Enquist Lab

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Enquist Lab Research

Overview

The Enquist Lab focuses on mechanisms of herpesvirus pathogenesis. Most alphaherpesviruses e.g., herpes simplex virus HSV; varicella-zoster virus, VZV; and pseudorabies virus, PRV) invade the peripheral nervous system (PNS) in their natural hosts. This life style is remarkable because of all the neurotropic viruses that also enter the PNS (e.g., rabies), only the alphaherpesviruses routinely STOP in the PNS of their natural hosts and establish a reactivatable, latent infection. Normally, this PNS infection is relatively benign, promoting survival of both virus and host. However, aberrations in this pathway give rise to the set of common diseases caused by these viruses. For example, invasion of the CNS is a rare, but an exceedingly serious possibility. The directional spread of a herpes infection from epithelial surfaces to PNS neurons where latency is established, and then, upon reactivation, spread back to epithelial surfaces constitutes the virus survival strategy. Research in my laboratory is directed toward answering several basic questions: What are the virus- and cell-encoded mechanisms that direct virus particles into and back out of the PNS? Why does the virus only occasionally enter the CNS in its natural host? What are the molecular roadblocks that make CNS infection rare in the natural host and frequent in the non-natural host? What are the viral gene products that promote efficient infection and how do they work? How do the PNS and CNS respond to viral infection? These basic questions continue to lead us into exciting and sometimes unexpected areas. Several examples are outlined below.

 

Pseudorabies Virus

Pseudorabies Virus (PRV) as a Model System

Our a-herpesvirus of choice is PRV, a broad host range herpesvirus that causes fatal encephalitis in a wide variety of animal species except its natural host, the adult pig. PRV is not a human pathogen and grows well in the lab. Using rodent and chick embryo models and defined mutations in specific PRV genes, we are studying mechanisms of spread from site of primary infection, evasion of innate and acquired immune defense, and cell/tissue damage. We have identified several PRV gene products that affect the extent of PRV pathogenesis in both model systems affecting cell to cell spread, direction of spread, and host response to infection. We have constructed infectious bacterial artificial chromosomes carrying the entire PRV genome and are using E. coli mutagenesis and recombination techniques for genetic analysis of PRV. cDNA analyses coupled with gene array technology are being developed to understand the role of virus and host genes in virus replications in various cell types and tissues of infected animals.

Read more: Pseudorabies Virus (PRV)

Herpesvirus Replication Cycle in an Epithelial Cell
Herpesvirus Latent Infection
Herpesvirus Evolution
PRV Virion Structure
PRV Genome and Gene Organization

 

Genetics of directional spread of virus in and between neurons

Axonal Sorting of Pseudorabies Virus

During alpha-herpesvirus egress in neurons, the capsid/tegument complex is released into the cytosol where it undergoes a secondary envelopment step into vesicles derived from the trans-Golgi network (TGN). These vesicles, containing enveloped virus particles, are then transported to the plasma membrane for local release from the cell body. Viral components are also targeted to the axon for long distance transport and release at axon termini. The mechanisms involved in axonal sorting are a key interest of our laboratory. Until recently it has been unclear what is actually sorted into axons, namely whether PRV capsid/tegument complexes are sorted separately from viral membrane proteins, or whether both are transported together as a mature virus particle contained within a vesicle. Using Campenot chamber technology coupled with transmission electron microscopy (TEM), we have been able to further elucidate this process.

EMPRVBecker1The trichamber neuronal culturing system allows for the physical separation of neuronal cell bodies (soma) from axon termini. Dissociated rat embryonic neurons are plated in the soma (S) chamber and allowed to mature for two weeks. During this period, axons are directed between a series of grooves across the methocellulose (M) chamber to the neurite (N) chamber. Cell bodies in the S chamber are then infected, and virus structural components are sorted into axons in the anterograde direction (into the middle and neurite compartments). The initial infection is confined to the S chamber via silicone vacuum grease and a methocellulose barrier. Therefore, input inoculum or newly replicated virus released from cell bodies is unable to confound analyses examining virus components sorted into the axon. In the experiment shown above, wild-type Becker was used to infect cell bodies in the soma compartment, and EM analysis was subsequently performed in the M compartment to examine the nature of viral capsids in axons. These findings suggested that mature virus particles, found within a transport vesicle, were directed into axons.


