Correction: The replication initiator protein of a geminivirus interacts with host monoubiquitination machinery and stimulates transcription of the viral genome.

[This corrects the article DOI: 10.1371/journal.ppat.1006587.].

T-bet suppresses proliferation of malignant B cells in chronic lymphocytic leukemia.

The T-box transcription factor T-bet is known as a master regulator of T-cell response but its role in malignant B cells is not sufficiently explored. Here, we conducted single-cell resolved multi-omics analyses of malignant B cells from patients with chronic lymphocytic leukemia (CLL) and studied a CLL mouse model with genetic knockout of TBX21. We found that T-bet acts as a tumor suppressor in malignant B cells by decreasing their proliferation rate. NF-κB activity induced by inflammatory signals provided by the microenvironment, triggered T-bet expression which impacted on promoter proximal and distal chromatin co-accessibility and controlled a specific gene signature by mainly suppressing transcription. Gene set enrichment analysis identified a positive regulation of interferon signaling, and a negative control of proliferation by T-bet. In line, we showed that T-bet represses cell cycling and is associated with longer overall survival of CLL patients. Our study uncovers a novel tumor suppressive role of T-bet in malignant B cells via its regulation of inflammatory processes and cell cycling which has implications for stratification and therapy of CLL patients. Linking T-bet activity to inflammation explains the good prognostic role of genetic alterations in inflammatory signaling pathways in CLL.

Selective REcruitmeNt of plant DNA polymerases by geminivirus.

Geminiviruses reprogram host machineries to ensure their own propagation. They do not encode any DNA polymerase. Furthermore, the absence of direct evidence about the precise role of any host-encoded DNA polymerase has made geminivirus replication an enigma. Wu et al. recently resolved this puzzle by revealing that geminiviruses utilize plant DNA polymerase α and δ to drive their replication.

Inhibition of MYC translation through targeting of the newly identified PHB-eIF4F complex as a therapeutic strategy in CLL.

Dysregulation of messenger RNA (mRNA) translation, including preferential translation of mRNA with complex 5' untranslated regions such as the MYC oncogene, is recognized as an important mechanism in cancer. Here, we show that both human and murine chronic lymphocytic leukemia (CLL) cells display a high translation rate, which is inhibited by the synthetic flavagline FL3, a prohibitin (PHB)-binding drug. A multiomics analysis performed in samples from patients with CLL and cell lines treated with FL3 revealed the decreased translation of the MYC oncogene and of proteins involved in cell cycle and metabolism. Furthermore, inhibiting translation induced a proliferation arrest and a rewiring of MYC-driven metabolism. Interestingly, contrary to other models, the RAS-RAF-(PHBs)-MAPK pathway is neither impaired by FL3 nor implicated in translation regulation in CLL cells. Here, we rather show that PHBs are directly associated with the eukaryotic initiation factor (eIF)4F translation complex and are targeted by FL3. Knockdown of PHBs resembled FL3 treatment. Importantly, inhibition of translation controlled CLL development in vivo, either alone or combined with immunotherapy. Finally, high expression of translation initiation-related genes and PHBs genes correlated with poor survival and unfavorable clinical parameters in patients with CLL. Overall, we demonstrated that translation inhibition is a valuable strategy to control CLL development by blocking the translation of several oncogenic pathways including MYC. We also unraveled a new and direct role of PHBs in translation initiation, thus creating new therapeutic opportunities for patients with CLL.

Macrophage- and BCR-derived but not TLR-derived signals support the growth of CLL and Richter syndrome murine models in vivo.

