Dystonin/BPAG1 Promotes Plus-End-Directed Transport of Herpes Simplex Virus 1 Capsids on Microtubules during Entry

McElwee, Marion; Beilstein, Frauke; Labétoulle, Marc; Rixon, Frazer J.; Pasdeloup, David

doi:10.1128/jvi.01633-13

Cited by 38 publications

(36 citation statements)

References 40 publications

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“…Nuclear transport is a process of viral particles transfer from the cell membrane to the nucleus. During this process, the cytoplasmic microtubules in host cells act as the piping system for viral delivery (22). There is a variety of host proteins participating in the process of cellular transportation, and each protein has its own driving direction (23).…”

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confidence: 99%

Pentagalloylglucose Blocks the Nuclear Transport and the Process of Nucleocapsid Egress to Inhibit HSV-1 Infection

Jin

Chen

et al. 2016

Jpn J Infect Dis

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SUMMARY: Herpes simplex virus type 1 (HSV-1), a widespread virus, causes a variety of human viral diseases worldwide. The serious threat of drug-resistance highlights the extreme urgency to develop novel antiviral drugs with different mechanisms of action. Pentagalloylglucose (PGG) is a natural polyphenolic compound with significant anti-HSV activity; however, the mechanisms underlying its antiviral activity need to be defined by further studies. In this study, we found that PGG treatment delays the nuclear transport process of HSV-1 particles by inhibiting the upregulation of dynein (a cellular major motor protein) induced by HSV-1 infection. Furthermore, PGG treatment affects the nucleocapsid egress of HSV-1 by inhibiting the expression and disrupting the cellular localization of pEGFP-UL31 and pEGFP-UL34, which are indispensable for HSV-1 nucleocapsid egress from the nucleus. However, the over-expression of pEGFP-UL31 and pEGFP-UL34 could decrease the antiviral effect of PGG. In this study, for the first time, the antiviral activity of PGG against acyclovir-resistant virus was demonstrated in vitro, and the possible mechanisms of its anti-HSV activities were identified based on the inhibition of nuclear transport and nucleocapsid egress in HSV-1. It was further confirmed that PGG could be a promising candidate for HSV therapy, especially for drug-resistant strains.

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mentioning

confidence: 99%

Pentagalloylglucose Blocks the Nuclear Transport and the Process of Nucleocapsid Egress to Inhibit HSV-1 Infection

Jin

Chen

et al. 2016

Jpn J Infect Dis

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“…In dystonin-depleted cells, HSV-1 capsids could reach the centrosome of fibroblasts but the transport of capsids away from the centrosome towards the nucleus was significantly blocked, indicating a defect in the polarity switch of viral transport occurring at the centrosome (85). This work was the first to illustrate how non-motile MAPs can regulate the directionality of transport along MTs.…”

Section: Maps Facilitate Interaction Of Viruses With Microtubulesmentioning

confidence: 78%

Role of non-motile microtubule-associated proteins in virus trafficking

Portilho

Persson²,

Arhel

2016

Biomolecular Concepts

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Viruses are entirely dependent on their ability to infect a host cell in order to replicate. To reach their site of replication as rapidly and efficiently as possible following cell entry, many have evolved elaborate mechanisms to hijack the cellular transport machinery to propel themselves across the cytoplasm. Long-range movements have been shown to involve motor proteins along microtubules (MTs) and direct interactions between viral proteins and dynein and/or kinesin motors have been well described. Although less well-characterized, it is also becoming increasingly clear that non-motile microtubule-associated proteins (MAPs), including structural MAPs of the MAP1 and MAP2 families, and microtubule plus-end tracking proteins (+ TIPs), can also promote viral trafficking in infected cells, by mediating interaction of viruses with filaments and/or motor proteins, and modulating filament stability. Here we review our current knowledge on nonmotile MAPs, their role in the regulation of cytoskeletal dynamics and in viral trafficking during the early steps of infection.

