The HIV Rev gene was discovered more than 15 years ago and has been the subject of multiple studies. We now know that the Rev protein interacts not only with the RRE, but also with the cellular machinery in a complicated export pathway that enables the efficient expression of proteins from mRNAs that contain complete introns. In spite of the great insight into these processes that have been made in recent years, much remains to be elucidated. This proposal is focused on some of the aspects of Rev/RRE function that are not well understood.
The specific aims are:
Aim #1 : To further evaluate the importance of regions of the HIV RRE outside of stem loop II and the basis for changes in the RRE leading to RevM10 resistance.
Aim# 2: To further analyze the role of the cellular protein Sam68 in Rev function.
Aim#3 : To analyze Rev phosphorylation and its potential role in Rev function. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI054335-04
Application #
7038395
Study Section
Special Emphasis Panel (ZRG1-AARR-1 (11))
Program Officer
Young, Janet M
Project Start
2003-04-15
Project End
2008-03-31
Budget Start
2006-04-01
Budget End
2007-03-31
Support Year
4
Fiscal Year
2006
Total Cost
$287,726
Indirect Cost
Name
University of Virginia
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
065391526
City
Charlottesville
State
VA
Country
United States
Zip Code
22904
Rekosh, David; Hammarskjold, Marie-Louise (2018) Intron retention in viruses and cellular genes: Detention, border controls and passports. Wiley Interdiscip Rev RNA 9:e1470
Coyle, John H; Bor, Yeou-Cherng; Rekosh, David et al. (2011) The Tpr protein regulates export of mRNAs with retained introns that traffic through the Nxf1 pathway. RNA 17:1344-56
Shuck-Lee, Deidra; Chang, Hua; Sloan, Emily A et al. (2011) Single-nucleotide changes in the HIV Rev-response element mediate resistance to compounds that inhibit Rev function. J Virol 85:3940-9
Ward, Alex M; Rekosh, David; Hammarskjold, Marie-Louise (2009) Trafficking through the Rev/RRE pathway is essential for efficient inhibition of human immunodeficiency virus type 1 by an antisense RNA derived from the envelope gene. J Virol 83:940-52
Shuck-Lee, Deidra; Chen, Fei Fei; Willard, Ryan et al. (2008) Heterocyclic compounds that inhibit Rev-RRE function and human immunodeficiency virus type 1 replication. Antimicrob Agents Chemother 52:3169-79
Legiewicz, Michal; Badorrek, Christopher S; Turner, Kevin B et al. (2008) Resistance to RevM10 inhibition reflects a conformational switch in the HIV-1 Rev response element. Proc Natl Acad Sci U S A 105:14365-70
Swartz, Jennifer E; Bor, Yeou-Cherng; Misawa, Yukiko et al. (2007) The shuttling SR protein 9G8 plays a role in translation of unspliced mRNA containing a constitutive transport element. J Biol Chem 282:19844-53
Levesque, Lyne; Bor, Yeou-Cherng; Matzat, Leah H et al. (2006) Mutations in tap uncouple RNA export activity from translocation through the nuclear pore complex. Mol Biol Cell 17:931-43
Bor, Yeou-cherng; Swartz, Jennifer; Morrison, Avril et al. (2006) The Wilms' tumor 1 (WT1) gene (+KTS isoform) functions with a CTE to enhance translation from an unspliced RNA with a retained intron. Genes Dev 20:1597-608
Forrest, Scott T; Barringhaus, Kurt G; Perlegas, Demetra et al. (2004) Intron retention generates a novel Id3 isoform that inhibits vascular lesion formation. J Biol Chem 279:32897-903

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