Overexpression of SARS-CoV-2 protein ORF6 dislocates RAE1 and NUP98 from the nuclear pore complex

Kato, Kanefusa; Ikliptikawati, Dini Kurnia; Kobayashi, Akito; Kondo, Hiroya; Lim, Keesiang; Hazawa, Masaharu; Wong, Richard W.

doi:10.1016/j.bbrc.2020.11.115

Cited by 59 publications

(85 citation statements)

References 39 publications

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“…In this context, Met58 in ORF6 would play a critical role since structural differences are evident between both proteins (36,39). In line with this nuclear-cytoplasm trafficking inhibition, Kato and collaborators evidenced accumulation of heterogeneous ribonucleoprotein A (hnRNPA1) in the nucleus when expressing ORF6 protein when compared to their control counterparts (40).…”

Section: Orf6mentioning

confidence: 84%

SARS-CoV-2 Accessory Proteins in Viral Pathogenesis: Knowns and Unknowns

et al. 2021

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There are still many unanswered questions concerning viral SARS-CoV-2 pathogenesis in COVID-19. Accessory proteins in SARS-CoV-2 consist of eleven viral proteins whose roles during infection are still not completely understood. Here, a review on the current knowledge of SARS-CoV-2 accessory proteins is summarized updating new research that could be critical in understanding SARS-CoV-2 interaction with the host. Some accessory proteins such as ORF3b, ORF6, ORF7a and ORF8 have been shown to be important IFN-I antagonists inducing an impairment in the host immune response. In addition, ORF3a is involved in apoptosis whereas others like ORF9b and ORF9c interact with cellular organelles leading to suppression of the antiviral response in infected cells. However, possible roles of ORF7b and ORF10 are still awaiting to be described. Also, ORF3d has been reassigned. Relevant information on the knowns and the unknowns in these proteins is analyzed, which could be crucial for further understanding of SARS-CoV-2 pathogenesis and to design strategies counteracting their actions evading immune responses in COVID-19.

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Section: Orf6mentioning

confidence: 84%

SARS-CoV-2 Accessory Proteins in Viral Pathogenesis: Knowns and Unknowns

et al. 2021

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“…We found that, along with being able to impair nuclear import, SARS-CoV-2 Orf6 can also block nuclear export [76]. Our results show mislocalizations of Nup98 and Rae1 in Orf6-overexpressing cells [76]. In addition, nuclear accumulation of the nuclear RNAbinding protein hnRNPA1 was observed in Orf6-overexpressing cells.…”

Section: Mechanisms Of the Host Nuclear Transport Machinery Hijacking By Virusesmentioning

confidence: 61%

“…The associations suggested by these PPI analyses need to be validated by further experiments. To date, only Orf6 has been shown to interrupt the host nucleocytoplasmic trafficking [75][76][77][78] and to induce an aberrant distribution of Nups (Nup98 and Rae1) [76]. Xia et al found that Orf6 binds to importin-α1 to block the nuclear translocation of IRF3, resulting in an impaired type I IFN production in the HEK293T cell line [78].…”

Section: Mechanisms Of the Host Nuclear Transport Machinery Hijacking By Virusesmentioning

confidence: 99%

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How SARS-CoV-2 and Other Viruses Build an Invasion Route to Hijack the Host Nucleocytoplasmic Trafficking System

Sajidah

Lim

Wong

2021

Cells

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The host nucleocytoplasmic trafficking system is often hijacked by viruses to accomplish their replication and to suppress the host immune response. Viruses encode many factors that interact with the host nuclear transport receptors (NTRs) and the nucleoporins of the nuclear pore complex (NPC) to access the host nucleus. In this review, we discuss the viral factors and the host factors involved in the nuclear import and export of viral components. As nucleocytoplasmic shuttling is vital for the replication of many viruses, we also review several drugs that target the host nuclear transport machinery and discuss their feasibility for use in antiviral treatment.

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“…Striking examples are Dengue and Zika viruses of the Flaviviridae family since they encode a protease called NS3, which also targets FG-nucleoporins such as NUP153 and NUP98 to trigger mislocalization of cellular components between the nucleus and the cytoplasm [ 75 ]. Another timely example is the coronavirus SARS-CoV-2: ORF6 encoded by this virus interacts and misplaces NUP98 and RAE1 [ 76 ]. This induces a bidirectional perturbation of the nucleocytoplasmic traffic, a retention of mRNA in the nucleus [ 77 ], and a blockade of STAT1/2 dimer translocation into the nuclei resulting in interferon signaling inhibition [ 78 ].…”

Section: Conclusion and Discussionmentioning

confidence: 99%

Nucleocytoplasmic Trafficking Perturbation Induced by Picornaviruses

Lizcano-Perret

Michiels

2021

Viruses

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Picornaviruses are positive-stranded RNA viruses. Even though replication and translation of their genome take place in the cytoplasm, these viruses evolved different strategies to disturb nucleocytoplasmic trafficking of host proteins and RNA. The major targets of picornavirus are the phenylalanine-glycine (FG)-nucleoporins, which form a mesh in the central channel of the nuclear pore complex through which protein cargos and karyopherins are actively transported in both directions. Interestingly, while enteroviruses use the proteolytic activity of their 2A protein to degrade FG-nucleoporins, cardioviruses act by triggering phosphorylation of these proteins by cellular kinases. By targeting the nuclear pore complex, picornaviruses recruit nuclear proteins to the cytoplasm, where they increase viral genome translation and replication; they affect nuclear translocation of cytoplasmic proteins such as transcription factors that induce innate immune responses and retain host mRNA in the nucleus thereby preventing cell emergency responses and likely making the ribosomal machinery available for translation of viral RNAs.

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Overexpression of SARS-CoV-2 protein ORF6 dislocates RAE1 and NUP98 from the nuclear pore complex

Cited by 59 publications

References 39 publications

SARS-CoV-2 Accessory Proteins in Viral Pathogenesis: Knowns and Unknowns

SARS-CoV-2 Accessory Proteins in Viral Pathogenesis: Knowns and Unknowns

How SARS-CoV-2 and Other Viruses Build an Invasion Route to Hijack the Host Nucleocytoplasmic Trafficking System

Nucleocytoplasmic Trafficking Perturbation Induced by Picornaviruses

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