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Craig Miller
Oklahoma State University, Stillwater, USA

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Research
Published: 14 August 2021 in Parasites & Vectors
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Background Babesia species are intraerythrocytic Apicomplexan parasites that infect a wide range of vertebrate hosts. These pathogens are typically transmitted either by tick vectors or by direct blood-to-blood contact, and may cause life-threatening clinical disease, such as thrombocytopenia, hemolytic anemia and acute renal failure, in canine hosts. While Babesia vogeli and Babesia gibsoni infections have both been reported in Oklahoma, reports of Babesia conradae infections have been limited to California. Methods Four separate kennels of coyote-hunting dogs were identified in Oklahoma after the kennels had consulted with Oklahoma State University Boren Veterinary Medical Teaching Hospital (antemortem cases) or the Oklahoma Animal Disease Diagnostic Lab (postmortem cases). Upon owner consent, every accessible dog from each of the four kennels was briefly examined for ectoparasites, particularly ticks, and whole blood samples were collected in EDTA tubes. Clinically ill dogs were examined by a practicing veterinarian, and clinical signs included anorexia, vomiting, lethargy, fever and anemia. DNA was extracted from each blood sample, and a nested PCR was performed using general apicomplexan primers for the partial 18S rRNA gene. PCR products were electrophoresed in agarose matrix, and appropriately sized amplicons were sequenced. Sequences were compared to reference 18S rRNA gene sequences available in GenBank, and samples with > 98% homology to B. conradae (GenBank: AF158702) were considered positive. Babesia conradae-positive dogs were then treated with atovaquone (13.5 mg/kg three times per day) and azithromycin (10 mg/kg once daily) for 10 days and retested at 30 and 60 days post-treatment by PCR. Results Of 40 dogs tested, 15 (37.5%) were positive for B. conradae with 98–99% sequence homology to B. conradae from California. All positive cases were coyote-hunting Greyhounds. Ectoparasites were not identified on any of the dogs at the time of blood collection. Treatment of clinically ill dogs with atovaquone and azithromycin resulted in complete clinical recovery in all treated dogs with negative follow-up PCR at 30 and 60 days post-treatment. Conclusions Collectively, this study (i) documents the occurrence of B. conradae in Oklahoma, (ii) highlights this pathogen as a differential to be considered when clinical signs are present, (iii) supports the use of atovaquone and azithromycin as effective treatment in these cases and (iv) demonstrates chronic subclinical carrier dogs serving as potential reservoirs of B. conradae infection to naïve dogs. Graphical abstract

ACS Style

Erin Stayton; Megan Lineberry; Jennifer Thomas; Tina Bass; Kelly Allen; Ramaswamy Chandrashekar; Gene Yost; Mason Reichard; Craig Miller. Emergence of Babesia conradae infection in coyote-hunting Greyhounds in Oklahoma, USA. Parasites & Vectors 2021, 14, 1 -9.

AMA Style

Erin Stayton, Megan Lineberry, Jennifer Thomas, Tina Bass, Kelly Allen, Ramaswamy Chandrashekar, Gene Yost, Mason Reichard, Craig Miller. Emergence of Babesia conradae infection in coyote-hunting Greyhounds in Oklahoma, USA. Parasites & Vectors. 2021; 14 (1):1-9.

Chicago/Turabian Style

Erin Stayton; Megan Lineberry; Jennifer Thomas; Tina Bass; Kelly Allen; Ramaswamy Chandrashekar; Gene Yost; Mason Reichard; Craig Miller. 2021. "Emergence of Babesia conradae infection in coyote-hunting Greyhounds in Oklahoma, USA." Parasites & Vectors 14, no. 1: 1-9.

Journal article
Published: 05 August 2021 in Viruses
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The emergence and ensuing dominance of COVID-19 on the world stage has emphasized the urgency of efficient animal models for the development of therapeutics for and assessment of immune responses to SARS-CoV-2 infection. Shortcomings of current animal models for SARS-CoV-2 include limited lower respiratory disease, divergence from clinical COVID-19 disease, and requirements for host genetic modifications to permit infection. In this study, n = 12 specific-pathogen-free domestic cats were infected intratracheally with SARS-CoV-2 to evaluate clinical disease, histopathologic lesions, and viral infection kinetics at 4 and 8 days post-inoculation; n = 6 sham-inoculated cats served as controls. Intratracheal inoculation of SARS-CoV-2 produced a significant degree of clinical disease (lethargy, fever, dyspnea, and dry cough) consistent with that observed in the early exudative phase of COVID-19. Pulmonary lesions such as diffuse alveolar damage, hyaline membrane formation, fibrin deposition, and proteinaceous exudates were also observed with SARS-CoV-2 infection, replicating lesions identified in people hospitalized with ARDS from COVID-19. A significant correlation was observed between the degree of clinical disease identified in infected cats and pulmonary lesions. Viral loads and ACE2 expression were also quantified in nasal turbinates, distal trachea, lungs, and other organs. Results of this study validate a feline model for SARS-CoV-2 infection that results in clinical disease and histopathologic lesions consistent with acute COVID-19 in humans, thus encouraging its use for future translational studies.

