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. The Gastrointestinal tract (GIT) is a major target of HIV/SIV infection. Although our understanding of HIV/SIV enteropathy has greatly improved, the recent discovery of miRNAs has added yet another novel and complex regulator of gene expression with potential roles in the molecular pathogenesis of this disorder. microRNAs (miRNAs) are genomically transcribed, ~21-23 nucleotide noncoding RNAs that are highly conserved and suppress gene expression by targeting mRNAs for translational repression or degradation. We investigated the contribution of miRNAs to GIT disease and inflammation using the SIV-infected rhesus macaque model. Colon tissue was collected at necropsy from 8 acutely SIV-infected (G1) (n=3, 8 days post SIV infection and n=5, 13-30 days post SIV infection) and 5 uninfected control macaques (G2). The contribution of miRNAs to GIT disease and inflammation was investigated using TaqMan Low Density Array (TLDA), QRT-PCR, In situ hybridization/Immunofluorescence and histopathology. Approximately 70% of the 377 miRNAs on card A and 50% of the 377 miRNAs on card B cross-reacted with the rhesus macaque. Following data analysis using STATMINER we identified a total of 25 card A and 12 card B miRNAs to be differentially expressed (p 0.05) in response to SIV infection. Important differentially expressed card A miRNAs included miR-1, -26a, -29c, -34a, -125b, -126, -130a, -133b, -135a, -140-5p, -let7b, -let7c, -222, -224, -383. Similarly, notable differentially expressed card B miRNAs included -190b, -550, -1247. QRT-PCR to further confirm TLDA expression profiles and in situ hybridization studies to identify specific cell types expressing these miRNAs are currently in progress. Our findings suggest that deregulation in cell/tissue-specific expression of miRNAs occurring in response to HIV/SIV infection may disrupt the functional relationship between the intestinal epithelium and the mucosal immune system causing alterations in intestinal structure and function.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Primate Research Center Grants (P51)
Project #
5P51RR000164-50
Application #
8358100
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
$45,154
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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