|Department Affiliations||Director-Molecular and Comparative Pathobiology, Pathology, Neurology|
|SOM Address||811 Miller Research Building|
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. In addition, we are pursuing identification of surrogate biomarkers of HIV disease progression that can shed light on disease mechanisms and also be translated to the clinical setting. For example, we have recently characterized CSF markers (IL-6 and 14-3-3 proteins) and hematologic markers (platelet decline) that precede and predict SIV and HIV CNS disease. Close ties to clinical groups in JHU Neurology and Cardiology facilitate these efforts.
Our group is also interested in defining how glial and endothelial cells in the brain respond to systemic immune stimuli including the mechanisms underlying transduction of pro-inflammatory peripheral immune signals to the CNS across the blood-brain barrier. To investigate these fundamental issues in communication biology, we use the SIV-macaque model of HIV CNS disease.
- Mangus LM, Dorsey JL, Laast VA, Ringkamp M, Ebenezer GJ, Hauer P, Mankowski JL. Unraveling the pathogenesis of HIV peripheral neuropathy: insights from a simian immunodeficiency virus macaque model.ILAR Journal, Feb 2014 54(3) 296-303.
- Kelly KM, Tocchetti CG, Lyashkov A, Bedja D, Graham DR, Beck SE, Metcalf Pate KA, Queen SE, Adams RJ, Paolocci N, Mankowski JL. CCR5 inhibition prevents cardiac dysfunction in the SIV/macaque model of HIV.. J American Heart Assoc, April 2, 2014, 3(2) e874.
- Metcalf Pate KA, Lyons CE, Dorsey JL, Queen SE, Adams RJ, Morrell CN, Mankowski JL. TGFβ-Mediated Downregulation of Thrombopoietin Is Associated With Platelet Decline in Asymptomatic SIV Infection.JAIDS, April 2014, 65(5) 510-6.
- Dorsey JL, Mangus LM, Oakley JD, Beck SE, Kelly KM, Queen SE, Metcalf Pate KA, Adams RJ, Marfurt CF, Mankowski JL. Loss of corneal sensory nerve fibers in SIV-infected macaques: an alternate approach to investigate HIV-induced PNS damage.. Am J Pathology, June 2014, 184(6):1652-9.
- Mangus LM, Dorsey JL, Laast VA, Hauer P, Queen SE, Adams RJ, McArthur JC, Mankowski JL. Neuroinflammation and virus replication in the spinal cord of simian immunodeficiency virus-infected macaques. J Neuropathology and Exptl Neurology, Jan 2015, 74(1):38-47.
- Beck SE, Kelly KM, Queen SE, Adams RJ, Tarwater PM, Mankowski JL. Macaque species susceptibility to simian immunodeficiency virus: increased incidence of SIV central nervous system disease in pigtailed macaques versus rhesus macaques. J Neurovirol. 2015 Apr;21(2):148-58.
- Beck SE, Queen SE, Witwer KW, Metcalf Pate KA, Mangus LM, Gama L, Adams RJ, Clements JE, Zink MC, Mankowski JL. Paving the path to HIV neurotherapy: Predicting SIV CNS disease.. Eur J Pharmacol. 2015 July; (759)301-312.
- Metcalf Pate KA, Pohlmeyer CW, Walker-Sperling VW, Foote JB, Najarro KM, Cryer CG, Salgado M, Engle E Shirk EN, Queen SE, Chioma S, Vermillion MS, Bullock B, Li M, Lyons CE, Adams RJ, Gama L, Zink MC, Clements JE, Mankowski JL, Blankson JN. A Murine Viral Outgrowth Assay to Detect Residual HIV Type 1 in Patients With Undetectable Viral Loads.Epub ahead of print, JID 2015. PMID 25883388
- Dorsey JL, Mangus LM, Hauer P, Ebenezer G, Queen SE, Laast VA, Adams RJ, Mankowski JL. Persistent Peripheral Nervous System Damage in Simian Immunodeficiency Virus-Infected Macaques Receiving Antiretroviral Therapy. Epub ahead of Print, J Neuropathology and Exptl Neurology, 2015. PMID 26426267
- Beck SE, Queen SE, Viscidi R, Johnson D, Kent SJ, Adams RJ, Tarwater PM, Mankowski JL. Central nervous system-specific consequences of simian immunodeficiency virus Gag escape from major histocompatibility complex class I-mediated control.. J Neurovirology Jan 4, 2016.