ACS Style

Jennifer M. Rudd; Miruthula Tamil Selvan; Shannon Cowan; Yun-Fan Kao; Cecily C. Midkiff; Sai Narayanan; Akhilesh Ramachandran; Jerry W. Ritchey; Craig A. Miller. Clinical and Histopathologic Features of a Feline SARS-CoV-2 Infection Model Are Analogous to Acute COVID-19 in Humans. Viruses 2021, 13, 1550 .

AMA Style

Jennifer M. Rudd, Miruthula Tamil Selvan, Shannon Cowan, Yun-Fan Kao, Cecily C. Midkiff, Sai Narayanan, Akhilesh Ramachandran, Jerry W. Ritchey, Craig A. Miller. Clinical and Histopathologic Features of a Feline SARS-CoV-2 Infection Model Are Analogous to Acute COVID-19 in Humans. Viruses. 2021; 13 (8):1550.

Chicago/Turabian Style

Jennifer M. Rudd; Miruthula Tamil Selvan; Shannon Cowan; Yun-Fan Kao; Cecily C. Midkiff; Sai Narayanan; Akhilesh Ramachandran; Jerry W. Ritchey; Craig A. Miller. 2021. "Clinical and Histopathologic Features of a Feline SARS-CoV-2 Infection Model Are Analogous to Acute COVID-19 in Humans." Viruses 13, no. 8: 1550.

Erratum
Published: 17 April 2021 in Veterinary Parasitology
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ACS Style

Yun-Fan Kao; Brittanie Peake; Robin Madden; Shannon R. Cowan; Ruth C. Scimeca; Jennifer E. Thomas; Mason V. Reichard; Akhilesh Ramachandran; Craig A. Miller. Corrigendum to “A probe-based droplet digital polymerase chain reaction assay for early detection of feline acute cytauxzoonosis” [Vet. Parasitol. 292 (2021) 109413]. Veterinary Parasitology 2021, 293, 109428 .

AMA Style

Yun-Fan Kao, Brittanie Peake, Robin Madden, Shannon R. Cowan, Ruth C. Scimeca, Jennifer E. Thomas, Mason V. Reichard, Akhilesh Ramachandran, Craig A. Miller. Corrigendum to “A probe-based droplet digital polymerase chain reaction assay for early detection of feline acute cytauxzoonosis” [Vet. Parasitol. 292 (2021) 109413]. Veterinary Parasitology. 2021; 293 ():109428.

Chicago/Turabian Style

Yun-Fan Kao; Brittanie Peake; Robin Madden; Shannon R. Cowan; Ruth C. Scimeca; Jennifer E. Thomas; Mason V. Reichard; Akhilesh Ramachandran; Craig A. Miller. 2021. "Corrigendum to “A probe-based droplet digital polymerase chain reaction assay for early detection of feline acute cytauxzoonosis” [Vet. Parasitol. 292 (2021) 109413]." Veterinary Parasitology 293, no. : 109428.

Preprint content
Published: 14 April 2021
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The emergence and ensuing dominance of COVID-19 on the world stage has emphasized the urgency of efficient animal models for the development of therapeutics and assessment of immune responses to SARS-CoV-2 infection. Shortcomings of current animal models for SARS-CoV-2 include limited lower respiratory disease, divergence from clinical COVID-19 disease, and requirements for host genetic modifications to permit infection. This study validates a feline model for SARS-CoV-2 infection that results in clinical disease and histopathologic lesions consistent with severe COVID-19 in humans. Intra-tracheal inoculation of concentrated SARS-CoV-2 caused infected cats to develop clinical disease consistent with that observed in the early exudative phase of COVID-19. A novel clinical scoring system for feline respiratory disease was developed and utilized, documenting a significant degree of lethargy, fever, dyspnea, and dry cough in infected cats. In addition, histopathologic pulmonary lesions such as diffuse alveolar damage, hyaline membrane formation, fibrin deposition, and proteinaceous exudates were observed due to SARS-CoV-2 infection, imitating lesions identified in people hospitalized with ARDS from COVID-19. A significant correlation exists between the degree of clinical disease identified in infected cats and pulmonary lesions. Viral loads and ACE2 expression were quantified in nasal turbinates, distal trachea, lung, and various other organs. Natural ACE2 expression, paired with clinicopathologic correlates between this feline model and human COVID-19, encourage use of this model for future translational studies.

