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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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Harnessing phytomicrobiome signals for phytopathogenic stress management.
Sharma, A, Raina, M, Kumar, D, Singh, A, Chugh, S, Jain, S, Kumar, M, Rustagi, A
Journal of biosciences. 2022
Abstract
Harnessing the phytomicrobiome offers a great opportunity to improve plant productivity and quality of food. In the recent past, several phytomicrobiome microbes have been explored for their potential involvement in increasing crop yield. This review strategically targets to harness the various dimensions of phytomicrobiome for biotic stress management of crop plants. The tripartite interaction involving plantmicrobiome-pathogen has been discussed. Positive interventions in this system so as to achieve disease tolerant plants has been forayed upon. The different signalling molecules sent out by interacting partners of phytomicrobiome have also been analysed. The novel concept of artificial microbial consortium in mitigation of pathogenic stress has also been touched upon. The aim of this review is to explore the hidden potential of phytomicrobiome diversity as a potent tool against phytopathogens, thereby improving crop health and productivity in a sustainable way.
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3.
Phytosterol metabolism in plant positive-strand RNA virus replication.
Altabella, T, Ramirez-Estrada, K, Ferrer, A
Plant cell reports. 2022;(2):281-291
Abstract
The genome of most plant viruses consists of a single positive-strand of RNA (+ ssRNA). Successful replication of these viruses is fully dependent on the endomembrane system of the infected cells, which experiences a massive proliferation and a profound reshaping that enables assembly of the macromolecular complexes where virus genome replication occurs. Assembly of these viral replicase complexes (VRCs) requires a highly orchestrated interplay of multiple virus and co-opted host cell factors to create an optimal microenvironment for efficient assembly and functioning of the virus genome replication machinery. It is now widely accepted that VRC formation involves the recruitment of high levels of sterols, but the specific role of these essential components of cell membranes and the precise molecular mechanisms underlying sterol enrichment at VRCs are still poorly known. In this review, we intend to summarize the most relevant knowledge on the role of sterols in ( +)ssRNA virus replication and discuss the potential of manipulating the plant sterol pathway to help plants fight these infectious agents.
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4.
Natural and Nature-Derived Products Targeting Human Coronaviruses.
Vougogiannopoulou, K, Corona, A, Tramontano, E, Alexis, MN, Skaltsounis, AL
Molecules (Basel, Switzerland). 2021;(2)
Abstract
The ongoing pandemic of severe acute respiratory syndrome (SARS), caused by the SARS-CoV-2 human coronavirus (HCoV), has brought the international scientific community before a state of emergency that needs to be addressed with intensive research for the discovery of pharmacological agents with antiviral activity. Potential antiviral natural products (NPs) have been discovered from plants of the global biodiversity, including extracts, compounds and categories of compounds with activity against several viruses of the respiratory tract such as HCoVs. However, the scarcity of natural products (NPs) and small-molecules (SMs) used as antiviral agents, especially for HCoVs, is notable. This is a review of 203 publications, which were selected using PubMed/MEDLINE, Web of Science, Scopus, and Google Scholar, evaluates the available literature since the discovery of the first human coronavirus in the 1960s; it summarizes important aspects of structure, function, and therapeutic targeting of HCoVs as well as NPs (19 total plant extracts and 204 isolated or semi-synthesized pure compounds) with anti-HCoV activity targeting viral and non-viral proteins, while focusing on the advances on the discovery of NPs with anti-SARS-CoV-2 activity, and providing a critical perspective.
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5.
Understanding Individual SARS-CoV-2 Proteins for Targeted Drug Development against COVID-19.
van de Leemput, J, Han, Z
Molecular and cellular biology. 2021;(9):e0018521
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Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the COVID-19 pandemic, responsible for millions of deaths globally. Even with effective vaccines, SARS-CoV-2 will likely maintain a hold in the human population through gaps in efficacy, percent vaccinated, and arising new strains. Therefore, understanding how SARS-CoV-2 causes widespread tissue damage and the development of targeted pharmacological treatments will be critical in fighting this virus and preparing for future outbreaks. Herein, we summarize the progress made thus far by using in vitro or in vivo models to investigate individual SARS-CoV-2 proteins and their pathogenic mechanisms. We have grouped the SARS-CoV-2 proteins into three categories: host entry, self-acting, and host interacting. This review focuses on the self-acting and host-interacting SARS-CoV-2 proteins and summarizes current knowledge on how these proteins promote virus replication and disrupt host systems, as well as drugs that target the virus and virus interacting host proteins. Encouragingly, many of these drugs are currently in clinical trials for the treatment of COVID-19. Future coronavirus outbreaks will most likely be caused by new virus strains that evade vaccine protection through mutations in entry proteins. Therefore, study of individual self-acting and host-interacting SARS-CoV-2 proteins for targeted therapeutic interventions is not only essential for fighting COVID-19 but also valuable against future coronavirus outbreaks.
