Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Virology. Aug 12, 2015; 4(3): 219-244
Published online Aug 12, 2015. doi: 10.5501/wjv.v4.i3.219
Post-transcriptional gene silencing, transcriptional gene silencing and human immunodeficiency virus
Catalina Méndez, Chantelle L Ahlenstiel, Anthony D Kelleher
Catalina Méndez, Chantelle L Ahlenstiel, Anthony D Kelleher, the Kirby Institute for Infection and Immunity, Wallace Wurth Building-Level 5, Faculty of Medicine, University of New South Wales, Kensington NSW 2052, Australia
Anthony D Kelleher, 2nd St Vincent’s Centre for Applied Medical Research, Darlinghurst NSW 2010, Australia
Author contributions: Méndez C, Ahlenstiel CL and Kelleher AD solely contributed to this paper.
Conflict-of-interest statement: The authors are named inventors on a provisional patent of a short RNA molecule that suppresses HIV-1 infection. Authors declare there are no conflicts of interest among them.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Correspondence to: Anthony D Kelleher, MBBS, PhD, Professor, the Kirby Institute for Infection and Immunity, Wallace Wurth Building- Level 5, Faculty of Medicine, University of New South Wales, Kensington NSW 2052, Australia.
Telephone: + 61-2-93850182 Fax: +61-2-93850468
Received: December 6, 2014
Peer-review started: December 6, 2014
First decision: December 26, 2014
Revised: January 24, 2015
Accepted: April 27, 2015
Article in press: April 29, 2015
Published online: August 12, 2015

While human immunodeficiency virus 1 (HIV-1) infection is controlled through continuous, life-long use of a combination of drugs targeting different steps of the virus cycle, HIV-1 is never completely eradicated from the body. Despite decades of research there is still no effective vaccine to prevent HIV-1 infection. Therefore, the possibility of an RNA interference (RNAi)-based cure has become an increasingly explored approach. Endogenous gene expression is controlled at both, transcriptional and post-transcriptional levels by non-coding RNAs, which act through diverse molecular mechanisms including RNAi. RNAi has the potential to control the turning on/off of specific genes through transcriptional gene silencing (TGS), as well as fine-tuning their expression through post-transcriptional gene silencing (PTGS). In this review we will describe in detail the canonical RNAi pathways for PTGS and TGS, the relationship of TGS with other silencing mechanisms and will discuss a variety of approaches developed to suppress HIV-1 via manipulation of RNAi. We will briefly compare RNAi strategies against other approaches developed to target the virus, highlighting their potential to overcome the major obstacle to finding a cure, which is the specific targeting of the HIV-1 reservoir within latently infected cells.

Keywords: Human immunodeficiency virus 1, RNA interference, Reservoirs, Epigenetics, Latency, Transcriptional gene silencing, Post-transcriptional gene silencing

Core tip: The lack of progress in developing an effective human immunodeficiency virus 1 (HIV-1) vaccine has motivated the pressing need for alternate therapies to cure HIV. RNAi therapeutics represent an alternate approach to a functional cure by offering specific targeting of the HIV-1 latent reservoir with the significant advantage of allowing cessation of combination antiretroviral therapy.