The role of viral regulatory protein ICP0 in herpes simplex type 1 keratitis
Herpes simplex keratitis (HSK) is the commonest cause of infectious blindness in the
developed world. It is caused by herpes simplex virus type 1 (HSV‐1) and is
characterised by recurrent episodes of infection and immune‐mediated corneal
inflammation that lead to significant loss of vision. Following transmission of HSV‐1
the virus is initially suspended in the tear film, where it encounters a multi‐pronged
defence comprising enzymes, complement, immunoglobulins and crucially, a range
of anti‐viral and pro‐inflammatory cytokines. HSV‐1, however, is able to overcome
innate immune responses, to establish lifelong latency and to reactivate throughout
susceptible individual’s lifetime with the potential of causing irreversible damage to
The crucial roles of viral regulatory protein ICP0 in the pathogenesis of HSV‐1
infection is well established. ICP0 is important for the virus’s ability to cause a
productive infection, to establish a latent state and to successfully reactivate.
However, the molecular mechanisms behind these processes are largely unknown.
The aim of this study was to investigate the interactions between ICP0 and key
elements of type I IFN pathway and to identify possible targets that contribute to
Our Luciferase studies have demonstrated the ability of ICP0 to inhibit type I IFN
activity downstream of TLRs 3, 4 and 7 which are known to be involved in host
antiviral defences. Further co‐transfection experiments have identified IRF7, a
crucial driver of IFN‐ as a potential target for ICP0. IRF7 stability experiment has
confirmed that IRF7 is targeted by ICP0 for degradation in a dose dependent
fashion. This finding is another step towards better understanding of the
pathogenesis of herpes simplex keratitis (HSK) and may become a potential
therapeutic target for HSK.
First SupervisorProfessor Conor C. Murphy
Second SupervisorProfessor Caroline Jefferies
CommentsA thesis submitted for the degree of Doctor of Medicine from the Royal College of Surgeons in Ireland in 2018.
Published CitationShahnazaryan D. The role of viral regulatory protein ICP0 in herpes simplex type 1 keratitis. [MD Thesis]. Dublin: Royal College of Surgeons in Ireland; 2019.
Degree NameDoctor of Medicine (MD)
Date of award30/06/2019
- Doctor of Medicine (MD)