Paul Kinchington

Summary

Dr. Kinchington’ s research program focuses on the biology of the human alpha-herpesvirus Varicella Zoster Virus (VZV) and its interaction with human neurons and skin using novel model systems. VZV causes Chickenpox upon primary infection, but then remains with the host for life in a latent state in sensory neurons. When the Virus reactivates, it causes Herpes Zoster or Shingles, a painful and debilitating disease that causes significant human morbidity and long-term consequences. Chief among those is the development of long-term, intractable and debilitating chronic pain called post-herpetic neuralgia, or PHN. Zoster also causes many eye diseases that affect vision and even cause blindness, including stromal and retinal disease, ocular inflammation, ophthalmoplegia and total loss of corneal sensation.  Zoster is a major side consequence of many types of cancer or their treatment, particularly when either cause immune suppression. 

Our research addresses two aspects of VZV. The first uses human cultured neurons to understand axonal transport of viruses in neurons, the maintenance of the latent state and reactivation from it.  We aim to identify the role of a set of RNAs made during latency termed VLT (For VZV latency Transcript) using human neuron cultures derived in vitro by differentiation of human stem cells or progenitors. We established this system as a solid experimental model in which VZV reactivation could be reliably achieved. A second VZV project is to identify the molecular determinants of the attenuation of the widely used live attenuated VZV vaccine, currently used to prevent chickenpox. While quite safe, the vaccine is not perfect, as  it often causes a rash, can cause full-blown chickenpox, and also go latent. It can give rise to Zoster in vaccinees.  We are evaluating how some of the 200+ changes in the vaccine (compared to its parent) contribute to attenuation, but placing them into a wild type virus background and assessing how the recombinant virus grows in validated human skin models and human neuron systems. Together, we may be able to develop an improved vaccine candidate that does not cause skin disease or reactivate to cause zoster.