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Viruses
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Viral Nuclear Import
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Viral Nuclear Import

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Animal Viruses".

Deadline for manuscript submissions: closed (31 October 2013) | Viewed by 100335

Special Issue Editors

Dr. Ariberto Fassati

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Guest Editor
University College London, Wohl Virion Centre, The Cruciform Building, Gower Street, London WC1E 6BT, UK
Dr. Aksana Labokha

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Co-Guest Editor
University College London, Wohl Virion Centre, The Cruciform Building, Gower Street, London WC1E 6BT, UK

Special Issue Information

Dear Colleagues,

This special issue will overview mechanisms of nuclear import used by different viruses, including Adenoviruses, herpesviruses, Retroviruses, Influenza viruses, Picorna viruses etc. It will highlight both common and divergent pathways evolved by viruses to access the nucleus and how virology research has contributed to understand important basic aspects of nuclear import. We shall draw attention to the import and export of viral proteins critical for replication and to viral proteins that perturb basic nuclear import mechanisms to the advantage of the virus. We shall also explore the relationship between intacellular trafficking of viral particles, their nuclear translocation and activation of the innate immune system.

Dr. Ariberto Fassati

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Keywords

  • nuclear import
  • nuclear pore
  • viruses
  • trafficking
  • nuclear transport receptors
  • nucleoporins
  • tropism

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Published Papers (9 papers)

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Review

878 KiB  
Review
Viral and Cellular Requirements for the Nuclear Entry of Retroviral Preintegration Nucleoprotein Complexes
by Kenneth A. Matreyek and Alan Engelman
Viruses 2013, 5(10), 2483-2511; https://doi.org/10.3390/v5102483 - 7 Oct 2013
Cited by 103 | Viewed by 13673
Abstract
Retroviruses integrate their reverse transcribed genomes into host cell chromosomes as an obligate step in virus replication. The nuclear envelope separates the chromosomes from the cell cytoplasm during interphase, and different retroviral groups deal with this physical barrier in different ways. Gammaretroviruses are [...] Read more.
Retroviruses integrate their reverse transcribed genomes into host cell chromosomes as an obligate step in virus replication. The nuclear envelope separates the chromosomes from the cell cytoplasm during interphase, and different retroviral groups deal with this physical barrier in different ways. Gammaretroviruses are dependent on the passage of target cells through mitosis, where they are believed to access chromosomes when the nuclear envelope dissolves for cell division. Contrastingly, lentiviruses such as HIV-1 infect non-dividing cells, and are believed to enter the nucleus by passing through the nuclear pore complex. While numerous virally encoded elements have been proposed to be involved in HIV-1 nuclear import, recent evidence has highlighted the importance of HIV-1 capsid. Furthermore, capsid was found to be responsible for the viral requirement of various nuclear transport proteins, including transportin 3 and nucleoporins NUP153 and NUP358, during infection. In this review, we describe our current understanding of retroviral nuclear import, with emphasis on recent developments on the role of the HIV-1 capsid protein. Full article
(This article belongs to the Special Issue Viral Nuclear Import)
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1082 KiB  
Review
Transport of the Influenza Virus Genome from Nucleus to Nucleus
by Edward C. Hutchinson and Ervin Fodor
Viruses 2013, 5(10), 2424-2446; https://doi.org/10.3390/v5102424 - 2 Oct 2013
Cited by 70 | Viewed by 14424
Abstract
The segmented genome of an influenza virus is encapsidated into ribonucleoprotein complexes (RNPs). Unusually among RNA viruses, influenza viruses replicate in the nucleus of an infected cell, and their RNPs must therefore recruit host factors to ensure transport across a number of cellular [...] Read more.
The segmented genome of an influenza virus is encapsidated into ribonucleoprotein complexes (RNPs). Unusually among RNA viruses, influenza viruses replicate in the nucleus of an infected cell, and their RNPs must therefore recruit host factors to ensure transport across a number of cellular compartments during the course of an infection. Recent studies have shed new light on many of these processes, including the regulation of nuclear export, genome packaging, mechanisms of virion assembly and viral entry and, in particular, the identification of Rab11 on recycling endosomes as a key mediator of RNP transport and genome assembly. This review uses these recent gains in understanding to describe in detail the journey of an influenza A virus RNP from its synthesis in the nucleus through to its entry into the nucleus of a new host cell. Full article
(This article belongs to the Special Issue Viral Nuclear Import)
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Graphical abstract

