Brain region-specific lesions in the early AIDS monkey model.
6 affiliations
- 1State Key Laboratory of Genetic Evolution & Animal Models, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650201, China.
- 2Key Laboratory of Bioactive Peptides of Yunnan Province, KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China.
- 3Medical School, University of Chinese Academy of Sciences, Beijing 101408, China.
- 4Key Laboratory of Animal Models and Human Disease Mechanisms of Yunnan Province, Laboratory of Learning and Memory, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China.
- 5KIZ-SU Joint Laboratory of Animal Model and Drug Development, College of Pharmaceutical Sciences, Soochow University, Suzhou 215021, China.
- 6National Research Facility for Phenotypic and Genetic Analysis of Model Animals (Primate Facility), National Resource Center for Non-Human Primates, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650107, China.
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.
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BibTeX
@article{song2026brain,
title = {{Brain region-specific lesions in the early AIDS monkey model.}},
author = {Tian-Zhang Song and Yan Hu and Shi-Zhe Wang and Huan-Zhi Chen and Bei-Bei Tang and Jin-Nan Li and Qing Li and Rong-Yao Huang and Li-Rong Zhang and Lin Xu and Yong-Tang Zheng},
journal = {Life medicine},
year = {2026},
month = sep,
doi = {10.1093/lifemedi/lnag033},
url = {https://europepmc.org/article/MED/42921619},
note = {CC BY},
}
RIS
TY - JOUR
TI - Brain region-specific lesions in the early AIDS monkey model.
AU - Tian-Zhang Song
AU - Yan Hu
AU - Shi-Zhe Wang
AU - Huan-Zhi Chen
AU - Bei-Bei Tang
AU - Jin-Nan Li
AU - Qing Li
AU - Rong-Yao Huang
AU - Li-Rong Zhang
AU - Lin Xu
AU - Yong-Tang Zheng
PY - 2026
DA - 2026/09/16
JO - Life medicine
DO - 10.1093/lifemedi/lnag033
UR - https://europepmc.org/article/MED/42921619
AB - 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.
SN - 2755-1733
ER -