The rev (trs/art) protein of human immunodeficiency virus type 1 affects viral mRNA and protein expression via a cis-acting sequence in the env region

Abstract

The study of expression of several human immunodeficiency virus type 1 proviral mutants in human cells in the presence or absence of rev (trslart) protein reveals that rev increases the levels of unspliced and env mRNA and the accumulated structural viral proteins. rev protein produced from appropriate expression vectors fully complements the rev-defective mutants. rev requires the presence of a specific cis-acting sequence for its function. This rev-responsive element sequence has been localized within a 520 base-pair fragment in the env region of human immunodeficiency virus type 1. gag and env expression is coordinately regulated by rev. Two independent cis-acting elements localized in the gag and env regions are responsible for the low levels ofgag and env mRNA in the absence of rev. These elements are different than the rev-responsive element and act independent of each other.

Translational control of retroviruses

“…The RRE/ Rev interaction. The Rev (regulator of expression of virion proteins) protein is a 116 amino-acid protein that induces the transport of incompletely spliced lentiviral RNAs harbouring the cis-acting Rev response element (RRE) between the nucleus and the cytoplasm [93][94][95][96] . The complete RRE of HIV-1 consists of 351 nucleotides and is a highly ordered RNA stem-loop structure located in the env gene [93][94][95][96][97] .…”

“…The Rev (regulator of expression of virion proteins) protein is a 116 amino-acid protein that induces the transport of incompletely spliced lentiviral RNAs harbouring the cis-acting Rev response element (RRE) between the nucleus and the cytoplasm [93][94][95][96] . The complete RRE of HIV-1 consists of 351 nucleotides and is a highly ordered RNA stem-loop structure located in the env gene [93][94][95][96][97] . Initially, the Rev protein binds with high affinity at a site located at the apex of the central stem of the RRE, where it can recruit additional Rev molecules through cooperative protein-protein and protein-RNA interactions [98][99][100][101][102] .…”

Nucleolar Localization of HIV-1 Rev Is Required, Yet Insufficient for Production of Infectious Viral Particles

“…We observed that Rev single-point mutations decrease the cytoplasmic export of the 9 kb HIV-1 mRNA, thereby leading to the decrease of p24 production, since p24 is derived from gag/pol precursors of 9 kb mRNA. 46,71 Two amino acid deletions of M8 did not significantly change the levels of the 9 kb mRNA, although disproportionately higher levels of 2 and 4 kb mRNA splice variants were observed. Impairment of Rev in facilitating nucleocytoplasmic transport of unspliced and partially spliced transcripts could result in the accumulation of fully spliced 2 kb transcripts, which encode Tat, Rev, and Nef proteins.…”

“…Functionality of Rev-NoLS mutations in the rescue of Rev deficiency during HIV-1 HXB2 production was investigated in HLfB, which upon expression of WT Rev generates viral particles. 46 Each Rev-EGFP NoLS variant was introduced into HLfB cells and viral particles collected 48 h afterward. Viral output of HIV-1 p24 capsid protein was quantified with enzyme-linked immunosorbent assay (ELISA) antigen capture assays ( Fig.…”

“…However, when deletions were expanded to residues WRE, resulting in complete elimination of WRERQRQ (amino acids [45][46][47][48][49][50][51], nuclear accumulation was observed. 34 Although a potential Rev-NoLS was identified at amino acids 45-51 downstream of the NLS, functionality of Rev nucleolar mutations was not investigated in the context of HIV-1 production and infection.…”