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Both virus and host immune factors dictate HSE onset and progression. Because programmed cell death pathways including necroptosis are important antiviral defense mechanisms in HSV1-associated peripheral diseases, they might also play critical roles in HSV1 neuropathogenesis. HSV1-encoded ICP6 prevents receptor-interacting protein kinase 3 (RIPK3)-mediated necroptosis during infection of human cells, but it also acts as a species-dependent inducer of necroptosis in murine cells and thereby restricts virus replication. We therefore used an established mouse model of HSE to investigate RIPK3-mediated necroptosis impact on HSV1 neuropathogenesis. Following corneal HSV1 inoculation, RIPK3 knockout mice showed increased susceptibility to HSE when compared with wildtype mice indicating RIPK3 helps to limit HSE progression. RIPK3-mediated defense against HSE was found to be independent of the kinase domain necessary to drive necroptosis implicating that a death independent function of RIPK3 protects against HSE. Conversely the pro-necroptotic kinase function RIPK3 served to limit viral replication in corneal tissue implicating a tissue-specific RIPK3 function in limiting HSV1. Further evaluation of the kinase-independent mechanism to restrict HSE revealed that the RIPK3 signaling partner, caspase 8, contributes to limiting HSE neuropathogenesis. Increased HSE susceptibility from loss of caspase 8 and RIPK3 correlated with decreased levels of chemokines, cytokines, and antiviral lymphocytes recruitment to the brain. We conclude that RIPK3 contributes toward host control of HSV1 replication in a tissue-specific fashion. Whereas RIPK3-mediated necroptosis restricts virus replication within the cornea, kinase-independent induction of inflammation by RIPK3 in collaboration with caspase 8 restricts virus replication within the brain during HSE neuropathogenesis.<\/jats:p>","DOI":"10.1371\/journal.ppat.1010857","type":"journal-article","created":{"date-parts":[[2022,9,19]],"date-time":"2022-09-19T17:40:49Z","timestamp":1663609249000},"page":"e1010857","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":26,"title":["RIPK3 and caspase 8 collaborate to limit herpes simplex encephalitis"],"prefix":"10.1371","volume":"18","author":[{"given":"Hongyan","family":"Guo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heather S.","family":"Koehler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward 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Li","year":"1998","journal-title":"Cell"},{"issue":"4","key":"ppat.1010857.ref051","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1016\/S0092-8674(00)81589-5","article-title":"Bid, a Bcl2 interacting protein, mediates cytochrome c release from mitochondria in response to activation of cell surface death receptors","volume":"94","author":"X Luo","year":"1998","journal-title":"Cell"},{"issue":"2","key":"ppat.1010857.ref052","doi-asserted-by":"crossref","first-page":"e1009285","DOI":"10.1371\/journal.ppat.1009285","article-title":"ASC-dependent inflammasomes contribute to immunopathology and mortality in herpes simplex encephalitis","volume":"17","author":"CK Hayes","year":"2021","journal-title":"PLoS Pathog"},{"key":"ppat.1010857.ref053","first-page":"JVI0178321","article-title":"The Astrocyte Type I Interferon Response is Essential for Protection Against Herpes Simplex Encephalitis","author":"CK Hayes","year":"2021","journal-title":"J 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