Purchase this article with an account.
Anthony B Nesburn, Pierre-Gregoire A Coulon, Nisha Dhanushkodi, Swayam Prakash, Ruchi Srivastava, Soumyabrata Roy, Lbachir BenMohamed; Infection with Virulent HSV-1 Strains Preferentially Activates NLRP-3, NLRP-12 and IFI-16 Inflammasome Pathways Associated with Severe Inflammatory Corneal Herpetic Disease. Invest. Ophthalmol. Vis. Sci. 2019;60(9):4624.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Ocular infection with herpes simplex virus type 1 (HSV-1) triggers severe inflammatory corneal herpetic disease, making HSV-1 a leading cause of infectious blindness. We hypothesize that virulent and non-virulent strains of HSV-1 produce different forms and levels of inflammasome activation.
Seven groups of B6 mice (n = 10) were ocularly infected with 2 x 105 pfu/eye of one of five known HSV-1 laboratory strains (i.e. McKrae, 17, RE, F or KOS) or one of two clinical isolates (i.e. KOS79 or KOS63) that present various degress of virulence. The severity of primary cornea herpetic disease was compared to the magnitude of inflammasomes activation and to the nature and size of corneal immune cell infiltrates (i.e. neutrophils, macrophages, dendritic cells, CD4+, and CD8+ T cells) using flow cytometry (FACS) assay.
(1) Virulent laboratory strains McKrae and 17 caused severe corneal herpetic disease, while less virulent RE, F and KOS induced intermediate to low corneal disease in B6 mice. (2) Similarly, the virulent clinical isolate KOS79 induced severe corneal disease compared to less virulent KOS63. (3) Compared to less virulent viral strains, the virulent strains induced higher levels of NLRP-3, NLRP-12 and IFI-16 activation associated with increased infiltrates of neutrophils and macrophages in inflamed corneas. Similarly, infection in vitro of human corneal epithelial cells (hTCEpi) with the virulent strains McKrae, 17 or KOS79: (4) triggered an early activation of NLRP-3, NLRP-12 and IFI-16 inflammasomes; (5) induced the formation of ASC specks and of activated cleaved caspase-1 in infected corneal epithelial cells but not in neighboring non-infected cells; and (6) boosted release of high levels of proinflammatory interleukines IL-1b and IL-18.
The findings: (i) shed light on the connection between virulence of HSV-1 and the host’s inflammasomes; (ii) demonstrate that virulent strains of HSV-1 selectively activated NLRP-3, NLRP-12 and IFI-16 inflammasomes and that this was associated with severe inflammatory corneal herpetic disease in B6 mice.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
This PDF is available to Subscribers Only