Cross-protection is a biocontrol method to protect plants - both annual and perennial species - from damage caused by pathogenic viruses. This strategy of cross-protecting a plant with a mild strain to prevent subsequent infection by related severe strains (challenge strains) was first proposed in 1926 by McKinney. Although cross-protection was first evidenced nearly a century ago, the underlying mechanism(s) remain(s) poorly understood. In particular, although the genetic relatedness between cross-protective and challenge strains has been emphasized in a number of papers, the degree of homology required for cross-protection remains unknown. This lack of data has led to a long and tedious, and sometimes unsuccessful, empirical search for cross-protective strains against some viral pathogenic ones. Recent papers have shown that cross-protection occurs only among variants of the same strain and not between variants of different strains for the citrus tristeza virus (Closterovirus) and the pepino mosaic virus (Potexvirus). In order to determine the degree of homology required between the cross-protective and the challenge strains for cross-protection to be effective against the grapevine fanleaf virus (GFLV, Nepovirus, Secoviridae), different cross-protective variants with decreasing sequence homology with respect to the challenge variant were selected and inoculated on Nicotiana benthamiana. Our preliminary results suggest that the degree of homology required differs depending on whether the variants are inoculated sequentially on the same leaves or on different leaves.