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Viroid diseases in pome and stone fruit trees and Koch s postulates: a critical assessment
[EN] Composed of a naked circular non-protein-coding genomic RNA, counting only a few hundred nucleotides, viroids¿the smallest infectious agents known so far¿are able to replicate and move systemically in herbaceous and woody host plants, which concomitantly may develop specific diseases or remain symptomless. Several viroids have been reported to naturally infect pome and stone fruit trees, showing symptoms on leaves, fruits and/or bark. However, Koch¿s postulates required for establishing on firm grounds the viroid etiology of these diseases, have not been met in all instances. Here, pome and stone fruit tree diseases, conclusively proven to be caused by viroids, are reviewed, and the need to pay closer attention to fulfilling Koch¿s postulates is emphasized. View Full-TextThis project has received funding from the European Union's Horizon 2020 Research and Innovation Scientific Exchange Program under the Marie Sklodowska-Curie grant agreement No. 734736. This publication reflects only the authors' view. The Agency is not responsible for any use that may be made of the information it contains.Di Serio, F.; Ambros Palaguerri, S.; Sano, T.; Flores Pedauye, R.; Navarro, B. (2018). Viroid diseases in pome and stone fruit trees and Koch s postulates: a critical assessment. Viruses. 10(11). https://doi.org/10.3390/v101106121011Diener, T. O. (1971). Potato spindle tuber «virus». Virology, 45(2), 411-428. doi:10.1016/0042-6822(71)90342-4Flores, R., Minoia, S., Carbonell, A., Gisel, A., Delgado, S., López-Carrasco, A., … Di Serio, F. (2015). Viroids, the simplest RNA replicons: How they manipulate their hosts for being propagated and how their hosts react for containing the infection. Virus Research, 209, 136-145. doi:10.1016/j.virusres.2015.02.027López-Carrasco, A., & Flores, R. (2016). 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Peach latent mosaic viroid variants inducing peach calico (extreme chlorosis) contain a characteristic insertion that is responsible for this symptomatology. Virology, 313(2), 492-501. doi:10.1016/s0042-6822(03)00315-5Puchta, H., Luckinger, R., Yang, X., Hadidi, A., & S�nger, H. L. (1990). Nucleotide sequence and secondary structure of apple scar skin viroid (ASSVd) from China. Plant Molecular Biology, 14(6), 1065-1067. doi:10.1007/bf00019406KOGANEZAWA, H. (1985). Transmission to apple seedlings of a low molecular weight RNA extracted from apple scar skin diseased trees. Japanese Journal of Phytopathology, 51(2), 176-182. doi:10.3186/jjphytopath.51.176Koganezawa, H. (1986). FURTHER EVIDENCE FOR VIROID ETIOLOGY OF APPLE SCAR SKIN AND DAPPLE APPLE DISEASES. Acta Horticulturae, (193), 29-34. doi:10.17660/actahortic.1986.193.2Yamaguch, A., & Yanase, H. (1976). POSSIBLE RELATIONSHIP BETWEEN THE CAUSAL AGENT OF DAPPLE APPLE AND SCAR SKIN. 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IDENTIFICATION OF APPLE DIMPLE FRUIT VIROID IN DIFFERENT COMMERCIAL VARIETIES OF APPLE GROWN IN ITALY. Acta Horticulturae, (472), 595-602. doi:10.17660/actahortic.1998.472.79Roumi, V., Gazel, M., & Caglayan, K. (2017). First report of Apple dimple fruit viroid in apple trees in Iran. New Disease Reports, 35, 3. doi:10.5197/j.2044-0588.2017.035.003He, Y.-H., Isono, S., Kawaguchi-Ito, Y., Taneda, A., Kondo, K., Iijima, A., … Sano, T. (2010). Characterization of a new Apple dimple fruit viroid variant that causes yellow dimple fruit formation in ‘Fuji’ apple trees. Journal of General Plant Pathology, 76(5), 324-330. doi:10.1007/s10327-010-0258-xChiumenti, M., Torchetti, E. M., Di Serio, F., & Minafra, A. (2014). Identification and characterization of a viroid resembling apple dimple fruit viroid in fig (Ficus carica L.) by next generation sequencing of small RNAs. 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The molecular characterization of 16 new sequence variants of Hop stunt viroid reveals the existence of invariable regions and a conserved hammerhead-like structure on the viroid molecule