A large amount of circumstantial evidence has accumulated suggesting that Toll-like receptor (TLR) signals are involved in driving chronic lymphocytic leukemia (CLL) cell proliferation, but direct in vivo evidence for this is still lacking. We have now further addressed this possibility by pharmacologically inhibiting or genetically inactivating the TLR pathway in murine CLL and human Richter syndrome (RS) patient-derived xenograft (PDX) cells. Surprisingly, we show that pharmacologic inhibition of TLR signaling by treatment with an IRAK1/4 inhibitor delays the growth of the transplanted malignant cells in recipient mice, but genetic inactivation of the same pathway by CRISPR/Cas9-mediated disruption of IRAK4 or its proximal adaptor MyD88 has no effect. We further show that treatment with the IRAK1/4 inhibitor results in depletion of macrophages and demonstrate that these cells can support the survival and enhance the proliferation of both murine Eµ-TCL1 leukemia and human RS cells. We also show that genetic disruption of the B-cell receptor (BCR) by CRISPR/Cas9 editing of the immunoglobulin M constant region gene inhibits the growth of human RS-PDX cells in vivo, consistent with our previous finding with murine Eµ-TCL1 leukemia cells. Finally, we show that genetic disruption of IRAK4 does not result in negative selection of human CLL cell lines xenografted in immunodeficient mice. The obtained data suggest that TLR signals are unlikely to represent a major driver of CLL/RS cell proliferation and provide further evidence that signals from macrophages and the BCR promote the growth and survival of CLL and RS cells in vivo.

The Sw5a gene confers resistance to ToLCNDV and triggers an HR response after direct AC4 effector recognition.

Several attempts have been made to identify antiviral genes against Tomato leaf curl New Delhi virus (ToLCNDV) and related viruses. This has led to the recognition of Ty genes (Ty1-Ty6), which have been successful in developing virus-resistant crops to some extent. Owing to the regular appearance of resistance-breaking strains of these viruses, it is important to identify genes related to resistance. In the present study, we identified a ToLCNDV resistance (R) gene, SlSw5a, in a ToLCNDV-resistant tomato cultivar, H-88-78-1, which lacks the known Ty genes. The expression of SlSw5a is controlled by the transcription factor SlMyb33, which in turn is regulated by microRNA159 (sly-miR159). Virus-induced gene silencing of either SlSw5a or SlMyb33 severely increases the disease symptoms and viral titer in leaves of resistant cultivar. Moreover, in SlMyb33-silenced plants, the relative messenger RNA level of SlSw5a was reduced, suggesting SlSw5a is downstream of the sly-miR159-SlMyb33 module. We also demonstrate that SlSw5a interacts physically with ToLCNDV-AC4 (viral suppressor of RNA silencing) to trigger a hypersensitive response (HR) and generate reactive oxygen species at infection sites to limit the spread of the virus. The "RTSK" motif in the AC4 C terminus is important for the interaction, and its mutation completely abolishes the interaction with Sw5a and HR elicitation. Overall, our research reports an R gene against ToLCNDV and establishes a connection between the upstream miR159-Myb33 module and its downstream target Sw5a to activate HR in the tomato, resulting in geminivirus resistance.

Betasatellite-encoded ßC1 protein regulates helper virus accumulation by interfering with the ATP hydrolysis activity of geminivirus-encoded replication initiator protein.

