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Delayed Rejection Of Mhc Class Ii-Disparate Skin Allografts In Mice Treated With Farnesyltransferase Inhibitors, Ken Field

Faculty Journal Articles

Farnesyltransferase inhibitors (FTIs), developed as anti-cancer drugs, have the potential to modulate immune responses without causing nonspecific immune suppression. We have investigated the possibility that FTIs, by affecting T cell cytokine secretion, can attenuate alloreactive immune responses. The effects of FTIs on murine alloreactive T cells were determined both in vitro, by measuring cytokine secretion or cell proliferation in mixed lymphocyte cultures, and in vivo, by performing skin allografts from H-2^bm12mice to MHC class II-disparate B6 mice. We found that two different FTIs, ABT-100 and L-744,832, blocked secretion of IFN-γ, IL-2, IL-4, and TNF-α from naïve …

Stat5 Regulation Of Bcl10 Parallels Constitutive Nfkappab Activation In Lymphoid Tumor Cells., Zsuzsanna S Nagy, Matthew J Lebaron, Jeremy A Ross, Abhisek Mitra, Hallgeir Rui, Robert A Kirken

Department of Cancer Biology Faculty Papers

BACKGROUND: Signal Transducer and Activator of Transcription 5 A and B (STAT5) are key survival factors in cells of the lymphoid lineage. Identification of novel, tissue-specific STAT5 regulated genes would advance the ability to combat diseases due to aberrant STAT5 signaling. In the present work a library of human STAT5 bound genomic elements was created and validated. RESULTS: Of several STAT5 responsive genomic regulatory elements identified, one was located within the first intron of the human BCL10 gene. Chromatin immuno-precipitation reactions confirmed constitutive in vivo STAT5 binding to this intronic fragment in various human lymphoid tumor cell lines. Interestingly, non-phosphorylated …

Trichostatin A Inhibits Corneal Haze In Vitro And In Vivo, Ajay Sharma, Maneesh M. Mehan, Sunilima Sinha, John W. Cowden, Rajiv R. Mohan

Pharmacy Faculty Articles and Research

PURPOSE. Trichostatin A (TSA), a histone deacetylase inhibitor, has been shown to suppress TGF- –induced fibrogenesis in many nonocular tissues. The authors evaluated TSA cytotoxicity and its antifibrogenic activity on TGF- –driven fibrosis in the cornea with the use of in vitro and in vivo models.

METHODS. Human corneal fibroblasts (HSFs) were used for in vitro studies, and New Zealand White rabbits were used for in vivo studies. Haze in the rabbit cornea was produced with photorefractive keratectomy (PRK) using excimer laser. Trypan blue exclusion and MTT assays evaluated TSA cytotoxicity to the cornea. Density of haze in the rabbit …

Regulation Of Alpha- And Beta-Actin Isoforms In The Contracting A7r5 Smooth Muscle Cell, Dawn Leah Brown-Turner

Theses, Dissertations and Capstones

Two isoforms of actin have been found to be present in A7r5 smooth muscle cells, α- and β-actin. This body of work sets out to examine the different regulatory factors of the two actin isoforms during smooth muscle contraction. The response of the actin isoforms to phorbol 12, 13-dibutyrate (PDBu) is markedly different. α-Actin remodels to podosomes around the periphery of the cell, while β-actin merely shortens. One protein involved in smooth muscle contraction induced by PDBu is protein kinase C (PKC). Two inhibitors of PKC, staurosporine and bisindolymaleimide, were used prior to PDBu stimulation and after PDBu stimulation to …

Human Chorionic Gonadotropin Levels In Serum And Follicular Fluid Are Correlated With Body Mass Index Rather Than The Route Of Administration Of Purified Hcg In Art Cycles, Özlem Moralioğlu Üçkardeşler, Sevtap Kiliç, Gülnur Özakşi̇t, Çi̇ğdem Kunt, Ayça Işik, Beri̇l Yüksel, Leyla Mollamahmutoğlu

Turkish Journal of Medical Sciences

Aim: To investigate hCG levels in follicular fluid and serum after intramuscular (IM) or subcutaneous (SC) administration of purified hCG, and their association with oocyte maturation and body mass index (BMI) in women undergoing IVF-ET. Materials and Methods: The study included 160 infertile women that were recruited between April and June 2007. Standard-dose long IVF protocols were used for ovulation induction. SC or IM injections were used to administer hCG. BMI, oocyte maturity, and serum and follicular fluid hCG levels were the main outcome measurements. Results: hCG levels in serum and follicular fluid in the 2 groups were similar. A …

