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Special Issue "Cytoskeleton in Virus Infections"

A special issue of Viruses (ISSN 1999-4915).

Deadline for manuscript submissions: 15 December 2018

Special Issue Editor

Guest Editor
Dr. Timothy P. Newsome

School of Life and Environmental Sciences, The University of Sydney
Website | E-Mail
Interests: vaccinia virus; virus transport; host–pathogen interactions; actin cytoskeleton; microtubule cytoskeleton; signalling

Special Issue Information

Dear Colleagues,

As obligate intracellular parasites or symbionts, the replication of viruses involves intimate contact with the host cytosol, and the cytoskeleton is a major constituent of this environment. The cytoskeleton can be a hindrance to the movement and sorting of viral components throughout the cell, such as the dense mesh of filamentous actin underlying the plasma membrane cortex. It can also be a potential ally. For example, the microtubule network and its associated motor complexes govern membrane traffic and the spatial organization of cellular organelles; functions that can be co-opted during viral replication to assemble and translocate virus particles, and establish replication centers. Viral manipulation of the cytoskeleton can also hold the key to subverting interactions with the surrounding matrix or with adjacent cells to orchestrate the efficient transmission of infection between cells.

In this Special Issue of Viruses, our goal is to attract research articles that reflect the exciting advances that are currently taking place regarding the role and mechanism of viral manipulation of the cytoskeleton. Topics may include structural or biochemical insights into the interface of viral–cytoskeletal interactions, viral subversion of host signaling pathways that regulate aspects of the cytoskeleton, mechanisms of anterograde or retrograde transport of virus during replication, imaging of virus assembly and/or transport, and changes elicited by infection to cell behavior and cellular interactions that are underpinned by the cytoskeleton.

Dr. Timothy P. Newsome
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Viruses is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Actin cytoskeleton

  • Microtubule cytoskeleton

  • Microtubule motor proteins

  • Virus transport

  • Cell migration

  • Microtubule associated proteins

  • Rho signaling

Published Papers (10 papers)

