SIV-specific antibodies protect against inflammasome-driven encephalitis in untreated macaques.
Cell Rep
; 43(10): 114833, 2024 Oct 08.
Article
em En
| MEDLINE
| ID: mdl-39383041
ABSTRACT
Viral encephalitis is a growing public health threat with limited diagnostic and treatment options. Simian immunodeficiency virus (SIV)-infected macaques are an established model for human immunodeficiency virus (HIV), and approximately 60% of untreated pigtail macaques rapidly progress to characteristic SIV encephalitis (SIVE). The immune responses of SIV-infected macaques are investigated in plasma, cerebrospinal fluid (CSF), and brain tissue to determine correlates with SIVE pathology. Macaques with SIVE show myeloid-dominant brain lesions with inflammasome activation in infected and bystander cells, as assessed by interleukin (IL)-1ß, IL-18, and apoptosis-associated speck-like protein containing a caspase activation and recruitment domain (ASC), and elevations in monocyte chemoattractant protein (MCP)-1, macrophage inflammatory protein (MIP)-1α, and tumor necrosis factor alpha (TNF-α). SIV-specific immunoglobulin (Ig)G in plasma and CSF is predictive of SIVE as early as 21 days post-inoculation; animals with SIVE continue to show negligible seroconversion 3 months after infection. This dichotomy in immune responses, wherein some macaques fail to initiate robust IgG responses and subsequently develop SIVE, provides insight into the pathogenesis and heterogeneous outcomes in viral encephalitis.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Idioma:
En
Revista:
Cell Rep
/
Cell reports
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Estados Unidos
País de publicação:
Estados Unidos