Viral Etiology And Symptoms Of Acute Upper Respiratory Tract Infections In Children, Emi̇n Ünüvar, İsmai̇l Yildiz, Ayşe Kiliç, Seyhan Selvi̇ Aslan, Bülent Çakal, Sadik Toprak, Seli̇m Badur, Fatma Oğuz, Müjgan Sidal

Turkish Journal of Medical Sciences

Aims: To determine viral causes of acute upper respiratory tract infections and clinical findings in children living in Istanbul, Turkey. Materials and Methods: This prospective study was carried out in 234 outpatient children (age range: 1-180 months) with acute upper respiratory tract infections, seen in the outpatient clinic at Istanbul Medical School Children´s Hospital. After clinical findings were recorded, nasal swab specimens were taken. In 201 specimens collected, influenza-A and -B, adenovirus, respiratory syncytial virus, and parainfluenza viruses were studied using direct fluorescence antibody, polymerase chain reaction (PCR), and cell culture techniques. Results: Rate of virus isolation was 29.8% (60/201). …

Is The Traditional Treatment Approach Adequate In Children With Adenoid Hypertrophy?, Baran Acar, Hayri̇ye Karabulut, Mehmet Ali̇ Babademez, Selahatti̇n Genç, R. Murat Karaşen

Turkish Journal of Medical Sciences

Aim: We aimed to show the necessity of 1) endoscopic assessment after adenoidectomy performed blindly by adenoid curette, adenotome or adenoid punch forceps after checking adenoid size with finger palpation, which is commonly used in routine practice and 2) extraction of residual adenoids with additional methods. Materials and Methods: Prospective intraoperative flexible endoscopic evaluation of the nasopharynx in a case series of 51 patients was performed. The degree of residual postnasal obstruction due to adenoid tissue was assessed endoscopically with 2.7-mm 0° telescope (small, moderate, large) after routine transoral adenoidectomy. The telescope was then introduced transnasally, and residual adenoid tissue …

Incorporation Of Membrane-Bound, Mammalian-Derived Immunomodulatory Proteins Into Influenza Whole Virus Vaccines Boosts Immunogenicity And Protection Against Lethal Challenge, Andrew S. Herbert, Lynn Heffron, Roy Sundick, Paul C. Roberts

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Influenza epidemics continue to cause morbidity and mortality within the human population despite widespread vaccination efforts. This, along with the ominous threat of an avian influenza pandemic (H5N1), demonstrates the need for a much improved, more sophisticated influenza vaccine. We have developed an in vitro model system for producing a membrane-bound Cytokine-bearing Influenza Vaccine (CYT-IVAC). Numerous cytokines are involved in directing both innate and adaptive immunity and it is our goal to utilize the properties of individual cytokines and other immunomodulatory proteins to create a more immunogenic vaccine.

Results

We have evaluated the immunogenicity of inactivated cytokine-bearing influenza …

Cellular And Molecular Mechanisms Of Toxin Resistance For Endoplasmic Reticulum Translocating Toxins, Christopher Massey

Electronic Theses and Dissertations

The endoplasmic reticulum (ER) is the site of co- and post-translational modification for secretory proteins. In order to prevent vesicular transport and secretion of misfolded or misassembled proteins, a highly regulated mechanism called ER-associated degradation (ERAD) is employed. This pathway recognizes misfolded proteins in the ER lumen and targets them to the cytosol for ubiquitination and subsequent degradation via the 26S proteasome. Sec61 and Derlin-1 are ER pores through which export occurs. AB-type protein toxins such as cholera toxin (CT), Shiga toxin (ST), exotoxin A (ETA), and ricin have evolved means of exploiting the ERAD pathway in order to reach …

Bacterial Selenoproteins: A Role In Pathogenesis And Targets For Antimicrobial Development, Sarah Rosario

Electronic Theses and Dissertations

Selenoproteins are unique proteins in which selenocysteine is inserted into the polypeptide chain by highly specialized translational machinery. They exist within all three kingdoms of life. The functions of these proteins in biology are still being defined. In particular, the importance of selenoproteins in pathogenic microorganisms has received little attention. We first established that a nosocomial pathogen, Clostridium difficile, utilizes a selenoenzyme dependent pathway for energy metabolism. Following this initial characterization, we demonstrate that this pathway is linked to production of toxins by this organism. Finally, we show that interruption of selenium metabolism is a viable pathway for development of …