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Research

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Open AccessArticle Respiratory Syncytial Virus Matrix (M) Protein Interacts with Actin In Vitro and in Cell Culture
Viruses 2018, 10(10), 535; https://doi.org/10.3390/v10100535
Received: 3 September 2018 / Revised: 24 September 2018 / Accepted: 28 September 2018 / Published: 30 September 2018
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Abstract
The virus–host protein interactions that underlie respiratory syncytial virus (RSV) assembly are still not completely defined, despite almost 60 years of research. RSV buds from the apical surface of infected cells, once virion components have been transported to the budding sites. Association of
[...] Read more.
The virus–host protein interactions that underlie respiratory syncytial virus (RSV) assembly are still not completely defined, despite almost 60 years of research. RSV buds from the apical surface of infected cells, once virion components have been transported to the budding sites. Association of RSV matrix (M) protein with the actin cytoskeleton may play a role in facilitating this transport. We have investigated the interaction of M with actin in vitro and cell culture. Purified wildtype RSV M protein was found to bind directly to polymerized actin in vitro. Vero cells were transfected to express full-length M (1–256) as a green fluorescent protein-(GFP) tagged protein, followed by treatment with the microfilament destabilizer, cytochalasin D. Destabilization of the microfilament network resulted in mislocalization of full-length M, from mostly cytoplasmic to diffused across both cytoplasm and nucleus, suggesting that M interacts with microfilaments in this system. Importantly, treatment of RSV-infected cells with cytochalasin D results in lower infectious virus titers, as well as mislocalization of M to the nucleus. Finally, using deletion mutants of M in a transfected cell system, we show that both the N- and C-terminus of the protein are required for the interaction. Together, our data suggest a possible role for M–actin interaction in transporting virion components in the infected cell. Full article
(This article belongs to the Special Issue Cytoskeleton in Virus Infections)
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Open AccessArticle Phototracking Vaccinia Virus Transport Reveals Dynamics of Cytoplasmic Dispersal and a Requirement for A36R and F12L for Exit from the Site of Wrapping
Viruses 2018, 10(8), 390; https://doi.org/10.3390/v10080390
Received: 29 June 2018 / Revised: 18 July 2018 / Accepted: 18 July 2018 / Published: 24 July 2018
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Abstract
The microtubule cytoskeleton is a primary organizer of viral infections for delivering virus particles to their sites of replication, establishing and maintaining subcellular compartments where distinct steps of viral morphogenesis take place, and ultimately dispersing viral progeny. One of the best characterized examples
[...] Read more.
The microtubule cytoskeleton is a primary organizer of viral infections for delivering virus particles to their sites of replication, establishing and maintaining subcellular compartments where distinct steps of viral morphogenesis take place, and ultimately dispersing viral progeny. One of the best characterized examples of virus motility is the anterograde transport of the wrapped virus form of vaccinia virus (VACV) from the trans-Golgi network (TGN) to the cell periphery by kinesin-1. Yet many aspects of this transport event are elusive due to the speed of motility and the challenges of imaging this stage at high resolution over extended time periods. We have established a novel imaging technology to track virus transport that uses photoconvertible fluorescent recombinant viruses to track subsets of virus particles from their site of origin and determine their destination. Here we image virus exit from the TGN and their rate of egress to the cell periphery. We demonstrate a role for kinesin-1 engagement in regulating virus exit from the TGN by removing A36 and F12 function, critical viral mediators of kinesin-1 recruitment to virus particles. Phototracking viral particles and components during infection is a powerful new imaging approach to elucidate mechanisms of virus replication. Full article
(This article belongs to the Special Issue Cytoskeleton in Virus Infections)
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Open AccessArticle Ectromelia Virus Affects Mitochondrial Network Morphology, Distribution, and Physiology in Murine Fibroblasts and Macrophage Cell Line
Viruses 2018, 10(5), 266; https://doi.org/10.3390/v10050266
Received: 3 May 2018 / Revised: 14 May 2018 / Accepted: 14 May 2018 / Published: 16 May 2018
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Abstract
Mitochondria are multifunctional organelles that participate in numerous processes in response to viral infection, but they are also a target for viruses. The aim of this study was to define subcellular events leading to alterations in mitochondrial morphology and function during infection with
[...] Read more.
