Last data update: May 06, 2024. (Total: 46732 publications since 2009)
Records 1-17 (of 17 Records) |
Query Trace: Genzer SC[original query] |
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Effect of adopting a Timothy Hay-Based Diet at weaning or in adulthood on urinary tract parameters in strain 13/n guinea pigs (Cavia porcellus)
Wier RC , Flietstra TD , Coleman-McCray JD , Genzer SC , Brake ME , Velazquez EM , Forero C , Welch SR , Tansey CM , Condrey JA , Spengler JR . J Am Assoc Lab Anim Sci 2024 Type of feed is an important consideration in herbivore colony management, yet limited studies report on the effects of diet on common conditions such as urolithiasis in guinea pigs. Urolithiasis is a well-documented cause of lower urinary tract disease in guinea pigs, with calcium carbonate uroliths reported as the predominant calculi formed in the guinea pig urinary tract. A calcium-rich diet has been suggested as a risk factor for of urolithiasis, with numerous commercially available guinea pig diets formulated for adults avoiding ingredients that are higher in calcium. Due to the high incidence of urolithiasis in our strain 13/N guinea pig colony, we conducted a prospective control study following the implementation of dietary changes aimed at improving overall urinary tract health and reducing risk factors for urolithiasis, thus improving colony welfare. A control group was kept on the original ad libitum alfalfa hay-based pellet diet with restricted loose timothy hay (control diet, 14 juveniles and 24 adults). An experimental group was placed on a portioned, 1 oz daily, timothy hay-based pellet diet with ad libitum loose timothy hay (experimental diet, 21 juveniles and 23 adults). Juveniles and adults were followed for a total of 14 and 26 wk, respectively. Longitudinal blood and urine samples were collected to evaluate blood chemistry and urinary parameters, along with weight and body condition scores to assess general health. Overall, dietary changes did not improve parameters associated with improved urinary tract health or reduced risk of urolithiasis; feeding strategy was not found to meaningfully affect calcium crystalluria, urine protein, urine specific gravity, or renal values. These data support alfalfa hay-based pellet or timothy hay-based pellet, when fed with loose timothy hay, as viable options and suggest that practices aimed at reducing dietary calcium by reducing pelleted diet portions are insufficient to mitigate risk factors for urolithiasis in guinea pigs. |
Effects of extended-release buprenorphine on mouse models of influenza
Brake ME , Russ BP , Gansebom S , Genzer SC , Tansey C , York IA . Comp Med 2023 73 (6) 466-73 Mice are widely used as small animal models for influenza infection and immunization studies because of their susceptibility to many strains of influenza, obvious clinical signs of infection, and ease of handling. Analgesia is rarely used in such studies even if nonstudy effects such as fight wounds, tail injuries, or severe dermatitis would otherwise justify it because of concerns that treatment might have confounding effects on primary study parameters such as the course of infection and/or the serological response to infection. However, analgesia for study-related or -unrelated effects may be desirable for animal welfare purposes. Opioids, such as extended-release buprenorphine, are well-characterized analgesics in mice and may have fewer immune-modulatory effects than other drug classes. In this study, BALB/c and DBA/2 mice were inoculated with influenza virus, and treatment groups received either no analgesics or 2 doses of extended-release buprenorphine 72 h apart. Clinical signs, mortality, and influenza-specific antibody responses were comparable in mice that did or did not receive buprenorphine. We therefore conclude that extended-release buprenorphine can be used to alleviate incidental pain during studies of influenza infection without altering the course of infection or the immune response. |
Characterization of humoral responses to Nipah virus infection in the Syrian Hamster model of disease
