@article{luff_weingart_may_murphy_2023, title={A subset of equine oral squamous cell carcinomas is associated with Equus caballus papillomavirus 2 infection}, volume={205}, ISSN={["1532-3129"]}, DOI={10.1016/j.jcpa.2023.06.003}, abstractNote={The aetiology of oral squamous cell carcinoma (SCC) in horses is unknown, but papillomavirus infection as well as chronic periodontal disease are suspected to play a pathogenic role. In humans, some oropharyngeal cancers develop in association with human papillomaviruses. Equus caballus papillomavirus 2 (EcPV2) is suspected to play a causal role in the development of equine genital SCC. Given that association, we hypothesized that EcPV2 is associated with the development of oral SCC in horses. We performed standard polymerase chain reaction (PCR) and in-situ hybridization (ISH) for EcPV2 on 31 formalin-fixed paraffin-embedded equine oral SCCs (lingual, gingival, palate) and 10 equine non-SCC oral samples. PCR for EcPV2 was positive in 10/31 (32%) oral SCCs while all non-SCC oral samples were negative. Intense hybridization signals for EcPV2 nucleic acid were detected by ISH within neoplastic epithelial cells in 8/31 (26%) oral SCCs but not in the adjacent normal oral mucosa. No hybridization signals were detected within control samples. This study provides additional support for a pathogenic association of EcPV2 in oral SCC in horses.}, journal={JOURNAL OF COMPARATIVE PATHOLOGY}, author={Luff, Jennifer and Weingart, Shaina and May, Susan and Murphy, Brian}, year={2023}, month={Aug}, pages={1–6} } @article{quinlan_may_weeks_yuan_luff_2021, title={Canine Papillomavirus 2 E6 Does Not Interfere With UVB-Induced Upregulation of p53 and p53-Regulated Genes}, volume={8}, ISSN={["2297-1769"]}, DOI={10.3389/fvets.2021.570982}, abstractNote={Cutaneous papillomaviruses are oncogenic viruses that cause severe, persistent infections that can develop into skin cancers within ultraviolet (UV)-exposed skin of immunodeficient individuals, such as those with X-linked severe combined immunodeficiency (XSCID). A canine research model of XSCID exhibits a similar phenotype; these dogs develop severe canine papillomavirus 2 (CPV2) infections that often progress to cancer. Thus, the dog is a natural, spontaneous model to investigate cutaneous papillomavirus infections in immunodeficient patients. The human papillomavirus oncogene E6 contributes to cancer development, in part, by initiating degradation of the tumor suppressor protein p53, or by inhibiting upregulation of p53-dependent genes required within the cell growth arrest and apoptotic pathways, thereby leading to an accumulation of DNA damage required for oncogenesis. Currently, little is known about CPV2, and how it promotes cancer development. The aim of this study was to determine if CPV2 oncogene E6 similarly affects p53 upon activation by UV radiation, as well as the downstream p53-regulated genes necessary to control growth arrest and apoptosis. We determined that cutaneous CPV2 E6 does not degrade p53, or interfere with the upregulation of p53-regulated genes p21, Bax, Bak, or lncRNA-p21, suggesting that CPV2 may use a p53-independent mechanism to contribute to oncogenesis.}, journal={FRONTIERS IN VETERINARY SCIENCE}, author={Quinlan, Sarah and May, Susan and Weeks, Ryan and Yuan, Hang and Luff, Jennifer}, year={2021}, month={Mar} } @article{alloway_linder_may_rose_delay_bender_tucker_luff_2020, title={A Subset of Equine Gastric Squamous Cell Carcinomas Is Associated With Equus Caballus Papillomavirus-2 Infection}, volume={57}, ISSN={["1544-2217"]}, DOI={10.1177/0300985820908797}, abstractNote={ Squamous cell carcinoma (SCC) is the most common neoplasm of the equine stomach. However, the mechanisms underlying malignant transformation are unknown. As Equus caballus papillomavirus–2 (EcPV-2) is a likely cause of some genital SCCs, we hypothesized that EcPV-2 is associated with a subset of equine gastric SCCs. To this aim, we performed polymerase chain reaction (PCR) and in situ hybridization (ISH) for EcPV-2 E6/ E7 oncogenes on 11 gastric SCCs and on gastric samples from 15 control horses with no SCC. PCR for EcPV-2 was positive in 7/11 (64%) gastric SCCs; non-SCC gastric samples were all negative. Intense hybridization signals for EcPV-2 E6/E7 nucleic acid were detected by ISH within tumor cells in 5/11 (45%) gastric SCCs, including distant metastases. No hybridization signals were detected within any of the non-SCC gastric cases. This study provides support for a potential association between EcPV-2 infection and a subset of equine gastric SCC. }, number={3}, journal={VETERINARY PATHOLOGY}, author={Alloway, Elizabeth and Linder, Keith and May, Susan and Rose, Trevor and DeLay, Josepha and Bender, Susan and Tucker, Alison and Luff, Jennifer}, year={2020}, month={May}, pages={427–431} } @article{quinlan_may_weeks_yuan_luff_2020, title={Abrogation of Constitutive and Induced Type I and Type III Interferons and Interferon-Stimulated Genes in Keratinocytes by Canine Papillomavirus 2 E6 and E7}, volume={12}, ISSN={["1999-4915"]}, DOI={10.3390/v12060677}, abstractNote={Cutaneous papillomaviruses can cause severe, persistent infections and skin cancer in immunodeficient patients, including people with X-linked severe combined immunodeficiency (XSCID). A similar phenotype is observed in a canine model of XSCID; these dogs