ACS Style

Jennifer M. Rudd; Miruthula Tamil Selvan; Shannon Cowan; Yun-Fan Kao; Cecily C. Midkiff; Jerry W. Ritchey; Craig A. Miller. Clinicopathologic features of a feline SARS-CoV-2 infection model parallel acute COVID-19 in humans. 2021, 1 .

AMA Style

Jennifer M. Rudd, Miruthula Tamil Selvan, Shannon Cowan, Yun-Fan Kao, Cecily C. Midkiff, Jerry W. Ritchey, Craig A. Miller. Clinicopathologic features of a feline SARS-CoV-2 infection model parallel acute COVID-19 in humans. . 2021; ():1.

Chicago/Turabian Style

Jennifer M. Rudd; Miruthula Tamil Selvan; Shannon Cowan; Yun-Fan Kao; Cecily C. Midkiff; Jerry W. Ritchey; Craig A. Miller. 2021. "Clinicopathologic features of a feline SARS-CoV-2 infection model parallel acute COVID-19 in humans." , no. : 1.

Journal article
Published: 15 March 2021 in Veterinary Parasitology
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Cytauxzoonosis is a tick-borne disease of domestic cats with high mortality and narrow therapeutic window, particularly in the southcentral and southeastern United States. The causative agent is the apicomplexan protozoal parasite Cytauxzoon felis and is primarily transmitted by Amblyomma americanum, the lone star tick. Currently there is no vaccine available to prevent cytauxzoonosis and treatment is often ineffective if not initiated early enough in the course of disease. Early diagnosis and therapeutic intervention are therefore crucial for the survival of infected cats. Several methods are available for diagnosis of cytauxzoonosis, with PCR being the most sensitive. However, current PCR assays, which employ double-stranded DNA intercalating dyes to detect C. felis infection, have inherent limitations such as the potential for false positive detection of non-specific amplification products and inability to provide absolute quantification of parasite load. The objective of this study was to develop a probe-based droplet digital PCR (ddPCR) assay capable of detection and quantification of C. felis load over time and during treatment. The C. felis ddPCR assay was able to (i) reliably detect and quantify C. felis DNA in clinical blood samples from cats with acute cytauxzoonosis and (ii) monitor clinical parasite load in response to anti-protozoal treatment through absolute quantification of C. felis DNA over time. When tested on blood samples from cats with experimental C. felis infection, the assay was able to detect infection in cats as early as 24 h prior to the development of clinical signs. In addition, we demonstrate that this probe-based design can be utilized in traditional real-time PCR systems, with similar detection capabilities as compared to ddPCR. The C. felis probe-based ddPCR was also able to detect infection in samples with lower parasite loads when compared to existing nested PCR assays, although these results were not significant due to small sample size. To the author’s knowledge, this is the first reported probe-based ddPCR assay to detect Cytauxzoon felis infection in domestic cats.

ACS Style

Yun-Fan Kao; Brittanie Peake; Robin Madden; Shannon R. Cowan; Ruth C. Scimeca; Jennifer E. Thomas; Mason V. Reichard; Akhilesh Ramachandran; Craig A. Miller. A probe-based droplet digital polymerase chain reaction assay for early detection of feline acute cytauxzoonosis. Veterinary Parasitology 2021, 292, 109413 .

AMA Style

Yun-Fan Kao, Brittanie Peake, Robin Madden, Shannon R. Cowan, Ruth C. Scimeca, Jennifer E. Thomas, Mason V. Reichard, Akhilesh Ramachandran, Craig A. Miller. A probe-based droplet digital polymerase chain reaction assay for early detection of feline acute cytauxzoonosis. Veterinary Parasitology. 2021; 292 ():109413.

