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Open Access Publications from the University of California

Scholarly Works (16 results)

  • Article
  • Peer Reviewed
UC Davis Previously Published Works (2001)
Feline infectious peritonitis (FIP) is a common cause of death in cats. Management of this disease has been hampered by difficulties identifying the infection and determining the immunological status of affected cats and by high variability in the clinical, pathological, and immunological characteristics of affected cats. Neurological FIP, which is much more homogeneous than systemic effusive or noneffusive FIP, appears to be a good model for establishing the basic features of FIP immunopathogenesis. Very little information is available about the immunopathogenesis of neurologic FIP, and it is reasonable to use research from the well-characterized mouse hepatitis virus (MHV) immune-mediated encephalitis system, as a template for FIP investigation, and to contrast findings from the MHV model with those of FIP. It is expected that the immunopathogenic mechanisms will have important similarities. Such comparative research may lead to better understanding of FIP immunopathogenesis and rational prospects for management of this frustrating disease.
    Cover page: A Review of Coronavirus Infection in the Central Nervous System of Cats and Mice
    • Article
    • Peer Reviewed
    UC Davis Previously Published Works (2024)
    Recent emerging zoonotic disease outbreaks, such as that of SARS-CoV-2, have demonstrated the need for wider companion animal disease surveillance. We tested 1000 dogs and cats belonging to employees of a US veterinary hospital network that were exposed to human COVID-19 cases in the household between 1 January 2020 and 10 March 2022 for SARS-CoV-2 and surveyed their owners about clinical signs and risk factors. The seropositivity was 33% for 747 dogs and 27% for 253 cats. Pet seropositivity correlated with the US human case rates over time, exhibiting peaks corresponding with the major COVID-19 surges. Antibodies persisted longer than previously documented (828 days in dogs; 650 days in cats). Increasing age and duration of proximity to infected people were associated with increased seropositivity in dogs but not cats. Cats were more likely to have clinical signs, but an association between seropositivity and the presence of clinical signs was not found in either species.
      Cover page: The Transmission of SARS-CoV-2 from COVID-19-Diagnosed People to Their Pet Dogs and Cats in a Multi-Year Surveillance Project.Creative Commons 'BY' version 4.0 license
      • Article
      • Peer Reviewed
      UC Davis Previously Published Works (2020)

      Objectives

      The aim of this study was to assess the effects of famciclovir administration in cats with spontaneously acquired acute upper respiratory tract disease.

      Methods

      Twenty-four kittens with clinical signs of acute upper respiratory tract disease were randomly allocated to receive doxycycline (5 mg/kg PO q12h) alone (group D; n = 12) or with famciclovir (90 mg/kg PO q12h; group DF; n = 12) for up to 3 weeks. Clinical disease severity was scored at study entry and daily thereafter. Oculo-oropharyngeal swabs collected at study entry and exit were assessed using quantitative PCR for nucleic acids of feline herpesvirus type 1 (FHV-1), feline calicivirus (FCV), Chlamydia felis, Bordetella bronchiseptica and Mycoplasma felis.

      Results

      The median (range) age of cats was 1.5 (1-6) months in group D vs 1.6 (1-5) months in group DF (P = 0.54). Pathogens detected in oculo-oropharyngeal swabs at study entry included FCV (n = 13/24; 54%), M felis (n = 8/24; 33%), FHV-1 (n = 7/24; 29%), C felis (n = 7/24; 29%) and B bronchiseptica (n = 3/24; 12%). Median (range) duration of clinical signs was 11.5 (3-21) days in group DF and 11 (3-21) days in group D (P = 0.75). Median (range) total disease score at the end of the study did not differ between groups (group D 1 [1-1] vs group DF 1 [1-3]; P = 0.08).

