scholarly journals Interferon Resistance of Emerging SARS-CoV-2 Variants

2021 ◽  
Author(s):  
Kejun Guo ◽  
Bradley S Barrett ◽  
Kaylee L Mickens ◽  
Kim J Hasenkrug ◽  
Mario Santiago
Keyword(s):  
Innate Immunity ◽  
Driving Force ◽  
Virus Infectivity ◽  
Novel Variants ◽  
Viral Genes ◽  
Interferon Resistance ◽  
Interferon Responses

The emergence of SARS-CoV-2 variants with enhanced transmissibility, pathogenesis and resistance to vaccines presents urgent challenges for curbing the COVID-19 pandemic. While Spike mutations that enhance virus infectivity may drive the emergence of these novel variants, studies documenting a critical a role for interferon responses in the early control of SARS-CoV-2 infection, combined with the presence of viral genes that limit these responses, suggest that interferons may also influence SARS-CoV-2 evolution. Here, we compared the potency of 17 different human interferons against 5 viral lineages sampled during the course of the global outbreak that included ancestral and emerging variants. Our data revealed increased interferon resistance in emerging SARS-CoV-2 variants, indicating that evasion of innate immunity is a significant driving force for SARS-CoV-2 evolution. These findings have implications for the increased lethality of emerging variants and highlight the interferon subtypes that may be most successful in the treatment of early infections.

scholarly journals SARS-CoV-2 Isolates Show Impaired Replication in Human Immune Cells but Differential Ability to Replicate and Induce Innate Immunity in Lung Epithelial Cells

2021 ◽  
Author(s):  
Miao Jiang ◽  
Pekka Kolehmainen ◽  
Laura Kakkola ◽  
Sari Maljanen ◽  
Krister Melén ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Epithelial Cells ◽  
Immune Cells ◽  
Human Lung ◽  
Lung Epithelial Cells ◽  
Lung Epithelial ◽  
Rapid Spread ◽  
Human Immune ◽  
Differential Ability ◽  
Interferon Responses

With the rapid spread of the coronavirus disease 2019 (COVID-19) pandemic, information on the replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and regulation of innate immunity in human immune cells and lung epithelial cells is needed. In the present study, we show that SARS-CoV-2 failed to productively infect human immune cells, but different isolates of SARS-CoV-2 showed differential ability to replicate and regulate innate interferon responses in human lung epithelial Calu-3 cells.

scholarly journals Innate immunity as a driving force in renal disease

2008 ◽  
Vol 73 (1) ◽  
pp. 7-8 ◽  
Author(s):  
E. de Heer ◽  
D.J.M. Peters
Keyword(s):  
Innate Immunity ◽  
Renal Disease ◽  
Driving Force

scholarly journals Crosstalk between Autophagy and Type I Interferon Responses in Innate Antiviral Immunity

Viruses ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 132 ◽  
Author(s):  
Yu Tian ◽  
Ming-Li Wang ◽  
Jun Zhao
Keyword(s):  
Innate Immunity ◽  
Immune System ◽  
Molecular Mechanisms ◽  
Viral Infections ◽  
Type I Interferon ◽  
Antiviral Immunity ◽  
Type I ◽  
Viral Components ◽  
Interferon Responses ◽  
Innate Antiviral Immunity

Autophagy exhibits dual effects during viral infections, promoting the clearance of viral components and activating the immune system to produce antiviral cytokines. However, some viruses impair immune defenses by collaborating with autophagy. Mounting evidence suggests that the interaction between autophagy and innate immunity is critical to understanding the contradictory roles of autophagy. Type I interferon (IFN-I) is a crucial antiviral factor, and studies have indicated that autophagy affects IFN-I responses by regulating IFN-I and its receptors expression. Similarly, IFN-I and interferon-stimulated gene (ISG) products can harness autophagy to regulate antiviral immunity. Crosstalk between autophagy and IFN-I responses could be a vital aspect of the molecular mechanisms involving autophagy in innate antiviral immunity. This review briefly summarizes the approaches by which autophagy regulates antiviral IFN-I responses and highlights the recent advances on the mechanisms by which IFN-I and ISG products employ autophagy against viruses.

scholarly journals InsP3R-SEC5 interaction on phagosomes modulates innate immunity to Candida albicans by promoting cytosolic Ca2+ elevation and TBK1 activity

