Herpes Simplex Virus Type 1 VP26 Is Not Essential for Replication in Cell Culture but Influences Production of Infectious Virus in the Nervous System of Infected Mice

Desai, Prashant; DeLuca, Neal A.; Person, Stanley

doi:10.1006/viro.1998.9230

Cited by 114 publications

(139 citation statements)

References 35 publications

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“…Although pUL35 is not essential for HSV-1 replication in vitro [63], its role during viral transport in vivo remains to be determined. In one previous study, the role of pUL35 in retrograde transport of HSV-1 to, and replication in, trigeminal ganglia was dissected in a mouse eye model [63].…”

Section: Dynein Cofactor: Dynactinmentioning

confidence: 99%

“…In one previous study, the role of pUL35 in retrograde transport of HSV-1 to, and replication in, trigeminal ganglia was dissected in a mouse eye model [63]. Deletion of pUL35 decreased the amount of infectious virus in trigeminal ganglia by 100-fold, whereas titres in cell culture (where retrograde transport is less critical) were decreased only twofold.…”

Section: Dynein Cofactor: Dynactinmentioning

confidence: 99%

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Transport and egress of herpes simplex virus in neurons

Diefenbach

Miranda-Saksena

Douglas

et al. 2007

Reviews in Medical Virology

164

150

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The mechanisms of axonal transport of the alphaherpesviruses, HSV and pseudorabies virus (PrV), in neuronal axons are of fundamental interest, particularly in comparison with other viruses, and offer potential sites for antiviral intervention or development of gene therapy vectors. These herpesviruses are transported rapidly along microtubules (MTs) in the retrograde direction from the axon terminus to the dorsal root ganglion and then anterogradely in the opposite direction. Retrograde transport follows fusion and deenvelopment of the viral capsid at the axonal membrane followed by loss of most of the tegument proteins and then binding of the capsid via one or more viral proteins (VPs) to the retrograde molecular motor dynein. The HSV capsid protein pUL35 has been shown to bind to the dynein light chain Tctex1 but is likely to be accompanied by additional dynein binding of an inner tegument protein. The mechanism of anterograde transport is much more controversial with different processes being claimed for PrV and HSV: separate transport of HSV capsid/tegument and glycoproteins versus PrV transport as an enveloped virion. The controversy has not been resolved despite application, in several laboratories, of confocal microscopy (CFM), realtime fluorescence with viruses dual labelled on capsid and glycoprotein, electron microscopy in situ and immunoelectron microscopy. Different processes for each virus seem counterintuitive although they are the most divergent in the alphaherpesvirus subfamily. Current hypotheses suggest that unenveloped HSV capsids complete assembly in the axonal growth cones and varicosities, whereas with PrV unenveloped capsids are only found travelling in a retrograde direction.

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Section: Dynein Cofactor: Dynactinmentioning

confidence: 99%

Section: Dynein Cofactor: Dynactinmentioning

confidence: 99%

Transport and egress of herpes simplex virus in neurons

Diefenbach

Miranda-Saksena

Douglas

et al. 2007

Reviews in Medical Virology

164

150

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“…The role of VP26 remains somewhat mysterious. It does not confer additional stability [45] and it is dispensable, although its absence somehow decreases infectious virion production [46]. Another consequence of HSV1 procapsid maturation is weakening of the interaction between the inner (scaffold) shell and the MCP.…”

Section: Capsid Maturation Of Herpes Simplex Virusmentioning

confidence: 99%

Virus maturation: dynamics and mechanism of a stabilizing structural transition that leads to infectivity

Steven

Heymann

Cheng

et al. 2005

Current Opinion in Structural Biology

159

142

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For many viruses, the final stage of assembly involves structural transitions that convert an innocuous precursor particle into an infectious agent. This process -maturation -is controlled by proteases that trigger large-scale conformational changes. In this context, protease inhibitor antiviral drugs act by blocking maturation. Recent work has succeeded in determining the folds of representative examples of the five major proteins -major capsid protein, scaffolding protein, portal, protease and accessory protein -that are typically involved in capsid assembly. These data provide a framework for detailed mechanistic investigations and elucidation of mutations that affect assembly in various ways. The nature of the conformational change has been elucidated: it entails rigid-body rotations and translations of the arrayed subunits that transfer the interactions between them to different molecular surfaces, accompanied by refolding and redeployment of local motifs. Moreover, it has been possible to visualize maturation at the submolecular level in movies based on time-resolved cryo-electron microscopy.