Chicago/Turabian Style

Yun-Fan Kao; Brittanie Peake; Robin Madden; Shannon R. Cowan; Ruth C. Scimeca; Jennifer E. Thomas; Mason V. Reichard; Akhilesh Ramachandran; Craig A. Miller. 2021. "A probe-based droplet digital polymerase chain reaction assay for early detection of feline acute cytauxzoonosis." Veterinary Parasitology 292, no. : 109413.

Journal article
Published: 12 March 2021 in Viruses
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Although the antibody response induced by primary vaccination with Fel-O-Vax® FIV (three doses, 2–4 weeks apart) is well described, the antibody response induced by annual vaccination with Fel-O-Vax® FIV (single dose every 12 months after primary vaccination) and how it compares to the primary antibody response has not been studied. Residual blood samples from a primary FIV vaccination study (n = 11), and blood samples from cats given an annual FIV vaccination (n = 10), were utilized. Samples from all 21 cats were tested with a commercially available PCR assay (FIV RealPCRTM), an anti-p24 microsphere immunoassay (MIA), an anti-FIV transmembrane (TM; gp40) peptide ELISA, and a range of commercially available point-of-care (PoC) FIV antibody kits. PCR testing confirmed all 21 cats to be FIV-uninfected for the duration of this study. Results from MIA and ELISA testing showed that both vaccination regimes induced significant antibody responses against p24 and gp40, and both anti-p24 and anti-gp40 antibodies were variably present 12 months after FIV vaccination. The magnitude of the antibody response against both p24 and gp40 was significantly higher in the primary FIV vaccination group than in the annual FIV vaccination group. The differences in prime versus recall post-vaccinal antibody levels correlated with FIV PoC kit performance. Two FIV PoC kits that detect antibodies against gp40, namely Witness® and Anigen Rapid®, showed 100% specificity in cats recently administered an annual FIV vaccination, demonstrating that they can be used to accurately distinguish vaccination and infection in annually vaccinated cats. A third FIV PoC kit, SNAP® Combo, had 0% specificity in annually FIV-vaccinated cats, and should not be used in any cat with a possible history of FIV vaccination. This study outlines the antibody response to inactivated Fel-O-Vax® FIV whole-virus vaccine, and demonstrates how best to diagnose FIV infection in jurisdictions where FIV vaccination is practiced.

ACS Style

Mark Westman; Dennis Yang; Jennifer Green; Jacqueline Norris; Richard Malik; Yasmin Parr; Mike McDonald; Margaret Hosie; Sue VandeWoude; Craig Miller. Antibody Responses in Cats Following Primary and Annual Vaccination against Feline Immunodeficiency Virus (FIV) with an Inactivated Whole-Virus Vaccine (Fel-O-Vax® FIV). Viruses 2021, 13, 470 .

AMA Style

Mark Westman, Dennis Yang, Jennifer Green, Jacqueline Norris, Richard Malik, Yasmin Parr, Mike McDonald, Margaret Hosie, Sue VandeWoude, Craig Miller. Antibody Responses in Cats Following Primary and Annual Vaccination against Feline Immunodeficiency Virus (FIV) with an Inactivated Whole-Virus Vaccine (Fel-O-Vax® FIV). Viruses. 2021; 13 (3):470.

Chicago/Turabian Style

Mark Westman; Dennis Yang; Jennifer Green; Jacqueline Norris; Richard Malik; Yasmin Parr; Mike McDonald; Margaret Hosie; Sue VandeWoude; Craig Miller. 2021. "Antibody Responses in Cats Following Primary and Annual Vaccination against Feline Immunodeficiency Virus (FIV) with an Inactivated Whole-Virus Vaccine (Fel-O-Vax® FIV)." Viruses 13, no. 3: 470.

