Shiftless antiviral inhibitor of ribosomal frameshifting protein (SHFL)

Shiftless antiviral inhibitor of ribosomal frameshifting protein (SHFL), encoded by the C19orf66 gene, is a broad-spectrum interferon-stimulated antiviral protein with structural features including a zinc-ribbon domain, nuclear localization/export signals, and domains involved in RNA and protein interactions[1][2]. SHFL restricts the replication of a range of RNA viruses (notably dengue, Zika, West Nile, hepatitis C, HIV-1) and some DNA viruses by binding viral RNA and inhibiting translation, frequently through suppression of −1 programmed ribosomal frameshifting (−1PRF) and destabilization of viral RNAs[1][2][3][4]. SHFL acts post-entry, interfering with multiple stages of viral gene expression, and collaborates with cellular partners such as PABPC1 and LARP1 to suppress viral translation[2]. Expression of SHFL is upregulated in response to type I interferon as part of the innate immune response, and genetic knockout in animal models leads to increased susceptibility and severity of viral neuropathogenesis[3]. SHFL is mainly cytoplasmic but also shuttles to the nucleus. No drugs are currently known to directly target SHFL, no biomarker use has been established, and there are no described safety concerns or therapeutic adverse effects in the literature[1][2][3][4].

Other names

C19orf66FLJ11286IRAVSFLRyDENUPF0515interferon-regulated antiviral proteinrepressor of yield of DENV proteinRepressor of yield of Dengue virusInterferon-regulated antiviral gene

Inhibition of programmed −1 ribosomal frameshifting (−1PRF), RNA binding and translation suppression, Destabilization of viral RNA, Interaction with host RNA-binding proteins to impair viral translation