Transport of viruses from cell to cell in plants typically involves one or more viral proteins that supply dedicated movement functions, Transport from leaf to leaf through phloem, or long-distance transport, is a poorly understood process with requirements differing from those of cell-to-cell movement, Through genetic analysis of tobacco etch virus (TEV; potyvirus group), a novel long-distance movement factor was identified that facilitates vascular-associated movement in tobacco, A mutation in the central region of the helper component proteinase (HC-Pro), a TEV-encoded protein with previously described activities in aphid-mediated transmission and polyprotein processing, inactivated long-distance movement, This mutant virus exhibited only minor defects in genome amplification and cell-to-cell movement functions, In situ histochemical analysis revealed that the mutant was capable of infecting mesophyll, bundle sheath, and phloem cells within inoculated leaves, suggesting that the long-distance movement block was associated with entry into or exit from sieve elements, The long-distance movement defect was specifically complemented by NO-Pro supplied in trans by a transgenic host, The data indicate that HC-Pro functions in one or more steps unique to long-distance transport.