Bovine herpesvirus type 4 infection modulates autophagy in a permissive cell line

Bovine herpesvirus type 4 (BoHV‐4), like other herpesviruses, induces a series of alterations in the host cell that modify the intracellular environment in favor of viral replication, survival and spread. This research examined the impact of BoHV‐4 infection on autophagy in BoHV‐4 infected Madin Darby bovine kidney (MDBK) cells. Protein extracts of BoHV‐4 infected and control MDBK cells were subjected to Western blot. The concentrations of the autophagy and apoptosis‐related proteins Beclin 1, p21, PI3 kinase, Akt1/2, mTOR, phospho mTOR, p62 and the light chain three (LC3) were normalized to the actin level and expressed as the densitometric ratio. Western blot analysis of virus‐infected cells revealed that autophagic degradation pathway was induced in the late phase of BoHV‐4 infection. After 48 h post‐infection the protein LC3II, which is essential for autophagy was found to be markedly increased, while infection of MDBK cells with BoHV‐4 resulted in a depletion of p62 levels. Becline 1, PI3 kinase, Akt1/2 and p21 expression increased between 24 and 48 h post‐infection. Surprisingly, mTOR and its phosphorylated form, which are negative regulators of autophagy, also increased after 24 h post‐infection. In conclusion, our findings suggest that BoHV‐4 has developed mechanisms for modulation of autophagy that are probably part of a strategy designed to enhance viral replication and to evade the immune system. Additional studies on the relationship between autophagy and BoHV‐4 replication and survival, in both lytic and latent replication phases, are needed to understand the role of autophagy in BoHV‐4 pathogenesis. J. Cell. Biochem. 114: 1529–1535, 2013. © 2013 Wiley Periodicals, Inc.