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“…12). These authors explained this phenotype based on the organization of the cellular MT network (53). Indeed, the MT network is typically organized around one or more MT-organizing centers (MTOC), with MT minus ends anchored at the MTOC while the plus ends radiate outwards.…”

Section: Discussionmentioning

confidence: 99%

“…Thus, they first have to travel to the MTOC by minus-end-directed transport and then must travel from the MTOC to the nucleus by plus-end-directed transport (48). In the HSV-1 context, it is postulated that dystonin has an important role in the plus-end-directed transport of capsids from the centrosome to the nucleus and that pUL37 mediates the interaction between capsids and dystonin (53). Dystonin silencing would therefore impair HSV-1 migration from the centrosome to the nucleus.…”

Section: Discussionmentioning

confidence: 99%

Deletion of Murid Herpesvirus 4 ORF63 Affects the Trafficking of Incoming Capsids toward the Nucleus

Latif

Machiels

Xiao

et al. 2016

J Virol

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Gammaherpesviruses are important human and animal pathogens. Despite the fact that they display the classical architecture of herpesviruses, the function of most of their structural proteins is still poorly defined. This is especially true for tegument proteins. Interestingly, a potential role in immune evasion has recently been proposed for the tegument protein encoded by Kaposi's sarcoma-associated herpesvirus open reading frame 63 (ORF63). To gain insight about the roles of ORF63 in the life cycle of a gammaherpesvirus, we generated null mutations in the ORF63 gene of murid herpesvirus 4 (MuHV-4). We showed that disruption of ORF63 was associated with a severe MuHV-4 growth deficit both in vitro and in vivo. The latter deficit was mainly associated with a defect of replication in the lung but did not affect the establishment of latency in the spleen. From a functional point of view, inhibition of caspase-1 or the inflammasome did not restore the growth of the ORF63-deficient mutant, suggesting that the observed deficit was not associated with the immune evasion mechanism identified previously. Moreover, this growth deficit was also not associated with a defect in virion egress from the infected cells. In contrast, it appeared that MuHV-4 ORF63-deficient mutants failed to address most of their capsids to the nucleus during entry into the host cell, suggesting that ORF63 plays a role in capsid movement. In the future, ORF63 could therefore be considered a target to block gammaherpesvirus infection at a very early stage of the infection. IMPORTANCEThe important diseases caused by gammaherpesviruses in human and animal populations justify a better understanding of their life cycle. In particular, the role of most of their tegument proteins is still largely unknown. In this study, we used murid herpesvirus 4, a gammaherpesvirus infecting mice, to decipher the role of the protein encoded by the viral ORF63 gene. We showed that the absence of this protein is associated with a severe growth deficit both in vitro and in vivo that was mainly due to impaired migration of viral capsids toward the nucleus during entry. Together, our results provide new insights about the life cycle of gammaherpesviruses and could allow the development of new antiviral strategies aimed at blocking gammaherpesvirus infection at the very early stages. G ammaherpesviruses (␥HVs) are widespread viruses that cause lifelong infections in many mammalian species (1) and represent a significant cause of diseases (2, 3). Epstein-Barr virus (EBV; genus Lymphocryptovirus) and Kaposi's sarcoma-associated herpesvirus (KSHV; genus Rhadinovirus genus) are highly prevalent in human populations (3, 4) and are associated with several cancers (5). Despite the burden associated with these infections in some regions of the world, there is still no standard treatment (6). A better understanding of their biological cycle is therefore needed to develop new prophylactic or therapeutic strategies. As EBV and KSHV replicate poorly in vitro and have no establi...

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Dystonin/BPAG1 Promotes Plus-End-Directed Transport of Herpes Simplex Virus 1 Capsids on Microtubules during Entry

Cited by 38 publications

References 40 publications

Pentagalloylglucose Blocks the Nuclear Transport and the Process of Nucleocapsid Egress to Inhibit HSV-1 Infection

Pentagalloylglucose Blocks the Nuclear Transport and the Process of Nucleocapsid Egress to Inhibit HSV-1 Infection

Role of non-motile microtubule-associated proteins in virus trafficking

Deletion of Murid Herpesvirus 4 ORF63 Affects the Trafficking of Incoming Capsids toward the Nucleus

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