The Mankowski lab group studies the immunopathogenesis of HIV infection using the SIV/macaque model.
Pathogenesis of HIV-induced nervous system and cardiac disease processes
HIV is well known for its ability to induce loss of CD4+ T-cells leading to immune suppression manifest as AIDS. HIV infection also causes debilitating disease in the brain, the peripheral nervous system and in the heart secondary to infection of macrophages. Although virus-induced damage to these organs is common, the pathogenesis remains poorly defined. Using the SIV/macaque model of HIV, we use a multidisciplinary approach to dissect the mechanisms underlying these diseases, including the central role of macrophage activation.
Host genetics and lentiviral-induced CNS disease
The role that host genetics play in HIV-associated cognitive disorders is poorly understood. We have identified a novel association between expression of a MHC class I allele in pigtailed macaques and SIV-induced CNS disease that sets the stage for studies defining how MHC class I-mediated control of SIV replication in the brain influences SIV CNS disease outcomes.
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Klein AH, Vyshnevska A, Hartke TV, De Col R, Mankowski JL, Turnquist BP, Bosmans F, Reeh PW, Schmelz M, Carr RW, Ringkamp M. Sodium channel NaV1.8 underlies TTX-resistant axonal action potential conduction in somatosensory C-fibers of distal cutaneous nerves. J Neurosci. 2017. doi: 10.1523/JNEUROSCI.3799-16.2017. PubMed PMID: 28450535.
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, Group L-SS. Reactivation of simian immunodeficiency virus reservoirs in the brain of virally suppressed macaques. AIDS. 2017;31(1):5-14. doi: 10.1097/QAD.0000000000001267. PubMed PMID: 27898590; PMCID: PMC5131686
Mangus LM, Dorsey JL, Weinberg RL, Ebenezer GJ, Hauer P, Laast VA, Mankowski JL. Tracking Epidermal Nerve Fiber Changes in Asian Macaques: Tools and Techniques for Quantitative Assessment. Toxicol Pathol. 2016;44(6):904-12. doi: 10.1177/0192623316650286. PubMed PMID: 27235324; PMCID: PMC4965306
Avalos CR, Price SL, Forsyth ER, Pin JN, Shirk EN, Bullock BT, Queen SE, Li M, Gellerup D, O'Connor SL, Zink MC, Mankowski JL, Gama L, Clements JE. Quantitation of Productively Infected Monocytes and Macrophages of Simian Immunodeficiency Virus-Infected Macaques. J Virol. 2016;90(12):5643-56. doi: 10.1128/JVI.00290-16. PubMed PMID: 27030272; PMCID: PMC4886778
Dorsey JL, Mangus LM, Hauer P, Ebenezer GJ, Queen SE, Laast VA, Adams RJ, Mankowski JL. Persistent Peripheral Nervous System Damage in Simian Immunodeficiency Virus-Infected Macaques Receiving Antiretroviral Therapy. J Neuropathol Exp Neurol. 2015;74(11):1053-60. doi: 10.1097/NEN.0000000000000249. PubMed PMID: 26426267; PMCID: PMC4607660