Grapevine (Vitis vinifera L.,) is among the world’s leading fruit crops. The production of grapes is severely affected by many diseases including gray mold, caused by the necrotrophic fungus Botrytis cinerea. Although all Vitis species can be hosts for B. cinerea, V. vinifera are particularly susceptible. Accordingly, this disease poses a significant threat to the grape industry and causes substantial economic losses. Development of resistant V. vinifera cultivars has progressed from incidental selection by farmers, to targeted selection through the use of statistics and experimental design, to the employment of genetic and genomic data. Emerging technologies such as marker-assisted selection and genetic engineering have facilitated the development of cultivars that possess resistance to B. cinerea. A promising method involves using the CRISPR/Cas9 system to induce targeted mutagenesis and develop genetically modified non-transgenic crops. Hence, scientists are now engaged in the active pursuit of identifying genes associated with susceptibility and resistance. This review focuses on the known mechanisms of interaction between the B. cinerea pathogen and its grapevine host. It also explores innate immune systems that have evolved in V. vinifera, with the objective of facilitating the rapid development of resistant grapevine cultivars.

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