Identification of Plant Virus Movement-Host Protein Interactions

Abstract After the discovery of ‘movement proteins’ as a peculiarity of plant viruses and with the help of novel methods for the detection and isolation of interacting host proteins new insights have been obtained to understand the mechanisms of virus movement in plant tissues. Rapid progress in studying the molecular mechanisms of systemic spread of plant infecting viruses revealed an interrelation between virus movement and macromolecular trafficking in plant tissues. This article summarizes current explorations on plant virus movement proteins (MPs) and introduces the state of the art in the identification and isolation of MP interacting host proteins.

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Variability, Functions and Interactions of Plant Virus Movement Proteins: What Do We Know So Far?

Microorganisms ◽

10.3390/microorganisms9040695 ◽

2021 ◽

Vol 9 (4) ◽

pp. 695

Author(s):

Gaurav Kumar ◽

Indranil Dasgupta

Keyword(s):

Current Knowledge ◽

Plant Viruses ◽

Host Protein ◽

Size Exclusion ◽

Host Proteins ◽

Movement Proteins ◽

Core Function ◽

Intercellular Channels ◽

Pass Through ◽

Cellular Components

Of the various proteins encoded by plant viruses, one of the most interesting is the movement protein (MP). MPs are unique to plant viruses and show surprising structural and functional variability while maintaining their core function, which is to facilitate the intercellular transport of viruses or viral nucleoprotein complexes. MPs interact with components of the intercellular channels, the plasmodesmata (PD), modifying their size exclusion limits and thus allowing larger particles, including virions, to pass through. The interaction of MPs with the components of PD, the formation of transport complexes and the recruitment of host cellular components have all revealed different facets of their functions. Multitasking is an inherent property of most viral proteins, and MPs are no exception. Some MPs carry out multitasking, which includes gene silencing suppression, viral replication and modulation of host protein turnover machinery. This review brings together the current knowledge on MPs, focusing on their structural variability, various functions and interactions with host proteins.

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Visualization of Host-Polerovirus Interaction Topologies Using Protein Interaction Reporter Technology

Journal of Virology ◽

10.1128/jvi.01706-15 ◽

2015 ◽

Vol 90 (4) ◽

pp. 1973-1987 ◽

Cited By ~ 25

Author(s):

Stacy L. DeBlasio ◽

Juan D. Chavez ◽

Mariko M. Alexander ◽

John Ramsey ◽

Jimmy K. Eng ◽

...

Keyword(s):

Mass Spectrometry ◽

Protein Interaction ◽

Protein Interactions ◽

Interaction Network ◽

Host Protein ◽

Host Proteins ◽

Content Type ◽

Host Pathogen ◽

Pathogen Protein ◽

Binding Interfaces

ABSTRACTDemonstrating direct interactions between host and virus proteins during infection is a major goal and challenge for the field of virology. Most protein interactions are not binary or easily amenable to structural determination. Using infectious preparations of a polerovirus (Potato leafroll virus[PLRV]) and protein interaction reporter (PIR), a revolutionary technology that couples a mass spectrometric-cleavable chemical cross-linker with high-resolution mass spectrometry, we provide the first report of a host-pathogen protein interaction network that includes data-derived, topological features for every cross-linked site that was identified. We show that PLRV virions have hot spots of protein interaction and multifunctional surface topologies, revealing how these plant viruses maximize their use of binding interfaces. Modeling data, guided by cross-linking constraints, suggest asymmetric packing of the major capsid protein in the virion, which supports previous epitope mapping studies. Protein interaction topologies are conserved with other species in theLuteoviridaeand with unrelated viruses in theHerpesviridaeandAdenoviridae. Functional analysis of three PLRV-interacting host proteinsin plantausing a reverse-genetics approach revealed a complex, molecular tug-of-war between host and virus. Structural mimicry and diversifying selection—hallmarks of host-pathogen interactions—were identified within host and viral binding interfaces predicted by our models. These results illuminate the functional diversity of the PLRV-host protein interaction network and demonstrate the usefulness of PIR technology for precision mapping of functional host-pathogen protein interaction topologies.IMPORTANCEThe exterior shape of a plant virus and its interacting host and insect vector proteins determine whether a virus will be transmitted by an insect or infect a specific host. Gaining this information is difficult and requires years of experimentation. We used protein interaction reporter (PIR) technology to illustrate how viruses exploit host proteins during plant infection. PIR technology enabled our team to precisely describe the sites of functional virus-virus, virus-host, and host-host protein interactions using a mass spectrometry analysis that takes just a few hours. Applications of PIR technology in host-pathogen interactions will enable researchers studying recalcitrant pathogens, such as animal pathogens where host proteins are incorporated directly into the infectious agents, to investigate how proteins interact during infection and transmission as well as develop new tools for interdiction and therapy.

