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. Inhibitors of miR122 have recently been shown to reduce HCV viral load by up to 2.6 logs in HCV infected chimpanzees. Analysis of hepatic gene expression revealed that the drop in viremia was accompanied by a reduction in the levels of hepatic transcripts for interferon stimulated genes (ISGs) or the normalization of the IFN pathway. HCV chronically infected chimpanzees do not exhibit an antiviral response to exogenous IFN? and resemble null responders in the human population in this regard. The null response phenotype in chimpanzees and in man correlates with elevated hepatic ISG expression, while IFN responders have low baseline ISG transcript levels. Thus, the reduction in ISG transcript levels during therapy with miR122 inhibitors likely results in the conversion of the null IFN phenotype to the responder phenotype. This study is designed to directly test this concept and to demonstrate that IFN? induces hepatic ISG expression and an antiviral effect in chimpanzees treated with miR122 inhibitors.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Primate Research Center Grants (P51)
Project #
5P51RR013986-13
Application #
8357716
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
13
Fiscal Year
2011
Total Cost
$72,347
Indirect Cost
Name
Texas Biomedical Research Institute
Department
Type
DUNS #
007936834
City
San Antonio
State
TX
Country
United States
Zip Code
78245
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Morosco, Danielle T; Cline, Curtis R; Owston, Michael A et al. (2017) Spontaneous mediastinal myeloid sarcoma in a common marmoset (Callithrix jacchus) and review of the veterinary literature. J Med Primatol 46:42-47
Muralimanoharan, Sribalasubashini; Li, Cun; Nakayasu, Ernesto S et al. (2017) Sexual dimorphism in the fetal cardiac response to maternal nutrient restriction. J Mol Cell Cardiol 108:181-193
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Neidig, Lauren E; Owston, Michael A; Ball, Erin et al. (2016) Pauci-immune glomerulonephritis in a captive chimpanzee (Pan troglodytes), and a review of spontaneous cases in animals. J Med Primatol 45:336-341
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Ákos Szabó, C; Salinas, Felipe S; Li, Karl et al. (2016) Modeling the effective connectivity of the visual network in healthy and photosensitive, epileptic baboons. Brain Struct Funct 221:2023-33
Schlabritz-Loutsevitch, Natalia E; Comuzzie, Anthony G; Mahaney, Michael M et al. (2016) Serum Vitamin D Concentrations in Baboons (Papio spp.) during Pregnancy and Obesity. Comp Med 66:137-42
Bauer, Cassondra; Harrison, Tara (2016) Retrospective Analysis of the Incidence of Retained Placenta in 3 Large Colonies of NHP. Comp Med 66:143-9

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