HBV secretion is regulated through the activation of endocytic and autophagic compartments mediated by Rab7 stimulation

Jun Inoue, Eugene W. Krueger, Jing Chen, Hong Cao, Masashi Ninomiya, Mark A Mc Niven

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

The cellular mechanisms by which hepatitis B virus (HBV) is assembled and exported are largely undefined. Recently, it has been suggested that these steps require the multivesicular body (MVB) and the autophagic machinery. However, the mechanisms by which HBV might regulate these compartments are unclear. In this study, we have found that by activating Rab7a, HBV alters its own secretion by inducing dramatic changes in the morphology of MVB and autophagic compartments. These changes are characterized by the formation of numerous tubules that are dependent upon the increase in Rab7 activity observed in the HBV-expressing HepG2.2.15 cells compared to HepG2 cells. Interestingly, transfection-based expression of the five individual viral proteins indicated that the precore protein, which is a precursor of HBeAg, was largely responsible for the increased Rab7 activity. Finally, small interfering RNA (siRNA)-mediated depletion of Rab7 significantly increased the secretion of virions, suggesting that reduced delivery of the virus to the lysosome facilitates viral secretion. These findings provide novel evidence indicating that HBV can regulate its own secretion through an activation of the endo-lysosomal and autophagic pathway mediated by Rab7 activation.

Original languageEnglish (US)
Pages (from-to)1696-1706
Number of pages11
JournalJournal of Cell Science
Volume128
Issue number9
DOIs
StatePublished - 2015

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Hepatitis B virus
Multivesicular Bodies
Hepatitis B e Antigens
Hep G2 Cells
Viral Proteins
Lysosomes
Virion
Small Interfering RNA
Transfection
Viruses
Proteins

Keywords

  • Autophagosome
  • HBV
  • MVB
  • Rab7
  • Tubule

ASJC Scopus subject areas

  • Cell Biology

Cite this

HBV secretion is regulated through the activation of endocytic and autophagic compartments mediated by Rab7 stimulation. / Inoue, Jun; Krueger, Eugene W.; Chen, Jing; Cao, Hong; Ninomiya, Masashi; Mc Niven, Mark A.

In: Journal of Cell Science, Vol. 128, No. 9, 2015, p. 1696-1706.

Research output: Contribution to journalArticle

Inoue, Jun ; Krueger, Eugene W. ; Chen, Jing ; Cao, Hong ; Ninomiya, Masashi ; Mc Niven, Mark A. / HBV secretion is regulated through the activation of endocytic and autophagic compartments mediated by Rab7 stimulation. In: Journal of Cell Science. 2015 ; Vol. 128, No. 9. pp. 1696-1706.
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