Iron-Induced Cerebellar Purkinje Cell Loss Is Ameliorated By Flunarizine, Ramazan Kozan, M. Ömer Bostanci, Tuncer Nacar, Ali̇ Aslan, Faruk Bağirici

Turkish Journal of Medical Sciences

Aim: In this study, we investigated the effect of intracerebroventricular-injected iron neurotoxicity on the total number of cerebellar Purkinje cells in rats and the possible neuroprotective effect of flunarizine, a piperazine-derived calcium channel blocker. Materials and Methods: Rats were divided into four groups: control, flunarizine, iron, and iron + flunarizine groups. Rats in the iron and iron + flunarizine groups received intracerebro-ventricular iron (FeCl_36H_2O, 200 mM, 2.5 µl), while those in flunarizine and iron + flunarizine groups were intraperitoneally injected with flunarizine (10 mg/kg/day) once a day after the operation for 10 days. After 10 days, all rats were perfused …

A Case Of Common Variable Immunodeficiency Disease And Thyroid Amyloidosis, Di̇lek Soysal, Ebru Türkkan, Volkan Karakuş, Erhan Tatar, Özlem Yersal Kabayeği̇t, Arzu Avci

Turkish Journal of Medical Sciences

A 37-year-old male patient with fever, mild respiratory distress, diffuse goiter, and hepatosplenomegaly was admitted to our hospital. Clinical and laboratory findings showed that he had recurrent respiratory tract infections-namely bronchiectasis-due to common variable immunodeficiency disease (CVID) and AA-type amyloid deposition in the thyroid gland. Although recurrent infections as a consequence of inadequate gammaglobulin (IVIG) substitution therapy are regarded as the main cause of the development of amyloidosis, amyloidosis in a patient with hypo/agammaglobulinemia is extremely rare. In this report we discuss the association of CVID and recurrent respiratory tract infections with secondary amyloidosis restricted to one organ, the thyroid …

The Effect Of Experimentally Induced Carbon Dioxide Pneumoperitoneum On Intra-Abdominal And Intra-Esophageal Ph, Tutku Soyer, Tolga Reşat Aydos, Zuhal Aktuna, Oğuzhan Korkut, Gökhan Osmanoğlu, Öymen Hançerli̇oğullari, Murat Çakmak

Turkish Journal of Medical Sciences

Aim: An experimental study was performed to evaluate the effect of CO_2 pneumoperitoneum on intra-abdominal (IA) and intra-esophageal (IE) pH. Material and methods: The study included 18 Wistar rats. In the control group (n = 6) a pH catheter was inserted into the peritoneal cavity via a left upper quadrant incision and another catheter was inserted into the lower esophagus via the oral route. Pre- and post-insufflation IA and IE pH were recorded every 5 min for 1 h. In the experimental groups, in addition to pH catheters, a 16-G catheter was inserted into the abdomen above the umbilicus. In …

Endoscopic Polypectomy: Outcomes Of 467 Cases In 20 Years, S. Selçuk Atamanalp, Fuat Şentürk, Nesri̇n Gürsan, Gürkan Öztürk, Abdul Meci̇t Kantarci, M. İlhan Yildirgan, Mahmut Başoğlu

Turkish Journal of Medical Sciences

Aim: Endoscopic polypectomy has an important place in the treatment of polyps—the preliminary lesions of colorectal cancers. This study aimed to discuss the outcomes of endoscopic polypectomy in 467 patients for 692 polyps over the course of 20 years. Materials and methods: The records of 692 endoscopic polypectomies performed in 467 patients between July 1988 and July 2008 were retrospectively evaluated. Results: Patient age ranged from 3 to 85 years (mean: 50.6 years), and 302 of the 467 (64.7%) patients were male. Polypectomy was performed for 692 polyps (mean: 1.5; range: 1-12). The most common polyp location was the rectum …

Imaging Liver Transplantation Candidates Using Gadolinium Enhanced Mdct Angiography, Abdul Meci̇t Kantarci, Irmak Durur Subaşi, Bülent Aydinli, Ci̇han Duran, Seli̇m Doğanay, K. Yalçin Polat, Ragi̇be Kantarci, Hayri̇ Oğul, S. Selçuk Atamanalp

