Herpes Simplex Virus Type 1 Enters Human Epidermal Keratinocytes, but Not Neurons, via a pH-Dependent Endocytic Pathway

Nicola, Anthony V.; Hou, Jean; Major, Eugene O.; Straus, Stephen E.

doi:10.1128/jvi.79.12.7609-7616.2005

Cited by 220 publications

(255 citation statements)

References 56 publications

(86 reference statements)

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“…Herpesviruses infect neuronal cells only by pHindependent fusion of the viral envelope with the plasma membrane while in non-neuronal cells they can enter also via a pH-dependent [41,42] or pH-independent endocytic pathway [43]. Once inside the cell, most HSV-1 tegument proteins are lost, leaving the capsid, with some associated tegument, to be transported to the cell nucleus [44][45][46].…”

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

171

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%

Transport and egress of herpes simplex virus in neurons

Diefenbach

Miranda-Saksena

Douglas

et al. 2007

Reviews in Medical Virology

171

150

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“…One possible explanation for this difference in signaling might again be the mode of viral entry. In CHO cells and primary corneal fibroblasts, Rho GTPase signaling is associated with a newly described phagocytosis-or micropinocytosis-like pH-dependent entry route of HSV particles [12,24] (Figure 1). It is noteworthy that phagocytic uptake of HSV is associated with activation of RhoA and Cdc42 but not Rac1 [12].…”

Section: Virus Entry In Host Cellsmentioning

confidence: 99%

Actin and Rho GTPases in herpesvirus biology

Favoreel¹,

Enquist²,

Feierbach³

2007

Trends in Microbiology

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Viruses have evolved a variety of interactions with host cells to create an optimal niche for viral replication, persistence and spread. The actin cytoskeleton of the host cell and actin-regulating Rho GTPase signaling pathways can be involved in several of these interactions. This review focuses on recent findings on herpesvirus interactions with actin and Rho GTPases during viral entry, replication in the nucleus and egress. Unraveling these often fascinating interactions might also provide additional insights into sometimes poorly known aspects of actin biology (e.g. its role in the nucleus) and in the development of novel antiviral therapies.Actin filaments and actin-regulating Rho GTPase signaling pathways Filamentous actin is a key structure of the cytoskeleton in every cell. The actin cytoskeleton is involved in many crucial cellular processes, including providing cell integrity, mobility and shape; driving cell division and contraction; and the uptake of extracellular molecules.Actin filaments consist of polarized ATP-bound globular actin monomers. These filamentous actin (F-actin) molecules can associate into bundles or networks through actin cross-linking molecules. The best characterized F-actin bundles and networks are filopodia, lamellipodia and actin stress fibers. Formation of the different actin bundles and networks is regulated by signal transduction pathways that depend on small Rho GTPases [1]. Of the 22 identified mammalian Rho GTPases, the best characterized are RhoA (stress fibers), Rac1 (lamellipodia) and Cdc42 (filopodia). These Rho GTPases act as molecular switches and alternate between their active GTP-bound form and their inactive GDP-bound form. Transition from the active to the inactive form is accompanied by phosphorylation and activation of different downstream effector molecules that initiate signal transduction pathways and subsequent rearrangements in the actin cytoskeleton. These three signal transduction pathways are interwoven and the RhoA pathway generally counteracts the Rac1 and Cdc42 pathways [2]. Details of Rho GTPase signaling networks can be found elsewhere [3].Because of the many cellular functions in which they are involved, it comes as no surprise that many intracellular pathogens interact with actin and actin-regulating signaling pathways. These interactions can occur at several points in the life cycle of the pathogens, including, although not limited to, internalization, intracellular movement and intercellular spread [4,5].There are recent indications that, in particular cell types, herpesviruses also interact with actin and/or Rho GTPases during three major phases of the replication cycle of herpesviruses: entry into the cytoplasm, replication and assembly in the nucleus and maturation and egress. This review presents an overview of these data and points to future directions in research in this new and potentially important field of herpesvirus biology. Special attention is given on the alphaherpesvirus subfamily of herpesviruses, but relevant references to wor...

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“…For instance, Epstein-Barr virus (EBV) enters primary B cells via endocytosis (1,2), yet it infects epithelial cells or transformed B cells by fusion of its envelope with the plasma membrane (1). Herpes simplex virus fuses with the plasma membrane of some cell types, but enters others by endocytosis (3)(4)(5)(6). Human cytomegalovirus (HCMV) infects multiple cell types in vivo (7), and it fuses with the plasma membranes of fibroblasts (8) but enters retinal pigmented epithelial cells and umbilical vein endothelial cells via endocytosis (9,10).…”

mentioning

confidence: 99%

Human cytomegalovirus uses two distinct pathways to enter retinal pigmented epithelial cells

Wang

Schröer

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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Human cytomegalovirus infects multiple cell types, including fibroblasts and epithelial cells. It penetrates fibroblasts by fusion at the cell surface but is endocytosed into epithelial cells. In this report, we demonstrate by electron microscopy that the virus uses two different routes to enter retinal pigmented epithelial cells, depending on the cell type in which the infecting virus was produced. Virus produced in epithelial cells preferentially fuses with the plasma membrane, whereas fibroblast-derived virus mostly enters by receptor-mediated endocytosis. Treatment of epithelial cells with agents that block endosome acidification inhibited infection by virus produced in fibroblasts but had only a modest effect on infection by virus from epithelial cells. Epithelial cell-generated virions had higher intrinsic ''fusion-from-without'' activity than fibroblast-generated particles, and the two virus preparations triggered different cellular signaling responses, as evidenced by markedly different transcriptional profiles. We propose that the cell type in which a human cytomegalovirus particle is produced likely influences its subsequent spread and its contribution to pathogenesis.host cell transcriptome ͉ pathogenesis ͉ virus spread

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Herpes Simplex Virus Type 1 Enters Human Epidermal Keratinocytes, but Not Neurons, via a pH-Dependent Endocytic Pathway

Cited by 220 publications

References 56 publications

Transport and egress of herpes simplex virus in neurons

Transport and egress of herpes simplex virus in neurons

Actin and Rho GTPases in herpesvirus biology

Human cytomegalovirus uses two distinct pathways to enter retinal pigmented epithelial cells

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