Attenuated SIV causes persisting neuroinflammation in the absence of a chronic viral load and neurotoxic ART.

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Ferguson D, Clarke S, Berry N, Almond N,

Ferguson D, Clarke S, Berry N, Almond N, (click to view)

Ferguson D, Clarke S, Berry N, Almond N,

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AIDS (London, England) 2016 6 1()

Using simian models where SIV chronic viral loads are naturally controlled in the absence of potentially neurotoxic therapies we investigated the neuropathological events occurring during times of suppressed viremia and when these events were initiated.

Cynomolgus macaques were infected with SIV strains that are naturally controlled to low levels of chronic viremia. Study one; animals were maintained upto 300 days post inoculation and analysed for viral induced neuropathology following sustained suppression of chronic viral loads. Study two; initiation and development of pathology was examined following 3, 10, 21, or 125 days SIVmacC8 infection.

Formalin fixed, paraffin embedded brain sections were analysed following immunohistochemical staining for SIV (KK41), blood brain barrier leakage (ZO-1, fibrinogen), apoptosis (active caspase 3), neuroinflammation (GFAP, COX-1, COX-2), microglia and macrophage (iba-1, CD68, CD16), oligodendrocytes (CNPase1), MHC class II expression and T cells (CD3, CD8). Replicating SIV was detected through in situ hybridisation.

Study one: Neuroinflammation was present despite prolonged suppressed viremia. Study two: Attenuated SIV entered the brain rapidly triggering acute phase neuroinflammatory responses. These did not return to naïve levels and GFAP and COX-2 responses continued to develop during a chronic phase with a suppressed viral load.

Neuroinflammatory responses similar to those in HIV neurocognitively impaired patients are present within macaque brains during prolonged periods of suppressed SIV viral load and in the absence of potentially neurotoxic antiretroviral drugs. These responses, initiated during acute infection, do not resolve despite the lack of on-going peripheral viremia to potentially re-seed the brain.

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