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6.
A SARS-CoV-2 -human metalloproteome interaction map.
Chasapis, CT, Georgiopoulou, AK, Perlepes, SP, Bjørklund, G, Peana, M
Journal of inorganic biochemistry. 2021;:111423
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Abstract
The recent pandemic caused by the novel coronavirus resulted in the greatest global health crisis since the Spanish flu pandemic of 1918. There is limited knowledge of whether SARS-CoV-2 is physically associated with human metalloproteins. Recently, high-confidence, experimentally supported protein-protein interactions between SARS-CoV-2 and human proteins were reported. In this work, 58 metalloproteins among these human targets have been identified by a structure-based approach. This study reveals that most human metalloproteins interact with the recently discovered SARS-CoV-2 orf8 protein, whose antibodies are one of the principal markers of SARS-CoV-2 infections. Furthermore, this work provides sufficient evidence to conclude that Zn2+ plays an important role in the interplay between the novel coronavirus and humans. First, the content of Zn-binding proteins in the involved human metalloproteome is significantly higher than that of the other metal ions. Second, a molecular linkage between the identified human Zn-binding proteome with underlying medical conditions, that might increase the risk of severe illness from the SARS-CoV-2 virus, has been found. Likely perturbations of host cellular metal homeostasis by SARS-CoV-2 infection are highlighted.
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iT4SE-EP: Accurate Identification of Bacterial Type IV Secreted Effectors by Exploring Evolutionary Features from Two PSI-BLAST Profiles.
Han, H, Ding, C, Cheng, X, Sang, X, Liu, T
Molecules (Basel, Switzerland). 2021;(9)
Abstract
Many gram-negative bacteria use type IV secretion systems to deliver effector molecules to a wide range of target cells. These substrate proteins, which are called type IV secreted effectors (T4SE), manipulate host cell processes during infection, often resulting in severe diseases or even death of the host. Therefore, identification of putative T4SEs has become a very active research topic in bioinformatics due to its vital roles in understanding host-pathogen interactions. PSI-BLAST profiles have been experimentally validated to provide important and discriminatory evolutionary information for various protein classification tasks. In the present study, an accurate computational predictor termed iT4SE-EP was developed for identifying T4SEs by extracting evolutionary features from the position-specific scoring matrix and the position-specific frequency matrix profiles. First, four types of encoding strategies were designed to transform protein sequences into fixed-length feature vectors based on the two profiles. Then, the feature selection technique based on the random forest algorithm was utilized to reduce redundant or irrelevant features without much loss of information. Finally, the optimal features were input into a support vector machine classifier to carry out the prediction of T4SEs. Our experimental results demonstrated that iT4SE-EP outperformed most of existing methods based on the independent dataset test.
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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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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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Evolution and Adaptation of Legionella pneumophila to Manipulate the Ubiquitination Machinery of Its Amoebae and Mammalian Hosts.
Price, CTD, Abu Kwaik, Y
Biomolecules. 2021;(1)
Abstract
The ubiquitin pathway is highly conserved across the eukaryotic domain of life and plays an essential role in a plethora of cellular processes. It is not surprising that many intracellular bacterial pathogens often target the essential host ubiquitin pathway. The intracellular bacterial pathogen Legionella pneumophila injects into the host cell cytosol multiple classes of classical and novel ubiquitin-modifying enzymes that modulate diverse ubiquitin-related processes in the host cell. Most of these pathogen-injected proteins, designated as effectors, mimic known E3-ubiquitin ligases through harboring F-box or U-box domains. The classical F-box effector, AnkB targets host proteins for K48-linked polyubiquitination, which leads to excessive proteasomal degradation that is required to generate adequate supplies of amino acids for metabolism of the pathogen. In contrast, the SidC and SdcA effectors share no structural similarity to known eukaryotic ligases despite having E3-ubiquitin ligase activity, suggesting that the number of E3-ligases in eukaryotes is under-represented. L. pneumophila also injects into the host many novel ubiquitin-modifying enzymes, which are the SidE family of effectors that catalyze phosphoribosyl-ubiquitination of serine residue of target proteins, independently of the canonical E1-2-3 enzymatic cascade. Interestingly, the environmental bacterium, L. pneumophila, has evolved within a diverse range of amoebal species, which serve as the natural hosts, while accidental transmission through contaminated aerosols can cause pneumonia in humans. Therefore, it is likely that the novel ubiquitin-modifying enzymes of L. pneumophila were acquired by the pathogen through interkingdom gene transfer from the diverse natural amoebal hosts. Furthermore, conservation of the ubiquitin pathway across eukaryotes has enabled these novel ubiquitin-modifying enzymes to function similarly in mammalian cells. Studies on the biological functions of these effectors are likely to reveal further novel ubiquitin biology and shed further lights on the evolution of ubiquitin.