The Centre for Perinatal Infection Research, Discipline of Paediatrics and Child Health, Kids Resarch Institute, Childrens at Westmead

Lab head: Professor Cheryl Jones
Location: The Children's Hospital Westmead

Our vision is to reduce the impacts of important perinatal viral infections and (re)emerging infectious diseases, and on infants and children by leadership of a collaborative translational research programme and by capacity building of clinician researchers (as described under Research Supervision and Mentoring), especially in the Asia-Pacific Region. Our affiliations and participation with in the University of Sydney Sydney Emerging Infectious Diseases and Biosecurity Institute (SEIB), and the newly awarded NHMRC Clinical centre for research excellence in Critical infections has enabled the Centre to develop research programs into emerging childhood diseases while at the same time building on our previous strengths of perinatal infections. The Centre for Perinatal Infection laboratory undertakes studies of viral immunopathogenesis using animal models of important viral infections in children, particuarly herpes simplex virus (HSV).

Lab members: C Jones (acad), A Ferguson (general), M Fernandez (affiliate) C Raynes Greenow (Acad) D Hanlon (general)
Funding: NHMRC project grant
Research approach equipment: Our laboratory uses a murine model of herpes simplex virus (HSV), to understand the parameters for immune protection against viruses in the skin and to define age-dependant differences in neonatal innate and adaptive antiviral immunity.

FK. Puttur, MA. Fernandez, R White, B Roediger, AL. Cunningham, W Weninger, & CA Jones. HSV infects skin γδ T cells before Langerhans cells, and impedes migration of infected LC by inducing apoptosis and blocking E-Cadherin downregulation. J Immunol. 2010;185:477-87

MA Fernandez, Puttur FK, YM Wang, Howden W, SI Alexander, CA Jones. T Regulatory Cells Contribute to the CD8+ and CD4+  T Cell Responses to Herpes Simplex Virus Type 2 in Neonatal Mice. J Immunol. 2008;180(3):1556-64.

Fernandez MA, Evans IC, EH HAssan, Carbone F, Jones  CA Neonatal CD8+ T cells are slow to develop into lytic effectors after HSV infection in vivo. Eur J Immunol 2008 Immunology, 38: 102-113. *cited in: “Newborn CD8+ T cells are slow off the mark after HSV infection”. In this Issue  Eur J Immunol. 2008 Jan;38(1):p.10

Comparing the effects of HSV cutaneous infection on the migration and function between skin gamma delta T cells in the murine epidermis and dermis in vivo

Primary supervisor: Cheryl Jones

The skin is the largest organ of the body and provides the first line of defence against many infections including herpes simplex virus. HSV enters the body through breaks in the skin or mucosa where it first encounters immune effectors within the skin. Understanding the immunological
mechanisms that govern protective cutaneous immunity e is critical to the development of vaccines, antivirals and topical microbicides. Our laboratory uses a murine model of herpes simplex virus (HSV), to understand the parameters for immune protection against viruses in the skin and to define age-dependantdifferences in antiviral immunity.T cell receptor γδ cells (γδ T cells) are a minor population of circulating T cells. Although they have been found in increased numbers in tissues during the course of several viral infections including HSV, their precise role remains unknown.  Recently, we have made the key observation using fluorescent HSV strains that γδ T cells are infected HSV shortly after skin infection.  In this project, we will extend our studies to compare changes in morphology, kinetics of migration and viability of HSV infected and bystander epidermal and dermal gdT cells in the ear skin after cutaneous HSV infection in mice.Utilising ear skin of adult mice in which skin gdT cellsare GFP+ (B6.CXCR6) we will visualise the juxtaposition and movement of skin gdT cells in the epidermis and dermis after acute HSV infection. Confocal microscopy observations will be confirmed by selected immunohisto-chemistry and histological studies.Techniques to be used: Virus preparation, Virus titration, cell culture, mouse inoculation, preparation of single cell suspensions dermal and epidermal sheets from mouse skin, immunofluorescence and confocal microscopy of murine skin, RT-PCR, immuno-histochemistry and evaluation of histopathology.

Discipline: Infectious diseases and Immunology
Co-supervisors: Angela Ferguson
Keywords: Virology, immunobiology, Herpes simplex virus