Geminivirus-betasatellite disease complexes are an epidemic threat to the majority of economically important crops across the world. Plant virus satellites including betasatellites are maintained by their associated helper virus. Geminivirus-betasatellites influence viral pathogenesis by substantially increasing or decreasing their helper virus accumulation. In the present study, we attempted to understand the mechanistic details of the geminivirus-betasatellite interaction. Here, we used tomato leaf curl Gujarat virus (ToLCGV) and tomato leaf curl Patna betasatellite (ToLCPaB) as a model system. This study reveals that ToLCGV can efficiently trans-replicate ToLCPaB in Nicotiana benthamiana plants, but ToLCPaB greatly reduced the accumulation of its helper virus DNA. For the first time, we have identified that the ToLCPaB-encoded ßC1 protein is able to interact with ToLCGV-encoded replication initiator protein (Rep). In addition, we demonstrate that the C-terminal region of ßC1 interacts with the C-terminus of Rep (RepC) protein. Our previous study had established that ßC1 proteins encoded by diverse betasatellites possess a novel ATP hydrolysis activity and the conserved lysine/arginine residues at positions 49 and 91 are necessary for this function. Here, we show that mutating lysine at positions 49 to alanine of ßC1 (ßC1K49A) protein did not affect its ability to interact with RepC protein. Biochemical studies performed with ATP hydrolysis activity-deficient K49A mutated ßC1 (ßC1K49A) and RepC proteins revealed that Rep-ßC1 interaction interferes with the ATP hydrolysis activity of Rep protein. Further, we demonstrate that ßC1 protein is able to interact with D227A and D289A mutated RepC proteins but not with D262A, K272A or D286A mutated RepC proteins, suggesting that the ßC1-interacting region of Rep protein encompasses its Walker-B and B' motifs. The results of docking studies supported that the ßC1-interacting region of Rep protein encompasses its motifs associated with ATP binding and ATP hydrolysis activities. Docking studies also provided evidence that the Rep-ßC1 interaction interferes with the ATP binding activity of Rep protein. Together, our findings suggest that ßC1 protein regulates helper virus accumulation by interfering with the ATP hydrolysis activity of helper virus Rep protein.

Recovery from virus infection: plant's armory in action.

MAIN CONCLUSION: This review focuses on different factors involved in promoting symptom recovery in plants post-virus infection such as epigenetics, transcriptional reprogramming, phytohormones with an emphasis on RNA silencing as well as role of abiotic factors such as temperature on symptom recovery. Plants utilize several different strategies to defend themselves in the battle against invading viruses. Most of the viral proteins interact with plant proteins and interfere with molecular dynamics in a cell which eventually results in symptom development. This initial symptom development is countered by the plant utilizing various factors including the plant's adaptive immunity to develop a virus tolerant state. Infected plants can specifically target and impede the transcription of viral genes as well as degrade the viral transcripts to restrict their proliferation by the production of small-interfering RNA (siRNA) generated from the viral nucleic acid, known as virus-derived siRNA (vsiRNA). To further escalate the degradation of viral nucleic acid, secondary siRNAs are generated. The production of virus-activated siRNA (vasiRNA) from the host genome causes differential regulation of the host transcriptome which plays a major role in establishing a virus tolerant state within the infected plant. The systemic action of vsiRNAs, vasiRNA, and secondary siRNAs with the help of defense hormones like salicylic acid can curb viral proliferation, and thus the newly emerged leaves develop fewer symptoms, maintaining a state of tolerance.

B-cell receptor signaling and genetic lesions in TP53 and CDKN2A/CDKN2B cooperate in Richter transformation.

B-cell receptor (BCR) signals play a critical role in the pathogenesis of chronic lymphocytic leukemia (CLL), but their role in regulating CLL cell proliferation has still not been firmly established. Unlike normal B cells, CLL cells do not proliferate in vitro upon engagement of the BCR, suggesting that CLL cell proliferation is regulated by other signals from the microenvironment, such as those provided by Toll-like receptors or T cells. Here, we report that BCR engagement of human and murine CLL cells induces several positive regulators of the cell cycle, but simultaneously induces the negative regulators CDKN1A, CDKN2A, and CDKN2B, which block cell-cycle progression. We further show that introduction of genetic lesions that downregulate these cell-cycle inhibitors, such as inactivating lesions in CDKN2A, CDKN2B, and the CDKN1A regulator TP53, leads to more aggressive disease in a murine in vivo CLL model and spontaneous proliferation in vitro that is BCR dependent but independent of costimulatory signals. Importantly, inactivating lesions in CDKN2A, CDKN2B, and TP53 frequently co-occur in Richter syndrome (RS), and BCR stimulation of human RS cells with such lesions is sufficient to induce proliferation. We also show that tumor cells with combined TP53 and CDKN2A/2B abnormalities remain sensitive to BCR-inhibitor treatment and are synergistically sensitive to the combination of a BCR and cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor both in vitro and in vivo. These data provide evidence that BCR signals are directly involved in driving CLL cell proliferation and reveal a novel mechanism of Richter transformation.