The sequences described in this work have been deposited in the EMBL database and received accession numbers AJ297825 to AJ297840. Journal of General Virology, 82(4), 953-962. doi:10.1099/0022-1317-82-4-953SANO, T., HATAYA, T., TERAI, Y., & SHIKATA, E. (1986). Association of a viroid-like RNA from plum dapple disease occurring in Japan. Proceedings of the Japan Academy. Ser. B: Physical and Biological Sciences, 62(3), 98-101. doi:10.2183/pjab.62.98Hernandez, C., & Flores, R. (1992). Plus and minus RNAs of peach latent mosaic viroid self-cleave in vitro via hammerhead structures. Proceedings of the National Academy of Sciences, 89(9), 3711-3715. doi:10.1073/pnas.89.9.3711Ambros, S. (1998). In vitro and in vivo self-cleavage of a viroid RNA with a mutation in the hammerhead catalytic pocket. Nucleic Acids Research, 26(8), 1877-1883. doi:10.1093/nar/26.8.1877Ambrós, S., Hernández, C., & Flores, R. (1999). Rapid generation of genetic heterogeneity in progenies from individual cDNA clones of peach latent mosaic viroid in its natural host
The data reported in this paper are in the EMBL nucleotide sequence database and assigned the accession nos AJ241818–AJ241850. Journal of General Virology, 80(8), 2239-2252. doi:10.1099/0022-1317-80-8-2239Fekih Hassen, I., Massart, S., Motard, J., Roussel, S., Parisi, O., Kummert, J., … Jijakli, M. H. (2007). Molecular features of new Peach Latent Mosaic Viroid variants suggest that recombination may have contributed to the evolution of this infectious RNA. Virology, 360(1), 50-57. doi:10.1016/j.virol.2006.10.021DUBÉ, A., BOLDUC, F., BISAILLON, M., & PERREAULT, J.-P. (2011). Mapping studies of the Peach latent mosaic viroid reveal novel structural features. Molecular Plant Pathology, 12(7), 688-701. doi:10.1111/j.1364-3703.2010.00703.xBussière, F., Ouellet, J., Côté, F., Lévesque, D., & Perreault, J. P. (2000). Mapping in Solution Shows the Peach Latent Mosaic Viroid To Possess a New Pseudoknot in a Complex, Branched Secondary Structure. Journal of Virology, 74(6), 2647-2654. doi:10.1128/jvi.74.6.2647-2654.2000FLORES, R., DELGADO, S., RODIO, M.-E., AMBRÓS, S., HERNÁNDEZ, C., & SERIO, F. D. (2006). Peach latent mosaic viroid: not so latent. Molecular Plant Pathology, 7(4), 209-221. doi:10.1111/j.1364-3703.2006.00332.xDesvignes, J. C. (1976). THE VIRUS DISEASES DETECTED IN GREENHOUSE AND IN FIELD BY THE PEACH SEEDLING GF 305 INDICATOR. Acta Horticulturae, (67), 315-323. doi:10.17660/actahortic.1976.67.41DESVIGNES, J. C. (1986). PEACH LATENT MOSAIC AND ITS RELATION TO PEACH MOSAIC AND PEACH YELLOW MOSAIC VIRUS DISEASES. Acta Horticulturae, (193), 51-58. doi:10.17660/actahortic.1986.193.6Flores, R., & Llácer, G. (1989). ISOLATION OF A VIROID-LIKE RNA ASSOCIATED WITH PEACH LATENT MOSAIC DISEASE. Acta Horticulturae, (235), 325-332. doi:10.17660/actahortic.1989.235.47Rodio, M.-E., Delgado, S., Flores, R., & Serio, F. D. (2006). Variants of Peach latent mosaic viroid inducing peach calico: uneven distribution in infected plants and requirements of the insertion containing the pathogenicity determinant. Journal of General Virology, 87(1), 231-240. doi:10.1099/vir.0.81356-0Rodio, M.-E., Delgado, S., De Stradis, A., Gómez, M.-D., Flores, R., & Di Serio, F. (2007). A Viroid RNA with a Specific Structural Motif Inhibits Chloroplast Development. The Plant Cell, 19(11), 3610-3626. doi:10.1105/tpc.106.049775Navarro, B., Gisel, A., Rodio, M. E., Delgado, S., Flores, R., & Di Serio, F. (2012). Small RNAs containing the pathogenic determinant of a chloroplast-replicating viroid guide the degradation of a host mRNA as predicted by RNA silencing. The Plant Journal, 70(6), 991-1003. doi:10.1111/j.1365-313x.2012.04940.xWang, L., He, Y., Kang, Y., Hong, N., Farooq, A. B. U., Wang, G., & Xu, W. (2013). Virulence determination and molecular features of peach latent mosaic viroid isolates derived from phenotypically different peach leaves: A nucleotide polymorphism in L11 contributes to symptom alteration. Virus Research, 177(2), 171-178. doi:10.1016/j.virusres.2013.08.005Zhang, Z., Qi, S., Tang, N., Zhang, X., Chen, S., Zhu, P., … Wu, Q. (2014). Discovery of Replicating Circular RNAs by RNA-Seq and Computational Algorithms. PLoS Pathogens, 10(12), e1004553. doi:10.1371/journal.ppat.1004553Serra, P., Messmer, A., Sanderson, D., James, D., & Flores, R. (2018). Apple hammerhead viroid-like RNA is a bona fide viroid: Autonomous replication and structural features support its inclusion as a new member in the genus Pelamoviroid. Virus Research, 249, 8-15. doi:10.1016/j.virusres.2018.03.001Messmer, A., Sanderson, D., Braun, G., Serra, P., Flores, R., & James, D. (2017). Molecular and phylogenetic identification of unique isolates of hammerhead viroid-like RNA from ‘Pacific Gala’ apple (Malus domestica) in Canada. Canadian Journal of Plant Pathology, 39(3), 342-353. doi:10.1080/07060661.2017.1354334Wu, Q., Wang, Y., Cao, M., Pantaleo, V., Burgyan, J., Li, W.