Preprint content
Published: 28 January 2021
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Background: Babesia species are intraerythrocytic Apicomplexan parasites that infect a wide range of vertebrate hosts. These pathogens are typically transmitted either by tick vectors or by direct blood-to-blood contact, and may cause life-threatening clinical disease such as thrombocytopenia, hemolytic anemia, and acute renal failure in canine hosts. While Babesia vogeli and Babesia gibsoni infections have both been reported in Oklahoma, reports of B. conradae infections have been limited to California. Methods: Whole blood samples were collected in EDTA tubes from all dogs in four separate kennels in Oklahoma. DNA was extracted from each blood sample and a nested PCR was performed using general Apicomplexan primers for the partial 18S rRNA gene. PCR products were electrophoresed in agarose matrix and appropriately sized amplicons were sequenced. Sequences were compared to reference 18S rRNA sequences available in GenBank, and samples with >98% homology to B. conradae (GenBank MK256976) were considered positive. B. conradae positive dogs were then treated with atovaquone (13.5 mg/kg TID) and azithromycin (10 mg/kg SID) for 10 days and retested at 30 and 60 days post treatment by PCR. Results: Fifteen of 40 dogs tested positive for B. conradae with 98–100% sequence homology to B. conradae from California. All positive cases were coyote-hunting Greyhounds. Treatment of clinically ill dogs with atovaquone and azithromycin resulted in complete clinical recovery in clinically ill dogs and all treated dogs had negative follow-up PCR at 30 and 60 days post treatment. Conclusions: Collectively, this study (i) documents the occurrence of B. conradae in Oklahoma, (ii) highlights this pathogen as a differential to be considered when clinical signs are present, and (iii) supports the use of atovaquone and azithromycin as effective treatment in these cases.

ACS Style

Erin M Stayton; Megan Lineberry; Jennifer Thomas; Tina Bass; Kelly Allen; Ramaswamy Chandrashekar; Gene Yost; Mason Reichard; Craig Miller. Emergence of Babesia Conradae Infection in Coyote-hunting Greyhounds in Oklahoma, USA. 2021, 1 .

AMA Style

Erin M Stayton, Megan Lineberry, Jennifer Thomas, Tina Bass, Kelly Allen, Ramaswamy Chandrashekar, Gene Yost, Mason Reichard, Craig Miller. Emergence of Babesia Conradae Infection in Coyote-hunting Greyhounds in Oklahoma, USA. . 2021; ():1.

Chicago/Turabian Style

Erin M Stayton; Megan Lineberry; Jennifer Thomas; Tina Bass; Kelly Allen; Ramaswamy Chandrashekar; Gene Yost; Mason Reichard; Craig Miller. 2021. "Emergence of Babesia Conradae Infection in Coyote-hunting Greyhounds in Oklahoma, USA." , no. : 1.

Journal article
Published: 07 September 2019 in Viruses
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Feline immunodeficiency virus (FIV) is a naturally occurring T-cell tropic lentiviral disease of felids with many similarities to HIV/AIDS in humans. Similar to primate lentiviral-host interactions, feline APOBEC3 (A3) has been shown to inhibit FIV infection in a host-specific manner and feline A3 degradation is mediated by FIV Vif. Further, infection of felids with non-native FIV strains results in restricted viral replication in both experimental and naturally occurring infections. However, the link between molecular A3-Vif interactions and A3 biological activity during FIV infection has not been well characterized. We thus examined expression of the feline A3 genes A3Z2, A3Z3 and A3Z2-Z3 during experimental infection of domestic cats with host-adapted domestic cat FIV (referred to as FIV) and non-adapted Puma concolor FIV (referred to as puma lentivirus, PLV). We determined A3 expression in different tissues and blood cells from uninfected, FIV-infected, PLV-infected and FIV/PLV co-infected cats; and in purified blood cell subpopulations from FIV-infected and uninfected cats. Additionally, we evaluated regulation of A3 expression by cytokines, mitogens, and FIV infection in cultured cells. In all feline cells and tissues studied, there was a striking difference in expression between the A3 genes which encode FIV inhibitors, with A3Z3 mRNA abundance exceeding that of A3Z2-Z3 by 300-fold or more. Interferon-alpha treatment of cat T cells resulted in upregulation of A3 expression, while treatment with interferon-gamma enhanced expression in cat cell lines. In cats, secondary lymphoid organs and peripheral blood mononuclear cells (PBMC) had the highest basal A3 expression levels and A3 genes were differentially expressed among blood T cells, B cells, and monocytes. Acute FIV and PLV infection of cats, and FIV infection of primary PBMC resulted in no detectable change in A3 expression with the exception of significantly elevated A3 expression in the thymus, the site of highest FIV replication. We conclude that cat A3 expression is regulated by cytokine treatment but, by and large, lentiviral infection did not appear to alter expression. Differences in A3 expression in different blood cell subsets did not appear to impact FIV viral replication kinetics within these cells. Furthermore, the relative abundance of A3Z3 mRNA compared to A3Z2-Z3 suggests that A3Z3 may be the major active anti-lentiviral APOBEC3 gene product in domestic cats.

