The APOBECs: A Biodefense Against 'Retro-threats' Foreign and Domestic |
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| Air date: | Wednesday, October 08, 2008, 3:00:00 PM |
| Category: | Wednesday Afternoon Lectures |
| Description: | APOBEC3G (A3G) corresponds to a human cytidine deaminase that can impair the replication of HIV and other retroviruses. When encapsidated into HIV virions, A3G induces extensive dC-dU mutations in the nascent minus strand DNA of the virus formed during reverse transcription. These antiviral effects of A3G are countered by HIV Vif, which binds to A3G, recruits a Cul5/ElonginB/C ubiquitin ligase complex, and triggers A3G degradation by the 26S proteasome thereby precluding effective virion encapsidation of this antiviral enzyme.
The identification of small molecules capable of blocking Vif binding to A3G or Vif recruitment of the E3 ligage complex could ultimately lead to an exciting new class of HIV therapeutics that might re-enable a powerful intrinsic defense against HIV. Apart from its antiviral effects in virions, A3G also exerts antiviral activity within select types of cells. Specifically, a low-molecular-mass form of cellular A3G found in resting CD4 T cells and monocytes potently impairs the replication of incoming viruses by interfering with reverse transcription. However, when T cells are activated, this defense is lost because LMM A3G is swept into high-molecular-mass ribonucleoprotein complexes. Interestingly, these HMM A3G complexes mediate a second important defensive function. They impair the retrotransposition of endogoneous nonautonomous retroelements most notably Alu. Indeed, the expression of Alu retroelement RNA during T cell activation triggers HMM A3G complex assembly- an event that unfortunately “opens the door” for HIV infection. In contrast to humans where seven APOBEC3 genes have been identified, mice express a single APOBEC3 gene. It appears likely that the expansion of the APOBEC3 family of genes in primates was driven by the need to limit retroelement retransposition. Additional studies describing unexpected functions of the murine APOBEC3 gene product gleaned from studies of Apobec3-deficient mice will also be presented. The NIH Director's Wednesday Afternoon Lecture Series includes weekly scientific talks by some of the top researchers in the biomedical sciences worldwide. For more information, visit http://www.gladstone.ucsf.edu/gladstone/site/greene/ |
| Author: | Warner Greene, Director and Senior Investigator, Gladstone Institute of Virology and Immunology, UCSF |
| Runtime: | 60 minutes |
| Download: | Download
Video How to download a Videocast |
| CIT File ID: | 14696 |
| CIT Live ID: | 7208 |
| Permanent link: | http://videocast.nih.gov/launch.asp?14696 |
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Enhanced Audio Podcast | 1:02:36 |
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Enhanced Video Podcast | 1:02:36 | |