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Biology subjects

Heck, M. L.

Publications and source records attributed to Heck, M. L..

11 recordsLinked to original sources

A scalable approach to inoculate plant viral vectors into plant tissue using non-pathogenic, transgenic galls

Vascular plant pathogens transmitted by insects inflict devastating economic losses on crops worldwide. By obstructing and usurping the natural flow of nutrients, plant infection by these pathogens drastically reduces yields, vigor and productivity. Treating fruit-bearing trees against persistent vascular pathogens poses a unique challenge, as systemic delivery of therapeutics must navigate the compartmentalized architecture of the trees vascular system under changing environmental conditions without disrupting fruit production or long-term tree health. Plant viruses have gained traction as a novel approach to deliver therapies to crop plants, including fruit trees, but delivery of viral vectors to orchards at scale remains a significant challenge. We tested whether transgenic galls can be used to systemically infect plants with a plant virus infectious clone. We combined the plant growth regulator gene cassette from Agrobacterium tumefaciens strain C58 with the wild-type strain of citrus yellow vein associated virus-1 (CY1) on a single plasmid within the T-DNA for plant cell transformation. Using EHA105, a disarmed strain of A. tumefaciens, we inoculated stems with these gall-forming plasmids and initiated systemic CY1 infection in citrus and Arabidopsis thaliana over three independent experiments. We provide proof-of-concept that transgenic galls, referred to as symbionts, can launch the systemic infection of CY1 in economically important and model plants. Symbiont delivery of therapeutic viral vectors is theoretically scalable from inoculation of mother trees within the nursery to millions of trees in the field and may be a valuable tool for the commercial delivery of therapeutic plant viral vectors.

plant biology↗

The "Grove-First" Framework: Starting in the Grove to Find Therapies for Huanglongbing

Citrus greening disease, also known as huanglongbing (HLB), is the most serious vector-borne bacterial disease of citrus world-wide1,2. There is an immediate global need to provide the citrus industry with relief from HLB and a return to profitable citrus production. Standard screening methods for HLB therapeutic treatments typically involve various laboratory-based assays to select treatments with antimicrobial properties3, which then advance to greenhouse and eventually field testing in a workflow that takes multiple years. Unlike traditional lab-first screening, we present a design of experiments framework4,5, referred to as Grove-First, that rapidly screens treatments with regulatory-friendly profiles in commercial citrus groves using trunk injection to select treatments that improve tree health and fruit yield over the course of a single growing season. Using this framework, we identified candidate treatments with effects comparable to or better than the standard oxytetracycline (OTC) on visual tree-health and/or yield indices in an initial screen of HLB-positive 8-year-old Valencia sweet orange trees. Expanded trials in commercial citrus groves allowed us to validate the initial screening results at other locations and in other citrus varieties. Grove-First rapidly accelerated the identification and large-scale field testing of HLB therapies, some of which are available for growers to use immediately and others that require further field testing and/or regulatory actions.

plant biology↗

Viral silencing suppressor activity in plants modifies aphid antiviral immunity and fecundity

Plants defend themselves from viral infection using RNA interference (RNAi), an evolutionarily conserved mechanism that degrades viral RNA through the production of small interfering RNAs. As a counter defense, plant viruses evolved suppressors of RNA silencing (VSRs) to inhibit plant RNAi machinery, aiding viral replication and transmission. P0, a VSR encoded by the potato leafroll virus (PLRV), family Polerovirus, suppresses RNAi by targeting the plant protein ARGONATE 1 for degradation through its F-box motif interaction with a Skp1 subunit of the family of E3 ubiquitin ligases. Our previous work shows PLRV P0 suppresses antiviral immunity in its aphid vector Myzus persicae, leading to an increase in aphid infection by the insect virus Myzus persicae densovirus (MpDNV). Here, we expand on these findings and show that the P0 protein also regulates aphid fecundity. Using a series of F-box mutants, we demonstrate that a functional P0 F-box motif is required for inhibition MpDNV antiviral immunity but not modulation of aphid fecundity. We further show that silencing suppressors from non-aphid-borne plant viruses that target other components of the plants RNAi machinery also modulate aphid fecundity but not MpDNV titer. Collectively, the results show that aphids have been favored by selection to modulate their anti-viral immunity and fecundity in response to changes in the plant RNAi pathways induced by plant viral infection. These data highlight the intricate co-evolution of plant viruses, their vectors, and host defenses. This knowledge may open new avenues for managing vector-borne plant diseases by targeting viral proteins to manipulate insect vectors.

