The dependence of viral RNA replication on co-opted host factors

Nagy, Peter D.; Pogany, Judit

doi:10.1038/nrmicro2692

Cited by 391 publications

(426 citation statements)

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“…Plant RNA viruses must interact and use host factors at every step of the replication cycle (e.g., RNA synthesis, virus assembly, movement, counterdefense, and transmission). Examples include eukaryotic translation initiation factors, RNA-binding proteins, membrane trafficking machinery, and lipid-generating enzymes (17,19,20,55,56). These host factors simultaneously serve as virus restriction determinants if they have mutations that are unfavorable for virus replication (56).…”

Section: Discussionmentioning

confidence: 99%

“…RBOH-derived ROS induce stomatal closure to keep out invading bacteria, cross-linking the plant cell wall to block pathogen entry, and trigger local and systemic transcriptional reprogramming to activate plant immunity (1, 4, 9, 10). However, the function of ROS in plant-virus interactions remains largely unknown.Plant viruses are obligate intracellular pathogens, and their replication cycle completely depends on host cells, thus requiring many host factors for completion (17)(18)(19)(20). Positive-strand RNA [(+)RNA] viruses are the most abundant plant viruses and include many pathogens economically important in agriculture.…”

mentioning

confidence: 99%

“…Plant viruses are obligate intracellular pathogens, and their replication cycle completely depends on host cells, thus requiring many host factors for completion (17)(18)(19)(20). Positive-strand RNA [(+)RNA] viruses are the most abundant plant viruses and include many pathogens economically important in agriculture.…”

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confidence: 99%

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Harnessing host ROS-generating machinery for the robust genome replication of a plant RNA virus

Hyodo

Hashimoto

Kuchitsu

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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As sessile organisms, plants have to accommodate to rapid changes in their surrounding environment. Reactive oxygen species (ROS) act as signaling molecules to transduce biotic and abiotic stimuli into plant stress adaptations. It is established that a respiratory burst oxidase homolog B of Nicotiana benthamiana (NbRBOHB) produces ROS in response to microbe-associated molecular patterns to inhibit pathogen infection. Plant viruses are also known as causative agents of ROS induction in infected plants; however, the function of ROS in plant-virus interactions remains obscure. Here, we show that the replication of red clover necrotic mosaic virus (RCNMV), a plant positive-strand RNA [(+)RNA] virus, requires NbRBOHB-mediated ROS production. The RCNMV replication protein p27 plays a pivotal role in this process, redirecting the subcellular localization of NbRBOHB and a subgroup II calcium-dependent protein kinase of N. benthamiana (NbCDPKiso2) from the plasma membrane to the p27-containing intracellular aggregate structures. p27 also induces an intracellular ROS burst in an RBOH-dependent manner. NbCDPKiso2 was shown to be an activator of the p27-triggered ROS accumulations and to be required for RCNMV replication. Importantly, this RBOH-derived ROS is essential for robust viral RNA replication. The need for RBOHderived ROS was demonstrated for the replication of another (+) RNA virus, brome mosaic virus, suggesting that this characteristic is true for plant (+)RNA viruses. Collectively, our findings revealed a hitherto unknown viral strategy whereby the host ROS-generating machinery is diverted for robust viral RNA replication.positive-strand RNA virus | viral RNA replication | reactive oxygen species | respiratory burst oxidase homolog | calcium-dependent protein kinase P lants have evolved complicated and sophisticated strategies to survive environmental changes. The rapid generation of reactive oxygen species (ROS) is one of the hallmarks of plant responses to various biotic and abiotic stresses (1). Plant NADPH oxidase, termed RBOHs (respiratory burst oxidase homologs), localize at the plasma membrane (PM) and intracellular compartments including the Golgi apparatus (2, 3) and play a key role in ROS production upon the perception of environmental stresses (4). In Nicotiana benthamiana, an RBOHB (NbRBOHB) plays important roles in ROS production triggered by microbe-associated molecular patterns (MAMPs), such as bacterial flagellin and fungal chitin, and facilitates plant immunity against biotrophic pathogens including an oomycete pathogen Phytophthola infestance and tobacco mosaic virus (5-8). RBOH activity is tightly and coordinately regulated posttranslationally [e.g., activation by Ca 2+ , phosphatidic acid (PA), G proteins, or protein kinases] (9-12). It has recently been shown that receptor-like cytoplasmic kinases and calciumdependent protein kinases (CDPKs) regulate RBOHs activity via direct phosphorylation or through modulating regulators of RBOHs during recognition of MAMPs via corresponding surface-loca...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Harnessing host ROS-generating machinery for the robust genome replication of a plant RNA virus

Hyodo

Hashimoto

Kuchitsu

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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“…An important target for BSA is the cellular lipid metabolism [78][79][80] . Examples are anionic phospholipids such as phosphatidylinositols that are found predominantly in early endosomes and intracellular membranes 81,82 .…”