-X., & Ding, S.-W. (2012). Homology-independent discovery of replicating pathogenic circular RNAs by deep sequencing and a new computational algorithm. Proceedings of the National Academy of Sciences, 109(10), 3938-3943. doi:10.1073/pnas.1117815109Hadidi, A., Flores, R., Candresse, T., & Barba, M. (2016). Next-Generation Sequencing and Genome Editing in Plant Virology. Frontiers in Microbiology, 7. doi:10.3389/fmicb.2016.0132
Predictors of Daily Mobility of Adults in Peri-Urban South India
Daily mobility, an important aspect of environmental exposures
and health behavior, has mainly been investigated in high-income
countries. We aimed to identify the main dimensions of mobility
and investigate their individual, contextual, and external
predictors among men and women living in a peri-urban area of
South India. We used 192 global positioning system
(GPS)-recorded mobility tracks from 47 participants (24 women,
23 men) from the Cardiovascular Health effects of Air pollution
in Telangana, India (CHAI) project (mean: 4.1 days/person). The
mean age was 44 (standard deviation: 14) years. Half of the
population was illiterate and 55% was in unskilled manual
employment, mostly agriculture-related. Sex was the largest
determinant of mobility. During daytime, time spent at home
averaged 13.4 (3.7) h for women and 9.4 (4.2) h for men. Women's
activity spaces were smaller and more circular than men's. A
principal component analysis identified three main mobility
dimensions related to the size of the activity space, the
mobility in/around the residence, and mobility inside the
village, explaining 86% (women) and 61% (men) of the total
variability in mobility. Age, socioeconomic status, and
urbanicity were associated with all three dimensions. Our
results have multiple potential applications for improved
assessment of environmental exposures and their effects on
health
MicroRNA enrichment among short ‘ultraconserved’ sequences in insects
MicroRNAs are short (∼22 nt) regulatory RNA molecules that play key roles in metazoan development and have been implicated in human disease. First discovered in Caenorhabditis elegans, over 2500 microRNAs have been isolated in metazoans and plants; it has been estimated that there may be more than a thousand microRNA genes in the human genome alone. Motivated by the experimental observation of strong conservation of the microRNA let-7 among nearly all metazoans, we developed a novel methodology to characterize the class of such strongly conserved sequences: we identified a non-redundant set of all sequences 20 to 29 bases in length that are shared among three insects: fly, bee and mosquito. Among the few hundred sequences greater than 20 bases in length are close to 40% of the 78 confirmed fly microRNAs, along with other non-coding RNAs and coding sequence
Two Brassica napus cultivars differ in gene expression, but not in their response to submergence
Recommended from our members
Segmental chromosomal alterations have prognostic impact in neuroblastoma: a report from the INRG project
Background: In the INRG dataset, the hypothesis that any segmental chromosomal alteration might be of prognostic impact in neuroblastoma without MYCN amplification (MNA) was tested. Methods: The presence of any segmental chromosomal alteration (chromosome 1p deletion, 11q deletion and/or chromosome 17q gain) defined a segmental genomic profile. Only tumours with a confirmed unaltered status for all three chromosome arms were considered as having no segmental chromosomal alterations. Results: Among the 8800 patients in the INRG database, a genomic type could be attributed for 505 patients without MNA: 397 cases had a segmental genomic type, whereas 108 cases had an absence of any segmental alteration. A segmental genomic type was more frequent in patients >18 months and in stage 4 disease (P<0.0001). In univariate analysis, 11q deletion, 17q gain and a segmental genomic type were associated with a poorer event-free survival (EFS) (P<0.0001, P=0.0002 and P<0.0001, respectively). In multivariate analysis modelling EFS, the parameters age, stage and a segmental genomic type were retained in the model, whereas the individual genetic markers were not (P<0.0001 and RR=2.56; P=0.0002 and RR=1.8; P=0.01 and RR=1.7, respectively). Conclusion: A segmental genomic profile, rather than the single genetic markers, adds prognostic information to the clinical markers age and stage in neuroblastoma patients without MNA, underlining the importance of pangenomic studies