Mitochondria are multifunctional organelles that participate in numerous processes in response to viral infection, but they are also a target for viruses. The aim of this study was to define subcellular events leading to alterations in mitochondrial morphology and function during infection with ectromelia virus (ECTV). We used two different cell lines and a combination of immunofluorescence techniques, confocal and electron microscopy, and flow cytometry to address subcellular changes following infection. Early in infection of L929 fibroblasts and RAW 264.7 macrophages, mitochondria gathered around viral factories. Later, the mitochondrial network became fragmented, forming punctate mitochondria that co-localized with the progeny virions. ECTV-co-localized mitochondria associated with the cytoskeleton components. Mitochondrial membrane potential, mitochondrial fission–fusion, mitochondrial mass, and generation of reactive oxygen species (ROS) were severely altered later in ECTV infection leading to damage of mitochondria. These results suggest an important role of mitochondria in supplying energy for virus replication and morphogenesis. Presumably, mitochondria participate in transport of viral particles inside and outside of the cell and/or they are a source of membranes for viral envelope formation. We speculate that the observed changes in the mitochondrial network organization and physiology in ECTV-infected cells provide suitable conditions for viral replication and morphogenesis. Full article
(This article belongs to the Special Issue Cytoskeleton in Virus Infections)
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Open AccessArticle Overexpression of MAP2 and NF-H Associated with Dendritic Pathology in the Spinal Cord of Mice Infected with Rabies Virus
Viruses 2018, 10(3), 112; https://doi.org/10.3390/v10030112
Received: 9 December 2017 / Revised: 29 January 2018 / Accepted: 8 February 2018 / Published: 6 March 2018
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Abstract
Rabies is a viral infection that targets the nervous system, specifically neurons. The clinical manifestations of the disease are dramatic and their outcome fatal; paradoxically, conventional histopathological descriptions reveal only subtle changes in the affected nervous tissue. Some researchers have considered that the
[...] Read more.
Rabies is a viral infection that targets the nervous system, specifically neurons. The clinical manifestations of the disease are dramatic and their outcome fatal; paradoxically, conventional histopathological descriptions reveal only subtle changes in the affected nervous tissue. Some researchers have considered that the pathophysiology of rabies is based more on biochemical changes than on structural alterations, as is the case with some psychiatric diseases. However, we believe that it has been necessary to resort to other methods that allow us to analyze the effect of the infection on neurons. The Golgi technique is the gold standard for studying the morphology of all the components of a neuron and the cytoskeletal proteins are the structural support of dendrites and axons. We have previously shown, in the mouse cerebral cortex and now with this work in spinal cord, that rabies virus generates remarkable alterations in the morphological pattern of the neurons and that this effect is associated with the increase in the expression of two cytoskeletal proteins (MAP2 and NF-H). It is necessary to deepen the investigation of the pathogenesis of rabies in order to find therapeutic alternatives to a disease to which the World Health Organization classifies as a neglected disease. Full article
(This article belongs to the Special Issue Cytoskeleton in Virus Infections)
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Open AccessArticle Loss of Actin-Based Motility Impairs Ectromelia Virus Release In Vitro but Is Not Critical to Spread In Vivo
Viruses 2018, 10(3), 111; https://doi.org/10.3390/v10030111
Received: 15 February 2018 / Revised: 1 March 2018 / Accepted: 1 March 2018 / Published: 5 March 2018
Cited by 1 | PDF Full-text (5231 KB) | HTML Full-text | XML Full-text
Abstract
Ectromelia virus (ECTV) is an orthopoxvirus and the causative agent of mousepox. Like other poxviruses such as variola virus (agent of smallpox), monkeypox virus and vaccinia virus (the live vaccine for smallpox), ECTV promotes actin-nucleation at the surface of infected cells during virus
[...] Read more.
Ectromelia virus (ECTV) is an orthopoxvirus and the causative agent of mousepox. Like other poxviruses such as variola virus (agent of smallpox), monkeypox virus and vaccinia virus (the live vaccine for smallpox), ECTV promotes actin-nucleation at the surface of infected cells during virus release. Homologs of the viral protein A36 mediate this function through phosphorylation of one or two tyrosine residues that ultimately recruit the cellular Arp2/3 actin-nucleating complex. A36 also functions in the intracellular trafficking of virus mediated by kinesin-1. Here, we describe the generation of a recombinant ECTV that is specifically disrupted in actin-based motility allowing us to examine the role of this transport step in vivo for the first time. We show that actin-based motility has a critical role in promoting the release of virus from infected cells in vitro but plays a minor role in virus spread in vivo. It is likely that loss of microtubule-dependent transport is a major factor for the attenuation observed when A36R is deleted. Full article
(This article belongs to the Special Issue Cytoskeleton in Virus Infections)
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Review

