Herpes Neuropathogenesis Group

Around 80 per cent of Australian adults are infected with herpes simplex virus (HSV-1). The virus causes lifelong infection by laying dormant in sensory nerve cells and, in most cases, it causes mild or no symptoms.  However, in immuno-compromised patients and infants, the virus can cause painful and life-threatening infection that can spread throughout the body. While symptoms can be reduced with antiviral treatment, there is no cure for HSV-1 infection.

We study how the virus invades and replicates in nerve cells. We have developed techniques to visualise the virus in nerve cells using fluorescence imaging and electron microscopy. This is helping us to understand how the virus enters and travels along nerve cells and then exits the tip of the nerve to invade skin cells.

The group’s research focuses on the elucidation of the mechanisms of Herpes simplex virus type 1 (HSV-1) transport and exit from sensory nerves to define how HSV-1 spreads from nerves to the skin or mucosa during recurrent herpes. The work aims to develop new antiviral strategies for the treatment and control of recurrent herpes.  The lab has established several in vitro models for HSV-1 infection of primary human and rat sensory neurons for in vitro viral and nerve imaging including confocal, electron and immunoelectron microscopy, proteomics and molecular virology.

The group’s work advances understanding of viral behavior within host systems, with implications for the development of novel antiviral therapies and strategies to enhance immune responses. By unraveling mechanisms of viral transport, assembly, and immune evasion, the research contributes to improving treatments for viral neuropathies and infections that compromise the immune system.

Key Research Areas

  • Mechanisms of Viral Transport in Neurons:
    • Investigation into the anterograde and retrograde transport of HSV in human and rat dorsal root ganglion neurons.
    • Elucidation of the role of cytoskeletal components and molecular motors, such as kinesin and dynein, in the intracellular transport of viral proteins and capsids.
    • Understanding tegument formation and transport dynamics in neuronal cell bodies.
  • Immune System-Virus Interactions:
    • Study of HSV’s effects on dendritic cells, including rapid cell death, functional impairment, and cross-presentation via uninfected dendritic cells.
    • Examination of HIV uptake, processing, and two-phase transfer within human dendritic cells, shedding light on immune evasion mechanisms.
  • Host-Virus Molecular Interactions:
    • Characterization of HSV tegument protein US11’s interaction with conventional kinesin and the role of capsid protein VP26 in retrograde transport.
    • Investigation of molecular interactions that drive viral assembly and transport within infected cells.
  • Viral Pathogenesis and Immune Evasion:
    • Analysis of HSV-induced apoptosis in dendritic cells and its implications for immune evasion and cross-presentation.
    • Study of viral synergism in HIV co-infections, offering insights into enhanced pathogenesis.
  • Kevin Denastas: Postdoctoral Research Scientist
  • Daisy Wu: Research Assistant

 

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