Infectious Eye Diseases: Zoster Laboratory

Paul (Kip) R. Kinchington, PhD
Professor of Ophthalmology, Molecular Genetics and Biochemistry
The Campbell Laboratory for Infectious Eye Diseases
University of Pittsburgh School of Medicine

Lab Personnel

Michael Yee (Lab Manager and Sr. Research Technician)

Ben Warner, Graduate student, Program in Microbiology and Immunology

Betty Wu, Graduate student, Program in Microbiology and Immunology

Benjamin Treat, Graduate student, Molecular Virology and Microbiology

Lillian Laemmle, PhD, Post doctoral Research Associate.

Tianbing Yang, PhD, Post doctoral Research Associate

Shenghuo Tian, PhD, Post doctoral Research Associate and specialist in Molecular Biology

Research Interests

Paul (Kip) Kinchington, Ph. D. heads the Molecular Herpesvirus unit of the Campbell Laboratory of Infectious Diseases in The Department of Ophthalmology. His research addresses viruses that cause ocular complications and potential blindness, particularly Varicella Zoster Virus, the cause of Herpes Zoster (“Shingles”).

Herpes zoster is also known as “shingles”, a debilitating and crippling disease seen mostly in the elderly and in patients whose immunity is weakened by disease, cancer or its treatment. Zoster arises from within us when the human herpesvirus Varicella Zoster Virus (VZV) awakens from a quiet “latent” state that was established in a person’s sensory nerves during the childhood disease, “chickenpox”. Most people over 30 years old have VZV within us,  and a third will get zoster in their lifetime.  Zoster can have devastating consequences on vision and well-being, potentially infecting any part of the eye. For example, the cornea may become cloudy and onscure vision. It can also become totally numb, so that one does not sense it when there is damage to the front of the eye.  It can also destroy the retina and the means to transmit light to the brain, causing blindness, Finally there are a host of neurological problems that follow zoster that affect how we see, including tics, palsies, uncontrollable eye movements and most important, an intractable, debilitating and difficult-to-treat pain that may last for months to years.

Our group is one of only a few in the world that study VZV and its biology. The goals of our research are to understanding how VZV remains quiet in a person’s nerves for so long after chickenpox (usually decades), what makes the virus awaken and how the virus causes chronic, long lasting pain after zoster.  A huge step to studying these was our development of cultured model of human neurons, which is allowing us with an unprecedented look at what happens to VZV at the dormant ‘latency’ phase in human nerves.  We can now assess what must happen for the virus to reactivate, and seek means to target the mechanisms and keep the virus latent.  We use this same system to visualize virus moving along the nerves, which the virus does to reaches the skin and eye (and can be blocked).   

A second important development is our new animal models that are allowing us to study how VZV  causes pain.  The models are enabling us to address the underlying mechanisms, and also the testing of pain alleviating strategies that do not rely on problematic opioids or similar drugs with side effects.  Indeed, we now have a potetntial treatment strategy that could potentially allow the patient to tune their own relief by topical treatments. Given that zoster and the associated pain are important diseases of the elderly, and that pain is more likely to be more severe as one ages, our work could improve the quality of life of many patients that reach their twilight years.

Dr. Kinchington is also the Director of a Molecular Biology Core facility in the Department of Ophthalmology, which has long been supported by the National Eye Institute. This allows all vision researchers in Pittsburgh to use molecular biology applications and DNA/RNA manipulation in their research.

For more information on Dr Kinchington, please follow http://www.pmi.pitt.edu/person/paul-r-kip-kinchington-phd

 

