The Restrictome of Flaviviruses

Abstract

Flaviviruses are a genus of mostly arthropod-borne RNA viruses that cause a range of pathologies in humans. Basic knowledge on flaviviruses is rapidly expanding, partly due to their status as frequent emerging or re-emerging pathogens. Flaviviruses include the dengue, Zika, West Nile, tick-borne encephalitis and yellow fever viruses (DENV, ZIKV, WNV, TBEV and YFV, respectively). As is the case with other families of viruses, the success of productive infection of human cells by flaviviruses depends in part on the antiviral activity of a heterogeneous group of cellular antiviral proteins called restriction factors. Restriction factors are the effector proteins of the cell-autonomous innate response against viruses, an immune pathway that also includes virus sensors as well as intracellular and extracellular signal mediators such as type I interferons (IFN-I). In this review, I summarize recent progress toward the identification and characterization of flavivirus restriction factors. In particular, I focus on IFI6, Schlafen 11, FMRP, OAS-RNase L, RyDEN, members of the TRIM family of proteins (TRIM5a, TRIM19, TRIM56, TRIM69 and TRIM79a) and a new mechanism of action proposed for viperin. Recent and future studies on this topic will lead to a more complete picture of the flavivirus restrictome, defined as the ensemble of cellular factors with demonstrated anti-flaviviral activity.

Human plasmacytoid dendritic cells at the crossroad of type I interferon-regulated B cell differentiation and antiviral response to tick-borne encephalitis virus

“…Therefore, investigating the human immune response to this infection is important to gain further understanding into treatment and prevention of the disease. As for other viral families, in the case of several flaviviruses, the innate host defense mostly depends on the antiviral activity of a heterogeneous group of cellular antiviral proteins that include virus sensors and intra- and extracellular signal mediators such as type I interferon (IFN) [ 8 ]. Indeed, the IFN response is a fundamental part of the innate immune system due to its capacity to activate the expression of several genes, known as IFN-stimulated genes (ISGs), which in turn inhibit virus multiplication at the level of transcription, translation, genome replication, assembly and exit and stimulate subsequent adaptive immune response [ 9 , 10 ].…”

West Nile Virus Restriction in Mosquito and Human Cells: A Virus under Confinement

“…Furthermore, many IRFs, such as IRF3 [ 90 , 91 ], IRF7 [ 91 , 92 ], and IRF5 [ 91 , 93 ], were demonstrated as being crucial for WNV restriction by mediating the IFN-dependent and/or IFN-independent response. Most restriction factors active against WNV identified so far are ISGs [ 94 ], thus confirming the importance of the IFN system upon WNV infection.…”

Transcriptional analysis of lung epithelial cells using WGCNA revealed the role of IRF9 and IFI6 genes in SARS-CoV-2 pathogenicity

“…On the other hand, it is identi ed that IFI6 up-regulation potentiates the antiviral activity of IFN-α and restricts replication of several RNA viruses including dengue, Zika, West Nile and yellow fever viruses (Dengue virus (DENV), Zika virus (ZIKV), West Nile virus (WNV) and Yellow fever virus (YFV) respectively) as shown by its ability to interfere in YFV replication indirectly via preventing viral invagination into endoplasmic reticulum (ER) [47][48][49]. However, this antiviral mechanism of IFI6 localized in ER seem to be speci c to aviviruses due to lack of inhibitory effect on neither HCV nor coronavirus replication in COS-7 cells that organized in double-membrane ER structures [48].…”