EMPRVBecker2Our lab has also developed another in vitro chamber system that physically separates cell bodies from axon termini. Rat embryonic ganglion explants are plated and allowed to extend axons for one week in the presence of nerve growth factor (NGF). A non-septated, Teflon chamber disk is then placed on top of the axons thereby capturing a subpopulation of axon ends. One can then infect the explant and image inside the chamber ring to examine anterograde transport of viral structural proteins. EM analysis of axons from Becker infected explants also showed the presence of enveloped virus particles within a vesicle, supporting previous data generated in the trichamber system. The notion that mature virus particles are sorted into the axon has been further supported by live-cell imaging experiments using GFP and RFP tagged structural proteins (Greg Smith, Northwestern University) in addition to indirect immunofluorescene of infected neurons in the isolator chamber system (our lab). The idea that virus encodes a mechanism to direct trafficking of cellular vesicles into the axon (which may or may not contain a virus particle) is very intriguing. What viral genes are involved in this process?

PRV Us9 Is Primarily Responsible for Axonal Sorting of Virus Particles

The PRV Us9 gene product is a phosphorylated, type II membrane protein that is "tail-anchored," meaning that it has no identifiable signal sequence, and has an amino-terminus that resides in the cytosol, and a carboxy-terminal anchor that spans the lipid bilayer. Its steady state concentration is highest in or near the trans-Golgi network, and is heavily enriched in lipid raft microdomains. The absence of Us9 does not affect cell-to-cell spread in Madin-Darby bovine kidney cells, but has a dramatic effect on anterograde spread of infection in the visual circuitry of the rat brain and neuron-to-cell spread in vitro, suggesting that Us9 performs a neuronal specific function during replication. Work in our lab has shown that Us9 is essential for the anterograde transport of viral capsids as well as viral glycoproteins. The heterodimeric complex gE/gI also impacts the sorting of virus particles into the axon, but to a lesser extent than Us9. Thus, our model is that gE/gI may play an accessory role to Us9, and that all three proteins working together lead to efficient axonal sorting of vesicles (see below).


EMPRVBecker3 We propose a model in which Us9, gE/gI, and lipid rafts direct the sorting of vesicles into the axon of infected neurons. Us9 and gE/gI likely associate with lipid rafts in the trans-Golgi network (TGN), the proposed site of viral assembly. The presence of Us9 and gE/gI in lipid rafts (those decorating the surface of cellular vesicles) would recruit axonal sorting machinery to a small number of viral assembly complexes in the TGN, i.e. vesicles with viral membrane proteins only, those containing mature virus particles, or L-particles. A limited number of vesicles containing virion components would then be targeted to the axon.

Tracing the hardwiring of the nervous system using virus

Unlike infections of the natural host (the adult pig), PRV infections of all other permissive species (e.g., baby pigs, chicken embryos, rodents, dogs, cats, and cows, to name a few) are lethal and quickly transmitted through peripheral nerves to the brain and spinal cord. These infections enable us to study not only mechanisms of virulence and how the nervous system responds to infection, but also how the virus spreads in the nervous system. Amazingly enough, in all permissive species, the virus spreads only in chains of synaptically connected neurons (trans-neuronal spread). Therefore, PRV can be used as a self-amplifying tracer of neuronal circuits. The ability to reveal a neural circuit (neuron A is wired to neuron B is wired to neuron C etc) is powerful technology, but demands attention to many details. Tracing studies are rewarding because they require close collaboration between neurobiologists and virologists. For example, circuit tracing requires use of mutant viruses that are much less virulent than wild type PRV. Understanding why these mutants are good tracing strains has led us to a better understanding of virulence and mechanisms by which virus spreads between neurons. In addition, we capitalize on our ability to manipulate PRV to construct less virulent, innovative tracing viruses: e.g., viruses expressing b-galactosidase and variants of green fluorescent protein, as well as viruses that replicate only in certain neurons and not others. These viruses provide powerful tools to study neural circuits and how the nervous system responds to infection.