Geminiviral betasatellites: critical viral ammunition to conquer plant immunity.

Geminiviruses have mastered plant cell modulation and immune invasion to ensue prolific infection. Encoding a relatively small number of multifunctional proteins, geminiviruses rely on satellites to efficiently re-wire plant immunity, thereby fostering virulence. Among the known satellites, betasatellites have been the most extensively investigated. They contribute significantly to virulence, enhance virus accumulation, and induce disease symptoms. To date, only two betasatellite proteins, ßC1, and ßV1, have been shown to play a crucial role in virus infection. In this review, we offer an overview of plant responses to betasatellites and counter-defense strategies deployed by betasatellites to overcome those responses.

Geminivirus Betasatellite-Encoded ßC1 Protein Exhibits Novel ATP Hydrolysis Activity That Influences Its DNA-Binding Activity and Viral Pathogenesis.

Plant virus satellites are maintained by their associated helper viruses, and satellites influence viral pathogenesis. Diseases caused by geminivirus-betasatellite complexes can become epidemics and therefore have become a threat to economically important crops across the world. Here, we identified a novel molecular function of the betasatellite-encoded pathogenicity determinant ßC1. The tomato leaf curl Patna betasatellite (ToLCPaB)-encoded ßC1 protein was found to exhibit novel ATPase activity in the presence of the divalent metal ion cofactor MgCl2. Moreover, ATPase activity was confirmed to be ubiquitously displayed by ßC1 proteins encoded by diverse betasatellites. Mutational and sequence analysis showed that conserved lysine/arginine residues at positions 49/50 and 91 of ßC1 proteins are essential for their ATPase activity. Biochemical studies revealed that the DNA-binding activity of the ßC1 protein was interfered with by the binding of ATP to the protein. Mutating arginine 91 of ßC1 to alanine reduced its DNA-binding activity. The results of docking studies provided evidence for an overlap of the ATP-binding and DNA-binding regions of ßC1 and for the importance of arginine 91 for both ATP-binding and DNA-binding activities. A mutant betasatellite with a specifically ßC1-ATPase dominant negative mutation was found to induce symptoms on Nicotiana benthamiana plants similar to those induced by wild-type betasatellite infection. The ATPase function of ßC1 was found to be negatively associated with geminivirus-betasatellite DNA accumulation, despite the positive influence of this ATPase function on the accumulation of replication-associated protein (Rep) and ßC1 transcripts. IMPORTANCE Most satellites influence the pathogenesis of their helper viruses. Here, we characterized the novel molecular function of ßC1, a nonstructural pathogenicity determinant protein encoded by a betasatellite. We demonstrated the display of ATPase activity by this ßC1 protein. Additionally, we confirmed the ubiquitous display of ATPase activity by ßC1 proteins encoded by diverse betasatellites. The lysine/arginine residues conserved at positions 49 and 91 of ßC1 were found to be crucial for its ATPase function. DNA-binding activity of ßC1 was found to be reduced in the presence of ATP. Inhibition of ATPase activity of ßC1 in the presence of an excess concentration of cold ATP, GTP, CTP, or UTP suggested that the purified ßC1 can also hydrolyze other cellular nucleoside triphosphates (NTPs) besides ATP in vitro. These results established the importance of the ATPase and DNA-binding activities of the ßC1 protein in regulating geminivirus-betasatellite DNA accumulation in the infected plant cell.

The diverse roles of histone 2B monoubiquitination in the life of plants.

