Shiftless antiviral inhibitor of ribosomal frameshifting protein

Definition

Inhibits programmed -1 ribosomal frameshifting (-1PRF) of a variety of mRNAs from viruses, such as HIV1, and cellular genes, such as PEG10. Interacts with the -1PRF signal of target mRNA and translating ribosomes and causes premature translation termination at the frameshifting site. Regulates HIV1 GAG-POL expression by inhibiting -1PRF. Exhibits antiviral activity against dengue virus (DENV) and can inhibit the replication of all DENV serotypes. May block the protein translation of DENV RNA via its association with cellular mRNA-binding proteins and viral RNA. Interrupts also Zika virus replication by promoting viral NS3 degradation via a lysosome-dependent pathway. Can also limit the replication of hepatitis C virus (HCV) by restricting formation of viral replication organelle, West Nile virus (WNV), Chikungunya virus (CHIKV), herpes simplex virus type 1 (HHV-1), herpes virus type 8 (HHV-8) and human adenovirus. Binds nucleic acids with a higher affinity for ssRNA and ssDNA than for dsDNA.; Isoform 4 does not inhibit programmed ribosomal frameshifting (-1PRF). Does not bind to ribosomes.

References:

[1]. Yun Wu, et al. C19orf66 interrupts Zika virus replication by inducing lysosomal degradation of viral NS3. PLoS Negl Trop Dis. 2020 Mar 9;14(3):e0008083. [Content Brief]

[2]. Xinlu Wang, et al. Regulation of HIV-1 Gag-Pol Expression by Shiftless, an Inhibitor of Programmed -1 Ribosomal Frameshifting. Cell. 2019 Jan 24;176(3):625-635.e14. [Content Brief]

[3]. Corey A Balinsky, et al. IRAV ( FLJ11286), an Interferon-Stimulated Gene with Antiviral Activity against Dengue Virus, Interacts with MOV10. J Virol. 2017 Feb 14;91(5):e01606-16. [Content Brief]

[4]. Volker Kinast, et al. C19orf66 is an interferon-induced inhibitor of HCV replication that restricts formation of the viral replication organelle. J Hepatol. 2020 Sep;73(3):549-558. [Content Brief]

[5]. William Rodriguez, et al. C19ORF66 Broadly Escapes Virus-Induced Endonuclease Cleavage and Restricts Kaposi's Sarcoma-Associated Herpesvirus. J Virol. 2019 May 29;93(12):e00373-19. [Content Brief]

[6]. Youichi Suzuki, et al. Characterization of RyDEN (C19orf66) as an Interferon-Stimulated Cellular Inhibitor against Dengue Virus Replication. PLoS Pathog. 2016 Jan 6;12(1):e1005357. [Content Brief]

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