Macroautophagy Proteins Assist Epstein Barr Virus Production and Get Incorporated Into the Virus Particles

EBioMedicine. 2014 Nov 8;1(2-3):116-25. doi: 10.1016/j.ebiom.2014.11.007. eCollection 2014 Dec.


Epstein Barr virus (EBV) persists as a latent herpes virus infection in the majority of the adult human population. The virus can reactivate from this latent infection into lytic replication for virus particle production. Here, we report that autophagic membranes, which engulf cytoplasmic constituents during macroautophagy and transport them to lysosomal degradation, are stabilized by lytic EBV replication in infected epithelial and B cells. Inhibition of autophagic membrane formation compromises infectious particle production and leads to the accumulation of viral DNA in the cytosol. Vice versa, pharmacological stimulation of autophagic membrane formation enhances infectious virus production. Atg8/LC3, an essential macroautophagy protein and substrate anchor on autophagic membranes, was found in virus preparations, suggesting that EBV recruits Atg8/LC3 coupled membranes to its envelope in the cytosol. Our data indicate that EBV subverts macroautophagy and uses autophagic membranes for efficient envelope acquisition during lytic infection.

Keywords: Atg, autophagy related gene; Atg12; Atg16; Atg8/LC3; B cell; BALF1, BamH1 A fragment leftward reading frame 1; BALF4, BamH1 A fragment leftward reading frame 4; BHRF1, BamH1 H fragment rightward reading frame 1; BMRF1, BamH1 M fragment rightward reading frame 1; BNRF1, BamH1 N fragment rightward reading frame 1; BRLF1, BamH1 R fragment leftward reading frame 1; BZLF1; BZLF1, BamH1 Z fragment leftward reading frame 1; EBNA1, Epstein Barr virus nuclear antigen 1; EBV, Epstein Barr virus; Epithelial cell; LMP1, latent membrane protein 1; Lytic EBV replication; vFLIP, viral FLICE-like inhibitor protein.