462 KiB  
Review
Viruses Challenge Selectivity Barrier of Nuclear Pores
by Aksana A. Labokha and Ariberto Fassati
Viruses 2013, 5(10), 2410-2423; https://doi.org/10.3390/v5102410 - 30 Sep 2013
Cited by 16 | Viewed by 7012
Abstract
Exchange between the nucleus and the cytoplasm occurs through nuclear pore complexes (NPCs) embedded in the double membrane of the nuclear envelope. NPC permeability barrier restricts the entry of inert molecules larger than 5 nm in diameter but allows facilitated entry of selected [...] Read more.
Exchange between the nucleus and the cytoplasm occurs through nuclear pore complexes (NPCs) embedded in the double membrane of the nuclear envelope. NPC permeability barrier restricts the entry of inert molecules larger than 5 nm in diameter but allows facilitated entry of selected cargos, whose size can reach up to 39 nm. The translocation of large molecules is facilitated by nuclear transport receptors (NTRs) that have affinity to proteins of NPC permeability barrier. Viruses that enter the nucleus replicate evolved strategies to overcome this barrier. In this review, we will discuss the functional principles of NPC barrier and nuclear transport machinery, as well as the various strategies viruses use to cross the selective barrier of NPCs. Full article
(This article belongs to the Special Issue Viral Nuclear Import)
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718 KiB  
Review
Regulated Transport into the Nucleus of Herpesviridae DNA Replication Core Proteins
by Gualtiero Alvisi, David A. Jans, Daria Camozzi, Simone Avanzi, Arianna Loregian, Alessandro Ripalti and Giorgio Palù
Viruses 2013, 5(9), 2210-2234; https://doi.org/10.3390/v5092210 - 16 Sep 2013
Cited by 16 | Viewed by 9259
Abstract
The Herpesvirdae family comprises several major human pathogens belonging to three distinct subfamilies. Their double stranded DNA genome is replicated in the nuclei of infected cells by a number of host and viral products. Among the latter the viral replication complex, whose activity [...] Read more.
The Herpesvirdae family comprises several major human pathogens belonging to three distinct subfamilies. Their double stranded DNA genome is replicated in the nuclei of infected cells by a number of host and viral products. Among the latter the viral replication complex, whose activity is strictly required for viral replication, is composed of six different polypeptides, including a two-subunit DNA polymerase holoenzyme, a trimeric primase/helicase complex and a single stranded DNA binding protein. The study of herpesviral DNA replication machinery is extremely important, both because it provides an excellent model to understand processes related to eukaryotic DNA replication and it has important implications for the development of highly needed antiviral agents. Even though all known herpesviruses utilize very similar mechanisms for amplification of their genomes, the nuclear import of the replication complex components appears to be a heterogeneous and highly regulated process to ensure the correct spatiotemporal localization of each protein. The nuclear transport process of these enzymes is controlled by three mechanisms, typifying the main processes through which protein nuclear import is generally regulated in eukaryotic cells. These include cargo post-translational modification-based recognition by the intracellular transporters, piggy-back events allowing coordinated nuclear import of multimeric holoenzymes, and chaperone-assisted nuclear import of specific subunits. In this review we summarize these mechanisms and discuss potential implications for the development of antiviral compounds aimed at inhibiting the Herpesvirus life cycle by targeting nuclear import of the Herpesvirus DNA replicating enzymes. Full article
(This article belongs to the Special Issue Viral Nuclear Import)
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395 KiB  
Review
Viral Subversion of the Nuclear Pore Complex
by Valerie Le Sage and Andrew J. Mouland
Viruses 2013, 5(8), 2019-2042; https://doi.org/10.3390/v5082019 - 16 Aug 2013
Cited by 66 | Viewed by 13452
Abstract
The nuclear pore complex (NPC) acts as a selective barrier between the nucleus and the cytoplasm and is responsible for mediating communication by regulating the transport of RNA and proteins. Numerous viral pathogens have evolved different mechanisms to hijack the NPC in order [...] Read more.
The nuclear pore complex (NPC) acts as a selective barrier between the nucleus and the cytoplasm and is responsible for mediating communication by regulating the transport of RNA and proteins. Numerous viral pathogens have evolved different mechanisms to hijack the NPC in order to regulate trafficking of viral proteins, genomes and even capsids into and out of the nucleus thus promoting virus replication. The present review examines the different strategies and the specific nucleoporins utilized during viral infections as a means of promoting their life cycle and inhibiting host viral defenses. Full article
(This article belongs to the Special Issue Viral Nuclear Import)
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2161 KiB  
Review
Nucleocytoplasmic Shuttling of Viral Proteins in Borna Disease Virus Infection
by Tomoyuki Honda and Keizo Tomonaga
Viruses 2013, 5(8), 1978-1990; https://doi.org/10.3390/v5081978 - 8 Aug 2013
Cited by 34 | Viewed by 7719
Abstract
Nuclear import and export of viral RNA and proteins are critical to the replication cycle of viruses that replicate in the nucleus. Borna disease virus (BDV) is a nonsegmented, negative-strand RNA virus that belongs to the order Mononegavirales. BDV has several distinguishing [...] Read more.
Nuclear import and export of viral RNA and proteins are critical to the replication cycle of viruses that replicate in the nucleus. Borna disease virus (BDV) is a nonsegmented, negative-strand RNA virus that belongs to the order Mononegavirales. BDV has several distinguishing features, one of the most striking being the site of its replication. BDV RNA is transcribed and replicated in the nucleus, while most other negative-strand RNA viruses replicate in the cytoplasm. Therefore, the nucleocytoplasmic trafficking of BDV macromolecules plays a key role in virus replication. Growing evidence indicates that several BDV proteins, including the nucleoprotein, phosphoprotein, protein X and large protein, contribute to the nucleocytoplasmic trafficking of BDV ribonucleoprotein (RNP). The directional control of BDV RNP trafficking is likely determined by the ratios of and interactions between the nuclear localization signals and nuclear export signals in the RNP. In this review, we present a comprehensive view of several unique mechanisms that BDV has developed to control its RNP trafficking and discuss the significance of BDV RNP trafficking in the replication cycle of BDV. Full article
(This article belongs to the Special Issue Viral Nuclear Import)
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Figure 1

