Nuclear Imprisonment: Viral Strategies to Arrest Host mRNA Nuclear Export

Kuss, Sharon K.; Mata, Miguel A.; Zhang, Liang; Fontoura, Beatriz M. A.

doi:10.3390/v5071824

Cited by 59 publications

(60 citation statements)

References 185 publications

(273 reference statements)

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“…Many viruses, including cytoplasmic replicating or nuclear replicating viruses, have been shown to target the nuclear transport machinery (for a complete review please see references “45,46”. Regulation of the nuclear transport machinery can facilitate major proviral outcomes: reduce competition with host factors for gene expression and prevent host antiviral responses.…”

Section: Mrna Export In Viral Infection and Metabolismmentioning

confidence: 99%

“…This effect prevents expression of host mRNAs that encode antiviral factors and makes the translation machinery available for expression of viral mRNAs. The mechanism of action of M protein is discussed elsewhere [45,46]. As a counterattack, the nuclear transport machinery can be up-regulated by antiviral cytokines, such as interferons, to antagonize the mRNA export block and promote antiviral response [47,48].…”

Section: Mrna Export In Viral Infection and Metabolismmentioning

confidence: 99%

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Nuclear Trafficking in Health and Disease

Mor¹,

White²,

Fontoura³

2014

Current Opinion in Cell Biology

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In eukaryotic cells, the cytoplasm and the nucleus are separated by a double-membraned nuclear envelope (NE). Thus, transport of molecules between the nucleus and the cytoplasm occurs via gateways termed the nuclear pore complexes (NPCs), which are the largest intracellular channels in nature. While small molecules can passively translocate through the NPC, large molecules are actively imported into the nucleus by interacting with receptors that bind nuclear pore complex proteins (Nups). Regulatory factors then function in assembly and disassembly of transport complexes. Signaling pathways, cell cycle, pathogens, and other physiopathological conditions regulate various constituents of the nuclear transport machinery. Here, we will discuss several findings related to modulation of nuclear transport during physiological and pathological conditions, including tumorigenesis, viral infection, and congenital syndrome. We will also explore chemical biological approaches that are being used as probes to reveal new mechanisms that regulate nucleocytoplasmic trafficking and that are serving as starting points for drug development.

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Section: Mrna Export In Viral Infection and Metabolismmentioning

confidence: 99%

Section: Mrna Export In Viral Infection and Metabolismmentioning

confidence: 99%

Nuclear Trafficking in Health and Disease

Mor¹,

White²,

Fontoura³

2014

Current Opinion in Cell Biology

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“…EBV is a well known DNA virus to interact with different nuclear export factors and co-opt many cellular proteins for replication within the nucleus, and transport of viral transcripts to the cytoplasm for protein synthesis [5].…”

Section: Introductionmentioning

confidence: 99%

Characterization of the Nucleocytoplasmic Transport Mechanisms of Epstein-Barr Virus BFLF2

Chen

Zou

et al. 2018

Cell Physiol Biochem

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Background/Aims: Epstein-Barr virus (EBV) BFLF2, the homologue of herpes simplex virus 1 (HSV-1) UL31, is crucial for the efficient viral DNA packaging and primary egress across the nuclear membrane. However, we still do not know its subcellular transport mechanisms. Methods: Interspecies heterokaryon assays were utilized to detect the nucleocytoplasmic shuttling of BFLF2, and mutation analysis, plasmid transfection and fluorescence microscopy assays were performed to identify the functional nuclear localization sequence (NLS) and nuclear export sequence (NES) of BFLF2 in live cells. Furthermore, the nuclear import and export of BFLF2 were assessed by confocal microscopy, co-immunoprecipitation and immunoblot assays. Results: BFLF2 was confirmed to shuttle between the nucleus and cytoplasm. Two predicted NESs were shown to be nonfunctional, yet we proved that the nuclear export of BFLF2 was mediated through transporter associated with antigen processing (TAP), but not chromosomal region maintenance 1 (CRM1) dependent pathway. Furthermore, one functional NLS, ²²RRLMHPHHRNYTASKASAH⁴⁰, was identified, and the aa22-23, aa22-25, aa28-30 and aa37-40 had an important role in the nuclear localization of BFLF2. Besides, the nuclear import of BFLF2 was demonstrated through Ran-, importin α7-, importin β1- and transportin-1-dependent mechanism that does not require importin α1, α3 and α5. Conclusion: These works are of significance for the further study of the functions of BFLF2 during EBV infection, as well as for further insights into the design of new antiviral drug target and vaccine development against EBV.

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“…This allows ICP27 to simultaneously block host nuclear import receptors, which prevents an antiviral response and facilitates viral production [110]. A more in-depth review of the viral modulation of nucleocytoplasmic transport has been conducted recently [111]. …”

Section: Npcs In Viral Infections and Immunitymentioning

confidence: 99%

The roles of the nuclear pore complex in cellular dysfunction, aging and disease

Sakuma

D’Angelo

2017

Seminars in Cell & Developmental Biology

115

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The study of the Nuclear Pore Complex (NPC), the proteins that compose it (nucleoporins), and the nucleocytoplasmic transport that it controls has revealed an unexpected layer to pathogenic disease onset and progression. Recent advances in the study of the regulation of NPC composition and function suggest that the precise control of this structure is necessary to prevent diseases from arising or progressing. Here we discuss the role of nucleoporins in a diverse set of diseases, many of which directly or indirectly increase in occurrence and severity as we age, and often shorten the human lifespan. NPC biology has been shown to play a direct role in these diseases and therefore in the process of healthy aging.

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Nuclear Imprisonment: Viral Strategies to Arrest Host mRNA Nuclear Export

Cited by 59 publications

References 185 publications

Nuclear Trafficking in Health and Disease

Nuclear Trafficking in Health and Disease

Characterization of the Nucleocytoplasmic Transport Mechanisms of Epstein-Barr Virus BFLF2

The roles of the nuclear pore complex in cellular dysfunction, aging and disease

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