Center of Neuroanatomy with Neurotropic Viruses

Probing the host response to herpesviruses using microarrays

The Enquist lab has investigated the host response to alphaherpesvirus infection using microarray technology. First, we used rat embryonic fibroblasts (REF cells) as a model to investigate cellular responses to infection by either PRV or HSV-1 (Ray and Enquist, 2004). This study used Affymetrix rat RGU34A arrays. Next, we followed up one of the largest increases in gene expression observed during PRV infection of REF cells, that of cyclooxygenase-2 (COX-2). This study found that the inhibition of COX would in turn inhibit PRV replication (Ray et al., 2004). We then investigated the in vivo host response to PRV infection, using the rat eye model of infection. We measured gene expression responses of hypothalamus and cerebellum using Affymetrix rat RG-U34A arrays (Paulus et al., 2006). This study involved a variety of input virus strains, including the virulent PRV Becker, attenuated PRV Bartha, and the gE/gI-deleted recombinant PRV99. Finally, we carried out a meta-analysis of these and other published studies of the neuronal response to alphaherpesvirus infection, to discern which of the observed responses were the most frequent and prominent (Szpara et al., 2010).

Ray N, Enquist LW. 2004. Transcriptional response of a common permissive cell type to infection by two diverse alphaherpesviruses. J. Virol., 78(7):3489-3501.

PUMAdb (Access to all data from these experiments)


Ray N, Bisher ME, Enquist LW. 2004. Cyclooxygenase-1 and -2 are required for production of infectious pseudorabies virus. J. Virol., 78(23):12964-12974.


Paulus C, Sollars PH, Pickard GE, Enquist LW. 2006. Transcriptome signature of virulent and attenuated pseudorabies virus-infected rodent brain. J Virol. 2006 Feb;80(4):1773-86.

PUMAdb (Access to all data from these experiments)


Szpara ML, Kobiler O, Enquist LW. 2010. A common neuronal response to alphaherpesvirus infection. J Neuroimmune Pharmacol 5(3): 418-427.

Viral genome variation

The Enquist and Mettenleiter labs collaborated to complete the first PRV genome sequence, which was a mosaic of six strains assembled from Sanger-sequenced clones (Klupp et al., 2004). Later, we developed the use of deep sequencing technology for alphaherpesviruses, using this approach to reveal genome-wide variation between different strains. We began by using Illumina high-throughput short read sequencing to determine the genome sequence of HSV-1 strains F and H129 (Szpara et al., 2010). This helped us narrow in on genes potentially responsible for the unique anterograde-limited spread phenotype of HSV-1 strain H129. We then improved and expanded our deep sequencing efforts to sequence the first single-strain genomes of PRV, revealing the sequence of the virulent strains PRV Becker and Kaplan, as well as the attenuated vaccine strain Bartha (Szpara et al., 2011). PRV Bartha was attenuated for vaccine use by multiple passages in vitro, and this study revealed for the first time the breadth of genes with variations that could contribute to vaccine attenuation (46 of 67 total proteins). Additional sequencing work will be continued in Moriah Szpara’s lab at Penn State University.

Klupp BG, Hengartner CJ, Mettenleiter TC, Enquist LW. 2004. Complete, annotated sequence of the pseudorabies virus genome. J Virol 78(1): 424-440.
GenBank mosaic PRV reference genome


Szpara ML, Parsons L, Enquist LW. 2010. Sequence variability in clinical and laboratory isolates of herpes simplex virus 1 reveals new mutations. J Virol 84(10): 5303-5313.
HSV Viral Genome Browser
GenBank links for HSV-F and H129
Raw sequence data for strains HSV F and H129


Szpara ML, Tafuri YR, Parsons L, Shamim SR, Verstrepen KJ, Legendre M, Enquist LW. 2011. A wide extent of inter-strain diversity in virulent and vaccine strains of alphaherpesviruses. PLoS Pathog 7(10): e1002282.

