Plant-microbe interactions

Geminiviruses: masters at redirecting and reprogramming plant processes

Journal name:
Nature Reviews Microbiology
Volume:
11,
Pages:
777–788
Year published:
DOI:
doi:10.1038/nrmicro3117
Published online

Abstract

The family Geminiviridae is one of the largest and most important families of plant viruses. The small, single-stranded DNA genomes of geminiviruses encode 5–7 proteins that redirect host machineries and processes to establish a productive infection. These interactions reprogramme plant cell cycle and transcriptional controls, inhibit cell death pathways, interfere with cell signalling and protein turnover, and suppress defence pathways. This Review describes our current knowledge of how geminiviruses interact with their plant hosts and the functional consequences of these interactions.

At a glance

Figures

  1. The begomovirus life cycle.
    Figure 1: The begomovirus life cycle.

    Infection begins in a plant cell when viral single-stranded DNA (ssDNA) is released from virions and copied to generate double-stranded DNA (dsDNA). The dsDNA, which assembles with nucleosomes, is transcribed by host RNA polymerase II, allowing production of replication initiator protein (Rep). Rep initiates rolling-circle replication by introducing a nick into a viral dsDNA molecule to generate a free 3′-hydroxyl end that primes ssDNA synthesis, leading to displacement of the parental strand (inset). The released ssDNA is converted to dsDNA to re-enter the replication cycle. Viral replication transitions to recombination-dependent replication, which is initiated by homologous recombination between a partially replicated ssDNA and a closed, circular dsDNA to form a looped molecule that serves as a template for both ssDNA and dsDNA synthesis (inset). Later in infection, Rep represses its own transcription, leading to activation of transcriptional activator protein (TrAP) expression, which in turn activates coat protein (CP) and nuclear shuttle protein (NSP) expression. Circular ssDNA can then be encapsidated by CP into virions, which are available for whitefly acquisition. NSP binds to viral DNA and moves it across the nuclear envelope, where movement protein (MP) traffics it across a plasmodesma. It is not known whether viral DNA moves as ssDNA versus dsDNA or as a linear versus a circular molecule.

  2. Reprogramming plant cell cycle and methyl cycle controls.
    Figure 2: Reprogramming plant cell cycle and methyl cycle controls.

    The diagram shows virus–host interactions that are necessary to create a cellular environment that is favourable for geminivirus DNA replication. Geminiviruses can infect plant cells in the G1 phase (2C DNA content) of the mitotic cycle or in the G phase of the endocycle (when the cell has a 4C DNA content) and induce them to enter the S phase. Replication initiator protein (Rep) and replication enhancer protein (REn) interact with and inhibit retinoblastoma-related protein (RBR) to relieve inhibition of E2F transcription factors and activate the expression of plant genes encoding host DNA polymerases and accessory factors that are required for viral replication. These interactions reprogramme cell cycle controls and induce mature plant cells to progress through the endocycle or the mitotic cell cycle. Rep also activates the expression of transcriptional activator protein (TrAP; known as C2 in some viruses), which interacts with adenosine kinase (ADK) and S-adenosyl methionine decarboxylase 1 (SAMDC1) to inhibit the plant methyl cycle. The protein βC1 also interferes with the methyl cycle through its interactions with S-adenosyl homocysteine hydrolase (SAHH). Suppression of the methyl cycle facilitates geminivirus replication by reducing viral DNA methylation. The geminivirus Rep-interacting kinase (GRIK)–SNF1-related protein kinase 1 (SNRK1) protein kinase cascade links Rep to suppression of the methyl cycle. Figure is modified, with permission, from Ref. 26 © (2008) American Society of Plant Biologists.

  3. Modulation of ubiquitylation and ubiquitylation-like pathways.
    Figure 3: Modulation of ubiquitylation and ubiquitylation-like pathways.

    The diagram shows interactions between geminivirus proteins (grey) and components of the ubiquitin and ubiquitin-like protein (Ub/Ubl) pathways. Modification of a substrate (S) requires the activating (E1) and conjugating (E2) enzymes and usually an E3 ligase that confers specificity. In plants, the multisubunit cullin RING ligases (CRLs) for ubiquitin constitute the most abundant family of E3 ligases. They are formed by the RING subunit RBX1, which binds to E2, and a substrate adaptor formed by S-phase kinase-associated protein 1 (SKP1) and an F-box (FB) protein in the cullin 1 (CUL1)-based group ligases. CRL activity is regulated by a cycle of covalent attachment and removal of the ubiquitin-like protein RUB, which is required for robust CRL activity. The constitutive photomorphogenesis 9 signalosome (CSN) complex catalyses derubylation of cullins. Ubiquitin-modified proteins can be degraded by the 26S proteasome. Ub/Ubl modification can also regulate the activity of a target protein or alter its subcellular location, which can be reversed by deubiquitylating enzymes (DUBs). Rep, replication initiator protein.

