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Small RNAs Participate in Plant-Virus Interaction and Their Application in Plant Viral Defense.
Deng, Z, Ma, L, Zhang, P, Zhu, H
International journal of molecular sciences. 2022;(2)
Abstract
Small RNAs are significant regulators of gene expression, which play multiple roles in plant development, growth, reproductive and stress response. It is generally believed that the regulation of plants' endogenous genes by small RNAs has evolved from a cellular defense mechanism for RNA viruses and transposons. Most small RNAs have well-established roles in the defense response, such as viral response. During viral infection, plant endogenous small RNAs can direct virus resistance by regulating the gene expression in the host defense pathway, while the small RNAs derived from viruses are the core of the conserved and effective RNAi resistance mechanism. As a counter strategy, viruses evolve suppressors of the RNAi pathway to disrupt host plant silencing against viruses. Currently, several studies have been published elucidating the mechanisms by which small RNAs regulate viral defense in different crops. This paper reviews the distinct pathways of small RNAs biogenesis and the molecular mechanisms of small RNAs mediating antiviral immunity in plants, as well as summarizes the coping strategies used by viruses to override this immune response. Finally, we discuss the current development state of the new applications in virus defense based on small RNA silencing.
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Exploiting Structural Modelling Tools to Explore Host-Translocated Effector Proteins.
Amoozadeh, S, Johnston, J, Meisrimler, CN
International journal of molecular sciences. 2021;(23)
Abstract
Oomycete and fungal interactions with plants can be neutral, symbiotic or pathogenic with different impact on plant health and fitness. Both fungi and oomycetes can generate so-called effector proteins in order to successfully colonize the host plant. These proteins modify stress pathways, developmental processes and the innate immune system to the microbes' benefit, with a very different outcome for the plant. Investigating the biological and functional roles of effectors during plant-microbe interactions are accessible through bioinformatics and experimental approaches. The next generation protein modeling software RoseTTafold and AlphaFold2 have made significant progress in defining the 3D-structure of proteins by utilizing novel machine-learning algorithms using amino acid sequences as their only input. As these two methods rely on super computers, Google Colabfold alternatives have received significant attention, making the approaches more accessible to users. Here, we focus on current structural biology, sequence motif and domain knowledge of effector proteins from filamentous microbes and discuss the broader use of novel modelling strategies, namely AlphaFold2 and RoseTTafold, in the field of effector biology. Finally, we compare the original programs and their Colab versions to assess current strengths, ease of access, limitations and future applications.
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3.
Current status and future perspectives of computational studies on human-virus protein-protein interactions.
Lian, X, Yang, X, Yang, S, Zhang, Z
Briefings in bioinformatics. 2021;(5)
Abstract
The protein-protein interactions (PPIs) between human and viruses mediate viral infection and host immunity processes. Therefore, the study of human-virus PPIs can help us understand the principles of human-virus relationships and can thus guide the development of highly effective drugs to break the transmission of viral infectious diseases. Recent years have witnessed the rapid accumulation of experimentally identified human-virus PPI data, which provides an unprecedented opportunity for bioinformatics studies revolving around human-virus PPIs. In this article, we provide a comprehensive overview of computational studies on human-virus PPIs, especially focusing on the method development for human-virus PPI predictions. We briefly introduce the experimental detection methods and existing database resources of human-virus PPIs, and then discuss the research progress in the development of computational prediction methods. In particular, we elaborate the machine learning-based prediction methods and highlight the need to embrace state-of-the-art deep-learning algorithms and new feature engineering techniques (e.g. the protein embedding technique derived from natural language processing). To further advance the understanding in this research topic, we also outline the practical applications of the human-virus interactome in fundamental biological discovery and new antiviral therapy development.
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4.
Recognition and defence of plant-infecting fungal pathogens.
