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Paul Kinchington

Paul Kinchington

Program: Cancer Virology

412-647-6590 Eye and Ear Institute
203 Lothrop Street, Room 1016
Pittsburgh PA

Dr. Kinchington's research program addresses the biology of two human alpha-herpesviruses (VZV and HSV) and their interaction with neurons in model systems. Both infect most of the human population, and have developed means to persist in the host sensory neurons, only to later reactivate and cause further disease that leads to significant human morbidity. Work is primarily focused on varicella-zoster virus (VZV), which causes chickenpox upon primary infection and the debilitating herpes zoster ("shingles") when the virus reactivates from latency. Zoster develops on a third of those infected with VZV, and most cases are painful. However, 30% develop long-term, intractable and debilitating chronic pain (post-herpetic neuralgia, or PHN) which is difficult to treat. Many neurological diseases, paralyses and brain infarctions are caused by VZV, and neurological problems may affect vision and cause blindness, such as stromal and retinal diseases, inflammation and ophthalmoplegia. Our work addresses two aspects of VZV. One addresses a model of VZV-induced pain in the rat, as a model of PHN. The model is not only used to address how VZV induces pain, but also to test new strategies for pain alleviation. A second VZV research program is using an in vitro model of VZV-human neuron interactions to address axonal transport and latency. The model uses human neurons derived in vitro from human stem cells and progenitors. We also study herpes simplex virus type 1 (HSV-1), which may repeatedly reactivate from latency and cause problematic recurrent diseases, such as blinding stromal keratitis. Using an HSV-1 mouse ocular infection model, we are seeking to evaluate and augment the blocking of reactivation of HSV-1 by the cellular immune response at the sensory nerve ganglion. Currently, we are determining the parameters required to modulate and improve the function, number and effectiveness of CD8 T cells that infiltrate the latently infected ganglia. This includes determining those viral proteins that are targeted by cellular immunity, and the factors governing HSV targets of immunodominance.

Research Interests and Keywords
  • herpes simplex virus
  • HSV
  • infectious eye disease
  • neuronal infection
  • pain and post-herpetic neuralgia
  • varicella
  • viral infection
  • viral latency
  • VZV
  • zoster
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