      Conclusions and relevance

      This study revealed no significant difference in response to therapy between cats treated with doxycycline alone or with famciclovir; cats improved rapidly in both groups. However, identification of FHV-1 DNA was relatively uncommon in this study and clinical trials focused on FHV-1-infected cats are warranted to better evaluate famciclovir efficacy.
        Cover page: Effects of famciclovir in cats with spontaneous acute upper respiratory tract disease
        • Article
        • Peer Reviewed
        UC Davis Previously Published Works (2017)
        We report here the first canine polyomavirus genome, identified by metagenomics in respiratory secretions of two dogs with severe pneumonia, which tested negative for all canine respiratory pathogens except Mycoplasma cynos The isolate, Canis familiaris polyomavirus 1 (DogPyV-1), is a beta polyomavirus whose closest known LT antigen relatives are primate polyomaviruses.
          Cover page: Genome Sequence of Canine Polyomavirus in Respiratory Secretions of Dogs with Pneumonia of Unknown Etiology
          • Article
          • Peer Reviewed
          UC Davis Previously Published Works (2013)
          Weaning, particularly the widespread practice of abrupt separation of the mare and foal, has been shown to be a stressful event for horses. Physiological changes in foals measured after weaning include increased blood cortisol concentrations and a subsequent decrease in cell-mediated immune responses. In the randomized, double-blinded, placebo-controlled trial reported here, we assessed the effect of an equine appeasing pheromone (EAP; Modipher EQ, E.A.P. Mist [Pherosynthese s.n.c., LeRieu Neuf, Saint-Saturnin-les-Apt, France]) as an aid for reducing the behavioral and physiological signs of stress during weaning. Fourteen quarter horse foals were separated from their dam (equid mother) between 105 and 146 days of age, in age-matched pairs, and placed in 3.66×3.66m stalls (one treated and one control foal in each stall). Treated foals received the synthetic analogue of the EAP by intranasal wipe 30 minutes before separation and twice daily thereafter for 48 hours. Control foals received placebo by intranasal wipe on the same schedule. The foals were continuously videotaped for 48 hours postweaning to monitor behavioral responses. Blood samples were drawn 24 hours pretreatment and 24 and 48 hours postweaning for evaluation of physiological indicators of stress (serum cortisol) and cytokines as stress-related and immune-mediated response parameters. Interestingly, although behavioral and serum cortisol measures were similar between groups, treatment with EAP had a significant (P<0.05) effect on interleukin 6 and transforming growth factor β, whereas monocyte opiate receptor 1 was significantly upregulated in both groups independent of treatment when compared with baseline values. Although the link between EAP treatment and activation of the measured cytokines remains unexplained, our findings suggest immune-related gene transcription focused on the acute causes of stress in a time frame shortly after weaning. © 2013 Elsevier Inc.
            Cover page: Behavioral and physiological responses of weaned foals&nbsp;treated with equine appeasing pheromone: A double-blinded, placebo-controlled, randomized trial
            • Article
            • Peer Reviewed
            UC Davis Previously Published Works (2015)
            Twenty specific pathogen free cats were experimentally infected with a virulent cat-passaged type I field strain of FIPV. Eighteen cats succumbed within 2-4 weeks to effusive abdominal FIP, one survived for 6 weeks, and one seroconverted without outward signs of disease. A profound drop in the absolute count of blood lymphocytes occurred around 2 weeks post-infection (p.i.) in cats with rapid disease, while the decrease was delayed in the one cat that survived for 6 weeks. The absolute lymphocyte count of the surviving cat remained within normal range. Serum antibodies as measured by indirect immunofluorescence appeared after 2 weeks p.i. and correlated with the onset of disease signs. Viral genomic RNA was either not detectable by reverse transcription quantitative real-time PCR (RT-qPCR) or detectable only at very low levels in terminal tissues not involved directly in the infection, including hepatic and renal parenchyma, cardiac muscle, lung or popliteal lymph node. High tissue virus loads were measured in severely affected tissues such as the omentum, mesenteric lymph nodes and spleen. High levels of viral genomic RNA were also detected in whole ascitic fluid, with the cellular fraction containing 10-1000 times more viral RNA than the supernatant. Replicating virus was strongly associated with macrophages by immunohistochemistry. Virus was usually detected at relatively low levels in feces and there was no evidence of enterocyte infection. Viral genomic RNA was not detected at the level of test sensitivity in whole blood, plasma, or the white cell fraction in terminal samples from the 19 cats that succumbed or in the single survivor. These studies reconfirmed the effect of lymphopenia on disease outcome. FIPV genomic RNA was also found to be highly macrophage associated within diseased tissues and effusions as determined by RT-qPCR and immunohistochemistry but was not present in blood.