Turkish Journal of Medical Sciences

Aim: To report our experience with gadolinium enhanced computed tomography angiography (Gd-CTA) for end-stage liver disease patients who are candidates for liver transplantation as an alternative to iodinated contrast enhanced CTA and gadolinium enhanced magnetic resonance (MR) angiography. Materials and methods: Seventeen patients with end-stage liver disease were evaluated with Gd-CTA. The patients were 10 men (58.8%) and 7 women (41.1%) (age range: 37-59 years). Multidetector CT (MDCT) was performed using 16-detector-row CT scanners. 3D images of the celiac artery, superior mesenteric artery, portal vein, and inferior vena cava (IVC) were obtained for thorough assessment using multiple plane reconstruction and …

Examination Of The Capacity Of The Cathelicidins To Control Bacillus Anthracis Pathogenesis, Mark W. Lisanby

All ETDs from UAB

cillus anthracis is a gram-positive, spore forming bacterium that causes infection through three routes: cutaneous, gastrointestinal and pulmonary. Historically, anthrax pathogenesis was thought to be initiated via the uptake of spores by resident macrophages, which then transited to the regional lymph nodes. While en-route, the spores germinated and developed into bacilli within the phagolysosome, escaped into the cytoplasm, killed the cell and eventually the host. Following the recent use of B. anthracis as a biological weapon, researchers began to reevaluate anthrax pathogenesis in order to develop novel treatments. One aspect of anthrax pathogenesis that saw renewed interest was the intracellular …

Regulation Of Neural Precursor Cell Apoptosis And Proliferation By Glycogen Synthase Kinase-3, Tae-Yeon Eom

All ETDs from UAB

Neurogenesis is a crucial process for development, plasticity, and regenerative capacity of the developing and adult brain. Impairment of neurogenesis has been implicated in the etiology of psychiatric disorders. Although substantial studies have shown that therapeutic interventions enhance neurogenesis, much less is known about what factors impair neurogenesis. Thus, the present work examined if glycogen synthase kinase-3 (GSK3) has a role in impaired neurogenesis, focusing on apoptosis and proliferation of neural precursor cells (NPCs). This investigation found that GSK3 promotes apoptotic signaling in cultured NPCs subjected to two insults, trophic factor withdrawal and genotoxic stress. Both stimuli activated GSK3, Bax, …

Pathological Modification Of Tau Induce Toxicity And Facilitate Cell Death, Tori A. Matthews

All ETDs from UAB

eimer’s disease (AD) is a progressive neurodegenerative disorder characterized by two major pathophysiological hallmarks, beta-amyloid (A��) plaques and tau tangles. In AD and other tau associated neurodegenerative disorders, termed tauopathies, a critical role in promoting neuronal degeneration has been demonstrated for hyperphosphorylated forms of tau. Recent findings suggest that cleavage of tau in the carboxyl-terminal region (Asp421) may also promote deleterious effects of tau on neuronal health. In the first half of my study, the relationship between Asp421 cleaved tau and a common AD associated stressor (endoplasmic reticulum [ER] stress) was investigated using an inducible cortical neuronal model. Cells expressing …

Mechanisms And Countermeasures Of Microgravity Induced Bone Loss: In Vitro And In Vivo Model Systems, Ritu Saxena

All ETDs from UAB

Rapid bone loss occurs during prolonged periods of weightlessness experienced by astronauts during spaceflights which leads to osteopenia and increased fracture risk upon return to earth. Spaceflight studies have shown that the bone loss occurs as a result of both a decrease in bone formation and an increase in bone resorption, however, the molecular mechanisms still need to be elucidated. Previous studies from our laboratory and other groups have indicated that modeled microgravity leads to inhibition of osteoblastogenesis and a stimulation of adipogenesis of human mesenchymal stem cells in osteogenic medium which is most likely mediated by a decrease in …

Where Do Mouse Embryos Thrive Best? Comparison Of Mammalian Embryo Development Under Varying Laboratory Environments, Yvonne K. Kao, H. Lee Higdon Iii, Ph.D, Jennifer E. Graves-Herring , M.S., William R. Boone Ph.D

Journal of the South Carolina Academy of Science

No abstract provided.