Scholte FEM , Rodriguez SE , Welch SR , Davies KA , Genzer SC , Coleman-McCray JD , Harmon JR , Sorvillo TE , Lo MK , Karaaslan E , Bergeron E , Montgomery JM , Spengler JR , Spiropoulou CF . J Infect Dis 2023 Nipah virus (NiV) is a highly pathogenic paramyxovirus. The Syrian hamster model recapitulates key features of human NiV disease and is a critical tool for evaluating antivirals and vaccines. Here we describe longitudinal humoral immune responses in NiV-infected Syrian hamsters. Samples were obtained 1-28 days after infection and analyzed by ELISA, neutralization, and Fc-mediated effector function assays. NiV infection elicited robust antibody responses against the nucleoprotein and attachment glycoprotein. Levels of neutralizing antibodies were modest and only detectable in surviving animals. Fc-mediated effector functions were mostly observed in nucleoprotein-targeting antibodies. Antibody levels and activities positively correlated with challenge dose. |
Vaccination with the Crimean-Congo hemorrhagic fever virus viral replicon vaccine induces NP-based T-cell activation and antibodies possessing Fc-mediated effector functions
Scholte FEM , Karaaslan E , O'Neal TJ , Sorvillo TE , Genzer SC , Welch SR , Coleman-McCray JD , Spengler JR , Kainulainen MH , Montgomery JM , Pegan SD , Bergeron E , Spiropoulou CF . Front Cell Infect Microbiol 2023 13 1233148 Crimean-Congo hemorrhagic fever virus (CCHFV; family Nairoviridae) is a tick-borne pathogen that frequently causes lethal disease in humans. CCHFV has a wide geographic distribution, and cases have been reported in Africa, Asia, the Middle East, and Europe. Availability of a safe and efficacious vaccine is critical for restricting outbreaks and preventing disease in endemic countries. We previously developed a virus-like replicon particle (VRP) vaccine that provides complete protection against homologous and heterologous lethal CCHFV challenge in mice after a single dose. However, the immune responses induced by this vaccine are not well characterized, and correlates of protection remain unknown. Here we comprehensively characterized the kinetics of cell-mediated and humoral immune responses in VRP-vaccinated mice, and demonstrate that they predominantly target the nucleoprotein (NP). NP antibodies are not associated with protection through neutralizing activity, but VRP vaccination results in NP antibodies possessing Fc-mediated antibody effector functions, such as complement activation (ADCD) and antibody-mediated cellular phagocytosis (ADCP). This suggests that Fc-mediated effector functions may contribute to this vaccine's efficacy. |
Single-dose mucosal replicon-particle vaccine protects against lethal Nipah virus infection up to 3 days after vaccination
Welch SR , Spengler JR , Genzer SC , Coleman-McCray JD , Harmon JR , Sorvillo TE , Scholte FEM , Rodriguez SE , O'Neal TJ , Ritter JM , Ficarra G , Davies KA , Kainulainen MH , Karaaslan E , Bergeron É , Goldsmith CS , Lo MK , Nichol ST , Montgomery JM , Spiropoulou CF . Sci Adv 2023 9 (31) eadh4057 Nipah virus (NiV) causes a highly lethal disease in humans who present with acute respiratory or neurological signs. No vaccines against NiV have been approved to date. Here, we report on the clinical impact of a novel NiV-derived nonspreading replicon particle lacking the fusion (F) protein gene (NiVΔF) as a vaccine in three small animal models of disease. A broad antibody response was detected that included immunoglobulin G (IgG) and IgA subtypes with demonstrable Fc-mediated effector function targeting multiple viral antigens. Single-dose intranasal vaccination up to 3 days before challenge prevented clinical signs and reduced virus levels in hamsters and immunocompromised mice; decreases were seen in tissues and mucosal secretions, critically decreasing potential for virus transmission. This virus replicon particle system provides a vital tool to the field and demonstrates utility as a highly efficacious and safe vaccine candidate that can be administered parenterally or mucosally to protect against lethal Nipah disease. |
Effect of parental age, parity, and pairing approach on reproduction in strain 13/N guinea pigs (Cavia porcellus)
Genzer SC , Flietstra T , Coleman-McCray JD , Tansey C , Welch SR , Spengler JR . Animals 2023 13 (5) Guinea pigs are important animal models for human disease, and both outbred and inbred lines are utilized in biomedical research. The optimal maintenance of guinea pig colonies, commercially and in research settings, relies on robust informed breeding programs, however, breeding data on specialized inbred strains are limited. Here, we investigated the effects of parental age, parity, and pairing approaches on mean total fetus count, percentage of female pups in the litter, and pup survival rate after 10 days in strain 13/N guinea pigs. Our analysis of colony breeding data indicates that the average litter size is 3.3 pups, with a 25.2% stillbirth rate, a failure-to-thrive outcome in 5.1% of pups, and a 10 day survival rate of 69.7%. The only variable to significantly affect the reproductive outcomes examined was parental age (p < 0.05). In comparison to adults, both juvenile and geriatric sows had lower total fetus counts; juvenile boars had a higher percentage of females in litters, and geriatric boars had a lower 10 day survival rate of pups. These studies provide valuable information regarding the reproductive characteristics of strain 13/N guinea pigs, and support a variety of breeding approaches without significant effects on breeding success. |
