Table 1 Various strategies involved in targeting Rev protein in HIV-1 infection
Strategy | Mechanism of action | Reference |
|---|---|---|
Romidepsin | It is a cyclic tetrapeptide HDAC inhibitor which is an investigational drug in Phase-2 clinical trials for HIV-1 infection treatment in combination with ART. It acts as a latency-reversing agent | [43] |
ADAR-1 protein | ADAR1 mediated inhibition of viral protein synthesis occurs at a post-transcriptional step of viral replication, at the step of nuclear export of viral Gag, Pol and Env mRNA. This effect of ADAR1 on nuclear export was seen to be due to ADAR1-induced A-to-G mutations on Rev and RRE region on env. These ADAR1 induced A-to-G mutations on HIV-1 rev and env mRNA correlated with inhibition of virus replication, production and infectivity | [44] |
Pyronin Y | Pyronin Y is an intercalating dye which has an ability to inhibit the complex formation between the HIV-1 Rev protein and RRE-containing RNA | [45] |
Aminoglycoside antibiotics | Certain aminoglycoside antibiotics, in particular neomycin B, can block binding of the HIV Rev protein to its viral RNA recognition element and found to be effective in vitro and in vivo | [46] |
miRNA | Human miR-186, 210, and 222 directly regulate the human genes Dicer1, HRB, and HIV-EP2, thus downregulating HIV-1 replication and miRNA biogenesis | [47] |
Benfluron | Benfluron inhibits RRE-Rev ribonucleoprotein formation by binding to the RRE RNA, and blocks Rev action and HIV-1 transcription | [48] |
Leptomycin B | It inhibits the nucleo-cytoplasmic translocation of Rev at nanomolar concentrations. Rev dependent export of mRNA into the cytoplasm is also blocked by leptomycin B, which inhibits Rev-dependent, but not Rev-independent gene expression in a short-term transfection assay | [49] |
Anti-Rev antibodies | An anti-Rev single-chain variable fragment (SFv) moiety can be efficiently expressed, using murine retroviral vectors, in human T lymphocytic cell lines as well as in primary human blood mononuclear cells (PBMC). Both mixed cellular populations and cell clones, transduced with the anti-Rev SFv, demonstrated significant resistance to productive human immunodeficiency virus type 1 (HFV-l) replication | [50] |
Rev aptamers | The lead aptamer designated as A-1 was fused to a siRNA that targeted the HIV-1 tat/rev RNAs that encode early regulatory proteins required for replication. The resulting chimeric construct (Ch A-1) is designed to deliver the siRNA to HIV-1-infected cells, resulting in targeted, RNAi-mediated knockdown of Tat/Rev expression | [35] |
Small molecule inhibitors (791, 833, 891) | All three compounds resulted in significant reduction in the accumulation of both Tat and Rev thus inhibit HIV-1 protein expression in vitro by blocking expression of both early (Rev, Tat) and late (Gag, Env) HIV-1 proteins | [42] |