Regulation Of Survivin Gene Expression In The Human Endometrium And Endometrial Cancer, Nancy H. Nabilsi

Dissertations and Theses (Open Access)

In the United States, endometrial cancer is the leading cancer of the female reproductive tract. There are 40,100 new cases and 7,470 deaths from endometrial cancer estimated for 2008 (47). The average five year survival rate for endometrial cancer is 84% however, this figure is substantially lower in patients diagnosed with late stage, advanced disease and much higher for patients diagnosed in early stage disease (47). Endometrial cancer (EC) has been associated with several risk factors including obesity, diabetes, hypertension, previously documented occurrence of hereditary non-polyposis colorectal cancer (HNPCC), and heightened exposure to estrogen (25). As of yet, there has …

Autistic Disorder Associated With A Paternally Derived Unbalanced Translocation Leading To Duplication Of Chromosome 15pter-Q13.2: A Case Report., David J Wu, Nicholas J Wang, Jennette Driscoll, Naghmeh Dorrani, Dahai Liu, Marian Sigman, N Carolyn Schanen

Department of Pediatrics Faculty Papers

Autism spectrum disorders have been associated with maternally derived duplications that involve the imprinted region on the proximal long arm of chromosome 15. Here we describe a boy with a chromosome 15 duplication arising from a 3:1 segregation error of a paternally derived translocation between chromosome 15q13.2 and chromosome 9q34.12, which led to trisomy of chromosome 15pter-q13.2 and 9q34.12-qter. Using array comparative genome hybridization, we localized the breakpoints on both chromosomes and sequence homology suggests that the translocation arose from non-allelic homologous recombination involving the low copy repeats on chromosome 15. The child manifests many characteristics of the maternally-derived duplication …

Glutamate Regulation In The Hippocampal Trisynaptic Pathway In Aging And Status Epilepticus, Michelle Lee Stephens

University of Kentucky Doctoral Dissertations

A positive correlation exists between increasing age and the incidence of hippocampal-associated dysfunction and disease. Normal L-glutamate neurotransmission is absolutely critical for hippocampal function, while abnormal glutamate neurotransmission has been implicated in many neurodegenerative diseases. Previous studies, overwhelmingly utilizing ex vivo methods, have filled the literature with contradicting reports about hippocampal glutamate regulation during aging. For our studies, enzyme-based ceramic microelectrode arrays (MEA) were used for rapid (2 Hz) measurements of extracellular glutamate in the hippocampal trisynaptic pathway of young (3-6 months), late-middle aged (18 mo.) and aged (24 mo.) urethane-anesthetized Fischer 344 rats. Compared to young animals, glutamate terminals …

Respecting, Rather Than Reacting To, Race In Biomedical Research: A Response To Professors Caulfield And Mwaria, Michael J. Malinowski

Journal Articles

This Commentary is part of a colloquy on race-based genetics research.

Pyramidobacter Piscolens Gen. Nov., Sp. Nov., A Member Of The Phylum ‘Synergistetes’ Isolated From The Human Oral Cavity, Julia Downes, Sonia R. Vartoukian, Floyd E. Dewhirst, Jacques Izard, Tsute Chen, Wen-Han Yu, Iain C. Sutcliffe, William G. Wade

Department of Food Science and Technology: Faculty Publications

Four strains of anaerobic, gram-negative bacilli isolated from the human oral cavity were subjected to a comprehensive range of phenotypic and genotypic tests and were found to comprise a homogeneous group distinct from any species with validly published names. 16S rRNA and 23S rRNA gene sequence analyses and DNA–DNA reassociation data revealed that the strains constituted a novel group within the phylum ‘Synergistetes’ and were most closely related to Jonquetella anthropi. Two libraries of randomly cloned DNA were prepared from strain W5455T and were sequenced to provide a genome survey as a resource for metagenomic studies. A new genus …

Human Ubc9 Contributes To Production Of Fully Infectious Human Immunodeficiency Virus Type 1 Virions, Tareq Jaber, Christopher R. Bohl, Gentry L. Lewis, Charles Wood, John T. West Jr., Robert A. Weldon Jr.