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Evolution of plant virus movement proteins from the 30K superfamily and of their homologs integrated in plant genomes

Virology ◽

10.1016/j.virol.2014.12.012 ◽

2015 ◽

Vol 476 ◽

pp. 304-315 ◽

Cited By ~ 34

Author(s):

Arcady R. Mushegian ◽

Santiago F. Elena

Keyword(s):

Plant Virus ◽

Virus Movement ◽

Movement Proteins ◽

Plant Genomes

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Did Silencing Suppression Counter-Defensive Strategy Contribute to Origin and Evolution of the Triple Gene Block Coding for Plant Virus Movement Proteins?

Frontiers in Plant Science ◽

10.3389/fpls.2012.00136 ◽

2012 ◽

Vol 3 ◽

Cited By ~ 10

Author(s):

Sergey Y. Morozov ◽

Andrey G. Solovyev

Keyword(s):

Plant Virus ◽

Triple Gene Block ◽

Virus Movement ◽

Defensive Strategy ◽

Movement Proteins ◽

Gene Block ◽

Origin And Evolution ◽

Block Coding ◽

Silencing Suppression

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A map of direct SARS-CoV-2 protein interactions implicates specific human host processes

10.1101/2021.03.15.433877 ◽

2021 ◽

Author(s):

Dae-Kyum Kim ◽

Benjamin Weller ◽

Chung-Wen Lin ◽

Dayag Sheykhkarimli ◽

Jennifer J Knapp ◽

...

Keyword(s):

Protein Interactions ◽

Membrane Trafficking ◽

Host Protein ◽

Host Proteins ◽

Systematic Map ◽

High Data ◽

Protein Ubiquitination ◽

Human Proteins ◽

Physical Interactions ◽

Key Steps

Key steps in viral propagation, immune suppression and pathology are mediated by direct, binary physical interactions between viral and host proteins. To understand the biology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, we generated an unbiased systematic map of binary physical interactions between viral and host interactions, complementing previous co-complex association maps by conveying more direct mechanistic understanding and enabling targeted disruption of direct interactions. To this end, we deployed two parallel strategies, identifying 205 virus-host and 27 intraviral binary interactions amongst 171 host and 19 viral proteins, with orthogonal validation by an internally benchmarked NanoLuc two-hybrid system to ensure high data quality. Host proteins interacting with SARS-CoV-2 proteins were enriched in various cellular processes, including immune signaling and inflammation, protein ubiquitination, and membrane trafficking. Specific subnetworks provide new hypotheses related to viral modulation of host protein homeostasis and T-cell regulation. The direct virus-host protein interactions we identified can now be prioritized as targets for therapeutic intervention. More generally, we provide a resource of systematic maps describing which SARS-CoV-2 and human proteins interact directly.

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Proteolytic processing of plant proteins by potyvirus NIa proteases

Journal of Virology ◽

10.1128/jvi.01444-21 ◽

2021 ◽

Author(s):

Huogen Xiao ◽

Etienne Lord ◽

Hélène Sanfaçon

Keyword(s):

Virus Infection ◽

Plant Virus ◽

Plant Viruses ◽

Proteolytic Processing ◽

Plum Pox Virus ◽

Plant Proteins ◽

Host Proteins ◽

Prediction Approach

The NIa protease of potyviruses is a chymotrypsin-like cysteine protease related to the picornavirus 3C protease. It is also a multifunctional protein known to play multiple roles during virus infection. Picornavirus 3C proteases cleave hundreds of host proteins to facilitate virus infection. However, whether or not potyvirus NIa proteases cleave plant proteins has so far not been tested. Regular expression search using the cleavage site consensus sequence [EQN]xVxH[QE]/[SGTA] for the plum pox virus (PPV) protease identified 90-94 putative cleavage events in the proteomes of Prunus persica (a crop severely affected by PPV), Arabidopsis thaliana and Nicotiana benthamiana (two experimental hosts). In vitro processing assays confirmed cleavage of six A. thaliana and five P. persica proteins by the PPV protease. These proteins were also cleaved in vitro by the protease of turnip mosaic virus (TuMV), which has a similar specificity. We confirmed in vivo cleavage of a transiently expressed tagged version of AtEML2, an EMSY-like protein belonging to a family of nuclear histone readers known to be involved in pathogen resistance. Cleavage of AtEML2 was efficient and was observed in plants that co-expressed the PPV or TuMV NIa proteases or in plants that were infected with TuMV. We also show partial in vivo cleavage of AtDUF707, a membrane protein annotated as lysine ketoglutarate reductase trans-splicing protein. Although cleavage of the corresponding endogenous plant proteins remains to be confirmed, the results show that a plant virus protease can cleave host proteins during virus infection and highlight a new layer of plant-virus interactions. Importance Viruses are highly adaptive and use multiple molecular mechanisms to highjack or modify the cellular resources to their advantage. They must also counteract or evade host defense responses. One well-characterized mechanism used by vertebrate viruses is the proteolytic cleavage of host proteins to inhibit the activities of these proteins and/or to produce cleaved protein fragments that are beneficial to the virus infection cycle. Even though almost half of the known plant viruses encode at least one protease, it was not known whether plant viruses employ this strategy. Using an in silico prediction approach and the well-characterized specificity of potyvirus NIa proteases, we were able to identify hundreds of putative cleavage sites in plant proteins, several of which were validated by downstream experiments. It can be anticipated that many other plant virus proteases also cleave host proteins and that the identification of these cleavage events will lead to novel antiviral strategies.

