A Conversation With Dr. Kinchington
Kip Kinchington, PhD has long been interested in the viruses that cause infections of the eye that can cause blindness. I started in the Department of Ophthalmology at Pitt at the beginning of 1991, because at that time there was a suspected big breakthrough in understanding how the herpesvirus herpes simplex virus (HSV) might switch between active growth, in which more virus is made and the virus inflicts repeated damage to cause recurrent eye diseases: and a quiet dormant state, in which the virus hides in nerves for the life of the host (also caused latency). I was a molecular virologist with experience in the much less understood herpesvirus Varicella zoster virus (VZV), which causes potentially devastating diseases of the eye during shingles. I felt the opportunity was ripe to combine molecular virology with ophthalmology. In addition to my research on VZV, I have worked on other viruses that cause eye disease, including adenoviruses (which cause infectious pink eye), herpesviruses (causing blinding stromal keratitis and anesthetic corneas), and some RNA viruses in the eye.
I was also excited by the opportunity to collaborate at Pitt. First with Dr Jerry Gordon, who was studying HSV ocular disease using animal models, who had lots of ideas, but little experience in molecular virology. Secondly, I would be directing a Molecular Biology core module of the NEI funded CORE grant EY08098 , something I have done now since (for 30 years). It allowed me to help many other researchers in vision, since the facility provides services and expertise to NEI funded researchers and Investigators. I knew how to manipulate DNA and RNA, make recombinant viruses and /or virus based expression systems, and have continually kept it up-to date so that I and the module can guide vision researchers in the ever-evolving methods, kits and techniques that are used in molecular biology and for transcriptome expression.
My passion with VZV is to understand how it grows to cause eye diseases and the problems associated with Shingles. I have three different projects. The first is address why VZV causes the pain and post herpetic neuralgia that often follows a bout of Shingles. We developed an exciting new facial model that mimics the pain seen in facial shingles that involves the eye, causing ocular pain. We are using it to test new pain relieving treatments. The second is to understand how the virus infects and co-operates with neurons and nerve cells to stay quiet, and then awaken to cause Shingles. The virus hides in neurons for decades, and then awakens to cause shingles (and eye disease if it’s on the head). We developed a new cultured human neuron platform to examine how virus spreads and moves up and down neurons to get from the eye to the nerve cell bodies in the ganglia. We are even testing ways to remove the latent virus from neurons using CRSPR-cas9. Finally we have projects to investigate why the live virus used in the vaccines are attenuated. If we know the cause of attenuation, we could improve the vaccines so it does not have the occasional problems associated with current vaccination.
1986-1990 Research Instructor, Dept. of Biochemistry, Uniformed Services University of the Health Sciences, Bethesda, MD
1991-1996 Assistant Professor, Dept. of Ophthalmology, University of Pittsburgh School of Medicine, and Dept. of Molecular Genetics & Biochemistry, University of Pittsburgh School of Medicine, Pittsburgh, PA
1996-2011 Associate Professor, Depts. of Ophthalmology and of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, Pittsburgh, PA.
2011- current Professor, Depts of Ophthalmology and Molecular Microbiology and Genetics, University of Pittsburgh
1991- current Director, Molecular Biology and Gene expression/array Module CORE Facility
Education & Training
- University of Leeds, Leeds, England 1979, Microbiology, B.Sc.(Honors)
- University of Leeds, Leeds, England 1983, Microbiology, Ph.D.
- Uniformed Services University of The Health Sciences, Bethesda MD Post docotoral fellowship (1983-1986)
1: 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 Jun
11. doi:pii: S0042-6822(13)00301-2. 10.1016/j.virol.2013.05.021. [Epub ahead of
print] PubMed PMID: 23769240.
2: 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.
3: 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
4: 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.
5: 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.
6: 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.
7: 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.
8: 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.
9: 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.
10: Walters MS, Kinchington PR, Banfield BW, Silverstein S. Hyperphosphorylation
of histone deacetylase 2 by alphaherpesvirus US3 kinases. J Virol. 2010
Oct;84(19):9666-76. doi: 10.1128/JVI.00981-10. Epub 2010 Jul 21. PubMed PMID:
20660201; PubMed Central PMCID: PMC2937806.
Recent Book Chapters
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 PMID: 20186610
Kinchington PR and A Abendroth. Immunity and immune evasion in varicella zoster virus. In “The alphaherpesviruses” 2nd Edition, Ed by S Weller (Published Mar 2011) Caister Academic Press
Abendroth A, P. R. Kinchington and B Slobedan. Immune evasion strategies employed by varicella zoster virus. Current Topics in Microbiology and Immunology 2010 342, 155-172 PMID: 20563710
Kinchington PR. CNS infections by Varicella Zoster Virus- Chapter in “Virus in CNS disease”
Ed By S. Singh, Taylor Publishing
Infectious Eye Diseases: Zoster Laboratory
NIH:- NEI RO1 EY015291 Kinchington (PI)
Gene expression in HSV-1 latency after corneal infection 03-01-2004 to 06-30-2014. The goal is to determine how the cellular immune system can be manipulated in the latently infected trigeminal ganglia to provide better protection from HSV-1 reactivation.
NIH:- NINDS R01 NS064022, Kinchington (PI)
"A rat model for Varicella Zoster Virus induced post herpetic neuralgia” 1-15-2009 to 12-30-2013. The work in this program aims to identify the mechanisms underlying the ability of VZV to induce long term behavioral responses indicative of pain. The project also aims to develop VZV mutants that lack the ability to induce pain, and uses novel viral delivery strategies to suppress the pain induced by VZV.
NIH:- NINDS R21 NS082662 Kinchington (PI)
A New in vitro model of axonal transport and latency of VZV. 03-01-2013-02-28-2015 The Project uses peripheral neurons developed from human embryonic stem cells, induced pluripotent stem cells and neural progenitor lines in conjunction with fluorescent reporter VZV to track virus nuclecapsid transport in axons as well as monitor latency and persistence.
NEI P30 EY08098 04/01/04-03/31/19)
"Core Grant For Vision Research" The Core Grant will provide support for the five centralized research modules including Histiology/Tissue Culture, Molecular Biology and Gene array, Flow Cytometry, Fabrication, and Image acquisition and analyses. Dr Kinchington is Director o9f the Molecular Biology and Gene array Module