Saur, IML, Hückelhoven, R
Journal of plant physiology. 2021;:153324
Abstract
Attempted infections of plants with fungi result in diverse outcomes ranging from symptom-less resistance to severe disease and even death of infected plants. The deleterious effect on crop yield have led to intense focus on the cellular and molecular mechanisms that explain the difference between resistance and susceptibility. This research has uncovered plant resistance or susceptibility genes that explain either dominant or recessive inheritance of plant resistance with many of them coding for receptors that recognize pathogen invasion. Approaches based on cell biology and phytochemistry have contributed to identifying factors that halt an invading fungal pathogen from further invasion into or between plant cells. Plant chemical defence compounds, antifungal proteins and structural reinforcement of cell walls appear to slow down fungal growth or even prevent fungal penetration in resistant plants. Additionally, the hypersensitive response, in which a few cells undergo a strong local immune reaction, including programmed cell death at the site of infection, stops in particular biotrophic fungi from spreading into surrounding tissue. In this review, we give a general overview of plant recognition and defence of fungal parasites tracing back to the early 20th century with a special focus on Triticeae and on the progress that was made in the last 30 years.
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5.
Influence of virus-host interactions on plant response to abiotic stress.
Rahman, A, Sinha, KV, Sopory, SK, Sanan-Mishra, N
Plant cell reports. 2021;(11):2225-2245
Abstract
Environmental factors play a significant role in controlling growth, development and defense responses of plants. Changes in the abiotic environment not only significantly alter the physiological and molecular pathways in plants, but also result in attracting the insect pests that carry a payload of viruses. Invasion of plants by viruses triggers the RNA silencing based defense mechanism in plants. In counter defense the viruses have gained the ability to suppress the host RNA silencing activities. A new paradigm has emerged, with the recognition that plant viruses also have the intrinsic capacity to modulate host plant response to environmental cues, in an attempt to favour their own survival. Thus, plant-virus interactions provide an excellent system to understand the signals in crosstalk between biotic (virus) and abiotic stresses. In this review, we have summarized the basal plant defense responses to pathogen invasion while emphasizing on the role of RNA silencing as a front line of defense response to virus infection. The emerging knowledge indicates overlap between RNA silencing with the innate immune responses during antiviral defense. The suppressors of RNA silencing serve as Avr proteins, which can be recognized by the host R proteins. The defense signals also function in concert with the phytohormones to influence plant responses to abiotic stresses. The current evidence on the role of virus induced host tolerance to abiotic stresses is also discussed.
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6.
Fungal effectors, the double edge sword of phytopathogens.
Pradhan, A, Ghosh, S, Sahoo, D, Jha, G
Current genetics. 2021;(1):27-40
Abstract
Phyto-pathogenic fungi can cause huge damage to crop production. During millions of years of coexistence, fungi have evolved diverse life-style to obtain nutrients from the host and to colonize upon them. They deploy various proteinaceous as well as non-proteinaceous secreted molecules commonly referred as effectors to sabotage host machinery during the infection process. The effectors are important virulence determinants of pathogenic fungi and play important role in successful pathogenesis, predominantly by avoiding host-surveillance system. However, besides being important for pathogenesis, the fungal effectors end-up being recognized by the resistant cultivars of the host, which mount a strong immune response to ward-off pathogens. Various recent studies involving different pathosystem have revealed the virulence/avirulence functions of fungal effectors and their involvement in governing the outcome of host-pathogen interactions. However, the effectors and their cognate resistance gene in the host remain elusive for several economically important fungal pathogens. In this review, using examples from some of the biotrophic, hemi-biotrophic and necrotrophic pathogens, we elaborate the double-edged functions of fungal effectors. We emphasize that knowledge of effector functions can be helpful in effective management of fungal diseases in crop plants.
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7.
Iron in immune cell function and host defense.
