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. Our studies aim to dissect the earliest events in rectal HIV/SIV infection in order to understand how HIV infection is established and spreads, and explore novel immunomodulatory strategies to prevent mucosal infection. Toll-like receptor (TLR) agonists can boost innate immunity through DC activation, with TLR3 the best characterized receptor of viral dsRNA. Poly(IC) is a synthetic dsRNA analog known to activate human and macaque DCs through both TLR3-dependent and independent mechanisms, and clinical grade poly(IC) (poly(ICLC) or Hiltonol) is commercially available and being used in humans, underscoring the potential for this mode of activation to be developed as an anti-HIV strategy. We have shown in vitro that poly(IC) signaling blocks HIV infection in DCs and DC-T cell co-cultures. Thus, we hypothesized that rectal application of Hiltonol in vivo might similarly activate mucosal DCs, triggering their immunostimulatory capability and limiting SIV replication while boosting protective immune responses. We are comparing the effects of Hiltonol on rectal challenge of Indian rhesus macaques with wt and the attenuated virus ?nef (nef deletion mutant) because we postulated that the effects of Hiltonol would be more pronounced in a setting devoid of the immune suppressive effects of nef, and where the attenuated replication of ?nef and its protective capacity against subsequent wt challenge would be enhanced. Following Hiltonol application and challenge, we are continuing to follow the animals over time for viral and immune parameters elicited in response to Hiltonol/SIV: plasma viral load, changes to blood DC and T cell subset numbers and activation, CK/CC levels, Ab production, and T cell responses (ELISPOT for IFN gamma and ICS for IFN gamma, TNF gamma, IL-2, and IL-17 secretion).

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Primate Research Center Grants (P51)
Project #
5P51RR000164-50
Application #
8358075
Study Section
Special Emphasis Panel (ZRR1-CM-8 (01))
Project Start
2011-05-01
Project End
2012-04-30
Budget Start
2011-05-01
Budget End
2012-04-30
Support Year
50
Fiscal Year
2011
Total Cost
$57,750
Indirect Cost
Name
Tulane University
Department
Obstetrics & Gynecology
Type
Schools of Medicine
DUNS #
053785812
City
New Orleans
State
LA
Country
United States
Zip Code
70118
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:
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
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
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
Robillard, Katelyn N; Lee, Kim M; Chiu, Kevin B et al. (2016) Glial cell morphological and density changes through the lifespan of rhesus macaques. Brain Behav Immun 55:60-69
Song, Ruijiang; Pace, Craig; Seaman, Michael S et al. (2016) Distinct HIV-1 Neutralization Potency Profiles of Ibalizumab-Based Bispecific Antibodies. J Acquir Immune Defic Syndr 73:365-373
Inglis, Fiona M; Lee, Kim M; Chiu, Kevin B et al. (2016) Neuropathogenesis of Chikungunya infection: astrogliosis and innate immune activation. J Neurovirol 22:140-8
Liu, David X; Didier, Peter J; Plauche, Gail et al. (2016) Septicemia in an Indian Rhesus Macaque (Macaca mulatta) associated with Providencia stuartii. J Med Primatol 45:330-332
Lee, Kim M; Chiu, Kevin B; Sansing, Hope A et al. (2016) The flavivirus dengue induces hypertrophy of white matter astrocytes. J Neurovirol 22:831-839

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