 

PRV Viral Genome Browser
PRV Supplementary Data Website GenBank links for PRV-Becker, and PRV-Kaplan
Raw sequence data for all PRV strains

Undergraduate Theses

2012

Porter, Derek (2012): Examination of the Effect of Tetherin Expression on Pseudorabies Virus Infection. (Thesis No. 27073)


2011

Hassani, Daisy B. (2011): An Analysis of the Effect of Pseudorabies Virus Infection on Mitochondrial DNA. (Thesis No. 25628)

Ludmir, Ethan Bernard (2011): A Toolbox of Pseudorabies Virus Recombinants, Derivatives, and Methods for Use in Neural Circuit Tracing. (Thesis No. 25644)


2010

Hudnall, Matthew T. (2010): An Imaging Analysis of Cellular Morphology in Pseudorabies Virus Infection. (Thesis No. 24337)


2009

Smith, Amanda C. (2009): Involvement of Kinesin-1 in Pseudorabies Virus Transport. (Thesis No. 22948)


2008

Gawande, Richa M. (2008): Altered Mitochondrial Distribution and Transport in the Pathogenesis of Pseudorabies Virus Infection. (Thesis No. 22628)

Liu, Wendy W. (2008): Transport of Alpha-herpesvirus Structural Proteins in Axons. (Thesis No. 22642)


2007

Beylin, Marie E. (2007): In Vitro Astrocyte Responses to Pseudorabies Virus. (Thesis No. 21389)

Cohen, Gabriel (2007): The Normalization of HIV Testing in The United States: The Effect of "Opt-Out" Routine Testing on Patient Autonomy. (Thesis No. 21394)

Goheen, Morgan (2007): Construction and Characterization of a Pseudorabies Virus Mutants Expressing gC-GFP. (Thesis No. 21403)

Okonkwo, Stephanie O. (2007): A Critical Review of Alzheimer's Disease Herpes Simplex Viral Pathogenesis Theory. (Thesis No. 21422)


2006

Bhat, Suneel Bhaskar (2006): Neuroprotective nature of the cytoplasmic prion protein and Us9 and gE intercellular trafficking: An approach using photoactivatable fluorescent molecules and live-cell imaging. (Thesis No. 19399)

Buerki, Robin Arthur (2006): The effects of authophagy on the replication of herpes simplex virus and pseudorabies virus. (Thesis No. 20239)

Kang, Kristopher (2006): Rotavirus vaccine implementation: Realizing the public health promise of Rotarix and Rotateq. (Thesis No. 20262)

Piccinotti, Silvia (2006): Herpesvirus infection induces the formation of nuclear actin filaments serving as a scaffold for capsid assembly. (Thesis No. 20275)

Zider, Jacqueline Elliott (2006): Engineering viruses to fight cancer: A review of selected antitumor therapies. (Thesis No. 20284)


2005

Carson, Katherine Lecker (2005): How Virulent and Attenuated Strains of PRV Counter the Apoptotic Response. (Thesis No. 19021)

Raldow, Ann Caroline (2005): Construction of an Attenuated Herpesvirus Recombinant that Expresses a Fluorescent Red Capsid Protein. (Thesis No. 19060)


2004

Bartlett, Edmund (2004): Isolation and Characterization of an Indomethacin Resistent Pseudorablies Virus Mutant. (Thesis No. 17271)


2003

Giron, Angela (2003): Sex Hormones & Human Papillomavirus: A Synergistic Effect on Cervical Cancer. (Thesis No. 16314)

Miller, Brian (2003): The Search for an ICP47 Homologue in PRV: Initial Characterization of the Putative UL21.5 Gene. (Thesis No. 16333)

Shackelton, Laura (2003): The Molecular Characterization of an Ancient Herpesvirus Gene: UL7 in Pseudorabies Virus. (Thesis No. 16345)


2002

Bratman, Scott Victor (2002): Intramolecular Determinants of Pseudorabies Virus Glycoprotein M. Subcellular Localization. (Thesis No. 15629)

