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. Biliary atresia (BA) is a devastating disease of childhood. The etiology of BA remains uncertain;however, increasing evidence supports a viral component in disease pathogenesis. The murine model of BA is induced by perinatal infection with rhesus rotavirus (RRV) but not by other strains of rotavirus an example of which is TUCH. Rotavirus is a double-stranded RNA virus that contains 11 gene segments. To determine which RRV gene segment is responsible for disease pathogenesis, we used the parental strains RRV and TUCH and the rotavirus property of reassortment to generate a complete set of single gene reassortants. Eleven single-gene """"""""loss-of-function"""""""" reassortants in which a TUCH gene replaced its RRV equivalent and eleven reciprocal single gene """"""""gain-of-function"""""""" reassortants in which a RRV gene replaced its TUCH equivalent were generated. Infection of mice with the """"""""loss-of-function"""""""" reassortant RT4 where gene segment 4 from TUCH was placed on an RRV background eliminated RRV's ability to cause murine BA. In a reciprocal fashion, the """"""""gain-of-function"""""""" reassortant TR4 resulted in murine BA with a mortality rate of 95%. Cholangiocyte binding and infectivity assays revealed RT4 binding ratio and titer (both in vivo and in vitro) were significantly attenuated as compared with RRV;moreover, TR4 binding and titer were significantly higher than TUCH. Reassortant RT3 and TR3 induced an intermediate phenotype. Gene segment 4 through its translated gene product VP4 plays a significant role governing RRV tropism for the biliary epithelial cell and induces the murine model of biliary atresia. The basis for tropism and how it induces biliary obstruction requires further study. Substitution of RRV gene segment 3 did not affect viral infectivity in vitro, but altered the in vivo effect.

National Institute of Health (NIH)
National Center for Research Resources (NCRR)
Primate Research Center Grants (P51)
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Special Emphasis Panel (ZRR1-CM-8 (01))
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Tulane University
Obstetrics & Gynecology
Schools of Medicine
New Orleans
United States
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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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