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Andrew Jerome, Bala Burugula, Subhash Gaddipati, Pushpa Rao, Susmit Suvas; Evaluation of the neuropeptide expression profile in the trigeminal ganglia after corneal herpes simplex virus 1 infection in C57BL/6 mice. Invest. Ophthalmol. Vis. Sci. 2017;58(8):3624. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Corneal herpes simplex virus-1 (HSV-1) infection leads to retrograde transport of the virus to the trigeminal ganglia (TG). As a result, immune cells infiltrate the TG to establish and maintain a latent HSV-1 infection in neuronal soma. However, the outcome of neuronal HSV-1 infection on the TG microenvironment, and its role in the establishment and maintenance of HSV-1 latency isn’t well known. In this study, we quantitated the expression of several neuropeptides and neurotrophic factors (NTFs) in TGs during productive and latent HSV-1 infection. Also, the effect of the absence of neurokinin-1 receptor (NK1R), the highest affinity receptor of the neuropeptide substance P (SP), on the establishment of latent HSV-1 infection was determined.
Mild corneal scratching was carried out prior to topical application of PBS only (scratch control) or infectious HSV-1. TGs were isolated at different time-points post-infection (p.i). Reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) was carried out on TGs to quantitate neuropeptide, NTF, and latency associated transcript (LAT) expression. NK1R knockout (KO) mice were used to ascertain the effect of the absence of NK1R on latent HSV-1 infection. Flow cytometry was used to measure the T cell response to HSV-1 infection in C57BL/6 (B6) and NK1R KO mice. ELISA and protein array were carried out to compare the level of cytokines in TGs isolated from infected B6 and NK1R KO mice.
Our data demonstrates a differential expression of galanin, somatostatin, SP, CGRP, PACAP, NGF, BDNF, CNTF, and NTF3 in TGs at different time-points p.i. NK1R KO mice, in comparison to B6, showed an increased proliferation and interferon-γ secretion of CD8 T cells in the draining lymph node on day 5 p.i. Flow cytometry of NK1R KO mouse TGs at 5 day p.i showed an increased frequency of CD4 and CD8 T cells compared to B6 mice. Increased viral copy number was detected in TGs of NK1R KO mice at 3 but not 5 days p.i. Experiments are being carried out to ascertain the effect of NK1R on the maintenance of HSV-1 latency.
Our data demonstrates a changing profile of TG neuropeptide expression after ocular HSV-1 infection, which may affect the establishment and maintenance of HSV-1 latency. Results from NK1R KO mouse experiments suggest NK1R may regulate the HSV-1 load in the TG at early time-points p.i.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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