              Cover page: Levels of feline infectious peritonitis virus in blood, effusions, and various tissues and the role of lymphopenia in disease outcome following experimental infection
              • Article
              • Peer Reviewed
              UC Davis Previously Published Works (2016)
              Polyomavirus infection often results in persistence of the viral genome with little or no virion production. However, infection of certain cell types can result in high viral gene transcription and either cytolysis or neoplastic transformation. While infection by polyomavirus is common in humans and many animals, major questions regarding viral persistence of most polyomaviruses remain unanswered. Specifically, identification of target cells for viral infection and the mechanisms polyomaviruses employ to maintain viral genomes within cells are important not only in ascribing causality to polyomaviruses in disease, but in understanding specific mechanisms by which they cause disease. Here, we characterize the cell of origin in raccoon polyomavirus (RacPyV)-associated neuroglial brain tumours as a neural stem cell. Moreover, we identify an association between the viral genome and the host cell bromodomain protein, BRD4, which is involved in numerous cellular functions, including cell cycle progression, differentiation of stem cells, tethering of persistent DNA viruses, and regulation of viral and host-cell gene transcription. We demonstrate that inhibition of BRD4 by the small molecule inhibitors (+)-JQ1 and IBET-151 (GSK1210151A) results in reduced RacPyV genome within cells in vitro, as well as significant reduction of viral gene transcripts LT and VP1, highlighting its importance in both maintenance of the viral genome and in driving oncogenic transformation by RacPyV. This work implicates BRD4 as a central protein involved in RacPyV neuroglial tumour cell proliferation and in the maintenance of a stem cell state.
                Cover page: BRD4 is associated with raccoon polyomavirus genome and mediates viral gene transcription and maintenance of a stem cell state in neuroglial tumour cells.
                • Article
                • Peer Reviewed
                UC Davis Previously Published Works (2012)
                Feline infectious peritonitis virus (FIPV) was presumed to arise from mutations in the 3c of a ubiquitous and largely nonpathogenic feline enteric coronavirus (FECV). However, a recent study found that one-third of FIPV isolates have an intact 3c and suggested that it is not solely involved in FIP but is essential for intestinal replication. In order to confirm these assumptions, 27 fecal and 32 FIP coronavirus isolates were obtained from resident or adopted cats from a large metropolitan shelter during 2008-2009 and their 3a-c, E, and M genes sequenced. Forty percent of coronavirus isolates from FIP tissues had an intact 3c gene, while 60% had mutations that truncated the gene product. The 3c genes of fecal isolates from healthy cats were always intact. Coronavirus from FIP diseased tissues consistently induced FIP when given either oronasally or intraperitoneally (i.p.), regardless of the functional status of their 3c genes, thus confirming them to be FIPVs. In contrast, fecal isolates from healthy cats were infectious following oronasal infection and shed at high levels in feces without causing disease, as expected for FECVs. Only one in three cats shed FECV in the feces following i.p. infection, indicating that FECVs can replicate systemically, but with difficulty. FIPVs having a mutated 3c were not shed in the feces following either oronasal or i.p. inoculation, while FIPVs with intact 3c genes were shed in the feces following oronasal but not i.p. inoculation. Therefore, an intact 3c appears to be essential for intestinal replication. Although FIPVs with an intact 3c were shed in the feces following oronasal inoculation, fecal virus from these cats was not infectious for other cats. Attempts to identify potential FIP mutations in the 3a, 3b, E, and M were negative. However, the 3c gene of FIPVs, even though appearing intact, contained many more non-synonymous amino acid changes in the 3' one-third of the 3c protein than FECVs. An attempt to trace FIPV isolates back to enteric strains existing in the shelter was only partially successful due to the large region over which shelter cats and kittens originated, housing conditions prior to acquisition, and rapid movement through the shelter. No evidence could be found to support a recent theory that FIPVs and FECVs are genetically distinct.
                  Cover page: Feline infectious peritonitis: Role of the feline coronavirus 3c gene in intestinal tropism and pathogenicity based upon isolates from resident and adopted shelter cats
                  • Article
                  • Peer Reviewed
                  UC Davis Previously Published Works (2008)

