Herpes simplex virus types 1 and 2 modulate autophagy in SIRC corneal cells

Abstract

Autophagy and apoptosis function as important early cellular defense mechanisms in infections and other diseases. The outcome of an infection is determined by a complex interplay between the pathogenic microorganism and these intracellular pathways. To better understand the cytopathogenicity of Herpes simplex virus types 1 and 2 (HSV-1 and -2), we studied the effect of these viruses on the autophagic and apoptotic processes in the SIRC corneal cell line. Infection with the KOS strain of HSV-1 and a wild-type strain of HSV-2 enhanced autophagosome formation, triggered cytoplasmic acidification, increased LC3B lipidation and elevated the ratio of apoptotic cells. The autophagy inhibitor bafilomycin A1 triggered a significant increase in the apoptotic responses of HSV-1-and HSV-2-infected cells. Thus, both HSV types affect autophagy and apoptosis in a coordinated fashion, and autophagy plays cytoprotective role in HSV-infected cells via antagonizing apoptosis. Together these data implicate autophagy in the pathogenic mechanism of herpetic keratitis.[Petrovski G, Pásztor K, Orosz L, Albert R, Mencel E, Moe MC, Kaarniranta K, Facskó A and Megyeri K 2014 Herpes simplex virus types 1 and 2 modulate autophagy in SIRC corneal cells.

Herpesvirus and Autophagy: “All Right, Everybody Be Cool, This Is a Robbery!”

“…Induction of autophagy by HSV-1 in THP-1 cells involved MyD88, since infection of MyD88-deficient cells does not trigger autophagy. Infection of rabbit corneal cells by HSV-1, but also by HSV-2 leads also to an activation of autophagy, which could be protective against apoptosis [ 69 ]. HSV-1 and HSV-2 are closely related viruses sharing around 50% of sequence identity.…”

The Chinese herbal prescription JZ-1 induces autophagy to protect against herpes simplex Virus-2 in human vaginal epithelial cells by inhibiting the PI3K/Akt/mTOR pathway

“…However, the related antiviral mechanism of JZ-1 is not fully understood and needs further explanation. Recent studies have shown that HSV-2 blocks autophagic flux but host cells increase autophagy levels to inhibit viral infection in the later stages of the viral replication cycle (Kristen et al, 2015;Petrovski et al, 2014). Therefore, this study explored the underlying mechanisms of JZ-1 in treating HSV-2 infection by inducing autophagy.…”

Programmed cell death: the battlefield between the host and alpha-herpesviruses and a potential avenue for cancer treatment

“…HSV-1 is able to prolong cell survival by autophagic resistance to apoptosis via the non-dependent mTOR pathway [ 115 ]. In addition, HSV-1 and HSV-2 infection of SIRC cells inhibited the occurrence of autophagy to increase the number of apoptotic cells, indicating that autophagy could resist the occurrence of apoptosis [ 116 ](121). Autophagy formation was detected in VZV-infected MRC-5 cells before 72 hours of infection, and a high percentage of apoptosis occurred after 72 hours.…”