This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. This Project within the PPG will investigate, using SIV and SHIV infection rhesus macaques, the effect of polyamine synthesis inhibitors (PBI) on pathogenesis AIDS and sequela of neuroAIDS. For this, we initially propose to investigate the polyamine analogues CG-047, synthetic guanidine compound PA-OO1 and CNI-1493 termed PA-OO2 in this application. We hypothesize the PBI will deactivate and/or selectively target populations of CD14 and CD16 monocyte/macrophages some of which are infected. We proposed to use a) a CD8+ lymphocyte depletion model of SIV infection that results in rapid, consistent and severe CNS disease, and b) a SHIV infection model that rapidly depletes CD4+ T lymphocytes resulting in high SIV replication in monocyte/macrophages, to study the effects of PBI delaying and/reversing CNS disease flushing monocyte/macrophage viral reservoirs. We propose three specific aims to test our hypothesis. Studies in aim 1 will determine whether PBI (PA-OO1 andPA-OO2) deactivate and/or kill select CD14 CD16 monocyte populations resulting in clearance of monocyte/macrophage reservoir of SIV during acute infection and the development of AIDS. Studies in aim 2 test the hypothesis that PBI deactivate and/or kill select CD14 CD16 monocyte populations, inhibiting and/or reversing SIVE. Studies in aim 3 test the hypothesis that PBI administered SHIV infected animals depleted of CD4+ T cells with high monocyte/macrophage SIV replication, clears or diminishes viral reservoirs in blood, lymphoid and CNS tissues.

National Institute of Health (NIH)
National Center for Research Resources (NCRR)
Primate Research Center Grants (P51)
Project #
Application #
Study Section
Special Emphasis Panel (ZRR1-CM-8 (01))
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Harvard University
Veterinary Sciences
Schools of Medicine
United States
Zip Code
Shang, L; Smith, A J; Reilly, C S et al. (2018) Vaccine-modified NF-kB and GR signaling in cervicovaginal epithelium correlates with protection. Mucosal Immunol 11:512-522
Sonntag, Kai-Christian; Woo, Tsung-Ung W (2018) Laser microdissection and gene expression profiling in the human postmortem brain. Handb Clin Neurol 150:263-272
Almodovar, Sharilyn; Swanson, Jessica; Giavedoni, Luis D et al. (2018) Lung Vascular Remodeling, Cardiac Hypertrophy, and Inflammatory Cytokines in SHIVnef-Infected Macaques. Viral Immunol 31:206-222
Duke, Angela N; Meng, Zhiqiang; Platt, Donna M et al. (2018) Evidence That Sedative Effects of Benzodiazepines Involve Unexpected GABAA Receptor Subtypes: Quantitative Observation Studies in Rhesus Monkeys. J Pharmacol Exp Ther 366:145-157
Kamberov, Yana G; Guhan, Samantha M; DeMarchis, Alessandra et al. (2018) Comparative evidence for the independent evolution of hair and sweat gland traits in primates. J Hum Evol 125:99-105
Seth, Nitin; Simmons, Heather A; Masood, Farah et al. (2018) Model of Traumatic Spinal Cord Injury for Evaluating Pharmacologic Treatments in Cynomolgus Macaques (Macaca fasicularis). Comp Med 68:63-73
Mauney, Sarah A; Woo, Tsung-Ung W; Sonntag, Kai C (2018) Cell Type-Specific Laser Capture Microdissection for Gene Expression Profiling in the Human Brain. Methods Mol Biol 1723:203-221
McLean, Will J; Yin, Xiaolei; Lu, Lin et al. (2017) Clonal Expansion of Lgr5-Positive Cells from Mammalian Cochlea and High-Purity Generation of Sensory Hair Cells. Cell Rep 18:1917-1929
Isakova, Irina A; Baker, Kate C; Dufour, Jason et al. (2017) Mesenchymal Stem Cells Yield Transient Improvements in Motor Function in an Infant Rhesus Macaque with Severe Early-Onset Krabbe Disease. Stem Cells Transl Med 6:99-109
Termini, James M; Church, Elizabeth S; Silver, Zachary A et al. (2017) Human Immunodeficiency Virus and Simian Immunodeficiency Virus Maintain High Levels of Infectivity in the Complete Absence of Mucin-Type O-Glycosylation. J Virol 91:

Showing the most recent 10 out of 365 publications