Abstract
The representative of the Lentivirus genus is the human immunodeficiency virus type 1 (HIV-1), the causative agent of acquired immunodeficiency syndrome (AIDS). To date, there is no cure for AIDS because of the existence of the HIV-1 reservoir. HIV-1 infection can persist for decades despite effective antiretroviral therapy (ART), due to the persistence of infectious latent viruses in long-lived resting memory CD4+ T cells, macrophages, monocytes, microglial cells, and other cell types. However, the biology of HIV-1 latency remains incompletely understood. Retroviral long terminal repeat region (LTR) plays an indispensable role in controlling viral gene expression. Regulation of the transcription initiation plays a crucial role in establishing and maintaining a retrovirus latency. Whether and how retroviruses establish latency and reactivate remains unclear. In this article, we describe what is known about the regulation of LTR-driven transcription in HIV-1, that is, the cis-elements present in the LTR, the role of LTR transcription factor binding sites in LTR-driven transcription, the role of HIV-1-encoded transactivator protein, hormonal effects on virus transcription, impact of LTR variability on transcription, and epigenetic control of retrovirus LTR. Finally, we focus on a novel clustered regularly interspaced short palindromic repeats-associated protein 9 (CRISPR/dCas9)-based strategy for HIV-1 reservoir purging.
Highlights
Received: 1 December 2020 Accepted: 24 December 2020 Published: 29 December 2020Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.The human immunodeficiency virus type 1 (HIV-1) belongs to the family of Retroviridae, subfamily Orthoretrovirinae, and genus Lentivirus
These results suggest that the glucocorticoid receptor binding site in HIV-1 long terminal repeat region (LTR) could mediate either activation or repression of viral gene expression depending on the target cell type
They showed that thymidine to guanosine (T > G) substitution at position 6 of the CCAAT/enhancer binding protein (C/EBP) site I resulted in increased C/EBP binding and LTR activity, and observed that the frequency of such particular mutation was higher in central nervous system (CNS)-derived viruses compared with those viruses obtained from peripheral blood [53]
Summary
Received: 1 December 2020 Accepted: 24 December 2020 Published: 29 December 2020. Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Certain cell types and the cell differentiation processes with respect to diversity of cell activation signals may contribute to substantial variations in transcriptional activity of LTR [3] All these variables generate a remarkably broad range in HIV-1 gene expression level. The latently infected cells are a source of viral reactivation and lead to marked increase of the viral load after a pause of highly active antiretroviral therapy (HAART). In this context, a better understanding of the molecular mechanisms responsible for the regulation of proviral latency and reactivation would define rational strategies aimed at purging the HIV-1 reservoirs in treated patients. We discuss a novel clustered regularly interspaced short palindromic repeats-associated protein 9 (CRISPR/dCas9)based strategy for HIV-1 reservoir purging
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