My project focuses on studying natural host genetic resistance to lentiviral CNS disease, specifically SIV.
This lab uses a unique animal model of HIV using pigtail macaques infected with a combination of SIV viruses that results in an accelerated progression to SIV encephalitis. Interestingly, some macaques do not develop encephalitis, and we believe that host genetics plays a large role in this resistance to CNS disease. MHC class I-restricted CD8 T cell responses are a critical part of the adaptive CMI response, and certain MHC class I alleles have been shown to be associated with different reponses to infection in both HIV and SIV. We have found that animals with the MHC class I allele Mane A*10 are much less likely to develop encephalitis. Associated with this allele, we have found a consensus viral escape mutation in the gag epitope recognized by this MHC class I allele. My project is largely focused on assessing the in vitro and in vivo fitness of this escape viral mutation using our pigtail macaque model.
Potential role of cervicovaginal extracellular particles in diagnosis of endometriosis. Muth DC, McAlexander MA, Ostrenga LJ, Pate NM, Izzi JM, Adams RJ, Pate KA, Beck SE, Karim BO, Witwer KW. BMC Vet Res. 2015 Aug 8;11:187. PMID:26253321
Paving the path to HIV neurotherapy: Predicting SIV CNS disease. Beck SE, Queen SE, Witwer KW, Metcalf Pate KA, Mangus LM, Gama L, Adams RJ, Clements JE, Christine Zink M, Mankowski JL. Eur J Pharmacol. 2015 Jul 15;759:303-12.. Epub 2015 Mar 24. Review. PMID:25818747
Macaque species susceptibility to simian immunodeficiency virus: increased incidence of SIV central nervous system disease in pigtailed macaques versus rhesus macaques. Beck SE, Kelly KM, Queen SE, Adams RJ, Zink MC, Tarwater PM, Mankowski JL. J Neurovirol. 2015 Apr;21(2):148-58. doi: 10.1007/s13365-015-0313-7. Epub 2015 Feb 12. PMID: 25672885
CCR5 inhibition prevents cardiac dysfunction in the SIV/macaque model of HIV. Kelly KM, Tocchetti CG, Lyashkov A, Tarwater PM, Bedja D, Graham DR, Beck SE, Metcalf Pate KA, Queen SE, Adams RJ, Paolocci N, Mankowski JL. J Am Heart Assoc. 2014 Apr 2;3(2):e000874. doi: 10.1161/JAHA.114.000874. PMID:24695652
Constitutive BDNF/TrkB signaling is required for normal cardiac contraction and relaxation. Feng N, Huke S, Zhu G, Tocchetti CG, Shi S, Aiba T, Kaludercic N, Hoover DB, Beck SE, Mankowski JL, Tomaselli GF, Bers DM, Kass DA, Paolocci N.Proc Natl Acad Sci U S A. 2015 Feb 10;112(6):1880-5. doi: 10.1073/pnas.1417949112. Epub 2015 Jan 12. Erratum in: Proc Natl Acad Sci U S A. 2015 Mar 31;112(13):E1691. PMID:25583515
Neuroprotective maraviroc monotherapy in simian immunodeficiency virus-infected macaques: reduced replicating and latent SIV in the brain. Kelly KM, Beck SE, Metcalf Pate KA, Queen SE, Dorsey JL, Adams RJ, Avery LB, Hubbard W, Tarwater PM, Mankowski JL. AIDS. 2013 Nov 28;27(18):F21-8.PMID:24051706
Loss of corneal sensory nerve fibers in SIV-infected macaques: an alternate approach to investigate HIV-induced PNS damage. Dorsey JL, Mangus LM, Oakley JD, Beck SE, Kelly KM, Queen SE, Metcalf Pate KA, Adams RJ, Marfurt CF, Mankowski JL. Am J Pathol. 2014 Jun;184(6):1652-9.. Epub 2014 May 12. PMID:24828391