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Dive into the research topics where Andrew N. Tauscher is active.

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Featured researches published by Andrew N. Tauscher.


Oncogene | 2004

The microvesicle as a vehicle for EMMPRIN in tumor-stromal interactions

Sukhvinder S. Sidhu; Aklilu T Mengistab; Andrew N. Tauscher; Jennifer H. LaVail; Carol Basbaum

EMMPRIN is a transmembrane glycoprotein expressed at high levels by tumor cells. It has been identified as a tumor-derived factor that can stimulate matrix metalloproteinase expression in fibroblasts and hence facilitate tumor invasion and metastasis. Recent studies have shown that full-length EMMPRIN is released by tumor cells, but the mechanism of release remains unclear. Here, we show that EMMPRIN is released from the surface of NCI-H460 cells via microvesicle shedding. However, these vesicles are unstable and rapidly break down to release bioactive EMMPRIN. Although microvesicle shedding has been considered a constitutive process in tumor cells, our data show that it can be amplified upon cell exposure to PMA, elucidating at least one signalling cascade responsible for EMMPRIN release. This pathway is dependent on protein kinase C, calcium mobilization and mitogen-activated protein kinase kinase (MEK 1/2). Thus, the results outline a novel form of tumor–stromal interaction in which extracellular matrix degradation by fibroblasts is controlled through the microvesicular release of EMMPRIN from tumor cells.


Journal of Virology | 2006

Characterization of a UL49-Null Mutant: VP22 of Herpes Simplex Virus Type 1 Facilitates Viral Spread in Cultured Cells and the Mouse Cornea

Carol Duffy; Jennifer H. LaVail; Andrew N. Tauscher; Elizabeth Wills; John A. Blaho; Joel D. Baines

ABSTRACT Herpes simplex virus type 1 (HSV-1) virions, like those of all herpesviruses, contain a proteinaceous layer termed the tegument that lies between the nucleocapsid and viral envelope. The HSV-1 tegument is composed of at least 20 different viral proteins of various stoichiometries. VP22, the product of the UL49 gene, is one of the most abundant tegument proteins and is conserved among the alphaherpesviruses. Although a number of interesting biological properties have been attributed to VP22, its role in HSV-1 infection is not well understood. In the present study we have generated both a UL49-null virus and its genetic repair and characterized their growth in both cultured cells and the mouse cornea. While single-step growth analyses indicated that VP22 is dispensable for virus replication at high multiplicities of infection (MOIs), analyses of plaque morphology and intra- and extracellular multistep growth identified a role for VP22 in viral spread during HSV-1 infection at low MOIs. Specifically, VP22 was not required for either virion infectivity or cell-cell spread but was required for accumulation of extracellular virus to wild-type levels. We found that the absence of VP22 also affected virion composition. Intracellular virions generated by the UL49-null virus contained reduced amounts of ICP0 and glycoproteins E and D compared to those generated by the wild-type and UL49-repaired viruses. In addition, viral spread in the mouse cornea was significantly reduced upon infection with the UL49-null virus compared to infection with the wild-type and UL49-repaired viruses, identifying a role for VP22 in viral spread in vivo as well as in vitro.


Neuroscience | 2007

Viral regulation of the long distance axonal transport of herpes simplex virus nucleocapsid.

Jennifer H. LaVail; Andrew N. Tauscher; Anatol Sucher; Ons Harrabi; Renato Brandimarti

Many membranous organelles and protein complexes are normally transported anterograde within axons to the presynaptic terminal, and details of the motors, adaptors and cargoes have received significant attention. Much less is known about the transport in neurons of non-membrane bound particles, such as mRNAs and their associated proteins. We propose that herpes simplex virus type 1 (HSV) can be used to study the detailed mechanisms regulating long distance transport of particles in axons. A critical step in the transmission of HSV from one infected neuron to the next is the polarized anterograde axonal transport of viral DNA from the host infected nerve cell body to the axon terminal. Using the in vivo mouse retinal ganglion cell model infected with wild type virus or a mutant strain that lacks the protein Us9, we found that Us9 protein was necessary for long distance anterograde axonal transport of viral nucleocapsid (DNA surrounded by capsid proteins), but unnecessary for transport of virus envelope. Thus, we conclude that nucleocapsid can be transported independently down axons via a Us9-dependent mechanism.


Journal of Virology | 2005

Genetic and Molecular In Vivo Analysis of Herpes Simplex Virus Assembly in Murine Visual System Neurons

Jennifer H. LaVail; Andrew N. Tauscher; James W. Hicks; Offs Harrabi; Gregory T. Melroe; David M. Knipe

ABSTRACT Herpes simplex virus (HSV) infects both epithelial cells and neuronal cells of the human host. Although HSV assembly has been studied extensively for cultured epithelial and neuronal cells, cultured neurons are biochemically, physiologically, and anatomically significantly different than mature neurons in vivo. Therefore, it is imperative that viral maturation and assembly be studied in vivo. To study viral assembly in vivo, we inoculated wild-type and replication-defective viruses into the posterior chamber of mouse eyes and followed infection in retinal ganglion cell bodies and axons. We used PCR techniques to detect viral DNA and RNA and electron microscopy immunohistochemistry and Western blotting to detect viral proteins in specific portions of the optic tract. This approach has shown that viral DNA replication is necessary for viral DNA movement into axons. Movement of viral DNA along ganglion cell axons occurs within capsid-like structures at the speed of fast axonal transport. These studies show that the combined use of intravitreal injections of replication-defective viruses and molecular probes allows the genetic analysis of essential viral replication and maturation processes in neurons in vivo. The studies also provide novel direct evidence for the axonal transport of viral DNA and support for the subassembly hypothesis of viral maturation in situ.


