The purpose of this study is to develop a nonhuman primate model of infection and disease due to human T lymphotropic virus, type I (HTLV-I). HTLV-I is an important human pathogen for which no effective treatment or vaccine exists. HTLV-I is the causative agent of Adult T Cell Leukemia/Lymphoma (ATLL), and a degenerative neurological disorder known as Tropical Spastic Paraparesis/HTLV-I-Associated Myelopathy (TSP/HAM). In addition, HTLV-I is associated with the development of several autoimmune diseases in which the virus may trigger the disease process. These diseases include polymyositis, uveitis, arthritis, lymphoid interstitial pneumonitis and thyroiditis. HTLV-I is transmitted through blood and body fluids, and co-infections with human immunodeficiency virus are very frequent (up to 5% of HIV-infected individuals are co-infected). Co-infections may hasten progression to AIDS and increase the risk for development of ATLL, TSP/HAM, and autoimmune diseases. A pathogenic strain of HTLV-I, isolated from a New Orleans, Louisiana, patient, has been used to inoculate seven juvenile rhesus macaques. All seven monkeys demonstrated evidence of infection, either by seroconversion or virus expression as determined by culture or polymerase chain reaction (PCR). One animal developed polymyositis, uveitis, and arthritis 5 months following inoculation. A second animal, co-infected with simian immunodeficiency virus (SIV), developed a hematological syndrome characterized by severe anemia, thrombocytopenia, and the presence of abnormal circulating lymphocytes resembling those seen in ATLL patients. The HTLV-I macaque model therefore will be useful for studying HTLV-I disease pathogenesis and also for designing treatment algorithms.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Primate Research Center Grants (P51)
Project #
5P51RR000164-36S1
Application #
2795508
Study Section
Project Start
Project End
Budget Start
1997-10-01
Budget End
1998-09-30
Support Year
36
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Tulane University
Department
Type
DUNS #
City
New Orleans
State
LA
Country
United States
Zip Code
70118
Mahalingam, Ravi; Kaufer, Benedikt B; Ouwendijk, Werner J D et al. (2018) Attenuation of Simian Varicella Virus Infection by Enhanced Green Fluorescent Protein in Rhesus Macaques. J Virol 92:
Kumar, Vinay; Mansfield, Joshua; Fan, Rong et al. (2018) miR-130a and miR-212 Disrupt the Intestinal Epithelial Barrier through Modulation of PPAR? and Occludin Expression in Chronic Simian Immunodeficiency Virus-Infected Rhesus Macaques. J Immunol 200:2677-2689
Parthasarathy, Geetha; Philipp, Mario T (2018) Intracellular TLR7 is activated in human oligodendrocytes in response to Borrelia burgdorferi exposure. Neurosci Lett 671:38-42
McNamara, Ryan P; Costantini, Lindsey M; Myers, T Alix et al. (2018) Nef Secretion into Extracellular Vesicles or Exosomes Is Conserved across Human and Simian Immunodeficiency Viruses. MBio 9:
Calenda, Giulia; Villegas, Guillermo; Barnable, Patrick et al. (2017) MZC Gel Inhibits SHIV-RT and HSV-2 in Macaque Vaginal Mucosa and SHIV-RT in Rectal Mucosa. J Acquir Immune Defic Syndr 74:e67-e74
Datta, Dibyadyuti; Bansal, Geetha P; Grasperge, Brooke et al. (2017) Comparative functional potency of DNA vaccines encoding Plasmodium falciparum transmission blocking target antigens Pfs48/45 and Pfs25 administered alone or in combination by in vivo electroporation in rhesus macaques. Vaccine 35:7049-7056
Yi, Fei; Guo, Jia; Dabbagh, Deemah et al. (2017) Discovery of Novel Small-Molecule Inhibitors of LIM Domain Kinase for Inhibiting HIV-1. J Virol 91:
Jorgensen, Matthew J; Lambert, Kelsey R; Breaux, Sarah D et al. (2017) Pair housing of Vervets/African Green Monkeys for biomedical research. Am J Primatol 79:1-10
Ramesh, Geeta; Martinez, Alejandra N; Martin, Dale S et al. (2017) Effects of dexamethasone and meloxicam on Borrelia burgdorferi-induced inflammation in glial and neuronal cells of the central nervous system. J Neuroinflammation 14:28
Parthasarathy, Geetha; Philipp, Mario T (2017) Receptor tyrosine kinases play a significant role in human oligodendrocyte inflammation and cell death associated with the Lyme disease bacterium Borrelia burgdorferi. J Neuroinflammation 14:110

Showing the most recent 10 out of 352 publications