Centre for Virus Research

Lab head: Professor Anthony Cunningham
Location: The Westmead Institute for Medical Research, Westmead Hospital

An Australian centre for HIV and Hepatitis Vilrology research, Westmead Millennium Institute, and one of the premier HIV reasearch laboratories in Australia.

How do herpes simplex viruses interact with dendritic cells in human skin: clues for vaccine development

Primary supervisor: Anthony Cunningham

Herpes Simplex Virus (HSV) can cause cold sores, genital herpes, keratitis, encephalitis and neonatal herpes, as well as increasing the risk of acquiring HIV by at least 3-fold. 70-80% of the Australian population is infected with HSV-1 and 12% with HSV-2. Once it infects the body, it persists throughout life. There is no vaccine available yet. Understanding HSV infection of genital skin/mucosa and its interactions with skin dendritic cells (DCs) is of key importance in elucidating how HSV specific CD4 and CD8 T cells are activated and home to the infected lesion and persist at the site of infection between lesions to eradicate infection. It is now known that the interaction between various classes of DCs in the skin is required for this process.

We have developed a unique model of HSV infected human foreskins, which shows the direct interaction between HSV infected epidermal LCs and dermal DCs, never before studies in the skin/mucosa of humans. Using this model, we have shown that HSV infects Langerhans cells (LCs) in the epidermis, which results in LCs undergoing a novel mode of apoptosis and viral transfer to three subsets of dermal DCs. In mice, it is known that these dermal DCs then exit the dermis and travel to lymph node.

This project will investigate the chemokines and cytokines that HSV infected LCs produce to attract dermal DCs, as well as discover the role of a newly identified epidermal DC subset in response to HSV infection and interaction with the other DC subsets. This study will provide fundamental understanding of how innate immune cells in skin epidermis and dermis cooperate in response to HSV, and may contribute to development of HSV vaccine candidates, particularly through comparisons between this study and parallel studies on the action of vaccine adjuvants.

Techniques to be used: Isolation of immune cell subsets from human tissue, FACS sorting and flow cytometry, cell culture, viral culture, ELISA, multiplexed cytokine and chemokine assays, chemotaxis/cell migration assays and blocking assays, skin explant culture/infection, immunofluorescence microscopy.

Discipline: Applied Medical Sciences, Westmead
Co-supervisors: Andrew Harman, Kerrie Sandgren, Naomi Truong
Keywords: Dendritic cells, Virus diseases, Herpes simplex virus