Journal of Virology | 2003

Axonal Transport and Sorting of Herpes Simplex Virus Components in a Mature Mouse Visual System

Jennifer H. LaVail; Andrew N. Tauscher; Elda Aghaian; Ons Harrabi; Sukhvinder S. Sidhu

ABSTRACT The time course for delivery and transport of two major proteins of herpes simplex virus (HSV) has been determined for mature mouse retinal ganglion cell axons in vivo. Twenty-four hours after intravitreal injection of HSV, valacyclovir was introduced into the drinking water of the mice to inhibit subsequent viral replication. Without treatment, viral spread and replication in periaxonal glial cells confound study of axonal transport. At 2 to 5 days after infection, the animals were sacrificed and contiguous segments of the optic pathway were removed. Immunofluorescence microscopy indicated that the number of infected astrocytes was reduced in the proximal optic nerve and eliminated in the optic tract. Western blots of the retina with antibodies for envelope and capsid components, glycoprotein D (gD) and VP5, respectively, revealed that both components were expressed in retinal homogenates by 2 days. Results of reverse transcription-PCR indicated that there was no gD mRNA present in the treated optic tract 5 days after infection. Therefore, we conclude that gD is transcribed from viral mRNA in the retinal ganglion cell bodies. The gD accumulated in the proximal ganglion cell axon by 2 days and reached the most distal segment after 3 days. The VP5 first appeared in the proximal axons at 4 days, about 48 h after the appearance of gD. Thus, gD entered the axon earlier and independent of VP5. These finding confirm the subassembly model of viral transport in neurons and suggest that there is a 4- to 5-day window for initiation of effective antiviral treatment with valacyclovir.


Brain Research | 2001

Two paths for dissemination of Herpes simplex virus from infected trigeminal ganglion to the murine cornea

Peter T. Ohara; Andrew N. Tauscher; Jennifer H. LaVail

Herpes simplex virus type 1 (HSV) was introduced into the mouse trigeminal ganglion by stereotaxic injection. We examined the form in which the virus was transported anterograde within axons and the spread of virus to glial and endoneurial cells of the nerve using EM immunocytochemistry. Our results indicate that viral dissemination in the trigeminal nerve may occur both within the axon and in the extracellular space of the endoneurium. HSV is intraaxonally transported at least in part as a nucleocapsid, i.e., with neither viral envelope nor additional cellular membranes. Schwann cells are infected as a result of spread in the endoneurium, as well as by nearby axons.


Brain Research Protocols | 2003

A procedure to deliver herpes simplex virus to the murine trigeminal ganglion

John L Whitehead; Peter T. Ohara; Andrew N. Tauscher; Jennifer H. LaVail

Although initial herpes simplex virus (HSV) infections of the cornea are relatively easily treated, recurrent infections following reactivation of latent virus in the sensory ganglion cells are more difficult to treat. Untreated infections may result in severe consequences, including corneal scarring, glaucoma, and encephalitis. To develop such treatments, an experimental in vivo model was needed in which HSV can be applied directly to trigeminal ganglion cells. We have previously developed such a model to examine the mechanisms of HSV spread from trigeminal neurons to corneal epithelial cells. The current paper describes in detail the technical steps required for implementation of that model. Immunocytochemistry and electron microscopy have been used to validate the efficacy of the described procedures. This technique will be useful for future in vivo studies of neurotrophic viral infections of trigeminal ganglion cells.


Current Eye Research | 2004

Temporal expression of herpes simplex virus type 1 mRNA in murine retina

Ons Harrabi; Andrew N. Tauscher; Jennifer H. LaVail

Purpose. During maturation of herpes simplex virus type 1 (HSV) in infected murine retinal F strain ganglion cells, new viral components are axonally transported in two phases. The viral envelope protein (gD) appears 48 hr before the capsid protein (VP5). Our hypothesis was that delayed appearance of VP5 mRNA in the infected eye causes the delayed expression of the VP5 protein in the axon. Methods. HSV was injected into the ocular posterior chamber. Three to 24 hr later, the mice were euthanized, and the posterior eye was isolated. RNA was extracted, DNAase-treated, and used for amplification by reverse transcription-polymerase chain reaction (RT-PCR) using primers specific to gD, VP5 and a tegument protein VP22. Results. VP22 and gD mRNAs are expressed 6 hr and VP5 mRNA is first detected 9 hr after infection. Conclusions. The results establish that delayed transcription does not play a significant role in the 48-hr delay in VP5 apppearance in the retinal axons


Investigative Ophthalmology & Visual Science | 2008

Viral Regulation of the Long Distance Axonal Transport of Herpes Simplex Virus Nucleocapsid in vivo

Jennifer H. LaVail; Andrew N. Tauscher; Ons Harrabi; Anatol Sucher


Investigative Ophthalmology & Visual Science | 2006

A Comparison of the Roles of HSV Tegument Proteins VP22 and US9 in Corneal Cell–Cell Spread and Retinal Anterograde Transport

Jennifer H. LaVail; Andrew N. Tauscher; Ons Harrabi; C. Duffy; Joel D. Baines; R. Brandimarti

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Ons Harrabi

University of California

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Anatol Sucher

University of California

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Peter T. Ohara

University of California

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