Recurrent infection of HSV-1 causes corneal scarring (CS) and is the leading cause of infectious corneal blindness in the United States. Passive transfer experiments have shown that antibody to HSV-1 glycoprotein K(gK) severely exacerbates CS in mice ocularly challenged with HSV-1. The gK antibody produces antibody dependent enhancement (ADE), which results in increased HSV-1 infectivity and higher viral load in the eye. This in turn leads to an increase of all immune responses examined in the eye, including the as yet undetermined immune response that directly causes exacerbation of CS. For whatever reason, protective immune responses, which are presumably also increased by gK antibody ADE, are not able to block the effect of the """"""""harmful"""""""" immune response and CS is severely exacerbated. We hypothesize that: (a) In humans anti-gK antibody correlates with HSV-1 induced corneal scarring (CS), and (b) blocking anti-gK antibody will decrease corneal scarring (CS) (by blocking ADE).
Our specific aims to test the above hypotheses are: (1) Confirm that anti-gK antibody correlates with CS in humans; (2) Map the gK epitopes that cause ADE and CS; and (3) Block anti-gK-antibody to decrease ADE and CS. If the studies proposed in this grant application confirm that gK antibody is involved in CS in humans, two exciting scenarios will be possible. (i) A method to interfere with or block anti-gK antibody could be developed (for example, blocking with gK peptides). This would decrease the severity of CS and subsequent loss of vision. (ii) Sera from HSV-1 seropositive individuals could be screened for anti-gK antibody titer and those with a high expected susceptibility to recurrent HSV-1 CS could receive prophylactic treatment (such as Acyclovir) even before their first incidence of severe recurrent disease.

National Institute of Health (NIH)
National Eye Institute (NEI)
Research Project (R01)
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Visual Sciences A Study Section (VISA)
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Shen, Grace L
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Cedars-Sinai Medical Center
Los Angeles
United States
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Jaggi, Ujjaldeep; Wang, Shaohui; Tormanen, Kati et al. (2018) Role of Herpes Simplex Virus Type 1 (HSV-1) Glycoprotein K (gK) Pathogenic CD8+ T Cells in Exacerbation of Eye Disease. Front Immunol 9:2895
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