microbiology↗

Viral and bacterial plant pathogens suppress antiviral defense against flaviviruses in their insect vectors

A positive, single-stranded RNA virus member within the Flavivirus genus was identified and characterized infecting Myzus persicae. This new insect-specific virus (ISV), Myzus persicae flavivirus (MpFV), is 23,236 nucleotides in length and encodes a large polyprotein from a single open reading frame. Analysis of conserved domains showed that helicases, NS3-proteases, Fts-J methyltransferase, and an RNA-dependent RNA polymerase are present in the coded polyprotein. Aphid-infecting ISVs have been reported to interact with plant viruses within the vector, modulating its titer and manipulating aphid behavior and morphology. Small RNA (sRNA) profile analysis of the M. persicae sRNA profile demonstrated that the circulative plant virus, potato leafroll virus (PLRV), modified the aphid antiviral immunity against MpFV. Abundant sRNA reads matching MpFV were detected when aphids were fed on healthy plants, sucrose diet, and potato virus Y-infected plants. In contrast, no MpFV reads were detected in aphids that had acquired PLRV from infected plants or artificial diet sachets containing purified virions. While the titer of M. persicae densovirus (MpDNV) was previously reported to be regulated by expression of the PLRV silencing suppressor protein P0, P0 had no effect on MpFV titer in the aphid. MpFV was transmitted 100% vertically to the offspring, and exhibited tissue tropisms for the body rather than the head. By artificial diet assays, other aphid species, including Aphis gossypii (cotton aphid), Schizaphis graminum (greenbug aphid), Rhopalosiphum padi (bird cherry-oat aphid), and R. maidis (corn leaf aphid), acquired the MpFV. These findings further support the idea that PLRV suppresses aphid immunity against ISVs, suggest the existence of at least two distinct pathways for PLRV-induced aphid immune system modulation. To test whether other circulative plant pathogens suppress insect anti-viral immunity against insect-specific flaviviruses, we quantified the small RNA response of Diaphorina citri, vector of "Candidatus Liberibacter asiaticus" (CLas) associated with citrus greening disease and showed that CLas also suppresses D. citri anti-viral immunity against D. citri-like flavivirus (DcLFV). These data reveal an evolutionary conserved, unexpected role for diverse circulative plant pathogens in modulating anti-viral immunity in hemipteran vectors.

microbiology↗

Data mining redefines the timeline and geographic spread of cotton leafroll dwarf virus

Cotton leafroll dwarf virus (CLRDV), a threat to the cotton industry, was first reported in the United States (US) as an emergent pathogen in 2017. Phylogenetic analysis supports the hypothesis that US CLRDV strains are genetically distinct from strains in South America and elsewhere, which is not consistent with the hypothesis that the virus is newly introduced into the country. Therefore, using database mining, we evaluated the timeline and geographic distribution of CLRDV in the country. We uncovered evidence that shows that CLRDV had been in the US for over a decade before its official first report. CLRDV sequences were detected in datasets derived from Mississippi in 2006, Louisiana in 2015, and California in 2018. Additionally, through field surveys of upland cotton in 2023, we confirmed that CLRDV is present in California, which had no prior reports of the virus. Viral sequences from these old and new datasets exhibited high nucleotide identities (>98%) with recently characterized US isolates, and phylogenetic analyses with their homologs placed these sequences within a US-specific clade, further supporting the earlier presence of CLRDV in the country. Moreover, potential new hosts, including another fiber crop, flax, were determined through data mining. Retrospective analysis suggests CLRDV presence in the US since at least 2006 (Mississippi). These findings necessitate a reevaluation of spread patterns, inoculum sources, symptomology variations, and control strategies. Our findings challenge the current understanding of the arrival and spread of CLRDV in the US, highlight the power of data mining for virus discovery, and underscore the need for further investigation into CLRDVs impact on US cotton.