Section: Targeting Common Host-factors Used For Viral Replicationmentioning

confidence: 99%

Antiviral drug discovery: broad-spectrum drugs from nature

et al. 2015

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, but cannot be converted to PDF. You must view these files (e.g. movies) online.Scheme 1_(structures 1-5)_named.cdx Scheme 2_(structures 6-8)_named.cdx Scheme 3_(structure 9)_named.cdx Scheme 4_(structure 10)_named.cdx Scheme 5_ (structures 11-12) The development of drugs with broad-spectrum antiviral activities is a long pursued goal in drug discovery. It has been shown that blocking co-opted host-factors abrogates the replication of many viruses, yet the development of such host-targeting drugs has been met with skepticism mainly due to toxicity issues and poor translation to in vivo models. With the advent of new and more powerful screening assays and prediction tools, the idea of a drug that can efficiently treat a wide range of viral infections by blocking specific host functions has rebloomed. Here we critically review the state-of-the-art in broad-spectrum antiviral drug discovery. We discuss putative targets and treatment strategies, taking particular focus on natural products as promising starting points for antiviral lead development.

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“…Sin embargo, a pesar de los diversos juegos de factores del hospedero que son reclutados por diferentes virus, los estudios funcionales sugieren que las diferentes proteínas de los hospederos podrían proporcionar funciones similares durante la replicación del ARN viral [9].…”

Section: Introductionunclassified

Exploración de la interacción entre la región 5´UTR del Sugarcane Mosaic Virus (SCMV) y proteínas del hospedero maíz

Chaves-Bedoya

2017

Respuestas

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Resumen Antecedentes: El virus del mosaico de la caña de azúcar, SCMV (Potyviridae) es un miembro de la gran familia de virus de ARN de cadena positiva, sin una estructura CAP en su extremo 5´no traducido (5`UTR), pero con una proteína viral unida al genoma (VPg) y una cola poli A en su extremo 3´UTR. Se ha sugerido que proteínas del hospedero hacen un puente entre las regiones no traducidas virales 5´y 3´ para potenciar la traducción viral. Dado que las regiones no traducidas presentes en los genomas virales contienen elementos involucrados en la regulación de su ciclo replicativo, es importante analizar la interacción entre estas regiones y las proteínas virales o del hospedero para inferir su función. Objetivo: Determinar si existen proteínas del hospedero maíz que pudieran estar interactuando con la región 5´UTR de SCMV. Metodología: La región 5´UTR de SCMV se amplificó por PCR incluyendo la secuencia del promotor T7 en la secuencia del oligo 5´ UTR y se generaron sus transcritos marcados radiactivamente. Los transcritos marcados fueron entrecruzados con extractos proteicos de hojas de maíz sanas e infectadas. Resultados: Los resultados sugieren la presencia de una proteína putativa de interacción del hospedante maíz de aproximadamente 53kDa, con la región 5´UTR de SCMV. Conclusión: Los ensayos de entrecruzamiento, especificidad y estabilidad de los complejos ARN-proteína sugieren que en el hospedante maíz existe al menos una proteína que interactúa con la región 5´ UTR de SCMV.Palabras Clave: Complejo ARN-proteína, entrecruzamiento UV, fracción proteica, Potyvirus, VPg.Abstract Background: Sugarcane mosaic virus is a member of the great family of positive sense RNA viruses, without a CAP structure in its 5´UTR end, but with a viral protein attached to the genome (VPg) and a poli A tail in its 3´UTR end. It has been suggested that some host proteins make a bridge between the untranslated 5´and 3´ regions (UTRs) to enhance the canonical and/or non-canonical virus translation. Since the UTR regions present in the viral genomes have some elements involved in the regulation of their replicative cycle, it is important to analyze the interaction that may occur between these regions and the viral or host proteins to infer regarding its function. Objective: To identify proteins of the host maize that could be interacting with the 5´UTR region of SCMV. Methodology: 5´UTR region of SCMV was amplified by PCR including the sequence of the T7 promoter in the 5´oligo sequence. The transcripts were radioactively labeled. Labeled transcripts were crosslinked with proteins extracts from healthy and infected maize leaves. Results: The results suggest the presence of a 53 kDa putative protein interacting with the 5 ´UTR region of SCMV. Conclusion: Crosslinking essays, specificity and the stability of the RNA-protein complex suggest that in maize host there is at least one protein that interacts with the 5´UTR region of SCMV.Keywords: RNA-Protein complex, UV crosslinking, protein fraction, Potyvirus, VPg

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The dependence of viral RNA replication on co-opted host factors

Cited by 391 publications

References 145 publications

Harnessing host ROS-generating machinery for the robust genome replication of a plant RNA virus

Harnessing host ROS-generating machinery for the robust genome replication of a plant RNA virus

Antiviral drug discovery: broad-spectrum drugs from nature

Exploración de la interacción entre la región 5´UTR del Sugarcane Mosaic Virus (SCMV) y proteínas del hospedero maíz

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