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“…Several viral proteins interact with components of the dynein motor complex (23,39,60). However, none of these proteins suggest a completely satisfactory mechanism by which viral retrograde transport occurs, either because they are not components of the complex that is transported to the nucleus (UL34, UL9, VP11/12) or because capsids lacking that protein retain retrograde transport activity (VP26) (2,17,21,28,37). This implies that additional viral proteins are involved in retrograde trafficking.…”

mentioning

confidence: 99%

Herpes Simplex Virus Type 1 Glycoprotein E Mediates Retrograde Spread from Epithelial Cells to Neurites

McGraw

Friedman

2009

J Virol

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In animal models of infection, glycoprotein E (gE) is required for efficient herpes simplex virus type 1 (HSV-1) spread from the inoculation site to the cell bodies of innervating neurons (retrograde direction).Retrograde spread in vivo is a multistep process, in that HSV-1 first spreads between epithelial cells at the inoculation site, then infects neurites, and finally travels by retrograde axonal transport to the neuron cell body. To better understand the role of gE in retrograde spread, we used a compartmentalized neuron culture system, in which neurons were infected in the presence or absence of epithelial cells. We found that gE-deleted HSV-1 (NS-gEnull) retained retrograde axonal transport activity when added directly to neurites, in contrast to the retrograde spread defect of this virus in animals. To better mimic the in vivo milieu, we overlaid neurites with epithelial cells prior to infection. In this modified system, virus infects epithelial cells and then spreads to neurites, revealing a 100-fold retrograde spread defect for NS-gEnull. We measured the retrograde spread defect of NS-gEnull from a variety of epithelial cell lines and found that the magnitude of the spread defect from epithelial cells to neurons correlated with epithelial cell plaque size defect, indicating that gE plays a similar role in both types of spread. Therefore, gE-mediated spread between epithelial cells and neurites likely explains the retrograde spread defect of gE-deleted HSV-1 in vivo.Herpes simplex virus type 1 (HSV-1) is an alphaherpesvirus that characteristically infects skin and mucosal surfaces before spreading to sensory neurons, where it establishes a lifelong persistent infection. The virus periodically returns to the periphery via sensory axons and causes recurrent lesions as well as asymptomatic shedding. This life cycle requires viral transport along axons in two directions: toward the neuron cell body (retrograde direction) and away from the neuron cell body (anterograde direction).Many studies of alphaherpesvirus neuronal spread have focused on pseudorabies virus (PRV), a virus whose natural host is the pig. Three PRV proteins, glycoprotein E (gE), gI, and Us9, have been shown to mediate anterograde neuronal spread both in animal models of infection and in cultured neurons. However, these three proteins are dispensable for retrograde spread (3,8,11,12,31,46). In contrast, numerous animal models of infection have shown that HSV-1 gE is required for retrograde spread from the inoculation site to the cell bodies of innervating neurons (4, 9, 44, 56). In the murine flank model, wild-type (WT) virus replicates in the skin and then infects sensory neurons and spreads in a retrograde direction to the dorsal root ganglia (DRG). In this model, gE-deleted HSV-1 replicates in the skin but is not detected in the DRG (9, 44). This phenotype differs from gE-deleted PRV, which is able to reach the DRG at WT levels (8). Thus, unlike PRV, gE-deleted HSV-1 viruses have a retrograde spread defect in vivo.HSV-1 gE is a 552-amino-...

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Herpes Simplex Virus Type 1 VP26 Is Not Essential for Replication in Cell Culture but Influences Production of Infectious Virus in the Nervous System of Infected Mice

Cited by 114 publications

References 35 publications

Transport and egress of herpes simplex virus in neurons

Transport and egress of herpes simplex virus in neurons

Virus maturation: dynamics and mechanism of a stabilizing structural transition that leads to infectivity

Herpes Simplex Virus Type 1 Glycoprotein E Mediates Retrograde Spread from Epithelial Cells to Neurites

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