plant biology↗

Grove-level analysis of titer and prevalence of Candidatus Liberibacter asiaticus and Wolbachia in Diaphorina citri, vector of citrus Huanglongbing

Huanglongbing (HLB, or citrus greening disease) affects all citrus varieties world-wide. In the USA, Asia, and South America the causal agent is "Candidatus Liberibacter asiaticus" (CLas), a phloem-limited, uncultured, alphaproteobacterium. The hemipteran insect vector, Diaphorina citri (Asian citrus psyllid) acquires and transmits CLas in a circulative, propagative manner. In addition to CLas, D. citri hosts multiple symbiotic bacterial species including Wolbachia (wDi). In D. citri, wDi has been sequenced and studied but specific roles in D. citri biology are unknown. Using well established quantitative PCR methods we measured CLas titer in D. citri collected from four groves in central Florida with distinct HLB management strategies and tested whether CLas and wDi titer were correlated in a sub-set of these insects. Grove site had the largest effect on CLas titer. Sex had no effect on CLas titer, while higher wDi titer was correlated with non-infected insects. Our results suggest that more directed follow-up research is necessary and important to clarify whether field management tactics influence CLas titer in D. citri and to better understand gene-by-environment interactions among D. citri, wDi and CLas. Now that millions of trees in Florida have been treated with injectable formulations of oxytetracycline, which is likely to decrease bacterial populations in D. citri, this study may represent the last biologically meaningful snapshot of grove-level vector-pathogen ecology in the state during the HLB epidemic.

plant biology↗

Plant-derived, nodule-specific cysteine rich peptides inhibit growth and psyllid acquisition of 'Candidatus Liberibacter asiaticus', the citrus Huanglongbing bacterium

AbstractThe Asian citrus psyllid, Diaphorina citri, is a vector of Candidatus Liberibacter asiaticus (CLas), a gram-negative, obligate biotroph whose infection in Citrus species is associated with citrus greening disease, or Huanglongbing (HLB). Strategies to block CLas transmission by D. citri remain the best way to prevent the spread of the disease into new citrus growing regions. However, identifying control strategies to block HLB transmission poses significant challenges, such as the discovery and delivery of antimicrobial compounds targeting the bacterium and overcoming consumer hesitancy towards accepting the treatment. Here, we computationally identified and tested a series of 20-mer nodule-specific cysteine-rich peptides (NCRs) derived from the Mediterranean legume, Medicago truncatula Gaertn. (barrelclover) to identify those peptides that could effectively prevent or reduce CLas infection in citrus leaves and/or prevent CLas acquisition by the bacteriums insect vector, D. citri. A set of NCR peptides were tested in a screening pipeline involving three distinct assays: a bacterial culture assay, a CLas-infected excised citrus leaf assay, and a CLas-infected nymph acquisition assay that included D. citri nymphs, the only stage of D. citris life-cycle that can acquire CLas leading to the development of vector competent adult insects. We demonstrate that a subset of M. truncatula-derived NCRs inhibit both CLas growth in citrus leaves and CLas acquisition by D. citri from CLas-infected leaves. These findings reveal NCR peptides as a new class and source of biopesticide molecules to control CLas for the prevention and/or treatment of HLB.

plant biology↗

Polerovirus N-terminal readthrough domain structures reveal novel molecular strategies for mitigating virus transmission by aphids

Poleroviruses, enamoviruses, and lutoeviruses are icosahedral, positive sense RNA viruses that cause economically important diseases in food and fiber crops. They are transmitted by phloem-feeding aphids in a circulative manner that involves the movement across and within insect tissues. The N-terminal portion of the viral readthrough domain (NRTD) has been implicated as a key determinant of aphid transmission in each of these genera. Here, we report crystal structures of the NRTDs from the poleroviruses turnip yellow virus (TuYV) and potato leafroll virus (PLRV) at 1.53-[A] and 2.22-[A] resolution, respectively. These adopt a two-domain arrangement with a unique interdigitated topology and form highly conserved dimers that are stabilized by a C-terminal peptide that is critical for proper folding. We demonstrate that the PLRV NRTD can act as an inhibitor of virus transmission and identify NRTD mutant variants that are lethal to aphids. Sequence conservation argues that enamovirus and luteovirus NRTDs will follow the same structural blueprint, which affords a novel approach to block the spread of these agricultural pathogens in a generalizable manner.