Peebles, Carol Lee (2002): PC12 Cell Line as a Model System for PRV Infection and Viral Glycoprotein Transport in Neurons. (Thesis No. 15661)


2001

Chen, SuAnn S. (2001): ): Arecholine-Induced Depression and its Effects on the Immune System Response.(Thesis No. 13065)

Dasgupta, Nabarun (2001): How to know a jumping gene when you see one. (Thesis No. 14504)

Kemp, Clinton D. (2001): A comparative analysis of alphaherpesvirus Us9 homologs and molelcular dissection of the conserved basic domain of PRV Us9.(Thesis No. 14519)

Shah, Sachin D. (2001): Disseminating scientific and medical information to the public: A case study of West Nile virus in New York City in 1999 and 2000. (Thesis No. 14534)


2000

Hsiao, Wayland (2000): Role of Proteins Encoded by the Unique Short Region during Pseudorabies Virus Infection of Cultured Primary Avian Cells. (Thesis No. 12531)

Kuipers, Katherine (2000): Yeast Two-Hybrid Screen for Cellular Proteins Binding to PRV Proteins Involved in Neuronal Spread. (Thesis No. 12537)

Werner, Heidi C. (2000): Characterization of VP22: A Pseudorabies Virus Protein. (Thesis No. 12563)


1999

Azzam, Helen (1999): Us9: Characterization and Functional Analysis in Varicella-Zoster Virus. (Thesis No. 10817)

Divakaruni, Monica (1999): Great Expectations: Assessing the Prospects for Human Immunodeficiency Virus Vaccine Development and Deployment. (Thesis No. 10828)

Iofin, Ilya (1999): Regulation of Apoptosis by Pseudorabies Virus. (Thesis No. 10847) [Not Received by the Mudd Library]

Liu, Audrey (1999): Construction of a Novel PRV-Bartha Infectious Clone. (Thesis No. 10857)


1998

Baynes, Jason Robert (1998): An Analysis of Reactive Oxygen Species as Initiators and Modulators of Neuronal Death. (Thesis No. 10023)

Jones, Thomas E. (1998): Combating Drug Resistant Malaria Parasites: Development and Distribution Strategies for Antimalarial Drugs. (Thesis No. 10042)

La, Ellen Y. (1998): Further Studies on UL21: A Pseudorabies Virus Neurovirulence Determinant. (Thesis No. 10045)

Newton, Isabel Gala (1998): Analysis of Pseudorabies Virus AK9 Spread through Rodent Neuronal Circuits between the Retinal Ganglion Cells and the Hippocampus. (Thesis No. 10053)


1997

Brodsky, Igor E. (1997): Construction and Analysis of PRV Recombinants Expressing HSV-1 Glycoproteins. (Thesis No. 8980)

Gandhi, Soniya S. (1997): Solving the HIV Crisis: Challenges in the Development and Implementation of an Effective Vaccine. (Thesis No. 8999)

Hitchcock, Amy L. (1997): Characterization of UL21, a Pseudorabies Virus Neurovirulence Determinant. (Thesis No. 9006)

Huang, Karen S. (1997): Construction of Infectious Pseudorabies Virus from Cosmid-cloned Subgenomic Fragments. (Thesis No. 9009)

Lee, Christina (1997): Introducing Traditional Chinese Medicine into a Modern Medical System. (Thesis No. 9065)


1996

Bunya, Vatinee Y. (1996): Role of the Cytoskeleton in Pseudorabies Virus Infection. (Thesis No. 7339)

Kuo, Timothy (1996): The Role of Pseudorabies Virus Gylcoproteins gE and gI in Ciruit-Specific Viral Spread within the Rodent Central Nervous System. (Thesis No. 7394)

Senecal, Emily L. (1996): The Role of Non-Essential Genes in the Infection of the Chick Embryo Visual Circuit by Pseudorabies Virus. (Thesis No. 7382)


1995

Barton, Gregory M. (1995): Construction of Neurotropic Herpesvirus Recombinants Carrying Novel Reporter Genes. (Thesis No. 6340)