Haschka, D, Hoffmann, A, Weiss, G
Seminars in cell & developmental biology. 2021;:27-36
Abstract
The control over iron availability is crucial under homeostatic conditions and even more in the case of an infection. This results from diverse properties of iron: first, iron is an important trace element for the host as well as for the pathogen for various cellular and metabolic processes, second, free iron catalyzes Fenton reaction and is therefore producing reactive oxygen species as a part of the host defense machinery, third, iron exhibits important effects on immune cell function and differentiation and fourth almost every immune activation in turn impacts on iron metabolism and spatio-temporal iron distribution. The central importance of iron in the host and microbe interplay and thus for the course of infections led to diverse strategies to restrict iron for invading pathogens. In this review, we focus on how iron restriction to the pathogen is a powerful innate immune defense mechanism of the host called "nutritional immunity". Important proteins in the iron-host-pathogen interplay will be discussed as well as the influence of iron on the efficacy of innate and adaptive immunity. Recently described processes like ferritinophagy and ferroptosis are further covered in respect to their impact on inflammation and infection control and how they impact on our understanding of the interaction of host and pathogen.
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8.
Metabolic Plasticity of Neutrophils: Relevance to Pathogen Responses and Cancer.
Rogers, T, DeBerardinis, RJ
Trends in cancer. 2021;(8):700-713
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Abstract
Neutrophils, the most abundant leukocyte population in humans, constantly patrol the body for foreign cells, including pathogens and cancer cells. Once neutrophils are activated, they engage distinct metabolic pathways to fulfill their specialized antipathogen functions. In this review, we examine current research on the metabolism of neutrophil differentiation and antipathogen responses. We also discuss how tumor-associated neutrophils (TANs) can be educated by cytokines and by the nutrient-restrictive milieu of the tumor microenvironment (TME) to suppress antitumor immunity, promote cancer progression, and contribute to biological heterogeneity among tumors. Last, we discuss the clinical implications of circulating neutrophils and infiltrating TANs and consider how targeting TAN metabolism may synergize with cancer immunotherapy.
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Geminivirus-Host Interactions: Action and Reaction in Receptor-Mediated Antiviral Immunity.
Ferreira, MA, Teixeira, RM, Fontes, EPB
Viruses. 2021;(5)
Abstract
In plant-virus interactions, the plant immune system and virulence strategies are under constant pressure for dominance, and the balance of these opposing selection pressures can result in disease or resistance. The naturally evolving plant antiviral immune defense consists of a multilayered perception system represented by pattern recognition receptors (PRR) and resistance (R) proteins similarly to the nonviral pathogen innate defenses. Another layer of antiviral immunity, signaling via a cell surface receptor-like kinase to inhibit host and viral mRNA translation, has been identified as a virulence target of the geminivirus nuclear shuttle protein. The Geminiviridae family comprises broad-host range viruses that cause devastating plant diseases in a large variety of relevant crops and vegetables and hence have evolved a repertoire of immune-suppressing functions. In this review, we discuss the primary layers of the receptor-mediated antiviral immune system, focusing on the mechanisms developed by geminiviruses to overcome plant immunity.
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Immune-Microbiota Interplay and Colonization Resistance in Infection.
Leshem, A, Liwinski, T, Elinav, E
Molecular cell. 2020;(4):597-613
Abstract
Commensal microbial communities inhabit biological niches in the mammalian host, where they impact the host's physiology through induction of "colonization resistance" against infections by a multitude of molecular mechanisms. These colonization-regulating activities involve microbe-microbe and microbe-host interactions, which induce, through utilization of complex bacterial networks, competition over nutrients, inhibition by antimicrobial peptides, stimulation of the host immune system, and promotion of mucus and intestinal epithelial barrier integrity. Distinct virulent pathogens overcome this colonization resistance and host immunity as part of a hostile takeover of the host niche, leading to clinically overt infection. The following review provides a mechanistic overview of the role of commensal microbes in modulating colonization resistance and pathogenic infections and means by which infectious agents may overcome such inhibition. Last, we outline evidence, unknowns, and challenges in developing strategies to harness this knowledge to treat infections by microbiota transfer, phage therapy, or supplementation by rationally defined bacterial consortia.