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

Autor: Claire Wynne, David Shahnazaryan, Joan Ní Gabhann-Dromgoole, Conor Murphy, Caroline A. Jefferies, Rana Khalil
Rok vydání: 2020
Předmět:
0301 basic medicine
Interferon Regulatory Factor-7
viruses
herpes simplex virus type 1 (HSV‑1) infection
Herpesvirus 1
Human
medicine.disease_cause
0302 clinical medicine
Herpes simplex keratitis (HSK)
Genes
Reporter
Interferon
commonest cause
Medicine and Health Sciences
Promoter Regions
Genetic
Multidisciplinary
Protein Stability
Immune evasion
Host-Pathogen Interactions
Interferon Type I
Medicine
Antibody
Protein Binding
medicine.drug
Transcriptional Activation
Pattern recognition receptors
developed world
Corneal diseases
Ubiquitin-Protein Ligases
Science
Immunology
Biology
Article
Virus
Immediate-Early Proteins
03 medical and health sciences
Immune system
medicine
Humans
Eye diseases
Binding Sites
Innate immune system
Base Sequence
Herpes Simplex
Interferon-beta
030104 developmental biology
Herpes simplex virus
Gene Expression Regulation
infectious blindness
biology.protein
IRF7
030217 neurology & neurosurgery
Interferon regulatory factors
Optometry
Zdroj: Articles
Scientific Reports, Vol 10, Iss 1, Pp 1-10 (2020)
Scientific Reports
Popis: 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.
Databáze: OpenAIRE
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