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      Directional Spread of Alphaherpesviruses in the Nervous System

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          Abstract

          Alphaherpesviruses are pathogens that invade the nervous systems of their mammalian hosts. Directional spread of infection in the nervous system is a key component of the viral lifecycle and is critical for the onset of alphaherpesvirus-related diseases. Many alphaherpesvirus infections originate at peripheral sites, such as epithelial tissues, and then enter neurons of the peripheral nervous system (PNS), where lifelong latency is established. Following reactivation from latency and assembly of new viral particles, the infection typically spreads back out towards the periphery. These spread events result in the characteristic lesions (cold sores) commonly associated with herpes simplex virus (HSV) and herpes zoster (shingles) associated with varicella zoster virus (VZV). Occasionally, the infection spreads transsynaptically from the PNS into higher order neurons of the central nervous system (CNS). Spread of infection into the CNS, while rarer in natural hosts, often results in severe consequences, including death. In this review, we discuss the viral and cellular mechanisms that govern directional spread of infection in the nervous system. We focus on the molecular events that mediate long distance directional transport of viral particles in neurons during entry and egress.

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          Actin, a central player in cell shape and movement.

          The protein actin forms filaments that provide cells with mechanical support and driving forces for movement. Actin contributes to biological processes such as sensing environmental forces, internalizing membrane vesicles, moving over surfaces, and dividing the cell in two. These cellular activities are complex; they depend on interactions of actin monomers and filaments with numerous other proteins. Here, we present a summary of the key questions in the field and suggest how those questions might be answered. Understanding actin-based biological phenomena will depend on identifying the participating molecules and defining their molecular mechanisms. Comparisons of quantitative measurements of reactions in live cells with computer simulations of mathematical models will also help generate meaningful insights.
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            Kinesin superfamily motor proteins and intracellular transport.

            Intracellular transport is fundamental for cellular function, survival and morphogenesis. Kinesin superfamily proteins (also known as KIFs) are important molecular motors that directionally transport various cargos, including membranous organelles, protein complexes and mRNAs. The mechanisms by which different kinesins recognize and bind to specific cargos, as well as how kinesins unload cargo and determine the direction of transport, have now been identified. Furthermore, recent molecular genetic experiments have uncovered important and unexpected roles for kinesins in the regulation of such physiological processes as higher brain function, tumour suppression and developmental patterning. These findings open exciting new areas of kinesin research.
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              Dynamic instability of microtubule growth.

              We report here that microtubules in vitro coexist in growing and shrinking populations which interconvert rather infrequently. This dynamic instability is a general property of microtubules and may be fundamental in explaining cellular microtubule organization.
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                Author and article information

                Journal
                Viruses
                Viruses
                viruses
                Viruses
                MDPI
                1999-4915
                11 February 2013
                February 2013
                : 5
                : 2
                : 678-707
                Affiliations
                [1 ]Princeton University, Department of Molecular Biology, Princeton, NJ 08544, USA; E-Mail: tal.kramer@ 123456childrens.harvard.edu
                [2 ]Children’s Hospital Boston and Harvard Medical School, F.M. Kirby Neurobiology Center, Boston, MA 02115, USA
                Author notes
                [* ] Author to whom correspondence should be addressed; E-Mail: lenquist@ 123456princeton.edu (L.W.E.); Tel.: +1-609-258-2415; Fax: +1-609-258-1035.
                Article
                viruses-05-00678
                10.3390/v5020678
                3640521
                23435239
                598a0700-00fe-47a6-a0a7-225464f0507b
                © 2013 by the authors; licensee MDPI, Basel, Switzerland.

                This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license ( http://creativecommons.org/licenses/by/3.0/).

                History
                : 03 January 2013
                : 04 February 2013
                : 05 February 2013
                Categories
                Review

                Microbiology & Virology
                alphaherpesvirus,herpes simplex virus,pseudorabies virus,axonal transport,directional spread,cytoskeleton

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