The types of cells and tissues infected by a virus define its tissue tropis
m. Determinants of tissue tropism in animal-infecting viruses have been ext
ensively investigated, but little is known about plant viruses in this rega
rd. Some geminiviruses in the genus Begomovirus exhibit phloem limitation a
nd are restricted to cells of the vascular system, whereas others can invad
e mesophyll tissue. To identify viral genetic determinants of tissue tropis
m, we established a model system using two begomoviruses and their common h
ost plant, Nicotiana benthamiana. Analysis by DNA in situ hybridization con
firmed that tomato golden mosaic virus invades mesophyll tissues in systemi
cally infected leaves, whereas bean golden mosaic virus remains phloem limi
ted. Through genetic complementation and analysis of recombinant hybrid vir
uses, we demonstrated that three genetic elements of tomato golden mosaic v
irus determine its mesophyll tissue tropism. A noncoding region of the vira
l genome is essential for the phenotype, but it must be accompanied by one
of two different coding regions. To our knowledge, this is the first exampl
e documented in a plant virus of noncoding DNA sequences that determine tis
sue tropism.