acquire severe cutaneous papillomavirus infections that can progress to cancer in association with canine papillomavirus type 2 (CPV2). This canine model system provides a natural spontaneous animal model for investigation of papillomavirus infections in immunodeficient patients. Currently, it is unknown if CPV2 can subvert the innate immune system and interfere with its ability to express antiviral cytokines, which are critical in the host defense against viral pathogens. The aim of the current study was to determine if the oncogenes E6 and E7 from CPV2 interfere with expression of antiviral cytokines in keratinocytes, the target cells of papillomavirus infections. We determined that E6 but not E7 interferes with the constitutive expression of some antiviral cytokines, including interferon (IFN)-β and the IFN-stimulated gene IFIT1. Both E6 and E7 interfere with the transcriptional upregulation of the antiviral cytokines in response to stimulation with the dsDNA Poly(dA:dT). In contrast, while E6 also interferes with the transcriptional upregulation of antiviral cytokines in response to stimulation with the dsRNA Poly(I:C), E7 interferes with only a subset of these antiviral cytokines. Finally, we demonstrated that E7 but not E6 abrogates signaling through the type I IFN receptor. Taken together, CPV2 E6 and E7 both impact expression of antiviral cytokines in canine keratinocytes, albeit likely through different mechanisms.}, number={6}, journal={VIRUSES-BASEL}, author={Quinlan, Sarah and May, Susan and Weeks, Ryan and Yuan, Hang and Luff, Jennifer A.}, year={2020}, month={Jun} } @article{spana_abrams_ellis_klein_ruderman_shi_zhu_stewart_may_2020, title={speck, First Identified inDrosophila melanogasterin 1910, Is Encoded by the Arylalkalamine N-Acetyltransferase (AANAT1) Gene}, volume={10}, ISSN={["2160-1836"]}, DOI={10.1534/g3.120.401470}, abstractNote={Abstract}, number={9}, journal={G3-GENES GENOMES GENETICS}, author={Spana, Eric P. and Abrams, Amanda B. and Ellis, Katharine T. and Klein, Jason C. and Ruderman, Brandon T. and Shi, Alvin H. and Zhu, Daniel and Stewart, Andrea and May, Susan}, year={2020}, month={Sep}, pages={3387–3398} } @article{armaleo_mueller_lutzoni_andresson_blanc_bode_collart_dal grande_dietrich_grigoriev_et al._2019, title={The lichen symbiosis re-viewed through the genomes of Cladonia grayi and its algal partner Asterochloris glomerata}, volume={20}, ISBN={1471-2164}, DOI={10.1186/s12864-019-5629-x}, abstractNote={Lichens, encompassing 20,000 known species, are symbioses between specialized fungi (mycobionts), mostly ascomycetes, and unicellular green algae or cyanobacteria (photobionts). Here we describe the first parallel genomic analysis of the mycobiont Cladonia grayi and of its green algal photobiont Asterochloris glomerata. We focus on genes/predicted proteins of potential symbiotic significance, sought by surveying proteins differentially activated during early stages of mycobiont and photobiont interaction in coculture, expanded or contracted protein families, and proteins with differential rates of evolution.A) In coculture, the fungus upregulated small secreted proteins, membrane transport proteins, signal transduction components, extracellular hydrolases and, notably, a ribitol transporter and an ammonium transporter, and the alga activated DNA metabolism, signal transduction, and expression of flagellar components. B) Expanded fungal protein families include heterokaryon incompatibility proteins, polyketide synthases, and a unique set of G-protein α subunit paralogs. Expanded algal protein families include carbohydrate active enzymes and a specific subclass of cytoplasmic carbonic anhydrases. The alga also appears to have acquired by horizontal gene transfer from prokaryotes novel archaeal ATPases and Desiccation-Related Proteins. Expanded in both symbionts are signal transduction components, ankyrin domain proteins and transcription factors involved in chromatin remodeling and stress responses. The fungal transportome is contracted, as are algal nitrate assimilation genes. C) In the mycobiont, slow-evolving proteins were enriched for components involved in protein translation, translocation and sorting.The surveyed genes affect stress resistance, signaling, genome reprogramming, nutritional and structural interactions. The alga carries many genes likely transferred horizontally through viruses, yet we found no evidence of inter-symbiont gene transfer. The presence in the photobiont of meiosis-specific genes supports the notion that sexual reproduction occurs in Asterochloris while they are free-living, a phenomenon with implications for the adaptability of lichens and the persistent autonomy of the symbionts. The diversity of the genes affecting the symbiosis suggests that lichens evolved by accretion of many scattered regulatory and structural changes rather than through introduction of a few key innovations. This predicts that paths to lichenization were variable in different phyla, which is consistent with the emerging consensus that ascolichens could have had a few independent origins.}, journal={BMC GENOMICS}, author={Armaleo, Daniele and Mueller, Olaf and Lutzoni, Francois and Andresson, Olafur S. and Blanc, Guillaume and Bode, Helge B. and Collart, Frank R. and Dal Grande, Francesco and Dietrich, Fred and Grigoriev, Igor V. and et al.}, year={2019} }