Intracellular bacteria and viruses must survive the vigorous antimicrobial responses of their hosts to replicate successfully. The cellular process of autophagy -in which compartments bound by double membranes engulf portions of the cytosol and then mature to degrade their cytoplasmic contents -is likely to be one such host-cell response. Several lines of evidence show that both bacteria and viruses are vulnerable to autophagic destruction and that successful pathogens have evolved strategies to avoid autophagy, or to actively subvert its components, to promote their own replication. The molecular mechanisms of the avoidance and subversion of autophagy by microorganisms will be the subject of much future research, not only to study their roles in the replication of these microorganisms, but also because they will provide -as bacteria and viruses so often have -unique tools to study the cellular process itself.
DAUER
An arrested stage inCaenorhabditis elegans development that can be formed in conditions of starvation or overcrowding. Cellular autophagy involves the sequestration of regions of the cytosol within double-membrane-bound compartments that then mature and degrade their cytoplasmic contents. It is a highly regulated process, the components of which have only recently been identified by extensive studies using yeast genetics. Owing to groundbreaking work in Saccharomyces cerevisiae, a host of autophagy genes have now been described, the mechanisms of action of many of their products determined and their mammalian and other homologues identified 1 .
Department of MicrobiologyIn this review, we will use the notation ATG, the newly adopted nomenclature, for the genes that function in autophagy 2 . There is a substantial body of literature describing studies in which new genetic tools have been used to show that autophagy, its machinery or both are required for many aspects of cellular function and organismal development. For example, human beclin1, a homologue of yeast ATG6, has been shown to be a tumour-suppressor gene 3 . Starvation responses also require autophagy: DAUER formation in Caenorhabditis elegans requires functional beclin1 (REF. 4) and the survival of Dictyostelium discoideum during nitrogen starvation requires functional homologues of yeast ATG5 and ATG7 (REF. 5). Furthermore, in both Arabidopsis thaliana 6,7 and C. elegans 4 , wild-type autophagy genes are required to prevent premature senescence.One attractive hypothesis is that the degradation of cytosolic structures by autophagy might have a general role in 'clearing away' intracellular pathogens. Observations of intracellular viruses and bacteria within multivesicular bodies have often been reported from electron-microscopy (EM) studies 8 . In addition, an unexplained phenomenon known as hepatic 'purging' is seen in hepatitis-B-infected chimpanzees. As many as 75% of the hepatic cells in these infected animals were shown to contain viral proteins at 10 weeks postinfection, but proved to be virus-free, in the absence of extensive cell de...