In:
Science Immunology, American Association for the Advancement of Science (AAAS), Vol. 8, No. 82 ( 2023-04-21)
Abstract:
Susceptibility to childhood herpes simplex encephalitis (HSE) caused by HSV-1 infection has been attributed to inborn errors of immunity affecting production or sensing of type I interferon. Using whole-exome sequencing, Liu et al . identified a patient with HSE bearing compound heterozygous variants in RIPK3, a key cytoplasmic regulator of cell death. Patient-derived RIPK3 was less stable, resulting in RIPK3 deficiency and defects in apoptosis and necroptosis, without affecting production of type I interferon. Both patient-specific and RIPK3 knockout human pluripotent stem cell–derived cortical neurons displayed enhanced HSV-1 replication and resistance to virus-induced cell death. These results identify a previously undescribed genetic etiology of childhood HSE and demonstrate that cell death–dependent control is a critical component of antiviral defenses against HSV-1. —CO
Type of Medium:
Online Resource
ISSN:
2470-9468
DOI:
10.1126/sciimmunol.ade2860
Language:
English
Publisher:
American Association for the Advancement of Science (AAAS)
Publication Date:
2023
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