Brain region-specific lesions in the early AIDS monkey model
Year: 2026
Type: article
Abstract: Brain lesions show pronounced regional heterogeneity during chronic or advanced human immunodeficiency virus (HIV) infection; however, the regional neuropathogenesis during the acute phase remains unclear. By establishing an acute simian immunodeficiency virus (SIV)-infection model in rhesus macaques, we found acute infection-induced robust neuroinflammation and neuronal damage. Compared with the cerebral cortex, subcortical nuclei displayed earlier and more severe neuronal degeneration and loss of Nissl bodies, accompanied by greater upregulation of immune-related genes. Although SIV RNA loads in cerebrospinal fluid (CSF) and plasma were strongly correlated and peaked during acute infection, brain tissues showed no evidence of early viral reservoir establishment. The viral transactivator Tat persisted in CSF and was broadly distributed throughout the brain via passive diffusion along perivascular spaces. Similar transcriptional and inflammatory profiles were observed between macaques with acute infection and mice receiving intracisternal Tat infusions identified Tat as a principal mediator of early SIV-induced neurotoxicity. Microglia in a primed immune-vigilant state exhibited considerable enrichment in subcortical nuclei, driving exaggerated responses to Tat exposure and resulting in region-specific neuropathological outcomes. Collectively, these findings delineate the spatiotemporal landscape of acute HIV/SIV-induced brain injury and establish viral Tat as a mechanistic driver of acute neuropathogenesis.
Source: Life Medicine
Language: English
Topic: HIV Research and Treatment
Subfield: Virology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: diamond
OpenAlex ID: W7213505161