Nebraska Center for Virology: Faculty Publications

Ubc9 was identified as a cellular protein that interacts with the Gag protein of Mason-Pfizer monkey virus. We show here that Ubc9 also interacts with the human immunodeficiency virus type 1 (HIV-1) Gag protein and that their interaction is important for virus replication. Gag was found to colocalize with Ubc9 predominantly at perinuclear puncta. While cells in which Ubc9 expression was suppressed with RNA interference produced normal numbers of virions, these particles were 8- to 10-fold less infectious than those produced in the presence of Ubc9. The nature of this defect was assayed for dependence on Ubc9 during viral assembly, …

Expression Of Hpv16 E5 Produces Enlarged Nuclei And Polyploidy Through Endoreplication, Lulin Hu, Tamara A. Potapova, Shibo Li, Susannah Rankin, Gary J. Gorbsky, Peter C. Angeletti, Brian P. Ceresa

Nebraska Center for Virology: Faculty Publications

Anogenital cancers and head and neck cancers are causally-associated with infection by high-risk

human papillomavirus (HPV). The mechanism by which high-risk HPVs contribute to

oncogenesis is poorly understood. HPV16 encodes three genes (HPV16 E5, E6, and E7) that can

transform cells when expressed independently. HPV16 E6 and E7 have well-described roles

causing genomic instability and unregulated cell cycle progression. The role of HPV16 E5 in cell

transformation remains to be elucidated. Expression of HPV16 E5 results in enlarged, polyploid

nuclei that are dependent on the level and duration of HPV16 E5 expression. Live-cell imaging

data indicate these changes do not …

Human Papillomavirus 16 E5 Induces Bi-Nucleated Cell Formation By Cell-Cell Fusion, Lulin Ha, Kendra Plafker, Valeriya Vorozhoko, Rosemary E. Zuna, Marie H. Hanigan, Gary J. Gorbsky, Scott M. Plafker, Peter C. Angeletti, Brian P. Ceresa

Nebraska Center for Virology: Faculty Publications

Human Papillomaviruses (HPV) 16 is a DNA virus encoding three oncogenes – E5, E6, and E7. The E6 and E7 proteins have well-established roles as inhibitors of tumor suppression, but the contribution of E5 to malignant transformation is controversial. Using spontaneously immortalized human keratinocytes (HaCaT cells), we demonstrate that expression of HPV16 E5 is necessary and sufficient for the formation of bi-nucleated cells, a common characteristic of precancerous cervical lesions. Expression of E5 from non-carcinogenic HPV6b does not produce bi-nucleate cells. Video microscopy and biochemical analyses reveal that bi-nucleates arise through cell-cell fusion. Although most E5-induced bi-nucleates fail to propagate, …

Protection Against Mucosal Shiv Challenge By Peptide And Helper-Dependent Adenovirus Vaccines, Eric A. Weaver, Pramod N. Nehete, Bharti P. Nehete, Stephanie J. Buchl, Donna Palmer, David C. Montefiori, Philip Ng, K. Jagannadha Sastry, Michael A. Barry

Nebraska Center for Virology: Faculty Publications

Groups of rhesus macaques that had previously been immunized with HIV-1 envelope (env) peptides and first generation adenovirus serotype 5 (FG-Ad5) vaccines expressing the same peptides were immunized intramuscularly three times with helper- dependent adenovirus (HD-Ad) vaccines expressing only the HIV-1 envelope from JRFL. No gag, pol, or other SHIV genes were used for vaccination. One group of the FG-Ad5- immune animals was immunized three times with HD-Ad5 expressing env. One group was immunized by serotype-switching with HD-Ad6, HD-Ad1, and HD-Ad2 expressing env. Previous work demonstrated that serum antibody levels against env were significantly higher in the serotype-switched group than …

A Herpesvirus Encoded Deubiquitinase Is A Novel Neuroinvasive Determinant, Joy I. Lee, Patricia J. Sollars, Scott B. Baver, Gary E. Pickard, Mindy Leelawong, Gregory A. Smith

School of Veterinary and Biomedical Sciences: Faculty Publications

The neuroinvasive property of several alpha-herpesviruses underlies an uncommon infectious process that includes the establishment of life-long latent infections in sensory neurons of the peripheral nervous system. Several herpesvirus proteins are required for replication and dissemination within the nervous system, indicating that exploiting the nervous system as a niche for productive infection requires a specialized set of functions encoded by the virus. Whether initial entry into the nervous system from peripheral tissues also requires specialized viral functions is not known. Here we show that a conserved deubiquitinase domain embedded within a pseudorabies virus structural protein, pUL36, is essential for initial …