Influence of segmental chromosome abnormalities on survival in children over the age of 12 months with unresectable localised peripheral neuroblastic tumours without MYCN amplification.
BACKGROUND: The prognostic impact of segmental chromosome alterations (SCAs) in children older than 1 year, diagnosed with localised unresectable neuroblastoma (NB) without MYCN amplification enrolled in the European Unresectable Neuroblastoma (EUNB) protocol is still to be clarified, while, for other group of patients, the presence of SCAs is associated with poor prognosis.
METHODS: To understand the role of SCAs we performed multilocus/pangenomic analysis of 98 tumour samples from patients enrolled in the EUNB protocol.
RESULTS: Age at diagnosis was categorised into two groups using 18 months as the age cutoff. Significant difference in the presence of SCAs was seen in tumours of patients between 12 and 18 months and over 18 months of age at diagnosis, respectively (P=0.04). A significant correlation (P=0.03) was observed between number of SCAs per tumour and age. Event-free (EFS) and overall survival (OS) were calculated in both age groups, according to both the presence and number of SCAs. In older patients, a poorer survival was associated with the presence of SCAs (EFS=46% vs 75%, P=0.023; OS=66.8% vs 100%, P=0.003). Moreover, OS of older patients inversely correlated with number of SCAs (P=0.002). Finally, SCAs provided additional prognostic information beyond histoprognosis, as their presence was associated with poorer OS in patients over 18 months with unfavourable International Neuroblastoma Pathology Classification (INPC) histopathology (P=0.018).
CONCLUSIONS: The presence of SCAs is a negative prognostic marker that impairs outcome of patients over the age of 18 months with localised unresectable NB without MYCN amplification, especially when more than one SCA is present. Moreover, in older patients with unfavourable INPC tumour histoprognosis, the presence of SCAs significantly affects OS
Plasma microRNAs are Associated with Atrial Fibrillation (the miRhythm Study) and Change After Catheter-ablation
Background: Atrial fibrillation (AF) is the most common dysrhythmia in the U.S. and Europe. Few biomarkers exist to identify individuals at risk for AF. Cardiac microRNAs (miRNAs) have been implicated in susceptibility to AF and are detectable in the circulation. Nevertheless, data are limited on how circulating levels of miRNAs relate to AF or change over time after catheter- ablation.
Methods: In 211 miRhythm participants (112 with paroxysmal or persistent AF; 99 without AF), we quantified plasma expression of 86 miRNAs associated with cardiac remodeling or disease by high-throughput quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR). We used qRT-PCR to examine change in plasma miRNA expression from baseline to 1-month after ablation in 47 participants. We also quantified expression of the 20 most variable miRNAs in atrial tissue in 31 participants undergoing cardiac surgery.
Results: The mean age of the miRhythm cohort was 59 years and 58% of participants were men. 21 miRNAs differed significantly between participants with AF and those with no AF in regression models adjusting for known AF risk factors (p value of ≤ 0.0006). Several miRNAs associated with AF, including miR-21, miR-29a, miR-122, miR-150, miR-320, and miR-92a, regulate expression of genes implicated in the pathogenesis of AF. Levels of 33 miRNAs, including 14 associated with AF, changed significantly between baseline and 1-month after catheter ablation (p value of ≤ 0.0006). Although all AF-related plasma miRNAs were expressed in atrial tissue, only miR-21 and miR-411 differed significantly with respect to preoperative AF status.
