SHFL

Last update 08 May 2025

Basic Info

Synonyms

C19orf66, FLJ11286, Interferon-regulated antiviral protein

+ [7]

Introduction

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 (PubMed:30682371). Regulates HIV1 GAG-POL expression by inhibiting -1PRF (PubMed:30682371). 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 (PubMed:32150556). 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 (PubMed:26735137, PubMed:27974568, PubMed:30944177, PubMed:32294532). Binds nucleic acids with a higher affinity for ssRNA and ssDNA than for dsDNA (PubMed:27974568). Isoform 4 does not inhibit programmed ribosomal frameshifting (-1PRF). Does not bind to ribosomes.

100 Clinical Results associated with SHFL

100 Translational Medicine associated with SHFL

0 Patents (Medical) associated with SHFL

112

Literatures (Medical) associated with SHFL

01 Apr 2025·International Immunopharmacology

C19orf66 restricts Coxsackievirus B infection by inducing lysosomal degradation of the viral proteins 3Dpol and 2Apro and exhibits neuroprotective effects in CVB-challenged mice

Article

Author: Qin, Xingliang ; Hong, Yu ; Li, Yangfan ; Tan, Yongyao ; Lei, Gewen ; He, Zhenjian ; Kang, Jiaqi ; Ren, Weishu ; Li, Xinyan ; Liu, Baichen ; Hou, Yuming ; Zhou, Wenle ; Zhu, Xun ; Wei, Guohong ; Zhou, Weiwei

Coxsackievirus B (CVB) represents one of the significant human pathogens that have been linked to several central nervous system disorders, particularly common among newborns and children. The annual outbreaks of CVB infection, pose a significant public health challenge and burden due to the absence of specific antiviral drugs and vaccines. However, the neuropathology of CVB infection remains elusive. The type I interferon response is well characterized for its role in controlling virus-induced neuropathogenesis. C19orf66 is known to be a potent interferon-stimulated gene with broad-spectrum antiviral activity, exerting its effects through diverse underlying molecular mechanisms. In this work, our study demonstrated that CVB induces the upregulation of C19orf66 both in host cells and in mice. Knockdown and overexpression of C19orf66 in CVB3-infected cells suggested that this factor could significantly suppress CVB3 replication. Our findings further revealed an intriguing mechanism by which C19orf66 could interact with the non-structural proteins 3D^pol and 2A^pro of CVB3, and promote the degradation of the viral 3D^pol and 2A^pro through a lysosome-dependent pathway. Furthermore, the zinc finger domain and amino acids 164-199 of C19orf66 were crucial for the interaction between C19orf66 and 3D^pol and 2A^pro of CVB3. In a mouse model of CVB neurological infection, C19orf66 knockout mice exhibited reduced survival, exacerbated neuropathological outcomes, and increased viral replication in the brain. Collectively, these findings demonstrated that C19orf66 is an important antiviral effector that contributes to host protection against CVB infection and CVB-induced neuropathological disease.

25 Mar 2025·Proceedings of the National Academy of Sciences

MITD1 is a brain-specific interferon-inducible factor that inhibits flavivirus replication

Article

Author: Wilson, Sam J. ; Davies, Emma ; Barthelemy, Jonathan ; Zoladek, Jim ; Simonin, Yannick ; Bribes, Ines ; Salinas, Sara ; Gorna, Kamila ; Palmarini, Massimo ; Arhel, Nathalie J. ; Coulpier, Muriel ; Desgraupes, Sophie ; Cannac, Marion ; Nisole, Sébastien ; Quellec, Jordan ; Seite, Maël

West Nile virus (WNV) and Usutu virus (USUV) are closely related mosquito-borne neurotropic flaviviruses that share common transmission cycle and can infect humans. However, while human infections by WNV are widespread, infections by USUV are comparatively less frequent, less severe, and currently limited to Africa and Europe. To identify human host factors that contribute to the pathogenic signatures of these two flaviviruses, we carried out an arrayed expression screen of over 1,300 interferon-stimulated genes (ISGs). Several ISGs known to target flaviviruses, including IFI6, SHFL, and RTP4 were among the strongest hits. Interestingly, we also found MITD1, an ISG with no previously reported antiviral activity, among the strongest hits. We demonstrated that the antiviral activity of MITD1 was not limited to USUV and WNV, since it also inhibited Zika and dengue virus replication. We found MITD1 to interfere with viral RNA replication by sequestering specific endosomal sorting complexes required for transport-III (ESCRT-III) proteins involved in the formation of viral replication factories. MITD1 expression was not increased by type I interferon (IFN-I) in most human cells and mouse tissues that we examined, although WNV and USUV replication was strongly inhibited by IFN-I. Strikingly, MITD1 was induced in the brain of USUV-infected mice and importantly, in human monocyte-derived microglia. Using human microglial-like cells, we confirmed that MITD1 is an essential mediator of the anti-flavivirus activity of IFN-I in these cells. We conclude that MITD1 plays a key role in the cellular defenses against neurotropic flaviviruses.

15 Jul 2024·The FASEB Journal

Dynamic changes of gut microbiota in mouse models of metabolic dysfunction‐associated steatohepatitis and its transition to hepatocellular carcinoma

Article

Author: Niu, Chen ; Wang, Yu‐Li ; Zhang, Li ; Guo, Xiao ; Yang, Yong‐Yu ; Liu, Chang ; Ding, Jia ; Wu, Jian ; Zhang, Ning‐Ping

AbstractDysbiosis of gut microbiota may account for pathobiology in simple fatty liver (SFL), metabolic dysfunction‐associated steatohepatitis (MASH), fibrotic progression, and transformation to MASH‐associated hepatocellular carcinoma (MASH‐HCC). The aim of the present study is to investigate gut dysbiosis in this progression. Fecal microbial rRNA‐16S sequencing, absolute quantification, histopathologic, and biochemical tests were performed in mice fed high fat/calorie diet plus high fructose and glucose in drinking water (HFCD‐HF/G) or control diet (CD) for 2, 16 weeks, or 14 months. Histopathologic examination verified an early stage of SFL, MASH, fibrotic, or MASH‐HCC progression with disturbance of lipid metabolism, liver injury, and impaired gut mucosal barrier as indicated by loss of occludin in ileum mucosa. Gut dysbiosis occurred as early as 2 weeks with reduced α diversity, expansion of Kineothrix, Lactococcus, Akkermansia; and shrinkage in Bifidobacterium, Lactobacillus, etc., at a genus level. Dysbiosis was found as early as MAHS initiation, and was much more profound through the MASH‐fibrotic and oncogenic progression. Moreover, the expansion of specific species, such as Lactobacillus johnsonii and Kineothrix alysoides, was confirmed by an optimized method for absolute quantification. Dynamic alterations of gut microbiota were characterized in three stages of early SFL, MASH, and its HCC transformation. The findings suggest that the extent of dysbiosis was accompanied with MASH progression and its transformation to HCC, and the shrinking or emerging of specific microbial species may account at least in part for pathologic, metabolic, and immunologic alterations in fibrogenic progression and malignant transition in the liver.

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SHFL

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