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Review
. 2019 Jun 8;8(6):559.
doi: 10.3390/cells8060559.

Viral Appropriation: Laying Claim to Host Nuclear Transport Machinery

Affiliations
Review

Viral Appropriation: Laying Claim to Host Nuclear Transport Machinery

Tanner M Tessier et al. Cells. .

Abstract

Protein nuclear transport is an integral process to many cellular pathways and often plays a critical role during viral infection. To overcome the barrier presented by the nuclear membrane and gain access to the nucleus, virally encoded proteins have evolved ways to appropriate components of the nuclear transport machinery. By binding karyopherins, or the nuclear pore complex, viral proteins influence their own transport as well as the transport of key cellular regulatory proteins. This review covers how viral proteins can interact with different components of the nuclear import machinery and how this influences viral replicative cycles. We also highlight the effects that viral perturbation of nuclear transport has on the infected host and how we can exploit viruses as tools to study novel mechanisms of protein nuclear import. Finally, we discuss the possibility that drugs targeting these transport pathways could be repurposed for treating viral infections.

Keywords: antiviral agents; infection; nuclear transport; protein localization; viral mimicry; virus.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Viral appropriation of cellular nucleocytoplasmic transport. (A) Classical protein nuclear import mediated by Importin-α (Imp-α; green) and Importin-β (Imp-β; blue), and nuclear export pathways mediated by Crm1 (pink). (BF) Selected examples of viruses perturbing or utilizing different components of the nuclear transport pathway. (B) Viruses can utilize the classical Imp-α/β pathway, Imp-β directly, the nuclear pore complex (NPC), or transportin through a PY-nuclear localization signal (PY-NLS) for nuclear import as well as Crm1 for nuclear export. (C) Viral proteins can perturb global nuclear transport by altering the dynamics of the NPC though the degradation or phosphorylation of nucleoporins (Nups). (D) Preventing nuclear import, or promoting export, of cellular proteins such as signal transducer and activator of transcription 1 (STAT1), interferon regulatory factor 3 (IRF3), or nuclear factor-kappa B (NF-κB) can block the antiviral innate immune response. (E) Venezuelan equine encephalitis virus (VEEV) capsid protein forms a tetrameric complex with Imp-α/β and Crm1 that “clogs” the NPC blocking import of other cellular proteins. (F) During hepatitis C virus (HCV) infection, key Nups are recruited to the membranous web, forming a “viral NPC”, to regulate transport of cellular and viral proteins as well as block access of pattern recognition receptors (PRRs) such as melanoma differentiation-associated protein 5 (MDA5) and retinoic acid-inducible gene I (RIG-I). Figure created with BioRender.

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