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Genetic architecture of host proteins interacting with SARS-CoV-2

10.1101/2020.07.01.182709 ◽

2020 ◽

Cited By ~ 3

Author(s):

Maik Pietzner ◽

Eleanor Wheeler ◽

Julia Carrasco-Zanini ◽

Johannes Raffler ◽

Nicola D. Kerrison ◽

...

Keyword(s):

Protein Interactions ◽

Host Response ◽

Drug Targets ◽

Genetic Architecture ◽

Large Scale ◽

Adverse Outcomes ◽

Host Protein ◽

Host Proteins ◽

Proteomic Data ◽

Cellular Assays

ABSTRACTStrategies to develop therapeutics for SARS-CoV-2 infection may be informed by experimental identification of viral-host protein interactions in cellular assays and measurement of host response proteins in COVID-19 patients. Identification of genetic variants that influence the level or activity of these proteins in the host could enable rapid ‘in silico’ assessment in human genetic studies of their causal relevance as molecular targets for new or repurposed drugs to treat COVID-19. We integrated large-scale genomic and aptamer-based plasma proteomic data from 10,708 individuals to characterize the genetic architecture of 179 host proteins reported to interact with SARS-CoV-2 proteins or to participate in the host response to COVID-19. We identified 220 host DNA sequence variants acting in cis (MAF 0.01-49.9%) and explaining 0.3-70.9% of the variance of 97 of these proteins, including 45 with no previously known protein quantitative trait loci (pQTL) and 38 encoding current drug targets. Systematic characterization of pQTLs across the phenome identified protein-drug-disease links, evidence that putative viral interaction partners such as MARK3 affect immune response, and establish the first link between a recently reported variant for respiratory failure of COVID-19 patients at the ABO locus and hypercoagulation, i.e. maladaptive host response. Our results accelerate the evaluation and prioritization of new drug development programmes and repurposing of trials to prevent, treat or reduce adverse outcomes. Rapid sharing and dynamic and detailed interrogation of results is facilitated through an interactive webserver (https://omicscience.org/apps/covidpgwas/).

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Impact Analysis of SARS-CoV2 on Signaling Pathways during COVID19 Pathogenesis using Codon Usage Assisted Host-Viral Protein Interactions

10.1101/2020.07.29.226217 ◽

2020 ◽

Author(s):

Jayanta Kumar Das ◽

Subhadip Chakraborty ◽

Swarup Roy

Keyword(s):

Codon Usage ◽

Signaling Pathways ◽

Protein Interaction ◽

Protein Interactions ◽

Viral Protein ◽

Viral Proteins ◽

Host Protein ◽

Host Proteins ◽

Disease Pathogenesis ◽

Pattern Similarity

AbstractUnderstanding the molecular mechanism of COVID19 disease pathogenesis helps in the rapid development of therapeutic targets. Usually, viral protein targets host proteins in an organized fashion. The pathogen may target cell signaling pathways to disrupt the pathway genes’ regular activities, resulting in disease. Understanding the interaction mechanism of viral and host proteins involved in different signaling pathways may help decipher the attacking mechanism on the signal transmission during diseases, followed by discovering appropriate therapeutic solutions.The expression of any viral gene depends mostly on the host translational machinery. Recent studies report the great significance of codon usage biases in establishing host-viral protein-protein interactions (PPI). Exploiting the codon usage patterns between a pair of co-evolved host and viral proteins may present novel insight into the host-viral protein interactomes during disease pathogenesis. Leveraging the codon usage pattern similarity (and dissimilarity), we propose a computational scheme to recreate the hostviral protein interaction network (HVPPI). We use seventeen (17) essential signaling pathways for our current work and study the possible targeting mechanism of SARS-CoV2 viral proteins on such pathway proteins. We infer both negatively and positively interacting edges in the network. We can find a relationship where one host protein may target by more than one viral protein.Extensive analysis performed to understand the network topologically and the attacking behavior of the viral proteins. Our study reveals that viral proteins, mostly utilize codons, rare in the targeted host proteins (negatively correlated interaction). Among non-structural proteins, NSP3 and structural protein, Spike (S) protein, are the most influential proteins in interacting multiple host proteins. In ranking the most affected pathways, MAPK pathways observe to be worst affected during the COVID-19 disease. A good number of targeted proteins are highly central in host protein interaction networks. Proteins participating in multiple pathways are also highly connected in their own PPI and mostly targeted by multiple viral proteins.

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