Infectious Eye Diseases: Zoster Laboratory

Paul (Kip) R. Kinchington, PhD
Associate 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)
Benjamin Treat (MVM Graduate student)

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 (also known as “shingles”) is a debilitating and crippling disease seen mostly in the elderly and in patients whose immunity is weakened by disease, cancer or treatment. Zoster is not “caught” from someone else, but rather arises from within us when the 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 adults over 30 have VZV within us and a third will get zoster in our lifetimes. Zoster can have devastating effects on vision. It may induce a cloudy cornea that reduces vision: it can destroy the retina and the means to see light at the back of the eye; It may make the cornea totally numb (atrophic cornea), resulting in blinding eye wounds and damage from simple tasks such as applying eye drops: And it can cause a host of drastic neurological problems that affect the eye and means to see. These include 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. Our research is geared to understanding how VZV remains quiet in a person’s nerves for so long (decades), what makes it awaken, and why the virus causes so much pain when it causes zoster. First, we have developed a tissue culture model of human neurons that is allowing us an unprecedented look at what happens to the virus at the dormant ‘latency’ phase in nerves and the factors are that awaken the virus from this state. We have also been able to use this same system to visualize the virus moving along the nerves and understand how it reaches the skin and eye (and can be blocked). Secondly, we have developed a model that is allowing us to address why VZV causes so much pain. This model is not only enabling us to address the mechanisms by which pain is induced, but is also allowing us to test and develop better strategies to treat or even prevent pain associated with zoster. These lines of research could well establish a highly novel approach to treatment that could give long lasting relief to patients with zoster and chronic pain. 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 Director of Molecular Biology facilities in the Department of Ophthalmology, which is an NEI funded and sponsored core facility to aid the programs of all vision researchers in Pittsburgh in cloning, DNA and RNA manipulation, development of vectors to express proteins, and bioinformatics analyses of large datasets assessing gene expression.

For more information, please follow visit Molecular Virology and Microbiology Program

Select Recent Publications

  1. 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
  2. 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
  3. 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.
  4. 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.
  5. 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.
  6. Kinchington PR. Targeting Host Pathways to Block HSV-1 at the Cornea. Invest Ophthalmol Vis Sci. 2014 Feb 3;55(2). pii: 716. doi: 10.1167/iovs.14-13879. PubMed PMID: 24492207.
  7. 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.
  8. 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.
  9. Swamynathan S, Buela KA, Kinchington P, Lathrop KL, Misawa H, Hendricks RL, Swamynathan SK. Klf4 regulates the expression of Slurp1, which functions as an immunomodulatory peptide in the mouse cornea. Invest Ophthalmol Vis Sci. 2012 Dec 19;53(13):8433-46. doi: 10.1167/iovs.12-10759. PubMed PMID: 23139280. 
  10. Grigoryan S, Kinchington PR, Yang IH, Selariu A, Zhu H, Yee M, Goldstein RS. Retrograde axonal transport of VZV: kinetic studies in hESC-derived neurons. J Neurovirol. 2012 Dec;18(6):462-70. doi: 10.1007/s13365-012-0124-z. Epub 2012 Aug 24. PubMed PMID: 22918852; PubMed Central PMCID: PMC3556991.
  11. Kinchington PR, Leger AJ, Guedon JM, Hendricks RL. Herpes simplex virus and varicella zoster virus, the house guests who never leave. Herpesviridae. 2012 Jun 12;3(1):5. doi: 10.1186/2042-4280-3-5. PubMed PMID: 22691604; PubMed Central PMCID: PMC3541251.
  12. Dukhovny A, Sloutskin A, Markus A, Yee MB, Kinchington PR, Goldstein RS. Varicella-zoster virus infects human embryonic stem cell-derived neurons and neurospheres but not pluripotent embryonic stem cells or early progenitors. J Virol. 2012 Mar;86(6):3211-8. doi: 10.1128/JVI.06810-11. Epub 2012 Jan 11. PubMed PMID: 22238301; PubMed Central PMCID: PMC3302301.
  13. Kinchington PR, Goins WF. Varicella zoster virus-induced pain and post-herpetic neuralgia in the human host and in rodent animal models. J Neurovirol. 2011 Dec;17(6):590-9. doi: 10.1007/s13365-011-0069-7. Epub 2011 Dec 28. PubMed PMID: 22205584; PubMed Central PMCID: PMC3946975.
  14. Markus A, Grigoryan S, Sloutskin A, Yee MB, Zhu H, Yang IH, Thakor NV, Sarid R, Kinchington PR, Goldstein RS. Varicella-zoster virus (VZV) infection of neurons derived from human embryonic stem cells: direct demonstration of axonal infection, transport of VZV, and productive neuronal infection. J Virol. 2011 Jul;85(13):6220-33. doi: 10.1128/JVI.02396-10. Epub 2011 Apr 27. PubMed PMID: 21525353; PubMed Central PMCID: PMC3126485.
  15. Erazo A, Yee MB, Banfield BW, Kinchington PR. The alphaherpesvirus US3/ORF66 protein kinases direct phosphorylation of the nuclear matrix protein matrin 3. J Virol. 2011 Jan;85(1):568-81. doi: 10.1128/JVI.01611-10. Epub 2010 Oct 20. PubMed PMID: 20962082; PubMed Central PMCID: PMC3014177.
  16. Ramachandran S, Davoli KA, Yee MB, Hendricks RL, Kinchington PR. Delaying the expression of herpes simplex virus type 1 glycoprotein B (gB) to a true late gene alters neurovirulence and inhibits the gB-CD8+ T-cell response in the trigeminal ganglion. J Virol. 2010 Sep;84(17):8811-20. doi: 10.1128/JVI.00496-10. Epub 2010 Jun 23. PubMed PMID: 20573821; PubMed Central PMCID: PMC2919033.
  17. Erazo A, Kinchington PR. Varicella-zoster virus open reading frame 66 protein kinase and its relationship to alphaherpesvirus US3 kinases. Curr Top Microbiol Immunol. 2010;342:79-98. doi: 10.1007/82_2009_7. Review. PubMed PMID: 20186610; PubMed Central PMCID: PMC3936600.

Contact Information

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