Peripheral neuropathy is the most common neurological complication of HIV-1 infection, affecting over onethird of infected individuals including those treated with antiretroviral therapy. The paradoxical increased incidence of peripheral neuropathy seen in HIV-infected patients following widespread use of HAART regimens reflects the additive effects of HIV-induced PNS damage and anti-retroviral neurotoxicity. Our extensive studies in SIV-infected macaques have detailed PNS damage closely resembling HIV-induced PNS disease;these findings set the stage for also examining neurotoxic damage caused by HAART regimens in the SIV/macaque model. Our follow-up studies have shown significant epidermal nerve fiber loss in SIV-infected macaques on HAART. Thus, despite suppression of viral replication, peripheral nerve damage still develops in SIV-infected macaques treated with HAART. This finding establishes a valuable SIV/macaque model for studying the mechanisms underlying peripheral nervous system damage caused by HIV and antiretroviral therapy. In studies focused on groups of animals including A) uninfected controls, B) SIV-infected, 3) SIV-infected HAART-treated, and 4) uninfected animals receiving HAART, we have three aims: 1) To determine whether HAART treatment that effectively controls SIV replication nonetheless exacerbates SIV-induced slowing of nerve conduction in small sensory nerve fibers (C-fibers), 2) To determine whether administration of HAART in SIV infection and independent of viral infection induces mitochondrial dysfunction in the PNS and 3) To determine whether administration of HAART impairs nerve regeneration in SIV infection (and independently of infection) using our macaque intracutaneous axotomy model of nerve regeneration. These proposed studies in the SIV/macaque HAART model will enable us to dentify the specific contributions to PNS damage attributable to virus versus neurotoxic HAART regimens.

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Beck, Sarah E; Queen, Suzanne E; Metcalf Pate, Kelly A et al. (2018) An SIV/macaque model targeted to study HIV-associated neurocognitive disorders. J Neurovirol 24:204-212
Croteau, Joshua D; Engle, Elizabeth L; Queen, Suzanne E et al. (2017) Marked Enteropathy in an Accelerated Macaque Model of AIDS. Am J Pathol 187:589-604
Gannon, Patrick J; Akay-Espinoza, Cagla; Yee, Alan C et al. (2017) HIV Protease Inhibitors Alter Amyloid Precursor Protein Processing via ?-Site Amyloid Precursor Protein Cleaving Enzyme-1 Translational Up-Regulation. Am J Pathol 187:91-109
Gama, Lucio; Abreu, Celina M; Shirk, Erin N et al. (2017) Reactivation of simian immunodeficiency virus reservoirs in the brain of virally suppressed macaques. AIDS 31:5-14
Beck, Sarah E; Queen, Suzanne E; Viscidi, Raphael et al. (2016) Central nervous system-specific consequences of simian immunodeficiency virus Gag escape from major histocompatibility complex class I-mediated control. J Neurovirol 22:498-507
Williams, Dionna W; Engle, Elizabeth L; Shirk, Erin N et al. (2016) Splenic Damage during SIV Infection: Role of T-Cell Depletion and Macrophage Polarization and Infection. Am J Pathol 186:2068-2087
Saylor, Deanna; Dickens, Alex M; Sacktor, Ned et al. (2016) HIV-associated neurocognitive disorder--pathogenesis and prospects for treatment. Nat Rev Neurol 12:234-48
Mangus, Lisa M; Dorsey, Jamie L; Weinberg, Rachel L et al. (2016) Tracking Epidermal Nerve Fiber Changes in Asian Macaques: Tools and Techniques for Quantitative Assessment. Toxicol Pathol 44:904-12
Avalos, Claudia R; Price, Sarah L; Forsyth, Ellen R et al. (2016) Quantitation of Productively Infected Monocytes and Macrophages of Simian Immunodeficiency Virus-Infected Macaques. J Virol 90:5643-5656
Drewes, Julia L; Meulendyke, Kelly A; Liao, Zhaohao et al. (2015) Quinolinic acid/tryptophan ratios predict neurological disease in SIV-infected macaques and remain elevated in the brain under cART. J Neurovirol 21:449-63

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