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Abstract Citrus tristeza virus (CTV) is a causal agent of diseases that have challenged the global citrus production for more than a century. The disease named ‘tristeza’, which means ‘sadness’ in Portuguese and Spanish, has spread by aphids and vegetative propagation, resulting in costly pandemics that reshaped the world citrus production by forcing the adaption of disease‐tolerant rootstocks. Furthermore, management of the second major CTV‐induced disease, stem pitting, became a unique example of the use of cross‐protection on a large nationwide scale, allowing many citrus growing regions to control the disease that could not be managed through horticultural practices. The information gathered in this review commemorates a hundred years of research on the virus and the respective diseases, which began with classical horticultural approaches and advanced toward the cutting‐edge molecular biology studies. In this regard, it is proper to mention that CTV research greatly benefited from close international collaboration between research institutions and scientists from the affected and nonaffected citrus areas. Moreover, despite the considerable initial losses caused by tristeza, the world's fresh fruit and juice concentrate citrus industries reemerged as highly productive following the research advancements, a situation that changed throughout Florida and Brazil in the past two decades or so with the outbreak of the devastating citrus greening (Huanglongbing) bacterial disease. This review encompasses past and recent advances in the CTV research positioning the citrus‐CTV pathosystem as a pivotal model system for investigating virus interactions with perennial woody hosts. The review will also serve as an updated version of the respective section on CTV in the Description of Plant Viruses that the Association of Applied Biologists manages. We dedicated this review to the 85th Birthday celebration of Prof. Moshe Bar‐Joseph, a world‐renowned plant pathologist whose half‐a‐century‐long career devoted to citrus diseases yielded many important, pioneering discoveries on CTV and other closteroviruses. Many of those are highlighted in this review. Prof. Bar‐Joseph retired from the Volcani Center, Agricultural Research Organization in Israel several years ago, yet he continues to be actively engaged in research and provides his expertise to citrus pathologists around the world in the present days. 

Due to the error-prone nature of viral RNA-dependent RNA polymerases, the replication of RNA viruses results in a diversity of viral genomes harboring point mutations, deletions, insertions, and genome rearrangements. Citrus tristeza virus (CTV), a causal agent of diseases of economically important citrus species, shows intrinsic genetic stability. While the virus appears to have some mechanism that limits the accumulation of single-nucleotide variants, the production of defective viral genomes (DVGs) during virus infection has been reported for certain variants of CTV. The intra-host diversity generated during plant infection with variant T36 (CTV-T36) remains unclear. To address this, we analyzed the RNA species accumulated in the initially infected and systemic leaves of Nicotiana benthamiana plants inoculated with an infectious cDNA clone of CTV-T36, which warranted that infection was initiated by a known, well-defined sequence variant of the virus. CTV-T36 limited the accumulation of single-nucleotide mutants during infection. With that, four types of DVGs—deletions, insertions, and copy- and snap-backs—were found in all the samples, with deletions and insertions being the most common types. Hot-spots across the genome for DVG recombination and short direct sequence repeats suggest that sequence complementarity could mediate DVG formation. In conclusion, our study illustrates the formation of diverse DVGs during CTV-T36 infection. To the best of our knowledge, this is the first study that has analyzed the genetic variability and recombination of a well-defined sequence variant of CTV in an herbaceous host.