Tat basic domain: A “Swiss army knife” of HIV‐1 Tat?

Abstract

Summary Tat (transactivator of transcription) regulates transcription from the HIV provirus. It plays a crucial role in disease progression, supporting efficient replication of the viral genome. Tat also modulates many functions in the host genome via its interaction with chromatin and proteins. Many of the functions of Tat are associated with its basic domain rich in arginine and lysine residues. It is still unknown why the basic domain exhibits so many diverse functions. However, the highly charged basic domain, coupled with the overall structural flexibility of Tat protein itself, makes the basic domain a key player in binding to or associating with cellular and viral components. In addition, the basic domain undergoes diverse posttranslational modifications, which further expand and modulate its functions. Here, we review the current knowledge of Tat basic domain and its versatile role in the interaction between the virus and the host cell.

HIV-1 Tat Activates Akt/mTORC1 Pathway and AICDA Expression by Downregulating Its Transcriptional Inhibitors in B Cells

“…The Akt/mTORC1 pathway is often upregulated in AIDS-related B-cell lymphomas [13,[16][17][18][19][20][21]. Tat is constantly present in detectable concentrations in patients' blood serum [12,50] and can potentially enter any cell in a human body due to its cell penetration domain [51]. Tat's presence leads to transient ROS activation and DNA damage, which in the long term may induce chromosomal aberrations typical of lymphomas [15].…”

Oncogenic Properties of the EBV ZEBRA Protein

“…ZEBRA CPD is rich in positively charged residues (seven lysines and seven arginines), mostly within DBD (basic region) ( Figure S1A in blue), whereas hydrophobic amino acids (one valine, five alanines, seven leucines) of CPD are mostly within DD (leucine zipper) (Figure S1B in red) [36]. In another protein possessing the CPD, human immunodeficiency virus (HIV)-1 Tat, the CPD region is also multifunctional [47]. Presumably, the cationic part serves for interaction with the negatively charged phosphate groups of membrane phospholipids as well as on DNA, while hydrophobic residues interact with the hydrophobic part of the phospholipid membrane and participate in ZEBRA's dimerization ( Figure S1C).…”

Tat-Based Therapies as an Adjuvant for an HIV-1 Functional Cure

“…The first 48 amino acids are the activation domain, followed by the basic domain (amino acids [49][50][51][52][53][54][55][56][57]. The basic domain of Tat is required for Tat's nuclear localization and the binding of Tat to the HIV RNA stem loop structure, called the transactivation response (TAR) RNA, as well as many other Tat functions [31]. Without Tat, HIV transcription by RNA polymerase II (RNAP II) is very inefficient and viral RNA transcripts corresponding to TAR RNA are less than 60 nucleotides long [32][33][34][35], as observed in cell line models of HIV latency and in HIV + people [36].…”

“…The basic domain of Tat is essential for TAR RNA interaction and has versatile roles in the interaction of Tat and the host cell factors, which have been reviewed by Kurnaeva et al [31]. Tat interacts with HIV reverse transcriptase and stimulates reverse transcription [61,62].…”