Advancing Our Understanding of Corneal Herpes Simplex Virus-1 Immune Evasion Mechanisms and Future Therapeutics

Herpes stromal keratitis (HSK) is a disease that commonly affects the cornea and external eye and is caused by Herpes Simplex Virus type 1 (HSV-1). This virus infects approximately 66% of people worldwide; however, only a small portion of these people will develop symptoms in their lifetime. There is no cure or vaccine available for HSV-1; however, there are treatments available that aim to control the inflammation caused by the virus and prevent its recurrence. While these treatments are beneficial to those suffering with HSK, there is a need for more effective treatments to minimise the need for topical steroids, which can have harmful effects, and to prevent bouts of disease reactivation, which can lead to progressive corneal scarring and visual impairment. This review details the current understanding of HSV-1 infection and discusses potential novel treatment options including microRNAs, TLRs, mAbs, and aptamers

Herpes Simplex Virus 1 Targets IRF7 via ICP0 to Limit Type I IFN Induction

Herpes simplex keratitis (HSK), caused by herpes simplex virus type 1 (HSV‑1) infection, is the commonest cause of infectious blindness in the developed world. Following infection the virus is initially suspended in the tear film, where it encounters a multi‑pronged immune response comprising enzymes, complement, immunoglobulins and crucially, a range of anti‑viral and pro‑inflammatory cytokines. However, given that HSV‑1 can overcome innate immune responses to establish lifelong latency throughout a susceptible individual’s lifetime, there is significant interest in understanding the mechanisms employed by HSV‑1 to downregulate the anti‑viral type I interferon (IFN) mediated immune responses. This study aimed to investigate the interactions between infected cell protein (ICP)0 and key elements of the IFN pathway to identify possible novel targets that contribute to viral immune evasion. Reporter gene assays demonstrated the ability of ICP0 to inhibit type I IFN activity downstream of pathogen recognition receptors (PRRs) which are known to be involved in host antiviral defences. Further experiments identified interferon regulatory factor (IRF)7, a driver of type I IFN, as a potential target for ICP0. These findings increase our understanding of the pathogenesis of HSK and suggest IRF7 as a potential therapeutic target

Advancing Our Understanding of Corneal Herpes Simplex Virus-1 Immune Evasion Mechanisms and Future Therapeutics

Herpes stromal keratitis (HSK) is a disease that commonly affects the cornea and external eye and is caused by Herpes Simplex Virus type 1 (HSV-1). This virus infects approximately 66% of people worldwide; however, only a small portion of these people will develop symptoms in their lifetime. There is no cure or vaccine available for HSV-1; however, there are treatments available that aim to control the inflammation caused by the virus and prevent its recurrence. While these treatments are beneficial to those suffering with HSK, there is a need for more effective treatments to minimise the need for topical steroids, which can have harmful effects, and to prevent bouts of disease reactivation, which can lead to progressive corneal scarring and visual impairment. This review details the current understanding of HSV-1 infection and discusses potential novel treatment options including microRNAs, TLRs, mAbs, and aptamers

Investigation of type I interferon responses in ANCA‑associated vasculitis

Type I interferon (IFN) dysregulation is a major contributory factor in the development of several autoimmune diseases, termed type I interferonopathies, and is thought to be the pathogenic link with chronic infammation in these conditions. Anti-neutrophil cytoplasmic antibody (ANCA)-Associated Vasculitis (AAV) is an autoimmune disease characterised by necrotising infammation of small blood vessels. The underlying biology of AAV is not well understood, however several studies have noted abnormalities in type I IFN responses. We hypothesised that type I IFN responses are systemically dysregulated in AAV, consistent with features of a type I interferonopathy. To investigate this, we measured the expression of seven interferon regulated genes (IRGs) (ISG15, SIGLEC1, STAT1, RSAD2, IFI27, IFI44L and IFIT1) in peripheral blood samples, as well as three type I IFN regulated proteins (CXCL10, MCP-1 and CCL19) in serum samples from AAV patients, healthy controls and disease controls. We found no difference in type I IFN regulated gene or protein expression between AAV patients and healthy controls. Furthermore, IRG and IFN regulated protein expression did not correlate with clinical measurements of disease activity in AAV patients. Thus, we conclude that systemic type I IFN responses are not key drivers of AAV pathogenesis and AAV should not be considered a type I interferonopathy