Crosstalk between autophagy and apoptosis during HSV-1 replication: possible role of Us11 viral protein

Autophagy and apoptosis are two of main processes involved in maintenance of cellular homeostasis as well as the innate immune defense. Herpes simplex virus type 1 (HSV-1) is known to regulate both processes. Recent studies have demonstrated that viral gene US11 is involved in control of autophagy. In order to demonstrate if there may be a crosstalk between both processes, we enrolled HSV-1 and a mutant virus R7023, with a deletion including US11 gene, to analyze autophagy and apoptosis markers. We observed that in THP-1 wt cell lines there was an activation of autophagy after infection of mutant virus R7023, but not with HSV-1. Recent studies have shown that Beclin-1, an autophagic marker, is degraded by caspase-8, which colocalizes with p62 protein on the surface of autophagosomes membrane. Activation of caspase-8 is regulated by FLIP protein. We observed that in cells infected with HSV-1, but not with mutant virus, there was a degradation of FLIP at 24, 48, 72 h.p.i. corresponding to an activation of caspase-8, that could lead to a blockage of autophagy. Based on these data we have obtained evidences about the interplays between autophagy and apoptosis pathways during viral replication.