Targeted inhibition of HIV-1 latency Summary Human Immunodeficiency Virus type 1 (HIV) ravages the immune system of infected individuals by prolonged latent infection of immune cells. An understanding of the molecular mechanisms regulating latency could lead to strategies aimed at either inhibiting this process and purging cellular reservoirs of HIV. We have learned that an HIV expressed antisense long non-coding RNA (lncRNA) functions in epigenetically modulating viral transcription. In this project we propose to mechanistically validate the role of this lncRNA in driving viral latency, determine what host proteins are involved in the process, and develop an innovative strategy to treat cells such that the virus cannot enter latency. The completion of this project will significantly expand our current understanding of HIV infection and provide new avenues to modulate viral expression that may prove relevant in both therapeutic strategies to purge viral reservoirs as well as possible approaches to develop an HIV vaccine.

Public Health Relevance

This project will develop and mechanistically characterize an innovative method to deliver non-coding RNAs capable of transcriptionally regulating the ability of HIV to enter viral latency. This method may also lead to significant insights into how non-coding RNAs regulate gene expression, which could also prove useful beyond the scope of HIV, in areas such as cancer and genetic diseases.

Agency
National Institute of Health (NIH)
Type
Research Project (R01)
Project #
1R01AI111139-01
Application #
8688737
Study Section
Special Emphasis Panel (ZAI1)
Program Officer
Voulgaropoulou, Frosso
Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Scripps Research Institute
Department
Type
DUNS #
City
La Jolla
State
CA
Country
United States
Zip Code
92037
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
Fortes, Puri; Morris, Kevin V (2016) Long noncoding RNAs in viral infections. Virus Res 212:1-11
Saayman, Sheena M; Lazar, Daniel C; Scott, Tristan A et al. (2016) Potent and Targeted Activation of Latent HIV-1 Using the CRISPR/dCas9 Activator Complex. Mol Ther 24:488-98
Hewson, Chris; Morris, Kevin V (2016) Form and Function of Exosome-Associated Long Non-coding RNAs in Cancer. Curr Top Microbiol Immunol 394:41-56
Saayman, Sheena; Ali, Stuart A; Morris, Kevin V et al. (2015) The therapeutic application of CRISPR/Cas9 technologies for HIV. Expert Opin Biol Ther 15:819-30
Morris, Kevin V; Mattick, John S (2014) The rise of regulatory RNA. Nat Rev Genet 15:423-37