This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. SIV infection in rhesus macaques of Chinese origin (Ch Rh) results in high frequency (30%) of long-term nonprogressing macaques which is a markedly larger incidence than can be found in HIV-1 infected humans or SIV-infected macaques of Indian origin ( 5%). We use this unique model for investigating the role of natural killer cells in the establishment of long-term nonprogressing state in LTNP Ch Rh, which could provide direct implications/guidance for vaccine design to combat HIV-1 infection. These LTNP animals have high peak viremia indistinguishable from progressing Ch Rh or Ind Rh, indicating that this is not due to inherent viral resistance, but more likely, that immune responses are responsible for the ultimate control of viral replication. Thus far, we found that neither neutralizing antibodies nor T-cell immune responses are clearly correlated with long-term nonprogression. Interestingly, in the study of innate immunity and NK cell responses, we found that NK cells had different levels of turnover between LTNP and NP during acute SIV infection;NK cells were potent killers through mechanisms of both cytotoxicity and release of antiviral cytokines by different NK subsets. We also found that high SIV-specific non-NAb responses were elicited, which may be related to NK cell-mediated antibody-dependent cell-mediated cytotoxicity (ADCC). Our data demonstrate that NK cells may play an important role in protection from disease. By manipulating NK cells and function to resist infection, new generation of vaccine development may be plausible for controlling infection under an aviremic long term nonprogressive state which will prolong AIDS-free survival and will possibly reduce viral transmission in a population level.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Primate Research Center Grants (P51)
Project #
5P51RR000164-48
Application #
7958690
Study Section
Special Emphasis Panel (ZRR1-CM-8 (01))
Project Start
2009-05-01
Project End
2010-04-30
Budget Start
2009-05-01
Budget End
2010-04-30
Support Year
48
Fiscal Year
2009
Total Cost
$60,376
Indirect Cost
Name
Tulane University
Department
Type
Other Domestic Higher Education
DUNS #
053785812
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

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