June 2022
Volume 63, Issue 7
Open Access
ARVO Annual Meeting Abstract  |   June 2022
Absence of signal peptide peptidase in peripheral sensory neurons affects latency-reactivation in HSV-1 ocularly infected mice
Author Affiliations & Notes
  • Shaohui Wang
    Surgery, Cedars-Sinai Medical Center, Los Angeles, California, United States
  • Ujjaldeep Jaggi
    Surgery, Cedars-Sinai Medical Center, Los Angeles, California, United States
  • Kati Tormanen
    Surgery, Cedars-Sinai Medical Center, Los Angeles, California, United States
  • Satoshi Hirose
    Surgery, Cedars-Sinai Medical Center, Los Angeles, California, United States
  • Homayon Ghiasi
    Surgery, Cedars-Sinai Medical Center, Los Angeles, California, United States
  • Footnotes
    Commercial Relationships   Shaohui Wang None; Ujjaldeep Jaggi None; Kati Tormanen None; Satoshi Hirose None; Homayon Ghiasi None
  • Footnotes
    Support  Public Health Service grant RO1 EY13615 from the National Eye Institute.
Investigative Ophthalmology & Visual Science June 2022, Vol.63, 966 – A0435. doi:
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      Shaohui Wang, Ujjaldeep Jaggi, Kati Tormanen, Satoshi Hirose, Homayon Ghiasi; Absence of signal peptide peptidase in peripheral sensory neurons affects latency-reactivation in HSV-1 ocularly infected mice. Invest. Ophthalmol. Vis. Sci. 2022;63(7):966 – A0435.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : We previously reported that HSV-1 glycoprotein K (gK) is involve in exacerbation of eye disease in ocularly infected mice and its binding to signal peptide peptidase (SPP) is required for increased eye disease. In the present study, we investigated the impact of absence of SPP expression in peripheral sensory neurons on HSV-1 infectivity using Avil-SPP-/- mice

Methods : We generated mice lacking SPP specifically in peripheral sensory neurons by crossing Advillin-Cre mice with SPPfl/fl mice. Avil-SPP-/- mice and control mice were infected ocularly with 2 X 105 PFU/eye of HSV-1 strain McKrae. Virus replication in the eye and trigeminal ganglia (TG), survival, eye disease, and latency-reactivation were determined in infected mice.

Results : Expression of SPP mRNA and protein were significantly lower in neurons of Avil-SPP-/- mice than in control mice despite similar levels of HSV-1 replication in the eyes of Avil-SPP-/- mice and control mice. Viral transcript levels in isolated neurons of infected mice on day 5 post infection were lower than in control mice. Significantly less LAT, gB, and PD-1 expression was seen during latency in isolated neurons and total trigeminal ganglia (TG) of Avil-SPP-/- mice than in control mice. Finally, reduced latency and reduced T cell exhaustion in infected Avil-SPP-/- mice correlated with slower or no reactivation.

Conclusions : Overall, our results suggest that blocking SPP expression in peripheral sensory neurons does not affect primary virus replication or eye disease but does reduce latency-reactivation. Thus, blocking of gK binding to SPP may be a useful tool to reduce latency-reactivation.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.

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