DeOrio, Joseph J. (1995): The P1 Cloning System as a Means for the Manipulation and Recovery of Pseudorabies Virus DNA. (Thesis No. 6326)

Yap, Gregory S. (1995): Establishing the Chick Embryo Visual Circuit as a Model for Pseudorabies Virus Infection: Studies in Neurotropism and Virulance. (Thesis No. 6350)

Journal Club Papers

Yordy et al. (2012) A Neuron-Specific Role for Autophagy in Antiviral Defense against Herpes Simplex Virus. Cell Host Microbe. 2012 Sep 13;12(3):334-45.

Mingo et al. (2012) Replication of herpes simplex virus: egress of progeny virus at specialized cell membrane sites. J Virol. 2012 Jul;86(13):7084-97. Epub 2012 Apr 24.

Strang et al. (2012) Human cytomegalovirus UL44 concentrates at the periphery of replication compartments, the site of viral DNA synthesis. J Virol. 2012 Feb;86(4):2089-95. Epub 2011 Dec 7.

Moughamian et al. (2012) Synaptic vesicle distribution by conveyor belt. Cell. 2012 Mar 2;148(5):849-51.

Wong et al. (2012) Neuropeptide delivery to synapses by long-range vesicle circulation and sporadic capture. Cell. 2012 Mar 2;148(5):1029-38.

Noyce et al. (2011) Membrane perturbation elicits an IRF3-dependent, interferon-independent antiviral response. J Virol. 2011 Oct;85(20):10926-31. Epub 2011 Aug 3.

Paladino et al. (2006) The IFN-independent response to virus particle entry provides a first line of antiviral defense that is independent of TLRs and retinoic acid-inducible gene I. J Immunol. 2006 Dec 1;177(11):8008-16.

Ibiricu et al. (2011) Cryo electron tomography of herpes simplex virus during axonal transport and secondary envelopment in primary neurons. PLoS Pathog. 2011 Dec;7(12):e1002406. Epub 2011 Dec 15.

Zivraj et al. (2010) Subcellular profiling reveals distinct and developmentally regulated repertoire of growth cone mRNAs. J Neurosci. 2010 Nov 17;30(46):15464-78.

Jolly et al. (2011) The regulated secretory pathway in CD4(+) T cells contributes to human immunodeficiency virus type-1 cell-to-cell spread at the virological synapse. PLoS Pathog. 2011 Sep;7(9):e1002226. Epub 2011 Sep 1.

Beier et. al. (2011) Anterograde or retrograde transsynaptic labeling of CNS neurons with vesicular stomatitis virus vectors. Proc Natl Acad Sci U S A. 2011 Sep 13;108(37):15414-9. Epub 2011 Aug 8.

Vega Thurber et al. (2008) Metagenomic analysis indicates that stressors induce production of herpes-like viruses in the coral Porites compressa. Proc Natl Acad Sci U S A. 2008 Nov 25;105(47):18413-8. Epub 2008 Nov 18.

Strunze et al. (2011) Kinesin-1-mediated capsid disassembly and disruption of the nuclear pore complex promote virus infection. Cell Host Microbe. 2011 Sep 15; 10(3):210-23.

Markus et al. (2011) Varicella zoster virus infection of neurons derived from human embryonic stem cells: direct demonstration of axonal infection, transport of VZV and productive neuronal infection. J Virol. 2011 Jul;85(13):6220-33. Epub 2011 Apr 27.

Tokarev et al. (2011) Serine-threonine ubiquitination mediates downregulation of BST-2/tetherin and relief of restricted virion release by HIV-1 Vpu. J Virol. 2011 Jan;85(1):51-63. Epub 2010 Oct 27.

Keil et al. (2010) Protein display by bovine herpesvirus type 1 glycoprotein B. Vet Microbiol. 2010 Jun 16;143(1):29-36. Epub 2010 Feb 11.

Keil et al. (2005) Engineering glycoprotein B of bovine herpesvirus 1 to function as transporter for secreted proteins: a new protein expression approach. J Virol. 2005 Jan;79(2):791-9.

