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Innate Immune Response to HIV

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Mishma:
It escaped my attention on the Zinc Finger Protease (nuclease) "stacking" posts that the gene cassette they use includes the innate pattern recognition receptors TRIM5 alpha, which recognizes the capsid of HIV within the cells cytoplasm and APOBEC3G, which interferes with viral replication. CCR5, which is edited out in this system, can also be considered an innate pattern recognition receptor (Yes it normally binds a chemokine but it's structure doesn't change over the course of the immune response) as well as one of the HIVs co-receptors required for entry. 



http://en.wikipedia.org/wiki/APOBEC3G
http://en.wikipedia.org/wiki/TRIM5alpha

http://www.amfar.org/Stopping-HIV-Using-a-Cocktail-of-Genes-Rather-than-Drugs/?msource=1302enews

Stopping HIV Using a Cocktail of Genes Rather than Drugs: An amfAR Grantee Update

By Jeffrey Laurence, M.D.
Published Friday, February 15, 2013


Dr. Matthew Porteus
 
The headline in The Huffington Post heralded this new amfAR-funded work by stating that, “HIV-resistant cells created by Stanford researchers could protect patients from AIDS.” An ABC News blog further declared that, “Genetically modified cells could prevent death from HIV/AIDS, study finds.” And what led to all this promise and excitement? amfAR grantees Dr. Matthew Porteus, working in the Department of Pediatrics at Stanford University, and Sara Sawyer at the University of Texas, have worked with colleagues to create, in the test tube, genetically modified human T cells resistant to HIV infection.

Porteus, Sawyer and colleagues took a lead from prior amfAR-funded research into so-called “restriction factors,” or normal cellular genes that have the capacity to limit the growth of HIV. Utilizing a novel and complex gene strategy based on enzymes that can cut into a host’s DNA, they were able to insert such factors—including APOBEC3G and TRIM5α—into a host gene, CCR5, disrupting that gene in the process. CCR5 normally codes for a critical receptor, or door, by which most strains of HIV enter a cell.

- See more at: http://www.amfar.org/Stopping-HIV-Using-a-Cocktail-of-Genes-Rather-than-Drugs/?msource=1302enews#sthash.W8D87keH.dpuf

Mishma:
I suspect everyone reading knows the "central dogma," of Molecular Biology, at least the simplist view we held onto until the 90's. DNA codes for RNA and RNA in turn is the blueprint for proteins, enzymes and other structural components that make us up. During the early 90's and continuing up till today we've become aware of what is called RNA interference, a process whereby a single strand of RNA is covered by it's complement and is therefore marked for degradation through a innate pattern/damage recognition receptor(s).

HIV is able to escape intracellular immune surveilance and integrates itself within our DNA, capturing along the way several important transcription factors which are involved in immune activation. Now we have long interferring RNA's, one of which is identified in this paper.

If you find this abstract too difficult I've given links further up this post that describe in detail the Innate Immune Responce.




http://www.sciencemag.org/content/341/6147/789.abstract?sid=33a13fed-1155-41aa-9d78-dbb398b3e9e2

Published Online August 1 2013
Science 16 August 2013:
Vol. 341 no. 6147 pp. 789-792
DOI: 10.1126/science.1240925
REPORT
A Long Noncoding RNA Mediates Both Activation and Repression of Immune Response Genes
Susan Carpenter1,2, Daniel Aiello1, Maninjay K. Atianand1, Emiliano P. Ricci3, Pallavi Gandhi1, Lisa L. Hall4, Meg Byron4, Brian Monks1, Meabh Henry-Bezy1, Jeanne B. Lawrence4, Luke A. J. O’Neill2, Melissa J. Moore3, Daniel R. Caffrey1,*,†, Katherine A. Fitzgerald1,*,†
+ Author Affiliations

1Division of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
2School of Biochemistry and Immunology, Trinity College Dublin, Dublin 2, Ireland.
3Howard Hughes Medical Institute, University of Massachusetts Medical School, Worcester, MA 01605, USA.
4Department of Cell and Developmental Biology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
↵†Corresponding author. E-mail: kate.fitzgerald@umassmed.edu (K.A.F.); daniel.caffrey@umassmed.edu (D.R.C.)
↵* These authors contributed equally to this work.

ABSTRACTEDITOR'S SUMMARY
An inducible program of inflammatory gene expression is central to antimicrobial defenses. This response is controlled by a collaboration involving signal-dependent activation of transcription factors, transcriptional co-regulators, and chromatin-modifying factors. We have identified a long noncoding RNA (lncRNA) that acts as a key regulator of this inflammatory response. Pattern recognition receptors such as the Toll-like receptors induce the expression of numerous lncRNAs. One of these, lincRNA-Cox2, mediates both the activation and repression of distinct classes of immune genes. Transcriptional repression of target genes is dependent on interactions of lincRNA-Cox2 with heterogeneous nuclear ribonucleoprotein A/B and A2/B1. Collectively, these studies unveil a central role of lincRNA-Cox2 as a broad-acting regulatory component of the circuit that controls the inflammatory response.

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