Covalent modification of histones is an important tool for gene transcriptional control in eukaryotes, which coordinates growth, development, and adaptation to environmental changes. In recent years, an important role for monoubiquitination of histone 2B (H2B) has emerged in plants, where it is associated with transcriptional activation. In this review, we discuss the dynamics of the H2B monoubiquitination system in plants and its role in regulating developmental processes including flowering, circadian rhythm, photomorphogenesis, and the response to abiotic and biotic stress including drought, salinity, and fungal, bacterial, and viral pathogens. Furthermore, we highlight the crosstalk between H2B monoubiquitination and other histone modifications which fine-tunes transcription and ensures developmental plasticity. Finally, we put into perspective how this versatile regulatory mechanism can be developed as a useful tool for crop improvement.

Application of machine learning in understanding plant virus pathogenesis: trends and perspectives on emergence, diagnosis, host-virus interplay and management.

BACKGROUND: Inclusion of high throughput technologies in the field of biology has generated massive amounts of data in the recent years. Now, transforming these huge volumes of data into knowledge is the primary challenge in computational biology. The traditional methods of data analysis have failed to carry out the task. Hence, researchers are turning to machine learning based approaches for the analysis of high-dimensional big data. In machine learning, once a model is trained with a training dataset, it can be applied on a testing dataset which is independent. In current times, deep learning algorithms further promote the application of machine learning in several field of biology including plant virology. MAIN BODY: Plant viruses have emerged as one of the principal global threats to food security due to their devastating impact on crops and vegetables. The emergence of new viral strains and species help viruses to evade the concurrent preventive methods. According to a survey conducted in 2014, plant viruses are anticipated to cause a global yield loss of more than thirty billion USD per year. In order to design effective, durable and broad-spectrum management protocols, it is very important to understand the mechanistic details of viral pathogenesis. The application of machine learning enables precise diagnosis of plant viral diseases at an early stage. Furthermore, the development of several machine learning-guided bioinformatics platforms has primed plant virologists to understand the host-virus interplay better. In addition, machine learning has tremendous potential in deciphering the pattern of plant virus evolution and emergence as well as in developing viable control options. CONCLUSIONS: Considering a significant progress in the application of machine learning in understanding plant virology, this review highlights an introductory note on machine learning and comprehensively discusses the trends and prospects of machine learning in the diagnosis of viral diseases, understanding host-virus interplay and emergence of plant viruses.

Insights into the multifunctional roles of geminivirus-encoded proteins in pathogenesis.

Geminiviruses are a major threat to agriculture in tropical and subtropical regions of the world. Geminiviruses have small genome with limited coding capacity. Despite this limitation, these viruses have mastered hijacking the host cellular metabolism for their survival. To compensate for the small size of their genome, geminiviruses encode multifunctional proteins. In addition, geminiviruses associate themselves with satellite DNA molecules which also encode proteins that support the virus in establishing successful infection. Geminiviral proteins recruit multiple host factors, suppress the host defense, and manipulate host metabolism to establish infection. We have updated the knowledge accumulated about the proteins of geminiviruses and their satellites in the context of pathogenesis in a single review. We also discuss their interactions with host factors to provide a mechanistic understanding of the infection process.

Revisiting regulatory roles of replication protein A in plant DNA metabolism.

MAIN CONCLUSION: This review provides insight into the roles of heterotrimeric RPA protein complexes encompassing all aspects of DNA metabolism in plants along with specific function attributed by individual subunits. It highlights research gaps that need further attention. Replication protein A (RPA), a heterotrimeric protein complex partakes in almost every aspect of DNA metabolism in eukaryotes with its principle role being a single-stranded DNA-binding protein, thereby providing stability to single-stranded (ss) DNA. Although most of our knowledge of RPA structure and its role in DNA metabolism is based on studies in yeast and animal system, in recent years, plants have also been reported to have diverse repertoire of RPA complexes (formed by combination of different RPA subunit homologs arose during course of evolution), expected to be involved in plethora of DNA metabolic activities. Here, we have reviewed all studies regarding role of RPA in DNA metabolism in plants. As combination of plant RPA complexes may vary largely depending on number of homologs of each subunit, next step for plant biologists is to develop specific functional methods for detailed analysis of biological roles of these complexes, which we have tried to formulate in our review. Besides, complete absence of any study regarding regulatory role of posttranslational modification of RPA complexes in DNA metabolism in plants, prompts us to postulate a hypothetical model of same in light of information from animal system. With our review, we envisage to stimulate the RPA research in plants to shift its course from descriptive to functional studies, thereby bringing a new angle of studying dynamic DNA metabolism in plants.

