Herpes simplex virus 1 (HSV-1) infection of the eye is the leading cause of corneal blindness by an infectious agent in the developed countries. In addition, HSV-1 causes encephalitis and contributes to 35-50% of new cases genital herpes. HSV-1 usually infects the epithelium where it undergoes viral gene expression, DNA replication, and maturation. Following lytic infection the virus goes into latency in the trigeminal ganglia, which represents a lifelong source of virus for recurrent lesions. A licensed vaccine currently does not exist. Although a variety of strategies are undertaken, precise determinants of an effective HSV vaccine is unclear. This partly stems from the complex nature of HSV. There is now increased recognition that Toll-like receptor and cytosolic receptor pathways play a pivotal role in initiating antiviral immunity. Upon activation, these pathways regulate the expression of type I interferon, cytokines, and co-stimulatory molecules. Notably, TANK binding kinase 1 (TBK1), a key factor in innate immune pathways, dictates vaccine responses. Preliminary studies suggest that an HSV mutant lacking the Us3 gene activates dendritic cells which are sentinels of innate and adaptive immunity. We propose to develop engineered HSV vaccines with superior immunity against wild type virus. Accordingly, we will selectively modify the HSV genome to delete the Us3 gene. Furthermore, we will harness TBK1 to potentiate protection. With state of the art technology, we will investigate protective efficacy in relation to viral replication and latency. We will also explore the underlying mechanism(s) by which engineered HSV skews innate immunity in dendritic cells, which translates into protective immunity. The long-term goal of this research is the development of vaccines for prevention and therapy of HSV induced-diseases.
Herpes simplex virus 1 is a leading cause of blindness by an infectious agent in the developed countries. It is also responsible for encephalitis and genital herpes. This research is designed to develop a vaccine to prevent or treat herpes virus diseases.
| Pan, Shuang; Liu, Xing; Ma, Yijie et al. (2018) Herpes Simplex Virus 1 ?134.5 Protein Inhibits STING Activation That Restricts Viral Replication. J Virol 92: |
| Ma, Yijie; Chen, Min; Jin, Huali et al. (2017) An Engineered Herpesvirus Activates Dendritic Cells and Induces Protective Immunity. Sci Rep 7:41461 |
