This project will characterize and develop the ability to transcriptionally modulate HIV-1 latency. We have recently discovered that antisense non-coding RNAs can regulate gene transcription and evidence suggests that HIV-1 also utilizes this mechanism to regulate latency. We will determine the underlying mechanism of action involved in antisense non-coding RNA regulation of viral latency and the ability to use this form of gene regulation to control HIV-1 expression. Results from this project will result in a paradigm shift with regards to controlled expression of HIV-1 that could prove valuable to society with regards to new anti-HIV therapeutics and vaccine design. 1

Public Health Relevance

Non-coding RNAs Involved in HIV-1 Latency This project will characterize and develop the ability to transcriptionally modulate HIV-1 latency. We have recently discovered that antisense non-coding RNAs can regulate gene transcription and evidence suggests that HIV-1 also utilizes this mechanism to regulate latency. We will determine the underlying mechanism of action involved in antisense non-coding RNA regulation of viral latency and the ability to use this form of gene regulation to control HIV-1 expression. Results from this project will result in a paradigm shift with regards to controlled expression of HIV-1 that could prove valuable to society with regards to new anti-HIV therapeutics and vaccine design.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI084406-02
Application #
7936316
Study Section
AIDS Discovery and Development of Therapeutics Study Section (ADDT)
Program Officer
Salzwedel, Karl D
Project Start
2009-09-23
Project End
2012-08-31
Budget Start
2010-09-01
Budget End
2012-08-31
Support Year
2
Fiscal Year
2010
Total Cost
$451,236
Indirect Cost
Name
Scripps Research Institute
Department
Type
DUNS #
781613492
City
La Jolla
State
CA
Country
United States
Zip Code
92037
Fortes, Puri; Morris, Kevin V (2016) Long noncoding RNAs in viral infections. Virus Res 212:1-11
Lazar, Daniel C; Morris, Kevin V; Saayman, Sheena M (2016) The emerging role of long non-coding RNAs in HIV infection. Virus Res 212:114-26
Saayman, Sheena; Ackley, Amanda; Turner, Anne-Marie W et al. (2014) An HIV-encoded antisense long noncoding RNA epigenetically regulates viral transcription. Mol Ther 22:1164-1175
Damski, Caio; Morris, Kevin V (2014) Targeted small noncoding RNA-directed gene activation in human cells. Methods Mol Biol 1173:1-10
Ackley, Amanda; Lenox, Alexandra; Stapleton, Kenneth et al. (2013) An Algorithm for Generating Small RNAs Capable of Epigenetically Modulating Transcriptional Gene Silencing and Activation in Human Cells. Mol Ther Nucleic Acids 2:e104
Vadaie, Nadia; Morris, Kevin V (2013) Long antisense non-coding RNAs and the epigenetic regulation of gene expression. Biomol Concepts 4:411-5
Turner, Anne-Marie W; Ackley, Amanda M; Matrone, Michael A et al. (2012) Characterization of an HIV-targeted transcriptional gene-silencing RNA in primary cells. Hum Gene Ther 23:473-83
Knowling, Stuart; Morris, Kevin V (2011) Non-coding RNA and antisense RNA. Nature's trash or treasure? Biochimie 93:1922-7
Morris, Kevin V (2011) The emerging role of RNA in the regulation of gene transcription in human cells. Semin Cell Dev Biol 22:351-8
Knowling, Stuart; Morris, Kevin V (2011) Epigenetic regulation of gene expression in human cells by noncoding RNAs. Prog Mol Biol Transl Sci 102:1-10

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