Molecular interplay between phytohormones and geminiviruses: a saga of a never-ending arms race.

Geminiviruses can infect a wide range of plant hosts worldwide and have hence become an emerging global agroeconomic threat. The association of these viruses with satellite molecules and highly efficient insect vectors such as whiteflies further prime their devastating impacts. Plants elicit a strong antiviral immune response to restrict the invasion of these destructive pathogens. Phytohormones help plants to mount this response and occupy a key position in combating these biotrophs. These defense hormones not only inhibit geminiviral propagation but also hamper viral transmission by compromising the performance of their insect vectors. Nonetheless, geminiviruses have co-evolved to have a few multitasking virulence factors that readily remodel host cellular machineries to circumvent the phytohormone-mediated manifestation of the immune response. Furthermore, these obligate parasites exploit plant growth hormones to produce a cellular environment permissive for virus replication. In this review, we outline the current understanding of the roles and regulation of phytohormones in geminiviral pathogenesis.

Plant responses to geminivirus infection: guardians of the plant immunity.

BACKGROUND: Geminiviruses are circular, single-stranded viruses responsible for enormous crop loss worldwide. Rapid expansion of geminivirus diversity outweighs the continuous effort to control its spread. Geminiviruses channelize the host cell machinery in their favour by manipulating the gene expression, cell signalling, protein turnover, and metabolic reprogramming of plants. As a response to viral infection, plants have evolved to deploy various strategies to subvert the virus invasion and reinstate cellular homeostasis. MAIN BODY: Numerous reports exploring various aspects of plant-geminivirus interaction portray the subtlety and flexibility of the host-pathogen dynamics. To leverage this pool of knowledge towards raising antiviral resistance in host plants, a comprehensive account of plant's defence response against geminiviruses is required. This review discusses the current knowledge of plant's antiviral responses exerted to geminivirus in the light of resistance mechanisms and the innate genetic factors contributing to the defence. We have revisited the defence pathways involving transcriptional and post-transcriptional gene silencing, ubiquitin-proteasomal degradation pathway, protein kinase signalling cascades, autophagy, and hypersensitive responses. In addition, geminivirus-induced phytohormonal fluctuations, the subsequent alterations in primary and secondary metabolites, and their impact on pathogenesis along with the recent advancements of CRISPR-Cas9 technique in generating the geminivirus resistance in plants have been discussed. CONCLUSIONS: Considering the rapid development in the field of plant-virus interaction, this review provides a timely and comprehensive account of molecular nuances that define the course of geminivirus infection and can be exploited in generating virus-resistant plants to control global agricultural damage.

Roles of two distinct alphasatellites modulating geminivirus pathogenesis.

