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    ItemOpen Access
    Pathogenesis of oral FIV infection
    (Colorado State University. Libraries, 2017) Miller, Craig A.
    Feline immunodeficiency virus (FIV) is the feline analogue of human immunodeficiency virus (HIV) and features many hallmarks of HIV infection and pathogenesis, including the development of concurrent oral lesions. While HIV is typically transmitted via parenteral transmucosal contact, recent studies prove that oral transmission can occur, and that saliva from infected individuals contains significant amounts of HIV RNA and DNA. While it is accepted that FIV is primarily transmitted by biting, few studies have evaluated FIV oral infection kinetics and transmission mechanisms over the last 20 years. Modern quantitative analyses applied to natural FIV oral infection could significantly further our understanding of lentiviral oral disease and transmission. We therefore characterized FIV salivary viral kinetics and antibody secretions to more fully document oral viral pathogenesis. Our results demonstrate that: (i) saliva of FIV-infected cats contains infectious virus particles, FIV viral RNA at levels equivalent to circulation, and lower but significant amounts of FIV proviral DNA; (ii) the ratio of FIV RNA to DNA is significantly higher in saliva than in circulation; (iii) FIV viral load in oral lymphoid tissues (tonsil, lymph nodes) is significantly higher than mucosal tissues (buccal mucosa, salivary gland, tongue); (iv) salivary IgG antibodies increase significantly over time in FIV-infected cats, while salivary IgA levels remain static; and, (v) saliva from naïve Specific Pathogen Free cats inhibits FIV growth in vitro. Collectively, these results suggest that oral lymphoid tissues serve as a site for enhanced FIV replication, resulting in accumulation of FIV particles and FIV-infected cells in saliva. Failure to induce a virus-specific oral mucosal antibody response, and/or viral capability to overcome inhibitory components in saliva may perpetuate chronic oral cavity infection. Based upon these findings, we propose a model of oral FIV pathogenesis and suggest alternative diagnostic modalities and translational approaches to study oral HIV infection.
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    ItemOpen Access
    Dataset associated with "Genome-wide association analysis of canine T zone lymphoma identifies link to hypothyroidism and a shared association with mast-cell tumors"
    (Colorado State University. Libraries, 2020) Labadie, Julia D.; Elvers, Ingegerd; Spencer Feigelson, Heather; Magzamen, Sheryl; Yoshimoto, Janna; Dossey, Jeremy; Burnett, Robert; Avery, Anne C.
    Background: T zone lymphoma (TZL), a histologic variant of peripheral T cell lymphoma, represents about 12% of all canine lymphomas. Golden Retrievers appear predisposed, representing over 40% of TZL cases. Prior research found that asymptomatic aged Golden Retrievers frequently have populations of T zone-like cells (phenotypically identical to TZL) of undetermined significance (TZUS), potentially representing a pre-clinical state. These findings suggest a genetic risk factor for this disease and caused us to investigate potential genes of interest. Methods: Privately-owned U.S. Golden Retrievers were categorized as TZL (n=95), TZUS (n=142), or control (n=101) using flow cytometry and genotyped using the Illumina CanineHD BeadChip. Single nucleotide polymorphism (SNP)-specific associations were evaluated using a mixed linear model adjusting for population stratification. Associated regions were subsequently sequenced using a custom sequence capture array (NimbleGen SeqCap EZ Developer Kit) on an Illumina NextSeq 500. Results: We found association with genome-wide significance in regions on chromosomes 8 and 14. The chromosome 14 peak included four SNPs (Odds Ratio=1.18–1.19, p=.3x10-5–5.1x10-5) near three hyaluronidase genes (SPAM1, HYAL4, and HYALP1). Targeted resequencing of this region identified missense mutations in all three genes; the variant in SPAM1 was predicted to be damaging. These mutations were also associated with risk for mast cell tumors among Golden Retrievers in an unrelated study. The chromosome 8 peak contained 7 SNPs (Odds Ratio=1.24–1.42, p= 2.7x10-7–7.5x10-5) near genes involved in thyroid hormone regulation (DIO2 and TSHR). A prior study from our laboratory found hypothyroidism is inversely associated with TZL risk. No coding mutations were found with targeted resequencing but identified variants may play a regulatory role for all or some of the genes. Conclusions: The pathogenesis of canine TZL may be related to hyaluronan breakdown and subsequent production of pro-inflammatory and pro-oncogenic byproducts. The association on chromosome 8 may indicate thyroid hormone is involved in TZL development, consistent with findings from a previous study evaluating epidemiologic risk factors for TZL. Future work is needed to elucidate these mechanisms.
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    ItemOpen Access
    Data associated with "Interpersonal relationships drive successful team science: an exemplary case-based study"
    (Colorado State University. Libraries, 2020) Love, Hannah; Cross, Jennifer; Fosdick, Bailey; Crooks, Kevin; VandeWoude, Susan; Fisher, Ellen
    Team science, or collaborations between groups of scientists with varying expertise, is required for researching solutions to complex problems of the 21st century. Despite the essential need for such transdisciplinary interactions, knowledge about training scientists and developing personal mastery, a set of principles and practices necessary for team learning, also referred to as the science of team science (SciTS) in productive team interactions is still in its nascent stages. This article reports on a longitudinal case study of an exemplary scientific team and evaluates the following question: How do scientists enhance their productivity through participation in transdisciplinary teams? Through a focused SciTS study applying mixed methods, including social network surveys, participant observation, focus groups, interviews, and historical social network data, we found that the interactions of an international, transdisciplinary scientific team trained scientists to become experts in their field, helped the team develop personal mastery, advanced their scientific productivity, and fulfilled the land grant mission. The team’s processes and practices to train new scientists propelled new ideas, collaborations, and research outcomes over a 15-year period. This case study highlights that in addition to specific scientific discoveries, scientific progress benefits from developing and forming interpersonal relationships among scientists from diverse disciplines.