The Herpes Research Laboratory at the Institute of Medical and Veterinary Science has a long-standing history and success in the field of herpes simplex viruses and their immunopathogenesis. Our special interest is herpes simplex virus and means by which it manipulates host immune responses in the peripheral nervous system, thus enabling its persistence and establishment of latency.

Herpes simplex virus (HSV) is a highly successful pathogen that has adapted to persist within neurons in humans. While over 90% of individuals are persistently infected, their nervous systems usually suffer little or no resulting ill-effects, even though this virus is noted for its destructive qualities in cell culture. In rare cases, HSV has been associated with severe (and sometimes fatal) disease states in eyes and the nervous system. However, implicit in our understanding of pathogenesis of HSV is that infected neurons are not destroyed by the host’s immune response.

Natural infection with HSV involves skin and the nervous system. Primary sensory neurons are the target for HSV and may undergo productive or latent infection. Productive infection of sensory neurons generates potential for lethal spread virus through the nervous system, but in immunocompetent hosts, viral replication is rapidly terminated by timely development of an adaptive immune response.

We have previously demonstrated that clearance of infectious virus from the nervous system is dependent on CD8⁺ cells but, paradoxically, not destruction of infected neurons, which unlike surrounding satellite and Schwann cells, do not express MHC class I antigens. Our detection, however, of transcripts resembling MHC class I mRNA in neurons and their upregulation on HSV infection, lead us to hypothesise that they encode non-classical MHC-like molecules.

We therefore investigated the role of CD1, an MHC-like molecule, in HSV-1 pathogenesis. CD1 has well-characterised antigen presenting functions, has high homology with MHC class I and II molecules, and presents lipid and glycolipid antigens to a subset of T cells known as NK-T cells. The interaction of antigen in the context of CD1 molecules with NK-T cells results in production of large amounts of cytokines. These NK T cells are thought to be potent activators of cells belonging to the adaptive immune response.

Our recent data on knockout mice indicate that CD1 and NK-T cells have a focal role in clearance of HSV-1 from skin and PNS of infected mice. This involvement of CD1 and NK-T cells in immunity to HSV is novel and exciting in view of the known role of CD1 to present lipid antigens. Ultimately the involvement of CD1 in immunity to HSV may create a new paradigm for viral immunity.

There is an opportunity in our lab for an Honours project aimed at investigating the expression of CD1 in skin and PNS during acute HSV-1 infection. Expression of CD1 has been detected in the central nervous system, thus its detection in the PNS would be groundbreaking. The Honours student would also enjoy strong support in the lab from a PhD student working on CD1 in HSV immunopathogenesis. There is strong collaboration with University of Texas Medical Branch, Northwestern University in Chicago, Monash University, Peter MacCallum Cancer Institute in Melbourne and University of Melbourne.

The project would involve generating HSV virus stocks, cell culture work, in vivo animal work, processing of tissues, fluorescent immunohistochemistry, confocal microscopy, northern blotting, western blotting, RT-PCR and in situ hybridisation.

This laboratory has had great success with Honours and PhD students. Previous students have obtained post-doctoral positions at Stanford University, Cambridge University, Oxford University, Northwestern University in Chicago and the US National Institutes of Health, from where many have gone on to become senior research scientists in the USA and Australia.