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Understanding of the functional role(s) of the Activating Transcription Factor 4(ATF4) in HIV regulation and production
Ji Chang You1,*
1Pathology, The catholic university of korea
Abstract
The activating transcription factor (ATF) 4 belongs to the ATF/CREB (cAMP Response Element Binding bZIP (Basic Leucine Zipper)) transcription factor family, and plays a central role in the UPR (Unfolded Protein Response) process in cells. The induction of ATF4 expression has previously been shown to increase the replication of HIV-1. However, the detailed mechanism underlying this effect and the factors involved in the regulation of ATF4 function are still unknown. Here, we demonstrate first that knocking out ATF4 using siRNA shows a strong negative effect on HIV-1 production, indicating that ATF4 is a functional positive cellular factor in HIV-1 production. To determine the mechanism by which ATF4 regulates the HIV-1 life cycle, we assessed the effect of the overexpression of wild type ATF4 and its various derivatives on HIV-1 LTR-mediated transcriptional activation and the production of HIV-1 particles. This effect was studied through co-transfection experiments with either reporter vectors or proviral DNA. We found that the N-terminal domains of ATF4 are involved in HIV-1 LTR-mediated transcriptional activation, and thus in HIV-1 production.
Abstract, Accepted Manuscript(in press) [Submitted on March 13, 2018, Accepted on March 31, 2018]
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