BMC Biology ◽  
2018 ◽  
Vol 16 (1) ◽  
Author(s):  
Long Yang ◽  
Wenwen Gu ◽  
King-Ho Cheung ◽  
Lan Yan ◽  
Benjamin Chun-Kit Tong ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Candida Albicans ◽  
Immune Responses ◽  
Critical Role ◽  
Innate Immune ◽  
Type I ◽  
Innate Immune Responses ◽  
Α Helix ◽  
Trisphosphate Receptor ◽  
Interferon Responses

Abstract Background Candida albicans (C. albicans) invasion triggers antifungal innate immunity, and the elevation of cytoplasmic Ca2+ levels via the inositol 1,4,5-trisphosphate receptor (InsP3R) plays a critical role in this process. However, the molecular pathways linking the InsP3R-mediated increase in Ca2+ and immune responses remain elusive. Results In the present study, we find that during C. albicans phagocytosis in macrophages, exocyst complex component 2 (SEC5) promotes InsP3R channel activity by binding to its C-terminal α-helix (H1), increasing cytosolic Ca2+ concentrations ([Ca2+]c). Immunofluorescence reveals enriched InsP3R-SEC5 complex formation on phagosomes, while disruption of the InsP3R-SEC5 interaction by recombinant H1 peptides attenuates the InsP3R-mediated Ca2+ elevation, leading to impaired phagocytosis. Furthermore, we show that C. albicans infection promotes the recruitment of Tank-binding kinase 1 (TBK1) by the InsP3R-SEC5 interacting complex, leading to the activation of TBK1. Subsequently, activated TBK1 phosphorylates interferon regulatory factor 3 (IRF-3) and mediates type I interferon responses, suggesting that the InsP3R-SEC5 interaction may regulate antifungal innate immune responses not only by elevating cytoplasmic Ca2+ but also by activating the TBK1-IRF-3 pathway. Conclusions Our data have revealed an important role of the InsP3R-SEC5 interaction in innate immune responses against C. albicans.

The anti-immune dengue subgenomic flaviviral RNA is found in vesicles in mosquito saliva and associated with increased infectivity

2021 ◽  
Author(s):  
Shih-Chia Yeh ◽  
Wei-Lian Tan ◽  
Avisha Chowdhury ◽  
Vanessa Chuo ◽  
R. Manjunatha Kini ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Dengue Virus ◽  
Extracellular Vesicles ◽  
Virus Transmission ◽  
Human Cells ◽  
Infected Mosquito ◽  
Virus Infectivity ◽  
Dengue Viruses ◽  
Mosquito Saliva

AbstractMosquito transmission of dengue viruses to humans starts with infection of skin resident cells at the biting site. There is great interest in identifying transmission-enhancing factors in mosquito saliva in order to counteract them. Here we report the discovery of high levels of subgenomic flaviviral RNA (sfRNA) in dengue virus 2-infected mosquito saliva. We show that salivary sfRNA is protected in detergent-sensitive, protease-resistant compartments. Furthermore, we show that incubation with mosquito saliva containing higher sfRNA levels results in higher virus infectivity in human cells. Since sfRNA potently inhibits innate immunity in human cells, we posit that sfRNA in mosquito saliva is present in extracellular vesicles that deliver it to cells at the biting site to inhibit innate immunity and enhance dengue virus transmission.

Paving the Way to Tospovirus Infection: Multilined Interplays with Plant Innate Immunity

2019 ◽  
Vol 57 (1) ◽  
pp. 41-62 ◽  
Author(s):  
Min Zhu ◽  
Irene Louise van Grinsven ◽  
Richard Kormelink ◽  
Xiaorong Tao
Keyword(s):  
Innate Immunity ◽  
Life Cycle ◽  
Rna Silencing ◽  
Plant Pathogens ◽  
State Of The Art ◽  
Innate Immune ◽  
Silencing Suppressor ◽  
Viral Genes ◽  
Effector Triggered Immunity ◽  
Cellular Machinery

Tospoviruses are among the most important plant pathogens and cause serious crop losses worldwide. Tospoviruses have evolved to smartly utilize the host cellular machinery to accomplish their life cycle. Plants mount two layers of defense to combat their invasion. The first one involves the activation of an antiviral RNA interference (RNAi) defense response. However, tospoviruses encode an RNA silencing suppressor that enables them to counteract antiviral RNAi. To further combat viral invasion, plants also employ intracellular innate immune receptors (e.g., Sw-5b and Tsw) to recognize different viral effectors (e.g., NSm and NSs). This leads to the triggering of a much more robust defense against tospoviruses called effector-triggered immunity (ETI). Tospoviruses have further evolved their effectors and can break Sw-5b-/Tsw-mediated resistance. The arms race between tospoviruses and both layers of innate immunity drives the coevolution of host defense and viral genes involved in counter defense. In this review, a state-of-the-art overview is presented on the tospoviral life cycle and the multilined interplays between tospoviruses and the distinct layers of defense.