ACS Style

Ryan M. Troyer; Jennifer L. Malmberg; Xin Zheng; Craig Miller; Martha Macmillan; Wendy S. Sprague; Britta A. Wood; Sue Vandewoude. Expression of APOBEC3 Lentiviral Restriction Factors in Cats. Viruses 2019, 11, 831 .

AMA Style

Ryan M. Troyer, Jennifer L. Malmberg, Xin Zheng, Craig Miller, Martha Macmillan, Wendy S. Sprague, Britta A. Wood, Sue Vandewoude. Expression of APOBEC3 Lentiviral Restriction Factors in Cats. Viruses. 2019; 11 (9):831.

Chicago/Turabian Style

Ryan M. Troyer; Jennifer L. Malmberg; Xin Zheng; Craig Miller; Martha Macmillan; Wendy S. Sprague; Britta A. Wood; Sue Vandewoude. 2019. "Expression of APOBEC3 Lentiviral Restriction Factors in Cats." Viruses 11, no. 9: 831.

Journal article
Published: 30 August 2019 in Viruses
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Feline immunodeficiency virus (FIV) induces opportunistic disease in chronically infected cats, and both prednisolone and cyclosporine A (CsA) are clinically used to treat complications such as lymphoma and stomatitis. However, the impact of these compounds on FIV infection are still unknown and understanding immunomodulatory effects on FIV replication and persistence is critical to guide safe and effective therapies. To determine the immunologic and virologic effects of prednisolone and CsA during FIV infection, FIV-positive cats were administered immunosuppressive doses of prednisolone (2 mg/kg) or CsA (5 mg/kg). Both prednisolone and CsA induced acute and transient increases in FIV DNA and RNA loads as detected by quantitative PCR. Changes in the proportion of lymphocyte immunophenotypes were also observed between FIV-infected and naïve cats treated with CsA and prednisolone, and both treatments caused acute increases in CD4+ lymphocytes that correlated with increased FIV RNA. CsA and prednisolone also produced alterations in cytokine expression that favored a shift toward a Th2 response. Pre-treatment with CsA slightly enhanced the efficacy of antiretroviral therapy but did not enhance clearance of FIV. Results highlight the potential for drug-induced perturbation of FIV infection and underscore the need for more information regarding immunopathologic consequences of therapeutic agents on concurrent viral infections.

ACS Style

Craig Miller; Jordan Powers; Esther Musselman; Ryan Mackie; John Elder; Sue Vandewoude. Immunopathologic Effects of Prednisolone and Cyclosporine A on Feline Immunodeficiency Virus Replication and Persistence. Viruses 2019, 11, 805 .

AMA Style

Craig Miller, Jordan Powers, Esther Musselman, Ryan Mackie, John Elder, Sue Vandewoude. Immunopathologic Effects of Prednisolone and Cyclosporine A on Feline Immunodeficiency Virus Replication and Persistence. Viruses. 2019; 11 (9):805.

Chicago/Turabian Style

Craig Miller; Jordan Powers; Esther Musselman; Ryan Mackie; John Elder; Sue Vandewoude. 2019. "Immunopathologic Effects of Prednisolone and Cyclosporine A on Feline Immunodeficiency Virus Replication and Persistence." Viruses 11, no. 9: 805.

Journal article
Published: 19 July 2019 in Viruses
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Foamy viruses (FVs) are globally prevalent retroviruses that establish apparently apathogenic lifelong infections. Feline FV (FFV) has been isolated from domestic cats with concurrent diseases, including urinary syndromes. We experimentally infected five cats with FFV to study viral kinetics and tropism, peripheral blood mononuclear cell (PBMC) phenotype, urinary parameters, and histopathology. A persistent infection of primarily lymphoid tropism was detected with no evidence of immunological or hematologic perturbations. One cat with a significant negative correlation between lymphocytes and PBMC proviral load displayed an expanded FFV tissue tropism. Significantly increased blood urea nitrogen and ultrastructural kidney changes were noted in all experimentally infected cats, though chemistry parameters were not outside of normal ranges. Histopathological changes were observed in the brain, large intestine, and other tissues. In order to determine if there is an association of FFV with Chronic Kidney Disease, we additionally screened 125 Australian pet cats with and without CKD for FFV infection and found that FFV is highly prevalent in older cats, particularly in males with CKD, though this difference was not statistically significant compared to controls. Acute FFV infection was clinically silent, and while some measures indicated mild changes, there was no overt association of FFV infection with renal disease.