                  Background

                  The small intestinal epithelium mediates vital functions of nutrient absorption and host defense. The spatial organization of the epithelial cells along the crypt-villus axis segregates them into regions of specialized function. However, the differences in transcriptional programming and the molecular machinery that governs the migration, adhesion, and differentiation of intestinal epithelial cell lineages in humans remain under-explored. To increase our understanding of these mechanisms, we have evaluated gene expression patterns of ileal epithelial cells isolated by laser capture microdissection from either the villus epithelial or crypt cell regions of healthy human small intestinal mucosa. Expression profiles in villus and crypt epithelium were determined by DNA microarray, quantitative real-time PCR, and immunohistochemistry based methods. The expression levels of selected epithelial biomarkers were also compared between gastrointestinal tissues.

                  Results

                  Previously established biomarkers as well as a novel and distinct set of genes believed to be linked to epithelial cell motility, adhesion, and differentiation were found to be enriched in each of the two corresponding cell populations (GEO accession: GSE10629). Additionally, high baseline expression levels of innate antimicrobials, alpha defensin 5 (HD5) and regenerating islet-derived 3 alpha (Reg3A), were detected exclusively within the small bowel crypt, most notably in the ileum in comparison to other sites along the gastrointestinal tract.

                  Conclusion

                  The elucidation of differential gene expression patterns between crypt and villus epithelial cell lineages in human ileal tissue provides novel insights into the molecular machinery that mediates their functions and spatial organization. Moreover, our findings establish an important framework of knowledge for future investigations of human gastrointestinal diseases.
                    Cover page: In vivo gene expression profiling of human intestinal epithelial cells: analysis by laser microdissection of formalin fixed tissues
                    • Article
                    Technical Completion Reports (2005)

                    Bivalve molluscs concentrate Cryptosporidium oocysts from fecal-contaminated aquatic environments and are useful for monitoring water quality. A real-time TaqMan polymerase chain reaction (PCR) system was developed to allow for large scale quantitative detection of Cryptosporidium spp. in mussels (Mytilus californianus). The TaqMan sensitivity and specificity were compared to conventional PCR and direct immunofluorescent antibody (DFA) methodologies, with and without immunomagnetic separation (IMS), to identify the best method for parasite detection in mussel hemolymph, gill washings and digestive glands. TaqMan PCR and two conventional PCR systems all detected 1 or more oocysts spiked into 1 ml hemolymph samples. The minimum oocyst detection limit in spiked 5 ml gill wash and 1 g digestive gland samples tested by TaqMan PCR and DFA was 100 oocysts, with a log10 improvement when samples were first processed by IMS. The most sensitive method for the detection of C. parvum in tank-exposed mussels was IMS concentration with DFA detection: 80% of individual and 100% of pooled digestive gland samples tested positive.

                    The wild mussel study was conducted to evaluate estuarine and nearshore marine Mytilus spp. as bioindicators of fecal contamination in coastal ecosystems of California. Hemolymph samples from 4680 mussels were tested for Cryptosporidium genotypes using PCR amplification and DNA sequence analysis. Cryptosporidium genotypes detected in hemolymph samples from individual mussels included Cryptosporidium parvum, Cryptosporidium felis, Cryptosporidium andersoni, and two novel Cryptosporidium spp. Factors significantly associated with detection of Cryptosporidium spp. in mussel batches were exposure to freshwater outflow and mussel collection within a week following a precipitation event.

                    The freshwater clam study evaluated Corbicula spp. as bioindicators of fecal protozoan contamination using three approaches: 1) clam tissue spiking experiments to compare several detection techniques, 2) clam tank exposure experiments to evaluate clams that that had filtered Cryptosporidium oocysts from inoculated water under a range of simulated environmental conditions, and 3) sentinel clam outplanting to assess the distribution and magnitude of fecal contamination in three riverine systems in California. The spiking and tank experiments showed that DFA, IMS in combination with DFA, and PCR techniques could be used to detect Cryptosporidium in clam tissues. In the tank experiment, oocyst dose and collection time were significant predictors for detection of C. parvum oocysts in clams. In the wild clam study, Cryptosporidium and Giardia were detected in clams from all three study regions by IMS in combination with DFA analysis of clam digestive glands, with significant variation by sampling year and season. These bivalve studies have shown that clams and mussels can be used to monitor water quality in California and suggests that humans and animals ingesting fecal-contaminated water and shellfish may be exposed to both host-specific and anthropozoonotic Cryptosporidium genotypes of public health significance.

                      Cover page: <em>Cryptosporidium</em> in Bivalves as Indicators of Fecal Pollution in the California Coastal Ecosystem
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