Jump to: Research

Open AccessReview Imaging, Tracking and Computational Analyses of Virus Entry and Egress with the Cytoskeleton
Viruses 2018, 10(4), 166; https://doi.org/10.3390/v10040166
Received: 8 February 2018 / Revised: 27 March 2018 / Accepted: 28 March 2018 / Published: 31 March 2018
Cited by 2 | PDF Full-text (7248 KB) | HTML Full-text | XML Full-text
Abstract
Viruses have a dual nature: particles are “passive substances” lacking chemical energy transformation, whereas infected cells are “active substances” turning-over energy. How passive viral substances convert to active substances, comprising viral replication and assembly compartments has been of intense interest to virologists, cell
[...] Read more.
Viruses have a dual nature: particles are “passive substances” lacking chemical energy transformation, whereas infected cells are “active substances” turning-over energy. How passive viral substances convert to active substances, comprising viral replication and assembly compartments has been of intense interest to virologists, cell and molecular biologists and immunologists. Infection starts with virus entry into a susceptible cell and delivers the viral genome to the replication site. This is a multi-step process, and involves the cytoskeleton and associated motor proteins. Likewise, the egress of progeny virus particles from the replication site to the extracellular space is enhanced by the cytoskeleton and associated motor proteins. This overcomes the limitation of thermal diffusion, and transports virions and virion components, often in association with cellular organelles. This review explores how the analysis of viral trajectories informs about mechanisms of infection. We discuss the methodology enabling researchers to visualize single virions in cells by fluorescence imaging and tracking. Virus visualization and tracking are increasingly enhanced by computational analyses of virus trajectories as well as in silico modeling. Combined approaches reveal previously unrecognized features of virus-infected cells. Using select examples of complementary methodology, we highlight the role of actin filaments and microtubules, and their associated motors in virus infections. In-depth studies of single virion dynamics at high temporal and spatial resolutions thereby provide deep insight into virus infection processes, and are a basis for uncovering underlying mechanisms of how cells function. Full article
(This article belongs to the Special Issue Cytoskeleton in Virus Infections)
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Open AccessReview Infection and Transport of Herpes Simplex Virus Type 1 in Neurons: Role of the Cytoskeleton
Viruses 2018, 10(2), 92; https://doi.org/10.3390/v10020092
Received: 24 January 2018 / Revised: 16 February 2018 / Accepted: 20 February 2018 / Published: 23 February 2018
Cited by 2 | PDF Full-text (1424 KB) | HTML Full-text | XML Full-text
Abstract
Herpes simplex virus type 1 (HSV-1) is a neuroinvasive human pathogen that has the ability to infect and replicate within epithelial cells and neurons and establish a life-long latent infection in sensory neurons. HSV-1 depends on the host cellular cytoskeleton for entry, replication,
[...] Read more.
Herpes simplex virus type 1 (HSV-1) is a neuroinvasive human pathogen that has the ability to infect and replicate within epithelial cells and neurons and establish a life-long latent infection in sensory neurons. HSV-1 depends on the host cellular cytoskeleton for entry, replication, and exit. Therefore, HSV-1 has adapted mechanisms to promote its survival by exploiting the microtubule and actin cytoskeletons to direct its active transport, infection, and spread between neurons and epithelial cells during primary and recurrent infections. This review will focus on the currently known mechanisms utilized by HSV-1 to harness the neuronal cytoskeleton, molecular motors, and the secretory and exocytic pathways for efficient virus entry, axonal transport, replication, assembly, and exit from the distinct functional compartments (cell body and axon) of the highly polarized sensory neurons. Full article
(This article belongs to the Special Issue Cytoskeleton in Virus Infections)
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Open AccessReview Cytoskeletons in the Closet—Subversion in Alphaherpesvirus Infections
Viruses 2018, 10(2), 79; https://doi.org/10.3390/v10020079
Received: 19 December 2017 / Revised: 30 January 2018 / Accepted: 7 February 2018 / Published: 13 February 2018
Cited by 1 | PDF Full-text (1838 KB) | HTML Full-text | XML Full-text
Abstract
Actin filaments, microtubules and intermediate filaments form the cytoskeleton of vertebrate cells. Involved in maintaining cell integrity and structure, facilitating cargo and vesicle transport, remodelling surface structures and motility, the cytoskeleton is necessary for the successful life of a cell. Because of the
[...] Read more.
