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Reactivation of SIV reservoirs in the brain of virally suppressed macaques.

Reactivation of SIV reservoirs in the brain of virally suppressed macaques.
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Gama L, Abreu CM, Shirk EN, Price SL, Li M, Laird GM, Pate KA, Wietgrefe SW, O'connor SL, Pianowski L, Haase AT, Van Lint C, Siliciano RF, Clements JE, Authors D, ,


Gama L, Abreu CM, Shirk EN, Price SL, Li M, Laird GM, Pate KA, Wietgrefe SW, O'connor SL, Pianowski L, Haase AT, Van Lint C, Siliciano RF, Clements JE, Authors D, , (click to view)

Gama L, Abreu CM, Shirk EN, Price SL, Li M, Laird GM, Pate KA, Wietgrefe SW, O'connor SL, Pianowski L, Haase AT, Van Lint C, Siliciano RF, Clements JE, Authors D, ,

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AIDS (London, England) 2016 9 20()

Abstract
OBJECTIVE
Resting CD4+ T cells have been recognized as the major cell reservoir of latent HIV-1 during antiretroviral therapy (ART). Using an SIV/macaque model for AIDS and HIV-related neurocognitive disorders we assessed the contribution of the brain to viral latency and reactivation.

DESIGN
Pigtailed macaques were dual inoculated with SIVDeltaB670 and SIV17E-Fr and treated with an efficacious CNS-penetrant ART. After 500 days of viral suppression animals were treated with two cycles of latency reversing agents (LRAs) and increases in viral transcripts were examined.

METHODS
Longitudinal plasma and CSF viral loads were analyzed by quantitative and digital droplet PCR. After necropsy, viral transcripts in organs were analyzed by PCR, in situ hybridization (ISH), and phylogenetic genotyping based on env V1 loop sequences. Markers for neuronal damage and CSF activation were measured by ELISA.

RESULTS
Increases in activation markers and plasma and CSF viral loads were observed in one animal treated with LRAs, despite ongoing ART. SIV transcripts were identified in occipital cortex macrophages by ISH and CD68+ staining. The most abundant SIV genotype in CSF was unique and expanded independent from viruses found in the periphery.

CONCLUSION
The CNS harbors latent SIV genomes after long-term viral suppression by ART indicating that the brain represents a potential viral reservoir and should be seriously considered during AIDS cure strategies.

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