ACS Style

Carmen Ledesma-Feliciano; Ryan M. Troyer; Xin Zheng; Craig Miller; Rachel Cianciolo; Matteo Bordicchia; Nicholas Dannemiller; Roderick Gagne; Julia Beatty; Jessica Quimby; Martin Löchelt; Sue Vandewoude. Feline Foamy Virus Infection: Characterization of Experimental Infection and Prevalence of Natural Infection in Domestic Cats with and without Chronic Kidney Disease. Viruses 2019, 11, 662 .

AMA Style

Carmen Ledesma-Feliciano, Ryan M. Troyer, Xin Zheng, Craig Miller, Rachel Cianciolo, Matteo Bordicchia, Nicholas Dannemiller, Roderick Gagne, Julia Beatty, Jessica Quimby, Martin Löchelt, Sue Vandewoude. Feline Foamy Virus Infection: Characterization of Experimental Infection and Prevalence of Natural Infection in Domestic Cats with and without Chronic Kidney Disease. Viruses. 2019; 11 (7):662.

Chicago/Turabian Style

Carmen Ledesma-Feliciano; Ryan M. Troyer; Xin Zheng; Craig Miller; Rachel Cianciolo; Matteo Bordicchia; Nicholas Dannemiller; Roderick Gagne; Julia Beatty; Jessica Quimby; Martin Löchelt; Sue Vandewoude. 2019. "Feline Foamy Virus Infection: Characterization of Experimental Infection and Prevalence of Natural Infection in Domestic Cats with and without Chronic Kidney Disease." Viruses 11, no. 7: 662.

Journal article
Published: 30 April 2018 in npj Vaccines
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Feline immunodeficiency virus (FIV) is the feline analogue to human immunodeficiency virus (HIV) and utilizes parallel modes of receptor-mediated entry. The FIV surface glycoprotein (SU) is an important target for induction of neutralizing antibodies, and autoantibodies to the FIV binding receptor (CD134) block infection ex vivo; thus highlighting the potential for immunotherapies which utilize anti-receptor antibodies to block viral infection. To determine whether vaccination with CD134-SU complexes could induce protection against FIV infection, cats (n = 5 per group) were immunized with soluble CD134, recombinant FIV-SU protein, and/or CD134+SU complexes. Two trials were performed with different antigen combinations and vaccination schedules. In vivo generation of anti-CD134 and anti-SU IgG antibodies was measured, and in vitro neutralization assays were conducted. Immunization induced production of anti-CD134 and anti-SU antibodies that significantly inhibited FIV infection in vitro. However, no vaccine combination protected cats from FIV infection, and neat serum from vaccinated cats enhanced FIV growth in vitro. CD134+SU vaccinated cats exhibited increased CD4:CD8 ratio immediately prior to challenge, and antibodies were much more efficiently generated against vaccine by-products versus target antigens. Results suggest vaccination against viral and cryptic receptor epitopes yields neutralizing antibodies that synergistically inhibit FIV infection in vitro. Factors contributing to vaccine failure may include: (1) Heat-labile serum factors that enhance viral replication, (2) changes in circulating target cell populations induced by vaccination, and (3) weak immunogenicity of neutralizing epitopes compared to off-target vaccine components. Results reinforce the need to monitor vaccine preparation components and avoid non-specific immune stimulation during vaccination. A vaccine candidate for feline immunodeficiency virus elicits strong immunological reaction in vitro, but no protection to live cats. The feline analog to human immunodeficiency virus, FIV shares a similar infection paradigm and has only one partially effective vaccine. A US team, led by Colorado State University’s Susan VandeWoude, immunized cats using a complex of an FIV surface protein and a feline cell-surface protein known to facilitate FIV’s entry into immune cells. Tissue culture assays yielded promising results; however, this did not translate to live-animal protection. The researchers highlighted multiple factors that could explain the lack of success, including circulatory pro-infection factors, and immune responses generated against vaccine by-products rather than intended targets. While the vaccine candidate failed, the research provides invaluable guidance for future efforts into FIV vaccination with implications for HIV vaccine trials.

ACS Style

Craig Miller; Mauren Emanuelli; Elizabeth Fink; Esther Musselman; Ryan Mackie; Ryan Troyer; John Elder; Sue Vandewoude. FIV vaccine with receptor epitopes results in neutralizing antibodies but does not confer resistance to challenge. npj Vaccines 2018, 3, 1 -12.

