SRA

Knowledge on immune activation in the brain during acute HIV infection is crucial for the prevention and treatment of HIV associated neurological disorders (HAND), which is prevalent in people living with HIV (PLWH), even in those treated with antiretroviral therapy. In this study, we determined regional brain (basal ganglia, thalamus, and frontal cortex) immune and virological profiles 7 and 14 days after infection (dpi) with SIVmac239 in rhesus macaques. Basal ganglia and thalamus were infected earlier (7dpi) than frontal cortex (14 dpi) and contained higher quantities of viruses than the latter. Increased immune activation of astrocytes and significant infiltration of monocytes/macrophages in thalamus at 14 dpi coincided with elevated plasma viral load, while SIV was only localized within monocytes/macrophages. RNA signatures of pro-inflammatory responses including IL-6 were detected at 7 dpi in microglia and interestingly preceded reliable detection of virus in tissues and was maintained long term in the brain of chronically infected macaques. Countering the pro-inflammatory response, the anti-inflammatory response was detectable, but delayed till 14 dpi, as TGF-ß expression in significantly higher numbers of perivascular monocytes/macrophages; though this anti-inflammatory response was not detected in chronic infection. Our data provide evidence that the interplay of acute pro-inflammatory and anti-inflammatory responses in the brain likely contribute to the overt neuro-inflammation, but that inflammatory markers such as IL-6 may serve as hyperacute biomarkers of low-level brain infection. Overall design: 11 adule male rhesus macaques were used. 8 were infected with SIVmac239. 3 were sacrificed on day 7, 5 were sacrificed on day 14. 3 were uninfected controls. Brain tissue from the frontal cortex and blood was sampled at necropsy. Basal ganglia and thalamus tissue were also collected from one animal.