Conclusions: Plasma levels of miRNAs associated with heart disease and cardiac remodeling were related to AF and changed after catheter-ablation. Our study suggests that AF has a unique circulating miRNA profile and that this profile is influenced by catheter-ablation
Transgenic overexpression of miR-133a in skeletal muscle
<p>Abstract</p> <p>Background</p> <p>MicroRNAs (miRNAs) are a class of non-coding regulatory RNAs of ~22 nucleotides in length. miRNAs regulate gene expression post-transcriptionally, primarily by associating with the 3' untranslated region (UTR) of their regulatory target mRNAs. Recent work has begun to reveal roles for miRNAs in a wide range of biological processes, including cell proliferation, differentiation and apoptosis. Many miRNAs are expressed in cardiac and skeletal muscle, and dysregulated miRNA expression has been correlated with muscle-related disorders. We have previously reported that the expression of muscle-specific miR-1 and miR-133 is induced during skeletal muscle differentiation and miR-1 and miR-133 play central regulatory roles in myoblast proliferation and differentiation in vitro.</p> <p>Methods</p> <p>In this study, we measured the expression of miRNAs in the skeletal muscle of mdx mice, an animal model for human muscular dystrophy. We also generated transgenic mice to overexpress miR-133a in skeletal muscle.</p> <p>Results</p> <p>We examined the expression of miRNAs in the skeletal muscle of <it>mdx </it>mice. We found that the expression of muscle miRNAs, including miR-1a, miR-133a and miR-206, was up-regulated in the skeletal muscle of <it>mdx </it>mice. In order to further investigate the function of miR-133a in skeletal muscle in vivo, we have created several independent transgenic founder lines. Surprisingly, skeletal muscle development and function appear to be unaffected in miR-133a transgenic mice.</p> <p>Conclusions</p> <p>Our results indicate that miR-133a is dispensable for the normal development and function of skeletal muscle.</p
Central nervous system relapse in high-risk stage 4 neuroblastoma : the HR-NBL1/SIOPEN trial experience
MIR376A is a regulator of starvation-induced autophagy
Background: Autophagy is a vesicular trafficking process responsible for the degradation of long-lived, misfolded or abnormal proteins, as well as damaged or surplus organelles. Abnormalities of the autophagic activity may result in the accumulation of protein aggregates, organelle dysfunction, and autophagy disorders were associated with various diseases. Hence, mechanisms of autophagy regulation are under exploration.
Methods: Over-expression of hsa-miR-376a1 (shortly MIR376A) was performed to evaluate its effects on autophagy. Autophagy-related targets of the miRNA were predicted using Microcosm Targets and MIRanda bioinformatics tools and experimentally validated. Endogenous miRNA was blocked using antagomirs and the effects on target expression and autophagy were analyzed. Luciferase tests were performed to confirm that 3’ UTR sequences in target genes were functional. Differential expression of MIR376A and the related MIR376B was compared using TaqMan quantitative PCR.
Results: Here, we demonstrated that, a microRNA (miRNA) from the DlkI/Gtl2 gene cluster, MIR376A, played an important role in autophagy regulation. We showed that, amino acid and serum starvation-induced autophagy was blocked by MIR376A overexpression in MCF-7 and Huh-7 cells. MIR376A shared the same seed sequence and had overlapping targets with MIR376B, and similarly blocked the expression of key autophagy proteins ATG4C and BECN1 (Beclin 1). Indeed, 3’ UTR sequences in the mRNA of these autophagy proteins were responsive to MIR376A in luciferase assays. Antagomir tests showed that, endogenous MIR376A was participating to the control of ATG4C and BECN1 transcript and protein levels. Moreover, blockage of endogenous MIR376A accelerated starvation-induced autophagic activity. Interestingly, MIR376A and MIR376B levels were increased with different kinetics in response to starvation stress and tissue-specific level differences were also observed, pointing out to an overlapping but miRNA-specific biological role.
Conclusions: Our findings underline the importance of miRNAs encoded by the DlkI/Gtl2 gene cluster in stress-response control mechanisms, and introduce MIR376A as a new regulator of autophagy
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