Rode et al. (2011) Uncoupling uncoating of Herpes Simplex Virus genomes from their nuclear import and gene expression. J Virol. 2011 May;85(9):4271-83. Epub 2011 Feb 23.

Card et al. (2011) Microdissection of neural networks by conditional reporter expression from a Brainbow herpesvirus. Proc Natl Acad Sci USA. 2011Feb 22;108(8):3377-82. Epub 2011 Feb 3.

Kaufer et al. (2010) The Varicella-Zoster Virus ORFS/L (ORF0) Gene Is Required for Efficient Viral Replication and Contains an Element Involved in DNA Cleavage. J Virol. 2010 Nov;84(22):11661-9. Epub 2010 Sep 15.

Atanasiu et al. (2010) Cascade of events governing cell-cell fusion induced by herpes simplex virus glycoproteins gD, gH/gL, and gB. J Virol. 2010 Dec;84(23):12292-9. Epub 2010 Sep 22.

Remillard-Labrosse et al. (2009) Protein Kinase D-Dependent Trafficking of the Large Herpes simplex Virus Type 1 Capsids from the TGN to Plasma Membrane. Traffic. 2009 Aug;10(8):1074-83. Epub 2009 May 5.

DeRegge et al. (2010) Interferon alpha induces establishment of alphaherpesvirus latency in sensory neurons in vitro. PLoS One. 2010 Sep 29;5(9). pii: e13076.

Brisac et al. (2010) Calcium Flux between the Endoplasmic Reticulum and Mitochondrion Contributes to Poliovirus-Induced Apoptosis. J Virol. 2010 Dec;84(23):12226-35. Epub 2010 Sep 22

Arii et al. (2010) Non-muscle myosin IIA is a functional entry receptor for herpes simplex virus-1. Nature 2010 Oct 14; 467(7317):859-623

Bower et al. (1999) Intrastrain Variants of Herpes Simplex Virus Type 1 Isolated from a Neonate with Fatal Disseminated Infection Differ in the ICP34.5 Gene, Glycoprotein Processing, and Neuroinvasiveness. Journal of Virology, May 1999, p. 3843-3853

Jackson et al. (2010) Reevaluating herpes simplex virus hemifusion. J Virol. 2010 Nov;84(22):11814-21. Epub 2010 Sep 15.

Antinone et al. (2010) Resolving the assembly state of herpes simplex virus during axon transport by live-cell imaging. J Virol. 2010 Dec;84(24):13019-30. Epub 2010 Sep 1.

van Lint et al. (2010) Herpes simplex virus immediate-early ICP0 protein inhibits Toll-like receptor 2-dependent inflammatory responses and NF-kappaB signaling. J Virol. 2010 Oct;84(20):10802-11. Epub 2010 Aug 4.

Anesti et al. (2008) Efficient delivery of RNA Interference to peripheral neurons in vivo using herpes simplex virus. Nucleic Acids Res. 2008 Aug;36(14):e86. Epub 2008 Jun 25.

Ku et al. (2010) Herpes simplex virus-1 induces expression of a novel MxA isoform that enhances viral replication. Immunol Cell Biol. 2011 Feb;89(2):173-82. Epub 2010 Jul 6.

Weiss et al. (2001) The estrous cycle affects pseudorabies virus (PRV) infection of the CNS. Brain Research 893: 215-226.

Zeng et al. (2010) Decision making at a subcellular level determines the outcome of bacteriophage infection. Cell. 141(4): 682-91.

Liu et al. (2010) ICP0 dismantles microtubule networks in herpes simplex virus-infected cells. PLoS One. 5(6):e10975.

Berarducci B et al. (2009) Deletion of the first cysteine-rich region of the varicella-zoster virus glycoprotein E ectodomain abolishes the gE and gI interaction and differentially affects cell-cell spread and viral entry. J Virol. 83(1):228-40.

Lin et al. (2010) Role of the UL41 Protein of Pseudorabies Virus in Host Shutoff, Pathogenesis and Induction of TNF-alpha Expression. J Vet Med Sci. 2010 Sep;72(9):1179-87. Epub 2010 Apr 24.

