<i>Et tu, Brute</i> ? TFEB promotes virus replication before being cleaved by a viral protease

The relationship between many viruses and cellular autophagy is complex; autophagy is a useful mechanism of membrane rearrangement and trafficking, but autophagosomes can degrade virus components and newly formed virions. Picornaviruses, whose relationship to autophagy has been studied for almost thirty years, cause a range of diseases, from mild respiratory illnesses such as the common cold to major paralysis syndromes such as poliomyelitis and acute flaccid myelitis. Like most viruses with RNA genomes, picornaviruses translate, replicate, and package their genome in the cytosol, often in association with membranes. Early in picornavirus infections, there is an extensive rearrangement of intracellular membranes to form a replication platform, the cytosolic surface of which serves as the site for viral RNA replication. Later in infection, autophagosome-like vesicles bud from the replication organelle and are used to traffic viruses to the cell surface, releasing virus packets surrounded by the former inner membrane of the double-membrane autophagosome-like vesicles. Thus, picornaviruses must inhibit the degradative aspects of the pathway to prevent viral proteins or even newly formed virions from being consumed in autolysosomes. With this in mind, we recently described the dual-natured role of host TFEB (transcription factor EB), in the picornavirus virus cycle. TFEB is required for early infection, but cleaved by a viral protease late in infection as part of a viral strategy to subvert the autophagy machinery to remodel membranes while inhibiting degradative autophagy. This is a story out of Shakespeare, in which viruses betray a cellular ally in a manner worthy of Brutus; first usurping the function of TFEB, then cleaving that same protein when the needs of the virus change late in infection.