Infectious bursal disease virus subverts autophagic vacuoles to promote viral maturation and release

Autophagy functions as an intrinsic antiviral defence. However, some viruses can subvert or even enhance host autophagic machinery to increase viral replication and pathogenesis. The role of autophagy during Avibirnavirus infection, especially late stage infection, remains unclear. In this study, infectious bursal disease virus (IBDV) was used to investigate the role of autophagy in Avibirnavirus replication. We demonstrated IBDV induction of autophagy as a significant increase in puncta of LC3+ autophagosomes, endogenous levels of LC3-II, and ultrastructural characteristics typical of autophagosomes during the late stage of infection. Induction of autophagy enhances IBDV replication, whereas inhibition of autophagy impairs viral replication. We also demonstrated that IBDV infection induced autophagosome–lysosome fusion, but without active degradation of their contents. Moreover, inhibition of fusion or of lysosomal hydrolysis activity significantly reduced viral replication, indicating that virions utilised the low pH environment of acidic organelles to facilitate viral maturation. Using immuno-transmission electron microscopy (TEM), we observed that a large number of intact IBDV virions were arranged in a lattice surrounded by p62 proteins, some of which laid between virions. Additionally, many virions were encapsulated within the vesicular membranes with an obvious release stage observed by TEM. The autophagic endosomal pathway facilitates low pH-mediated maturation of viral proteins and membrane-mediated release of progeny virions.IMPORTANCE IBDV is the most extensively studied virus in terms of molecular characteristics and pathogenesis; however, mechanisms underlying the IBDV life cycle require further exploration. The present study demonstrated that autophagy enhances viral replication at the late stage of infection, and the autophagy pathway facilitates IBDV replication complex function and virus assembly, which is critical to completion of the virus life cycle. Moreover, the virus hijacks the autophagic vacuoles to mature in an acidic environment and release progeny virions in a membrane-mediated cell-to-cell manner. This autophagic endosomal pathway is proposed as a new mechanism that facilitates IBDV maturation, release, and re-internalisation. This study presents a concordance in exit strategies among some RNA and DNA viruses, which exploit autophagy pathway for their release from cells.

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Publication
Contributors
Wang Y, Duan Y, Han C, Yao S, Qi X, Gao Y, Maier H J, Britton P, Chen L, Zhang L, Gao L, Gao H, Shen N, Wang J, Wang X
Year
2017
Journal
Journal of Virology
Volume
91
Issue
5
Pages
e01883-16
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