scholarly journals The Human Papillomavirus (HPV) E1 protein regulates the expression of cellular genes involved in immune response

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Leonardo Josué Castro-Muñoz ◽  
Joaquín Manzo-Merino ◽  
J. Omar Muñoz-Bello ◽  
Leslie Olmedo-Nieva ◽  
Alberto Cedro-Tanda ◽  
...  
Keyword(s):  
Immune Response ◽  
Human Papillomavirus ◽  
Defense Mechanisms ◽  
Viral Infections ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Antiviral Immune Response ◽  
E1 Protein ◽  
Cellular Genes ◽  
Proliferation And Differentiation

Abstract The Human Papillomavirus (HPV) E1 protein is the only viral protein with enzymatic activity. The main known function of this protein is the regulation of the viral DNA replication. Nevertheless, it has been demonstrated that the ablation of HPV18 E1 mRNA in HeLa cells promotes a deregulation of several genes, particularly those involved in host defense mechanisms against viral infections; however, the specific contribution of E1 protein in HPV-independent context has not been studied. The aim of this work was to determine the effect of the HPV E1 protein in the regulation of cellular gene expression profiles evaluated through RNA-seq. We found that E1 proteins from HPV16 and 18 induced an overexpression of different set of genes associated with proliferation and differentiation processes, as well as downregulation of immune response genes, including IFNβ1 and IFNλ1 and Interferon-stimulated gene (ISG), which are important components involved in the antiviral immune response. Together, our results indicate that HR-(High-Risk) and LR-(Low-Risk) HPV E1 proteins play an important role in inhibiting the anti-viral immune response.

scholarly journals Order Diptera as a model in the studies of insect immunity: a review

2020 ◽  
Vol 44 (6) ◽  
pp. 481-489
Author(s):  
Danail Ilchev TAKOV ◽  
Peter Vladislavov OSTOICH ◽  
Andrey Ivanov TCHORBANOV ◽  
Daniela Kirilova PILARSKA
Keyword(s):  
Immune Responses ◽  
Defense Mechanisms ◽  
Immune Defense ◽  
Insect Immunity ◽  
Model Organisms ◽  
Model Species ◽  
Important Group ◽  
Current Review ◽  
Different Types ◽  
Dipteran Species

Order Diptera is the most important group of animals when it comes to insect immunity research. The largest share of experimental data in the group falls on the genus Drosophila - a model species with a number of advantages. Other crucial representatives are those of the mosquito group, as they are vectors of a number of infectious diseases infecting higher vertebrates and humans. As representatives of the genera, Anopheles, Aedes and Culex are very significant model organisms. In total, more than 40 dipteran species are being actively studied as models in various aspects related to immunity. Together with the representatives of the order Lepidoptera, they are the major source of the knowledge gained so far on the defense mechanisms in insects. The current review demonstrates that the studies conducted on dipteran species concern all existing mechanisms of immune defense, namely antimicrobial peptides, signalingpathways, pathogen recognition, the different types of hemocytes, antiviral and other immune responses (phagocytosis, nodulation, melanization and encapsulation).

scholarly journals Antibiotics Against COVID-19 and Mitochondria? Urgent Thinking Out of the Box

2020 ◽  
Author(s):  
Jaroslaw Tyszka ◽  
Karolina Kobos ◽  
Aleksandra Tyszka
Keyword(s):  
Immune System ◽  
Immune Responses ◽  
Viral Infections ◽  
Treatment Strategies ◽  
Local Health ◽  
Antiviral Immune Response ◽  
Health Authorities ◽  
Treatment Data ◽  
The Moment ◽  
The Impact

Italian, Spanish, French vs German, Austrian or Norwegian COVID-19 tracks? Antibiotics might have a partial impact on COVID-19 death rates in various countries. Our working hypotheses based on recent publications is that that antibiotics may be a major factor that negatively affects patients’ immune system during viral infections. We are all aware that there is no specific and effective medical treatment for COVID-19 so far. However, we know that our immune system is the only efficient weapon that fights against this syndrome right now. In fact, antibiotics are very often prescribed to prevent secondary infections following an antiviral immune response. Various antibiotic therapies have also been commonly applied to support COVID-19 treatments in China and Italy. Unfortunately, the frequent antibiotic off-site targets include mitochondria that are genetically and evolutionary closely linked to bacteria. Mitochondria are multifunctional organelles responsible for bioenergetics in nearly all our cells, acting as signaling hubs in antiviral and antibacterial immune responses. Several studies have demonstrated that mitochondria are vulnerable to antibacterial treatments, interrupting their physiology. Inhibition of these processes by antibiotics might render the immune system less capable of fighting acute COVID-19 viral infections. Some antibiotics, including those prescribed for COVID-19 in Wuhan, have been shown to inhibit the synthesis of mitochondrial DNA. The question is whether antibiotics support such a treatment or weaken patient immune responses in this case. This hypothesis should be evaluated based on comparative clinical data that seem to be unavailable at the moment. Possibly the COVID-19 risk group should be extended to all patients being treated with antibiotics, including those who finished antibiotic therapies days up to several months before SARS-CoV-2 infection. We therefore urge health service response groups to evaluate the impact of antibiotics on COVID-19 recovery vs death retrospective data. We would like to motivate international, national and local health authorities to share available clinical treatment data, discuss and optimize treatment strategies.

scholarly journals Type III Interferons in Viral Infection and Antiviral Immunity