Actin filaments, microtubules and intermediate filaments form the cytoskeleton of vertebrate cells. Involved in maintaining cell integrity and structure, facilitating cargo and vesicle transport, remodelling surface structures and motility, the cytoskeleton is necessary for the successful life of a cell. Because of the broad range of functions these filaments are involved in, they are common targets for viral pathogens, including the alphaherpesviruses. Human-tropic alphaherpesviruses are prevalent pathogens carried by more than half of the world’s population; comprising herpes simplex virus (types 1 and 2) and varicella-zoster virus, these viruses are characterised by their ability to establish latency in sensory neurons. This review will discuss the known mechanisms involved in subversion of and transport via the cytoskeleton during alphaherpesvirus infections, focusing on protein-protein interactions and pathways that have recently been identified. Studies on related alphaherpesviruses whose primary host is not human, along with comparisons to more distantly related beta and gammaherpesviruses, are also presented in this review. The need to decipher as-yet-unknown mechanisms exploited by viruses to hijack cytoskeletal components—to reveal the hidden cytoskeletons in the closet—will also be addressed. Full article
(This article belongs to the Special Issue Cytoskeleton in Virus Infections)
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Open AccessReview Transcytosis Involvement in Transport System and Endothelial Permeability of Vascular Leakage during Dengue Virus Infection
Viruses 2018, 10(2), 69; https://doi.org/10.3390/v10020069
Received: 14 December 2017 / Revised: 19 January 2018 / Accepted: 1 February 2018 / Published: 8 February 2018
Cited by 2 | PDF Full-text (605 KB) | HTML Full-text | XML Full-text
Abstract
The major role of endothelial cells is to maintain homeostasis of vascular permeability and to preserve the integrity of vascular vessels to prevent fluid leakage. Properly functioning endothelial cells promote physiological balance and stability for blood circulation and fluid components. A monolayer of
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The major role of endothelial cells is to maintain homeostasis of vascular permeability and to preserve the integrity of vascular vessels to prevent fluid leakage. Properly functioning endothelial cells promote physiological balance and stability for blood circulation and fluid components. A monolayer of endothelial cells has the ability to regulate paracellular and transcellular pathways for transport proteins, solutes, and fluid. In addition to the paracellular pathway, the transcellular pathway is another route of endothelial permeability that mediates vascular permeability under physiologic conditions. The transcellular pathway was found to be associated with an assortment of disease pathogeneses. The clinical manifestation of severe dengue infection in humans is vascular leakage and hemorrhagic diatheses. This review explores and describes the transcellular pathway, which is an alternate route of vascular permeability during dengue infection that corresponds with the pathologic finding of intact tight junction. This pathway may be the route of albumin transport that causes endothelial dysfunction during dengue virus infection. Full article
(This article belongs to the Special Issue Cytoskeleton in Virus Infections)
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Open AccessReview All-Round Manipulation of the Actin Cytoskeleton by HIV
Viruses 2018, 10(2), 63; https://doi.org/10.3390/v10020063
Received: 13 December 2017 / Revised: 24 January 2018 / Accepted: 29 January 2018 / Published: 5 February 2018
Cited by 3 | PDF Full-text (1966 KB) | HTML Full-text | XML Full-text
Abstract
While significant progress has been made in terms of human immunodeficiency virus (HIV) therapy, treatment does not represent a cure and remains inaccessible to many people living with HIV. Continued mechanistic research into the viral life cycle and its intersection with many aspects
[...] Read more.
While significant progress has been made in terms of human immunodeficiency virus (HIV) therapy, treatment does not represent a cure and remains inaccessible to many people living with HIV. Continued mechanistic research into the viral life cycle and its intersection with many aspects of cellular biology are not only fundamental in the continued fight against HIV, but also provide many key observations of the workings of our immune system. Decades of HIV research have testified to the integral role of the actin cytoskeleton in both establishing and spreading the infection. Here, we review how the virus uses different strategies to manipulate cellular actin networks and increase the efficiency of various stages of its life cycle. While some HIV proteins seem able to bind to actin filaments directly, subversion of the cytoskeleton occurs indirectly by exploiting the power of actin regulatory proteins, which are corrupted at multiple levels. Furthermore, this manipulation is not restricted to a discrete class of proteins, but rather extends throughout all layers of the cytoskeleton. We discuss prominent examples of actin regulators that are exploited, neutralized or hijacked by the virus, and address how their coordinated deregulation can lead to changes in cellular behavior that promote viral spreading. Full article
(This article belongs to the Special Issue Cytoskeleton in Virus Infections)
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