Human herpes virus

Infections by the human herpes viruses, herpes simplex virus-1 (HSV-1) and varicella zoster virus (VZV), causing common cold sores and chicken pox respectively, are among the most common childhood infections. Although they usually cause mild disease, very rarely, infections can be life threatening. One such rare but serious complication is a brain infection known as encephalitis.

Although the reasons why VZV encephalitis affect otherwise healthy children remain unknown, childhood herpes simplex encephalitis (HSE) is known to result from genetic deficiencies of a particular antiviral pathway (the TLR3-IFN pathway).

Patients with these deficiencies are unable to produce protective factors following virus infection. Recently, genes in this pathway were found to play a role in another cellular process called autophagy. Autophagy is involved in the recycling of damaged cellular components, and in elimination of unwanted viral infections. It is especially important in specialised cells such as brain cells where infected cells must survive to limit the risk of brain or nerve damage. However, the role of autophagy has not been studied in HSE or VZV encephalitis patients.

Dr Sancho-Shimizu will investigate the role that autophagy plays in preventing brain damage caused by HSV1 and VZV infections. She will study the process of autophagy following viral infection in these patients’ brain cells to understand its role in disease. Vanessa will use a state-of-the-art method of culturing skin cells into brain cells to study patients’ brain cells in a non-invasive manner.

She plans to identify new genes involved in disease by sequencing DNA from a collection of HSE and VZV encephalitis patients. In a parallel approach she will use a novel zebrafish model of HSV1/VZV infection, a model which will allow her to watch the progression of whole-body infection in realtime to test deficiencies that she identifies n her patients. The identification of genes involved in this pathway will improve understanding of human herpes virus infections.

It is hoped that results from this study may lead to the development of new drug targets for HSV/VZV. It may also lead to the evelopment of therapies in the prevention of brain or nerve damage which remains a major cause of morbidity in HSV1/VZV diseases.