Lancaster KZ, Pfeiffer JK. (2010) Limited trafficking of a neurotropic virus through inefficient retrograde axonal transport and the type I interferon response. PLoS Pathog. 5;6(3):e1000791.

Maresch et al. (2010) Ultrastructural Analysis of Virion Formation and Anterograde Intraaxonal Transport of the Alphaherpesvirus Pseudorabies Virus in Primary Neurons. J Virol 84(11): 5528-5539.

Snijder et al. (2009) Population context determines cell-to-cell variability in endocytosis and virus infection. Nature 461(7263):520-3.

Arbuckle JH et al. (2010) The latent human herpesvirus-6A genome specifically integrates in telomeres of human chromosomes in vivo and in vitro. Proc Natl Acad Sci U S A. 107(12):5563-8.

Everett RD et al. (2010) Comparison of the biological and biochemical activities of several members of the alphaherpesvirus ICP0 family of proteins. J Virol. 84(7):3476-87.

Morgan GW et al. (2010) Vaccinia protein F12 has structural similarity to kinesin light chain and contains a motor binding motif required for virion export. PLoS Pathog. 26;6(2):e1000785.

Miyauchi et al. (2009) HIV enters cells via endocytosis and dynamin-dependent fusion with endosomes. Cell. 137(3):433-44.

Doceul et al. (2010) Repulsion of superinfecting virions: a mechanism for rapid virus spread. Science. 327(5967):873-6.

Yoon H et al. (2005) Olfactory inputs to hypothalamic neurons controlling reproduction and fertility. Cell 123(4):669-82.

Antinone SE, Smith GA. (2010) Retrograde axon transport of herpes simplex virus and pseudorabies virus: a live-cell comparative analysis. J Virol. 4(3):1504-12.

Livingston CM et al. (2009) Virus-Induced Chaperone-Enriched (VICE) domains function as nuclear protein quality control centers during HSV-1 infection. PLoS Pathog. (10):e1000619.

Chlanda et al. (2009) Membrane rupture generates single open membrane sheets during vaccinia virus assembly. Cell Host Microbe 6 (1) pp. 81-90.

Möhl et al (2009) Intracellular localization of the pseudorabies virus large tegument protein pUL36. J Virol. 83(19): 9641-51.

Yamamoto et al. (1973) Ultrastructure of Herpes simplex Virus Infection of the Nervous System of Mice. Acta neuropath. (Bert.) 26: 285-299.

Roussarie et al. (2007) The Role of Myelin in Theiler's Virus Persistence in the Central Nervous System. PLoS Pathog. 2007 Feb;3(2):e23.

Song et al. A selective filter for cytoplasmic transport at the axon initial segment. Cell (2009) vol. 136 (6) pp. 1148-60

Thompson et al. (2009) De Novo Synthesis of VP16 Coordinates the Exit from HSV Latency In Vivo. PLoS Pathog 5(3): e1000352.

Hübner et al. (2009) Quantitative 3D Video Microscopy of HIV Transfer Across T Cell Virological Synapses. Science 323(5922): 1743-1747.

Wisner et al. (2009) Herpesvirus gB-induced fusion between the virion envelope and outer nuclear membrane during virus egress is regulated by the viral US3 kinase. J Virol. 83(7):3115-26.

Miranda-Saksena M. (2009) Herpes Simplex Virus Utilizes The Large Secretory Vesicle Pathway For Anterograde Transport Of Tegument and Envelope proteins and For Viral Exocytosis From Growth Cones Of Human Fetal Axons. J Virol. 2009 Apr;83(7):3187-99.

Hedstrom et al. (2008) AnkyrinG is required for maintenance of the axon initial segment and neuronal polarity. J Cell Biol. 183(4):635-40.

Barcia et al. (2008) T cells' immunological synapses induce polarization of brain astrocytes in vivo and in vitro: a novel astrocyte response mechanism to cellular injury. PLoS ONE. Aug 20;3(8):e2977.

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