BACKGROUND: Alphasatellites are small coding DNA satellites frequently associated with a begomovirus/betasatellite complex, where they are known to modulate virulence and symptom development. Two distinct alphasatellites, namely, Cotton leaf curl Multan alphasatellite (CLCuMuA), and Gossypium darwinii symptomless alphasatellite (GDarSLA) associated with Cotton leaf curl Multan virus-India (CLCuMuV-IN) and Ludwigia leaf distortion betasatellite (LuLDB) were found to be associated with yellow mosaic disease of hollyhock (Alcea rosea) plants. In this study, we show that alphasatellites CLCuMuA and GDarSLA attenuate and delay symptom development in Nicotiana benthamiana. The presence of either alphasatellites reduce the accumulation of the helper virus CLCuMuV-IN. However, the levels of the associated betasatellite, LuLDB, remains unchanged. These results suggest that the alphasatellites could contribute to the host defence and understanding their role in disease development is important for developing resistance strategies. METHODS: Tandem repeat constructs of two distinct alphasatellites, namely, CLCuMuA and GDarSLA associated with CLCuMuV-IN and LuLDB were generated. N. benthamiana plants were co-agroinoculated with CLCuMuV and its associated alphasatellites and betasatellite molecules and samples were collected at 7, 14 and 21 days post inoculation (dpi). The viral DNA molecules were quantified in N. benthamiana plants by qPCR. The sequences were analysed using the MEGA-X tool, and a phylogenetic tree was generated. Genetic diversity among the CLCuMuA and GDarSLA was analysed using the DnaSP tool. RESULTS: We observed a reduction in symptom severity and accumulation of helper virus in the presence of two alphasatellites isolated from naturally infected hollyhock plants. However, no reduction in the accumulation of betasatellite was observed. The phylogenetic and genetic variability study revealed the evolutionary dynamics of these distinct alphasatellites , which could explain the role of hollyhock-associated alphasatellites in plants. CONCLUSIONS: This study provides evidence that alphasatellites have a role in symptom modulation and suppress helper virus replication without any discernible effect on the replication of the associated betasatellite.

Occurrence of Cotton leaf curl Multan virus and associated betasatellites with leaf curl disease of Bhut-Jolokia chillies (Capsicum chinense Jacq.) in India.

Geminiviridae comprises the largest family of plant viruses which causes severe crop losses in India. The highest pungency chilli Bhut-Jolokia or ghost pepper (Capsicum chinense Jaqc.) hails from North-East region of India and is used in many dishes to add flavors and also for its medicinal value. However, this chilli variety is also affected by viruses leading to crop and economic losses. The present study reports the identification of begomoviruses in the infected chilli Bhut-Jolokia leaf samples collected from eight different places of North-East region (Manipur) of India. The infected leaf samples were screened for the presence of viral genome by rolling circle amplification (RCA) followed by PCR using degenerate primer pairs. The subsequent analyses using restriction fragment length polymorphism and sequencing revealed the presence of Cotton leaf curl Multan virus (CLCuMuV), and Tomato leaf curl Patna betasatellite (ToLCPaB). The findings focus on the phylogenetic relatedness, probable recombinational hot-spots and evolutionary divergence of the viral DNA sequences with the current reported begomoviral genome. To the best of our knowledge, this is the first report showing the presence of CLCuMuV, and associated non-cognate ToLCPaB with leaf curl disease of Bhut-Jolokia chillies. The study reveals potential recombination sites on both viral genome and betsatellite which, during the course of evolution, may have aided the virus to progress and successfully establish infection in chilli plants. Taken together, our results suggest a possible spread of CLCuMuV to the hitherto non-host crop in the North-East region of India.

Impact of viral silencing suppressors on plant viral synergism: a global agro-economic concern.

Plant viruses are known for their devastating impact on global agriculture. These intracellular biotrophic pathogens can infect a wide variety of plant hosts all over the world. The synergistic association of plant viruses makes the situation more alarming. It usually promotes the replication, movement, and transmission of either or both the coexisting synergistic viral partners. Although plants elicit a robust antiviral immune reaction, including gene silencing, to limit these infamous invaders, viruses counter it by encoding viral suppressors of RNA silencing (VSRs). Growing evidence also suggests that VSRs play a driving role in mediating the plant viral synergism. This review briefly discusses the evil impacts of mixed infections, especially synergism, and then comprehensively describes the emerging roles of VSRs in mediating the synergistic association of plant viruses. KEY POINTS: • Synergistic associations of plant viruses have devastating impacts on global agriculture. • Viral suppressors of RNA silencing (VSRs) play key roles in driving plant viral synergism.