Select Recent Publications

  1. Treat BR, Bidula, SM, St Leger, AS, Ramachandran SR, Hendricks RL, and Kinchington PR. Influence of an Immunodominant Herpes Simplex Virus Type 1 CD8+ T Cell Epitope on the Target Hierarchy and Function of Subdominant CD8+ T Cells" PLOS Pathogens, 2017 In Press
  2. Markus A, Golani L, Ojha NK, Borodiansky-Shteinberg T, Kinchington PR,Goldstein RS. Varicella Zoster virus expresses multiple small non-coding RNAs. J Virol. 2017 Oct 11. pii: JVI.01710-17. doi: 10.1128/JVI.01710-17. [Epub ahead of print] PubMed PMID: 29021397.
  3. Kramer PR, Stinson C, Umorin M, Deng M, Rao M, Bellinger LL, Yee MB, Kinchington PR. Lateral thalamic control of nociceptive response after whisker pad injection of varicella zoster virus. Neuroscience. 2017 Jul 25;356:207-216. doi: 10.1016/j.neuroscience.2017.05.030. Epub 2017 May 24. PubMed PMID: 28549561; PubMed Central PMCID: PMC5516953.
  4. Stinson C, Deng M, Yee MB, Bellinger LL, Kinchington PR, Kramer PR. Sex differences underlying orofacial varicella zoster associated pain in rats. BMC Neurol. 2017 May 17;17(1):95. doi: 10.1186/s12883-017-0882-6. PubMed PMID: 28514943; PubMed Central PMCID: PMC5436469.
  5. Rowe AM, Yun H, Treat BR, Kinchington PR, Hendricks RL. Subclinical Herpes Simplex Virus Type 1 Infections Provide Site-Specific Resistance to an Unrelated Pathogen. J Immunol. 2017 Feb 15;198(4):1706-1717. doi: 10.4049/jimmunol.1601310. Epub 2017 Jan 6. PubMed PMID: 28062697.
  6. McNulty J, D'Aiuto L, Zhi Y, McClain L, Zepeda-Velázquez C, Ler S, Jenkins HA, Yee MB, Piazza P, Yolken RH, Kinchington PR, Nimgaonkar VL. iPSC Neuronal Assay Identifies Amaryllidaceae Pharmacophore with Multiple Effects against Herpesvirus Infections. ACS Med Chem Lett. 2015 Nov 19;7(1):46-50. doi:10.1021/acsmedchemlett.5b00318. eCollection 2016 Jan 14. PubMed PMID: 26819664; PubMed Central PMCID: PMC4716588.
  7. Markus A, Lebenthal-Loinger I, Yang IH, Kinchington PR, Goldstein RS. An in vitro model of latency and reactivation of varicella zoster virus in human stem cell-derived neurons. PLoS Pathog. 2015 Jun 4;11(6):e1004885. doi: 10.1371/journal.ppat.1004885. eCollection 2015 Jun. PubMed PMID: 26042814; PubMed Central PMCID: PMC4456082.
  8. Grigoryan S, Yee MB, Glick Y, Gerber D, Kepten E, Garini Y, Yang IH, Kinchington PR, Goldstein RS. Direct transfer of viral and cellular proteins from varicella-zoster virus-infected non-neuronal cells to human axons. PLoS One. 2015 May 14;10(5):e0126081. doi: 10.1371/journal.pone.0126081. eCollection 2015. PubMed PMID: 25973990; PubMed Central PMCID: PMC4431828.
  9. Guedon JG , Zhang M, Glorioso JC, Goins WF and Kinchington PR. Relief of Pain Induced by Varicella Zoster Virus (VZV) in a Rat Model of Post-Herpetic Neuralgia using a Herpes Simplex Virus (HSV) Vector Expressing Enkephalin Gene Therapy In press
  10. Sloutskin A, Yee MB, Kinchington PR, Goldstein RS. Var4icella zoster virus and herpes simplex virus 1 can infect and replicate in the same neurons whether co-or superinfected. J Virology, 2014 In Press
  11. D'Aiuto L, Prasad KM, Upton CH, Viggiano L, Milosevic J, Raimondi G, McClain L, Chowdari K, Tischfield J, Sheldon M, Moore JC, Yolken RH, Kinchington PR, Nimgaonkar VL. Persistent Infection by HSV-1 Is Associated With Changes in Functional Architecture of iPSC-Derived Neurons and Brain Activation Patterns Underlying Working Memory Performance. Schizophr Bull. 2014 Mar 12. [Epub ahead of print] PubMed PMID: 24622295.
  12. Sloutskin A, Yee MB, Kinchington PR, Goldstein RS. Varicella zoster virus and herpes simplex virus type 1 can infect and replicate in the same neurons whether co- or superinfected. J Virol. 2014 Feb 26. [Epub ahead of print] PubMed PMID:24574392.
  13. Jones M, Dry IR, Frampton D, Singh M, Kanda RK, Yee MB, Kellam P, Hollinshead M, Kinchington PR, O'Toole EA, Breuer J. RNA-seq analysis of host and viral gene expression highlights interaction between varicella zoster virus and keratinocyte differentiation. PLoS Pathog. 2014 Jan 30;10(1):e1003896. doi: 10.1371/journal.ppat.1003896. eCollection 2014 Jan. PubMed PMID: 24497829; PubMed Central PMCID: PMC3907375.
  14. Depledge DP, Kundu S, Jensen NJ, Gray ER, Jones M, Steinberg S, Gershon A, Kinchington PR, Schmid DS, Balloux F, Nichols RA, Breuer J. Deep sequencing of viral genomes provides insight into the evolution and pathogenesis of varicella zoster virus and its vaccine in humans. Mol Biol Evol. 2014 Feb;31(2):397-409. doi: 10.1093/molbev/mst210. Epub 2013 Oct 25. PubMed PMID: 24162921; PubMed Central PMCID: PMC3907055.
  15. Sloutskin A, Kinchington PR, Goldstein RS. Productive vs non-productive infection by cell-free varicella zoster virus of human neurons derived from embryonic stem cells is dependent upon infectious viral dose. Virology. 2013 Sep 1;443(2):285-93. doi: 10.1016/j.virol.2013.05.021. Epub 2013 Jun 12. PubMed PMID: 23769240; PubMed Central PMCID: PMC3733239.

 

Contact Information

Paul Kinchington, PhD
412-647-6319
kinchingtonp@upmc.edu
EEINS-1016, 203 Lothrop Street,
Pittsburgh PA 15213