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. Transmission of HIV-1 is a rare event that involves extreme, non-random selection of as few as one founder genotype out of as many as 100 million genotypes in the infected donor. The goal of this research proposal is to understand why transmission is so selective, and what biological properties define the rare, highly transmissible virus. The use of infectious molecular clones of founder viruses from 4 subtype C primary infections and 1 subtype B infection provides a key resource to distinguish the few highly transmissible viruses from the many non-transmissible viruses. The research proposal has two specific aims. The first is to model HIV transmission in vitro using transwell cultures where virus must cross an intact epithelial barrier to reach target cells. The hypothesis under test is that a highly transmissible virus must be able to both cross the epithelial cell barrier efficiently and infect the first available target cell efficiently, and that these two properties can be modeled in vitro to distinguish readily transmissible viruses from poorly transmissible viruses. Blood and PBMC are currently being shipped to the Scripps Res Institute to test this system. In the second specific aim, the results of the in vitro model will be put to the test by creating a simian-human immunodeficiency virus envelope chimera with the best transmitted HIV-1 envelope, and using the resulting SHIV for vaginal challenge studies in rhesus macaques. In both in vitro and in vivo studies, extensive analysis of the genotypic and biological properties of highly transmissible versus poorly transmissible viruses will allow the definition of the characteristics that define transmission success. The end product of this research program will thus be a better understanding of HIV-1 transmission, and one or more SHIV chimeric viruses that reflect founder viruses rather than late-stage isolates, and will provide a much more relevant reagent for preclinical prevention studies.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Primate Research Center Grants (P51)
Project #
5P51RR000164-50
Application #
8358178
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
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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
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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
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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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