Abstract
Antibodies protect against lethal infection by bacteria or nonenveloped viruses such as adenovirus (1). They are secreted by plasma cells at the rate of thousands of molecules per second, and it has long been assumed that they function exclusively in the extracellular milieu. The recent discovery of a cytoplasmic process called antibody-dependent intracellular neutralization (ADIN) put an end to this dogma: virion-associated antibodies that fail to prevent virus entry into susceptible target cells have a second chance to block infection from within the target cell cytoplasm (2). In PNAS, Hauler et al. (3) generate a din of excitement by showing that the host AAA ATPase valosin-containing protein (VCP) cooperates with the E3 ubiquitin ligase tripartite motif-containing protein 21 (TRIM21) to dismantle the antibody-coated virion, thus permitting the proteasome access to the building block proteins of the virion capsid.
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