  4. Silencing pathways targeting geminiviruses.
    Figure 4: Silencing pathways targeting geminiviruses.

    a | Primary small interfering RNAs (siRNAs). After bidirectional transcription of viral DNA, mRNA is cleaved at the polyA site and polyadenylated for nuclear export. Profiles of viral primary siRNAs produced in a geminvirus-infected RNA-dependent RNA polymerase (RDR) triple-mutant plant demonstrated that Dicer-like 2 (DCL2), DCL3 and DCL4 are active, but it is not clear how their double-stranded RNA (dsRNA) substrates are made. If it was by readthrough transcription, most siRNAs would map to the overlapping 3′ ends, but this is not the case98. Nevertheless, DCL3 cleaves dsRNA to produce siRNAs for the methylation of promoters (transcriptional gene silencing (TGS)) or siRNAs targeting coding sequences (post-transcriptional gene silencing (PTGS)). In the cytoplasm, siRNA incorporation into Argonaute 1 (AGO1) or AGO2 during infection could result in translational inhibition or mRNA cleavage. AGO-incorporated siRNAs have not yet been profiled during a geminivirus infection. b | A speculative model of RDR-associated secondary siRNAs. In the canonical TGS pathway, the RNA polymerases Pol IV and Pol V, along with RDR2, synthesize dsRNA for DCL3 to process into 24-nucleotide siRNAs, which are used for long-distance movement or de novo methylation of viral DNA. Direct evidence of an RDR2 requirement is lacking for geminiviruses, probably owing to the suppression of the methyl cycle (which acts before RDR2) by viral suppressors of RNA silencing (VSRs; in this case, transcriptional activator protein (TrAP; known as C2 in some viruses) and βC1). To prevent any de novo methylation from being propagated, DNA methyltransferase 1 (MET1) and chromomethylase 3 (CMT3), which are both needed for maintenance methylation, are downregulated by replication initiator protein (Rep) and C4 (Ref. 105). RDR6 is needed for long-distance siRNA activity, whereas RDR6, suppressor of gene silencing 3 (SGS3) and DCL4 are needed for cell-to-cell movement of silencing. SGS3 recognizes dsRNA with 5′ overhangs and recruits RDR6 to make the RNA double-stranded. DCL4 produces 21-nucleotide siRNAs that can move from cell to cell. The VSR V2 prevents SGS3 access to dsRNA with 5′ overhangs. βC1 and C4 (or AC4 in some viruses) bind to siRNAs, preventing their incorporation into AGO and their movement. Red arrows indicate RDR synthesis of the second RNA strand.

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Affiliations

  1. Department of Molecular and Structural Biochemistry, North Carolina State University, Raleigh, North Carolina 27695-7622, USA.

    • Linda Hanley-Bowdoin
  2. Departamento de Biología Celular, Genética y Fisiología, Instituto de Hortofruticultura Subtropical y Mediterranea 'La Mayora', Universidad de Málaga–Consejo Superior de Investigaciones Científicas (IHSM-UMA-CSIC), Universidad de Málaga, Campus Teatinos, 29071 Málaga, Spain.

    • Eduardo R. Bejarano
  3. Department of Plant and Microbial Biology, North Carolina State University, Raleigh, North Carolina 27695-7612, USA

    • Dominique Robertson
  4. Agricultural Biotechnology Division, National Institute for Biotechnology and Genetic Engineering (NIBGE), P.O. Box 577, Jhang Road, Faisalabad, Pakistan.

    • Shahid Mansoor

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The authors declare no competing interests.

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  • Linda Hanley-Bowdoin

    Linda Hanley-Bowdoin obtained her Ph.D. from the Rockefeller University in New York, USA, and was a postdoctoral scientist at Monsanto in St. Louis, Missouri, USA, where she began her research on geminiviruses. She continued studying geminiviruses as a faculty member at North Carolina State University, Raleigh, USA, where she is currently a William Neal Reynolds Distinguished Professor in biochemistry, plant biology and genetics. Her research group established that geminiviruses reprogramme plant cell controls to induce the synthesis of the host replication machinery. She is an expert on geminivirus–plant interactions related to viral replication, the cell cycle, the host transcriptome and protein kinase cascades. Linda Hanley-Bowdoin's homepage.

  • Eduardo R. Bejarano

    Eduardo R. Bejarano is a professor of genetics at the Institute for Mediterranean and Subtropical Horticulture UMA-CSIC (IHSM), Málaga, Spain. He obtained a Ph.D. in biology from the University of Cordoba, Spain, and performed postdoctoral research at Imperial College London, UK. His research focuses on geminivirus–host interactions involving post-translational modification of plant and viral proteins and jasmonate signalling, as well as on interactions among the plant, virus and insect vector.

  • Dominique Robertson

    Dominique Robertson received her Ph.D. from Cornell University, Ithaca, New York, USA, and is now a professor of plant biology and genetics at North Carolina State University, Raleigh, USA. She began working on geminiviruses when she brought her expertise in plant cell biology to a collaboration, which still continues, with Linda Hanley-Bowdoin. She also studies geminivirus interactions with host defence mechanisms mediated by gene silencing.

  • Shahid Mansoor

    Shahid Mansoor is Director of the National Institute for Biotechnology and Genetic Engineering (NIBGE) in Faisalabad, Pakistan. He received a Ph.D. from the John Innes Centre, Norwich, UK, where he studied begomovirus complexes. He did his postdoctoral research at The Sainsbury Laboratory, Norwich, UK, and was a Fulbright scholar at the University of Georgia, Athens, USA. He discovered alphasatellites and contributed to understanding the diversity and function of betasatellites. His areas of interest include geminivirus–host interactions involved in the suppression of gene silencing, the epigenetic modification of viral and host genomes, the inhibition of plant cell death, and the perturbation of plant hormones and microRNAs.

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    Geminivirus/host interactions

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