The Herpesvirus VP1/2 Protein Is an Effector of Dynein-Mediated Capsid Transport and Neuroinvasion

Microtubule transport of herpesvirus capsids from the cell periphery to the nucleus is imperative for viral replication and, in the case of many alphaherpesviruses, transmission into the nervous system. Using the neuroinvasive herpesvirus, pseudorabies virus (PRV), we show that the viral protein 1/2 (VP1/2) tegument protein associates with the dynein/dynactin microtubule motor complex and promotes retrograde microtubule transport of PRV capsids. Functional activation of VP1/2 requires binding to the capsid protein pUL25 or removal of the capsid-binding domain. A proline-rich sequence within VP1/2 is required for the efficient interaction with the dynein/ dynactin microtubule motor complex as well as for PRV virulence and retrograde axon transport in vivo. Additionally, in the absence of infection, functionally active VP1/2 is sufficient to move large surrogate cargoes via the dynein/dynactin microtubule motor complex. Thus, VP1/2 tethers PRV capsids to dynein/dynactin to enhance microtubule transport, neuroinvasion, and pathogenesis

The mating-specific Gα interacts with a kinesin-14 and regulates pheromone-induced nuclear migration in budding yeast

As a budding yeast cell elongates toward its mating partner, cytoplasmic microtubules connect the nucleus to the cell cortex at the growth tip. The Kar3 kinesin-like motor protein is then thought to stimulate plus-end depolymerization of these microtubules, thus drawing the nucleus closer to the site where cell fusion and karyogamy will occur. Here, we show that pheromone stimulates a microtubule-independent interaction between Kar3 and the mating-specific Gα protein Gpa1 and that Gpa1 affects both microtubule orientation and cortical contact. The membrane localization of Gpa1 was found to polarize early in the mating response, at about the same time that the microtubules begin to attach to the incipient growth site. In the absence of Gpa1, microtubules lose contact with the cortex upon shrinking and Kar3 is improperly localized, suggesting that Gpa1 is a cortical anchor for Kar3. We infer that Gpa1 serves as a positional determinant for Kar3-bound microtubule plus ends during mating. © 2009 by The American Society for Cell Biology

Regulation of a microtubule-associated motor protein and microtubule dynamics in yeast.

Regulation of a microtubule-associated motor protein and microtubule dynamics in yeast

Resolving the Assembly State of Herpes Simplex Virus during Axon Transport by Live-Cell Imaging ▿

Neurotropic herpesviruses depend on long-distance axon transport for the initial establishment of latency in peripheral ganglia (retrograde transport) and for viral spread in axons to exposed body surfaces following reactivation (anterograde transport). Images of neurons infected with herpes simplex virus type 1 (HSV-1), acquired using electron microscopy, have led to a debate regarding why different types of viral structures are seen in axons and which of these particles are relevant to the axon transport process. In this study, we applied time-lapse fluorescence microscopy to image HSV-1 virion components actively translocating to distal axons in primary neurons and neuronal cell lines. Key to these findings, only a small fraction of viral particles were engaged in anterograde transport during the egress phase of infection at any given time. By selective analysis of the composition of the subpopulation of actively transporting capsids, a link between transport of fully assembled HSV-1 virions and the neuronal secretory pathway was identified. Last, we have evaluated the seemingly opposing findings made in previous studies of HSV-1 axon transport in fixed cells and demonstrate a limitation to assessing the composition of individual HSV-1 particles using antibody detection methods

Alphaherpesviruses and the Cytoskeleton in Neuronal Infections

Following infection of exposed peripheral tissues, neurotropic alphaherpesviruses invade nerve endings and deposit their DNA genomes into the nuclei of neurons resident in ganglia of the peripheral nervous system. The end result of these events is the establishment of a life-long latent infection. Neuroinvasion typically requires efficient viral transmission through a polarized epithelium followed by long-distance transport through the viscous axoplasm. These events are mediated by the recruitment of the cellular microtubule motor proteins to the intracellular viral particle and by alterations to the cytoskeletal architecture. The focus of this review is the interplay between neurotropic herpesviruses and the cytoskeleton