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, MPH, Lab Manager and Sr. Research Technician
Ben Warner, MS, Graduate Student, Program in Microbiology and Immunology
Betty Wu, MS, Graduate Student, Program in Microbiology and Immunology
Tianbing Yang, PhD, Research Specialist
Shenghuo Tian, PhD, Research Scientist in Molecular Biology

Research Interests

Paul (Kip) Kinchington, Ph. D. heads the ‘Molecular Herpesvirus’ section of the Campbell Laboratory of Infectious Diseases in The Department of Ophthalmology. His research addresses viruses that cause eye infections, particularly Varicella Zoster Virus (VZV), the cause of Herpes Zoster (“Shingles”), and herpes simplex virus (HSV-1).

Dr Kinchington is recognized as a world expert on VZV and the diseases it causes.  The importance to vision comes from “Shingles”, a debilitating and crippling disease that is most often seen in the elderly and in patients whose immunity is weakened by disease, cancer or its treatment.  The disease arises from within, when 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 them and a third will get zoster in their lifetime.  It can have devastating consequences to vision when it occurs on the head. The eye becomes infected and the diseases that develop can be blinding.  The cornea may become cloudy and obscure vision: it can also become totally numb, so that it does not sense touch or damage to the cornea.  VZV can also destroy the retina quickly, or set up a painful inflammatory disease that can last months to years.  Last but not least, a host of neurological problems can develop that reduce quality of life and how we see, including tics, palsies, uncontrollable eye movements and an intractable, debilitating and difficult-to-treat pain.

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 human neurons, which allowing us to take an unprecedented look at the silent dormant state in human nerves.  We can now assess the events that lead to virus reawakening.  We are targeting those underlying mechanisms and keep the virus latent to zoster does not develop. We use this same system to visualize virus moving along the nerve axons, which virus must do to reach and infect the eye.   

A second important development is our new animal models that are allowing us to study how VZV causes pain.  These are being used to test new anti-pain strategies that do not rely on problematic opioids or drugs with serious side effects.  Indeed, we now have a potential treatment strategy that could allow the patient to tune their own relief by topical treatments. 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. Bisht P, Das B, Kinchington PR, Goldstein RS. VZVsncRNA antisense to the VZV latency-encoded transcript VLT enhance viral replication. J Virol. 2020 Apr 15:JVI.00123-20. doi: 10.1128/JVI.00123-20. Epub ahead of print. PMID: 32295909.
  2. Treat BR, Bidula SM, St Leger AJ, Hendricks RL, Kinchington PR. Herpes Simplex Virus 1-Specific CD8+ T Cell Priming and Latent Ganglionic Retention Are Shaped by Viral Epitope Promoter Kinetics. J Virol. 2020 Feb 14;94(5):e01193-19. doi: 10.1128/JVI.01193-19. PMID: 31826989; PMCID: PMC7022356.
  3. Carroll KL, Avery L, Treat BR, Kane LP, Kinchington PR, Hendricks RL, St Leger AJ. Differential Expression of Immune Checkpoint Molecules on CD8+ T Cells Specific for Immunodominant and Subdominant Herpes Simplex Virus 1 Epitopes. J Virol. 2020 Jan 6;94(2):e01132-19. doi: 10.1128/JVI.01132-19. PMID: 31645447; PMCID: PMC6955272.
  4. Laemmle L, Goldstein RS, Kinchington PR. Modeling Varicella Zoster Virus Persistence and Reactivation - Closer to Resolving a Perplexing Persistent State. Front Microbiol. 2019 Jul 24;10:1634. doi: 10.3389/fmicb.2019.01634. PMID: 31396173; PMCID: PMC6667558.
  5. Stinson C, Logan SM, Bellinger LL, Rao M, Kinchington PR, Kramer PR. Estradiol Acts in Lateral Thalamic Region to Attenuate Varicella Zoster Virus Associated Affective Pain. Neuroscience. 2019 Aug 21;414:99-111. doi:10.1016/j.neuroscience.2019.06.029. Epub 2019 Jul 2. PMID: 31271831; PMCID: PMC6944200.
  6. D'Aiuto L, Bloom DC, Naciri JN, Smith A, Edwards TG, McClain L, Callio JA, Jessup M, Wood J, Chowdari K, Demers M, Abrahamson EE, Ikonomovic MD, Viggiano L, De Zio R, Watkins S, Kinchington PR, Nimgaonkar VL. Modeling Herpes SimplexVirus 1 Infections in Human Central Nervous System Neuronal Cells Using Two- and Three-Dimensional Cultures Derived from Induced Pluripotent Stem Cells. J Virol.2019 Apr 17;93(9):e00111-19. doi: 10.1128/JVI.00111-19. PMID: 30787148; PMCID:PMC6475775.
  7. Kramer PR, Rao M, Stinson C, Bellinger LL, Kinchington PR, Yee MB. Aromatase Derived Estradiol Within the Thalamus Modulates Pain Induced by Varicella Zoster Virus. Front Integr Neurosci. 2018 Oct 12;12:46. doi: 10.3389/fnint.2018.00046. Erratum in: Front Integr Neurosci. 2019 Jan 31;12:66. PMID: 30369871; PMCID: PMC6194186.
  8. Treat BR, Bidula SM, Ramachandran S, St Leger AJ, Hendricks RL, 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 Pathog. 2017 Dec 4;13(12):e1006732. doi: 10.1371/journal.ppat.1006732. PMID: 29206240; PMCID: PMC573622
  9. 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.
  10. 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.
  11. 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.

 

Contact Information

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