AMA Style

Craig Miller, Mauren Emanuelli, Elizabeth Fink, Esther Musselman, Ryan Mackie, Ryan Troyer, John Elder, Sue Vandewoude. FIV vaccine with receptor epitopes results in neutralizing antibodies but does not confer resistance to challenge. npj Vaccines. 2018; 3 (1):1-12.

Chicago/Turabian Style

Craig Miller; Mauren Emanuelli; Elizabeth Fink; Esther Musselman; Ryan Mackie; Ryan Troyer; John Elder; Sue Vandewoude. 2018. "FIV vaccine with receptor epitopes results in neutralizing antibodies but does not confer resistance to challenge." npj Vaccines 3, no. 1: 1-12.

Review
Published: 20 April 2018 in Viruses
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Feline immunodeficiency virus (FIV) is a naturally-occurring retrovirus that infects domestic and non-domestic feline species, producing progressive immune depletion that results in an acquired immunodeficiency syndrome (AIDS). Much has been learned about FIV since it was first described in 1987, particularly in regard to its application as a model to study the closely related lentivirus, human immunodeficiency virus (HIV). In particular, FIV and HIV share remarkable structure and sequence organization, utilize parallel modes of receptor-mediated entry, and result in a similar spectrum of immunodeficiency-related diseases due to analogous modes of immune dysfunction. This review summarizes current knowledge of FIV infection kinetics and the mechanisms of immune dysfunction in relation to opportunistic disease, specifically in regard to studying HIV pathogenesis. Furthermore, we present data that highlight changes in the oral microbiota and oral immune system during FIV infection, and outline the potential for the feline model of oral AIDS manifestations to elucidate pathogenic mechanisms of HIV-induced oral disease. Finally, we discuss advances in molecular biology, vaccine development, neurologic dysfunction, and the ability to apply pharmacologic interventions and sophisticated imaging technologies to study experimental and naturally occurring FIV, which provide an excellent, but often overlooked, resource for advancing therapies and the management of HIV/AIDS.

ACS Style

Craig Miller; Zaid Abdo; Aaron Ericsson; John Elder; Sue Vandewoude. Applications of the FIV Model to Study HIV Pathogenesis. Viruses 2018, 10, 206 .

AMA Style

Craig Miller, Zaid Abdo, Aaron Ericsson, John Elder, Sue Vandewoude. Applications of the FIV Model to Study HIV Pathogenesis. Viruses. 2018; 10 (4):206.

Chicago/Turabian Style

Craig Miller; Zaid Abdo; Aaron Ericsson; John Elder; Sue Vandewoude. 2018. "Applications of the FIV Model to Study HIV Pathogenesis." Viruses 10, no. 4: 206.

Preprint
Published: 02 April 2018
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Feline immunodeficiency virus (FIV) is a naturally-occurring retrovirus that infects domestic and non-domestic feline species, producing progressive immune depletion that results in an acquired immunodeficiency syndrome (AIDS). Much has been learned about FIV since it was first described in 1987, particularly in regard to its application as a model to study the closely related lentivirus, human immunodeficiency virus (HIV). In particular, FIV and HIV share remarkable structure and sequence organization, utilize parallel modes of receptor-mediated entry, and result in a similar spectrum of immunodeficiency-related diseases due to analogous modes of immune dysfunction. This review summarizes current knowledge of FIV infection kinetics and mechanisms of immune dysfunction in relation to opportunistic disease, specifically in regard to studying HIV pathogenesis. Furthermore, we present data which highlight changes in the oral microbiota and oral immune system during FIV infection, and outline the potential for the feline model of oral AIDS manifestations to elucidate pathogenic mechanisms of HIV-induced oral disease. Finally, we discuss advances in molecular biology, vaccine development, neurologic dysfunction, and the ability to apply pharmacologic interventions and sophisticated imaging technologies to study experimental and naturally occurring FIV, which provide an excellent, but often overlooked resource for advancing therapies and management of HIV/AIDS.

ACS Style

Craig Miller; Zaid Abdo; Aaron Ericsson; John Elder; Sue Vandewoude. Applications of the FIV Model to Study HIV Pathogenesis. 2018, 1 .

AMA Style

Craig Miller, Zaid Abdo, Aaron Ericsson, John Elder, Sue Vandewoude. Applications of the FIV Model to Study HIV Pathogenesis. . 2018; ():1.

Chicago/Turabian Style

Craig Miller; Zaid Abdo; Aaron Ericsson; John Elder; Sue Vandewoude. 2018. "Applications of the FIV Model to Study HIV Pathogenesis." , no. : 1.