Grapevine leafroll-associated virus 3: A global threat to the grape and wine industries but a gold mine for scientific discovery.

Grapevine leafroll disease is the most damaging viral disease afflicting global grape and wine production. Of the five viruses likely associated with the disease, grapevine leafroll-associated virus 3 (GLRaV3) is believed to be the predominant agent, albeit its role as the causal agent has remained uncertain. GLRaV3 (species Ampelovirus trivitis, genus Ampelovirus, family Closteroviridae) has the third largest single-stranded, positive-sense RNA genome among plant viruses at ~18.5 kb, only surpassed by two other members of the family Closteroviridae, citrus tristeza virus, and GLRaV1. GLRaV3 is unique among plant viruses in several ways including the size of its genome, the long non-coding regions, and its association with the outer mitochondrial membrane for viral replication. Unfortunately, our understanding of the molecular mechanisms governing GLRaV3 genome replication, gene expression and virus-host interactions is poor due to many factors, including the unavailability of infectious cDNA clones and effective experimental system to initiate grapevine infection with viral clones until recently. In this review, we capture some recent advances in GLRaV3 research towards the establishment of infectious clones, grapevine inoculation systems, as well as approaches towards elucidating the function of GLRaV3-encoded proteins. We also present a working model to explain GLRaV3 pathogenesis.