plant biology↗

Direct DNA sequencing of "Candidatus Liberibacter asiaticus" from Diaphorina citri, the Asian citrus psyllid, and its implications for citrus greening disease management

The Asian citrus psyllid, Diaphorina citri is an invasive insect 1 and a vector of Candidatus Liberibacter asiaticus (CLas), a bacterium whose growth in Citrus species results in citrus greening disease 2,3. Methods to enrich and sequence CLas from D. citri often rely on biased genome amplification 4 and nevertheless contain significant quantities of host DNA 5,6. To overcome these hurdles, we developed a simple pre-treatment DNase and filtration (hereafter PDF) protocol to directly sequence CLas and the complete, primarily uncultivable, microbiome from D. citri adults. The PDF protocol yielded CLas abundances upwards of 60% and enabled detection of 156 genetic variants in these strains compared to progenitor strains in Florida, which included prophage encoding regions with key functions in CLas pathogenesis, putative antibiotic resistance loci, and a single secreted effector. These variants suggest laboratory propagation of CLas may result in different phenotypic trajectories among laboratories, and may confound CLas physiology or therapeutic design and evaluation if these differences remain undocumented. Finally, we obtained genetic signatures affiliated with Citrus nuclear and organellar genomes, entomopathogenic fungal mitochondria, and commensal bacteria from laboratory-reared and field-collected D. citri adults. Hence, the PDF protocol can inform agricultural management strategies related to pathogen evolution 7, insect microbiome surveillance 8, antibiotic resistance screening 9, and gut content analysis 10.

microbiology↗

Quantitative isotope-labeled crosslinker proteomics reveals developmental variation in protein interactions and posttranslational modifications in Diaphorina citri, the citrus greening insect vector

Acquisition of the citrus greening bacterial pathogen, Candidatus Liberibacter asiaticus (CLas) by Asian citrus psyllid (Diaphorina citri) nymphs is required efficient tree-to-tree transmission during the adult stage. Quantitative isotope-labeled protein interaction reporter (PIR) cross-linkers were used in parallel with protein quantification using spectral counting to quantify protein interactions within microbe-enriched cellular fractions of nymph and adult D. citri. Over 100 unique crosslinks were found between five insect histone proteins, and over 30% of these were more abundant in nymph compared to adult insects. Strikingly, some cross-links detected in D. citri proteins are conserved in cross-linking studies on human cells, suggesting these protein interaction topologies were present in the common ancestor ([~]750MYA) or are subject to convergent evolution. Analysis of posttranslational modifications of crosslinked histones revealed the presence of acetylated and methylated lysine residues, which may impact psyllid chromatin structure and gene expression. Histone H3 peptides acetylated in the N terminal tail region were found to be more abundant in nymph compared to adult insects in two orthogonal proteomics methods. The insect life stage-specific histone posttranslational modifications and protein interactions represent physical evidence that metamorphosis is associated with changes in chromatin structure that regulate genome-wide transcriptional reprogramming.

systems biology↗

Crystal structure of the potato leafroll virus coat protein and implications for viral assembly

Luteoviruses, poleroviruses, and enamoviruses are insect-transmitted, agricultural pathogens that infect a wide array of staple food crops. Previous cryo-electron microscopy studies of virus-like particles indicate that luteovirid viral capsids are built from a structural coat protein that organizes with T=3 icosahedral symmetry. Here we present the crystal structure of a truncated version of the coat protein monomer from potato leafroll virus at 1.57-[A] resolution. In the crystal lattice, monomers pack into flat sheets that preserve the two-fold and three-fold axes of icosahedral symmetry and show minimal structural deviations when compared to the full-length subunits of the assembled virus-like particle. These observations have important implications in viral assembly and maturation, suggesting that the CP N-terminus and its interactions with RNA serve as a key driver for generating capsid curvature.

biochemistry↗