HBV activates the tubulation of endocytic compartments through Rab7

Infection with hepatitis B virus (HBV) is still a major health problem despite there being an effective vaccine available. In order to identify new antiviral targets, a better understanding of the mechanisms by which HBV usurps established host cell pathways is essential. Here, Jun Inoue and colleagues (p. 1696) investigate how the late endocytic pathway participates in the final stages of HBV secretion. They found that cells infected with HBV formed an interconnected tubular network that linked multivesciular bodies (MVBs), autophagosomes and lysosomes. The formation of these tubules depended upon the action of Rab7, which was activated by the viral precore protein. Following siRNA-mediated depletion of Rab7 in infected cells, there was very little tubulation, a reduction in transport of HBV proteins to lysosomes and an increase in viral secretion. Inhibition of lysosome function also increased HBV secretion, suggesting that the function of the tubular network is to promote degradation of nascent virus in the lysosome. This paradoxical finding, whereby HBV inhibits its own secretion, nevertheless shows that the vesicle trafficking machinery could provide useful drug targets for future therapy.