2018 ◽  
Vol 51 (1) ◽  
pp. 173-185 ◽  
Author(s):  
Jian-hua Zhou ◽  
Yi-ning Wang ◽  
Qiu-yan Chang ◽  
Peng Ma ◽  
Yonghao Hu ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Viral Infection ◽  
Biological Activities ◽  
Adaptive Immune Response ◽  
Immune Defense ◽  
Th2 Cells ◽  
Type I ◽  
Antiviral Immune Response ◽  
Type Iii

Interferons (IFNs) can serve as the first line of immune defense against viral infection. The identification of IFN-λs 1, 2, 3 & 4 (termed as type III IFNs) has revealed that the antiviral immune response to viruses contains more components than the type I IFNs that have been known for more than 50 years. IFN-λs are IFN-λ1 (IL-29), IFN-λ2 (IL-28a), IFN-λ3 (IL-28b) and IFN-λ4, which resembles IFN-λ3. IFN-λs have type I-IFN-like immune responses and biological activities, but our knowledge of these novel players in the antiviral response is not well established. In this review, we try to describe the current information on the expression and function of IFN-λs in the innate antiviral immune defense and IFN-λ2’s role in regulating and shaping the adaptive immune response. We suggest that IFN-λs are key antiviral cytokines, directly performing an antiviral immune response at epithelial surfaces in the early stages of viral infection, and that these cytokines also skew the balance of Th1 and Th2 cells to Th1 phenotype. In addition, genetic polymorphisms in IFN-λ genes can impair antiviral immune responses in clinical treatment.

scholarly journals Antiviral Compounds from Myxobacteria

2018 ◽  
Vol 6 (3) ◽  
pp. 73 ◽  
Author(s):  
Lucky Mulwa ◽  
Marc Stadler
Keyword(s):  
Broad Spectrum ◽  
Viral Infections ◽  
Antiviral Agents ◽  
Antiviral Drug ◽  
Public Health Issue ◽  
Target Cells ◽  
Global Public Health ◽  
Drug Candidates ◽  
Antiviral Compounds ◽  
Spectrum Activity

Viral infections including human immunodeficiency virus (HIV), cytomegalovirus (CMV), hepatitis B virus (HBV), and hepatitis C virus (HCV) pose an ongoing threat to human health due to the lack of effective therapeutic agents. The re-emergence of old viral diseases such as the recent Ebola outbreaks in West Africa represents a global public health issue. Drug resistance and toxicity to target cells are the major challenges for the current antiviral agents. Therefore, there is a need for identifying agents with novel modes of action and improved efficacy. Viral-based illnesses are further aggravated by co-infections, such as an HIV patient co-infected with HBV or HCV. The drugs used to treat or manage HIV tend to increase the pathogenesis of HBV and HCV. Hence, novel antiviral drug candidates should ideally have broad-spectrum activity and no negative drug-drug interactions. Myxobacteria are in the focus of this review since they produce numerous structurally and functionally unique bioactive compounds, which have only recently been screened for antiviral effects. This research has already led to some interesting findings, including the discovery of several candidate compounds with broad-spectrum antiviral activity. The present review looks at myxobacteria-derived antiviral secondary metabolites.

scholarly journals Immunity and Viral Infections: Modulating Antiviral Response via CRISPR–Cas Systems

Viruses ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1373
Author(s):  
Sergey Brezgin ◽  
Anastasiya Kostyusheva ◽  
Ekaterina Bayurova ◽  
Elena Volchkova ◽  
Vladimir Gegechkori ◽  
...  
Keyword(s):  
Infectious Diseases ◽  
Immune Responses ◽  
Viral Infections ◽  
Antiviral Agents ◽  
Innate Immune ◽  
Host Factors ◽  
Innate Immune Responses ◽  
Host Interactions ◽  
Translational Studies ◽  
Short Time

Viral infections cause a variety of acute and chronic human diseases, sometimes resulting in small local outbreaks, or in some cases spreading across the globe and leading to global pandemics. Understanding and exploiting virus–host interactions is instrumental for identifying host factors involved in viral replication, developing effective antiviral agents, and mitigating the severity of virus-borne infectious diseases. The diversity of CRISPR systems and CRISPR-based tools enables the specific modulation of innate immune responses and has contributed impressively to the fields of virology and immunology in a very short time. In this review, we describe the most recent advances in the use of CRISPR systems for basic and translational studies of virus–host interactions.

scholarly journals Development of Broad-Spectrum Antiviral Agents—Inspiration from Immunomodulatory Natural Products

Viruses ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1257
Author(s):  
Mengxun Zhang ◽  
Jiaqing Zhong ◽  
Yongai Xiong ◽  
Xun Song ◽  
Chenyang Li ◽  
...  
Keyword(s):  
Natural Products ◽  
Broad Spectrum ◽  
Viral Infections ◽  
Antiviral Agents ◽  
Antiviral Drugs ◽  
Life Cycles ◽  
The Body ◽  
Host Cells ◽  
Immunomodulatory Effects ◽  
Antiviral Effects

Developing broad-spectrum antiviral drugs remains an important issue as viral infections continue to threaten public health. Host-directed therapy is a method that focuses on potential targets in host cells or the body, instead of viral proteins. Its antiviral effects are achieved by disturbing the life cycles of pathogens or modulating immunity. In this review, we focus on the development of broad-spectrum antiviral drugs that enhance the immune response. Some natural products present antiviral effects mediated by enhancing immunity, and their structures and mechanisms are summarized here. Natural products with immunomodulatory effects are also discussed, although their antiviral effects remain unknown. Given the power of immunity and the feasibility of host-directed therapy, we argue that both of these categories of natural products provide clues that may be beneficial for the discovery of broad-spectrum antiviral drugs.

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