scholarly journals Single-cell virus sequencing of influenza infections that trigger innate immunity

2018 ◽  
Author(s):  
Alistair B. Russell ◽  
Jacob R. Kowalsky ◽  
Jesse D. Bloom
Keyword(s):  
Immune Response ◽  
Innate Immunity ◽  
Genetic Variation ◽  
Amino Acid ◽  
Innate Immune ◽  
New Approach ◽  
Viral Genes ◽  
A Cell ◽  
Infected Cells ◽  
Amino Acid Mutations

SUMMARYThe outcome of viral infection is extremely heterogeneous, with infected cells only sometimes activating innate immunity. Here we develop a new approach to assess how the genetic variation inherent in viral populations contributes to this heterogeneity. We do this by determining both the transcriptome and full-length sequences of all viral genes in single influenza-infected cells. Most cells are infected by virions with defects such as amino-acid mutations, internal deletions, or failure to express a gene. We identify instances of each type of defect that increase the likelihood that a cell activates an innate-immune response. However, immune activation remains stochastic in cells infected by virions with these defects, and sometimes occurs even when a cell is infected by a virion that expresses unmutated copies of all genes. Our work shows that viral genetic variation substantially contributes to but does not fully explain the heterogeneity in single influenza-infected cells.

In situ TEM Studies of agglomeration of sub-nanometer Ru layers in Ru/C multilayers

1992 ◽  
Vol 50 (1) ◽  
pp. 256-257
Author(s):  
Tai D. Nguyen ◽  
Ronald Gronsky ◽  
Jeffrey B. Kortright
Keyword(s):  
Layered Structure ◽  
Driving Force ◽  
High Energy ◽  
Superior Performance ◽  
In Situ Tem ◽  
Rayleigh Instability ◽  
Practical Applications ◽  
Transmission Electron ◽  
Diffraction Patterns

Nanometer period Ru/C multilayers are one of the prime candidates for normal incident reflecting mirrors at wavelengths < 10 nm. Superior performance, which requires uniform layers and smooth interfaces, and high stability of the layered structure under thermal loadings are some of the demands in practical applications. Previous studies however show that the Ru layers in the 2 nm period Ru/C multilayer agglomerate upon moderate annealing, and the layered structure is no longer retained. This agglomeration and crystallization of the Ru layers upon annealing to form almost spherical crystallites is a result of the reduction of surface or interfacial energy from die amorphous high energy non-equilibrium state of the as-prepared sample dirough diffusive arrangements of the atoms. Proposed models for mechanism of thin film agglomeration include one analogous to Rayleigh instability, and grain boundary grooving in polycrystalline films. These models however are not necessarily appropriate to explain for the agglomeration in the sub-nanometer amorphous Ru layers in Ru/C multilayers. The Ru-C phase diagram shows a wide miscible gap, which indicates the preference of phase separation between these two materials and provides an additional driving force for agglomeration. In this paper, we study the evolution of the microstructures and layered structure via in-situ Transmission Electron Microscopy (TEM), and attempt to determine the order of occurence of agglomeration and crystallization in the Ru layers by observing the diffraction patterns.

The nucleation of cavities at grain boundaries

1987 ◽  
Vol 45 ◽  
pp. 288-291
Author(s):  
P. J. Goodhew
Keyword(s):  
Surface Tension ◽  
Surface Energy ◽  
Grain Boundaries ◽  
Radiation Damage ◽  
Impurity Concentration ◽  
Driving Force ◽  
Nucleation And Growth ◽  
Phase Boundaries ◽  
Cavity Nucleation ◽  
Spherical Bubble

Cavity nucleation and growth at grain and phase boundaries is of concern because it can lead to failure during creep and can lead to embrittlement as a result of radiation damage. Two major types of cavity are usually distinguished: The term bubble is applied to a cavity which contains gas at a pressure which is at least sufficient to support the surface tension (2g/r for a spherical bubble of radius r and surface energy g). The term void is generally applied to any cavity which contains less gas than this, but is not necessarily empty of gas. A void would therefore tend to shrink in the absence of any imposed driving force for growth, whereas a bubble would be stable or would tend to grow. It is widely considered that cavity nucleation always requires the presence of one or more gas atoms. However since it is extremely difficult to prepare experimental materials with a gas impurity concentration lower than their eventual cavity concentration there is little to be gained by debating this point.

Sign in / Sign up

Export Citation Format

Share Document