1111 KiB  
Review
Kaposi’s Sarcoma-Associated Herpesvirus ORF57 Protein: Exploiting All Stages of Viral mRNA Processing
by Sophie Schumann, Brian R. Jackson, Belinda Baquero-Perez and Adrian Whitehouse
Viruses 2013, 5(8), 1901-1923; https://doi.org/10.3390/v5081901 - 26 Jul 2013
Cited by 21 | Viewed by 9590
Abstract
Nuclear mRNA export is a highly complex and regulated process in cells. Cellular transcripts must undergo successful maturation processes, including splicing, 5'-, and 3'-end processing, which are essential for assembly of an export competent ribonucleoprotein particle. Many viruses replicate in the nucleus of [...] Read more.
Nuclear mRNA export is a highly complex and regulated process in cells. Cellular transcripts must undergo successful maturation processes, including splicing, 5'-, and 3'-end processing, which are essential for assembly of an export competent ribonucleoprotein particle. Many viruses replicate in the nucleus of the host cell and require cellular mRNA export factors to efficiently export viral transcripts. However, some viral mRNAs undergo aberrant mRNA processing, thus prompting the viruses to express their own specific mRNA export proteins to facilitate efficient export of viral transcripts and allowing translation in the cytoplasm. This review will focus on the Kaposi’s sarcoma-associated herpesvirus ORF57 protein, a multifunctional protein involved in all stages of viral mRNA processing and that is essential for virus replication. Using the example of ORF57, we will describe cellular bulk mRNA export pathways and highlight their distinct features, before exploring how the virus has evolved to exploit these mechanisms. Full article
(This article belongs to the Special Issue Viral Nuclear Import)
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Figure 1

622 KiB  
Review
Baculovirus Nuclear Import: Open, Nuclear Pore Complex (NPC) Sesame
by Shelly Au, Wei Wu and Nelly Panté
Viruses 2013, 5(7), 1885-1900; https://doi.org/10.3390/v5071885 - 23 Jul 2013
Cited by 26 | Viewed by 13264
Abstract
Baculoviruses are one of the largest viruses that replicate in the nucleus of their host cells. During infection, the rod-shape, 250-nm long nucleocapsid delivers its genome into the nucleus. Electron microscopy evidence suggests that baculoviruses, specifically the Alphabaculoviruses (nucleopolyhedroviruses) and the Betabaculoviruses (granuloviruses), [...] Read more.
Baculoviruses are one of the largest viruses that replicate in the nucleus of their host cells. During infection, the rod-shape, 250-nm long nucleocapsid delivers its genome into the nucleus. Electron microscopy evidence suggests that baculoviruses, specifically the Alphabaculoviruses (nucleopolyhedroviruses) and the Betabaculoviruses (granuloviruses), have evolved two very distinct modes for doing this. Here we review historical and current experimental results of baculovirus nuclear import studies, with an emphasis on electron microscopy studies employing the prototypical baculovirus Autographa californica multiple nucleopolyhedrovirus infecting cultured cells. We also discuss the implications of recent studies towards theories of nuclear transport mechanisms. Full article
(This article belongs to the Special Issue Viral Nuclear Import)
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Figure 1

9901 KiB  
Review
Nuclear Imprisonment: Viral Strategies to Arrest Host mRNA Nuclear Export
by Sharon K. Kuss, Miguel A. Mata, Liang Zhang and Beatriz M. A. Fontoura
Viruses 2013, 5(7), 1824-1849; https://doi.org/10.3390/v5071824 - 18 Jul 2013
Cited by 56 | Viewed by 11006
Abstract
Viruses possess many strategies to impair host cellular responses to infection. Nuclear export of host messenger RNAs (mRNA) that encode antiviral factors is critical for antiviral protein production and control of viral infections. Several viruses have evolved sophisticated strategies to inhibit nuclear export [...] Read more.
Viruses possess many strategies to impair host cellular responses to infection. Nuclear export of host messenger RNAs (mRNA) that encode antiviral factors is critical for antiviral protein production and control of viral infections. Several viruses have evolved sophisticated strategies to inhibit nuclear export of host mRNAs, including targeting mRNA export factors and nucleoporins to compromise their roles in nucleo-cytoplasmic trafficking of cellular mRNA. Here, we present a review of research focused on suppression of host mRNA nuclear export by viruses, including influenza A virus and vesicular stomatitis virus, and the impact of this viral suppression on host antiviral responses. Full article
(This article belongs to the Special Issue Viral Nuclear Import)
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