Event Title

Modulation of unfolded protein response to endoplasmic reticulum stress causes a potent antiviral response in HSV infection corneal epithelial cells.

Advisor(s)

Dr. Deepak Shukla, Lions of Illinois Eye Research Institute, University of Illinois at Chicago

Location

Room A155

Start Date

26-4-2019 10:25 AM

End Date

26-4-2019 10:40 AM

Abstract

Herpes simplex viruses (HSV) are one of the most ubiquitous pathogens with approximately 90% global seroprevalence. Recurrent infections lead to painful ulcerative keratitis and lesions in the ocular, oro-facial and genital regions in latently infected individuals. Currently there is only one approved treatment, acyclovir, which acts via the inhibition of a single aspect of viral life cycle, viral DNA replication. Among the many cellular pathways tightly regulated by the virus during its infectious life cycle, the unfolded protein response (UPR) to endoplasmic reticulum (ER) stress is an important pathway that regulates viral protein synthesis and folding. In this study, we tested multiple small-molecule inducers and alleviators of ER stress to understand its effects on HSV-1 infection. Through immunofluorescence, western blotting and quantitative PCR, our results showed that while external induction of ER stress using tunicamycin reduces HSV viral spread and protein synthesis, the alleviation of ER stress using salubrinal increases and promotes viral replication and protein synthesis in human corneal epithelial cells. Our results align with the existing hypothesis that HSV requires host ER machinery to effectively translate and fold viral proteins during its life cycle and inhibition of this pathway can result in a potent antiviral response.

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Apr 26th, 10:25 AM Apr 26th, 10:40 AM

Modulation of unfolded protein response to endoplasmic reticulum stress causes a potent antiviral response in HSV infection corneal epithelial cells.

Room A155

Herpes simplex viruses (HSV) are one of the most ubiquitous pathogens with approximately 90% global seroprevalence. Recurrent infections lead to painful ulcerative keratitis and lesions in the ocular, oro-facial and genital regions in latently infected individuals. Currently there is only one approved treatment, acyclovir, which acts via the inhibition of a single aspect of viral life cycle, viral DNA replication. Among the many cellular pathways tightly regulated by the virus during its infectious life cycle, the unfolded protein response (UPR) to endoplasmic reticulum (ER) stress is an important pathway that regulates viral protein synthesis and folding. In this study, we tested multiple small-molecule inducers and alleviators of ER stress to understand its effects on HSV-1 infection. Through immunofluorescence, western blotting and quantitative PCR, our results showed that while external induction of ER stress using tunicamycin reduces HSV viral spread and protein synthesis, the alleviation of ER stress using salubrinal increases and promotes viral replication and protein synthesis in human corneal epithelial cells. Our results align with the existing hypothesis that HSV requires host ER machinery to effectively translate and fold viral proteins during its life cycle and inhibition of this pathway can result in a potent antiviral response.