Mouse models of Ebola virus tolerance and lethality: Characterization of CD-1 mice infected with wild-type, guinea pig-adapted, or mouse-adapted variants
Spengler JR , Welch SR , Ritter JM , Harmon JR , Coleman-McCray JD , Genzer SC , Nascimento Seixas J , Scholte FEM , Davies KA , Bradfute SB , Montgomery JM , Spiropoulou CF . Antiviral Res 2022 210 105496 Development of lethal models of Ebola virus disease has been achieved by the serial passage of virus isolates from human cases in mice and guinea pigs. Use of mice infected with non-adapted virus has been limited due to the absence of overt clinical disease. In recent years, newly recognized sequelae identified in human cases has highlighted the importance of continued investigations of non-lethal infection both in humans and animal models. Here, we revisit the use of rodent-adapted and non-adapted Ebola virus (EBOV) variants in mice to investigate infection tolerance and future utility of these models in pathogenesis and therapeutic intervention studies. We found that like non-adapted wild-type EBOV, guinea pig-adapted EBOV results in widespread tissue infection, variably associated with tissue pathology, and alterations in clinical and immunological analytes in the absence of overt disease. Notably, infection with either non-lethal variant does not greatly differ from lethal mouse-adapted EBOV until near the time end-point criteria are reached in these mice, supporting use of these models of virus tolerance for continued investigations of non-lethal infection and sequelae. |
Tissue replication and mucosal swab detection of Sosuga virus in Syrian hamsters in the absence of overt tissue pathology and clinical disease
Welch SR , Ritter JM , Schuh AJ , Genzer SC , Sorvillo TE , Harmon JR , Coleman-McCray JD , Jain S , Shrivastava-Ranjan P , Seixas JN , Estetter LB , Fair PS , Towner JS , Montgomery JM , Albariño CG , Spiropoulou CF , Spengler JR . Antiviral Res 2022 209 105490 Human infection with Sosuga virus (SOSV), a recently discovered pathogenic paramyxovirus, has been reported in one individual to date. No animal models of disease are currently available for SOSV. Here, we describe initial characterization of experimental infection in Syrian hamsters, including kinetics of virus dissemination and replication, and the corresponding clinical parameters, immunological responses, and histopathology. We demonstrate susceptibility of hamsters to infection in the absence of clinical signs or significant histopathologic findings in tissues. |
Volume-Associated Clinical and Histopathological Effects of Intranasal Instillation in Syrian Hamsters: Considerations for Infection and Therapeutic Studies.
Forero C , Ritter JM , Seixas JN , Coleman-McCray JD , Brake M , Condrey JA , Tansey C , Welch SR , Genzer SC , Spengler JR . Pathogens 2022 11 (8) Syrian hamsters are a key animal model of SARS-CoV-2 and other respiratory viruses and are useful for the evaluation of associated medical countermeasures. Delivery of an infectious agent or intervention to the respiratory tract mirrors natural routes of exposure and allows for the evaluation of clinically relevant therapeutic administration. The data to support instillation or inoculation volumes are important both for optimal experimental design and to minimize or avoid effects of diluent alone, which may compromise both data interpretation and animal welfare. Here we investigate four intranasal (IN) instillation volumes in hamsters (50, 100, 200, or 400 µL). The animals were monitored daily, and a subset were serially euthanized at one of four pre-determined time-points (1, 3, 7, and 14 days post-instillation). Weight, temperature, oxygen saturation, CBC, radiographs, and respiratory tissue histopathology were assessed to determine changes associated with instillation volume alone. With all the delivery volumes, we found no notable differences between instilled and non-instilled controls in all of the parameters assessed, except for histopathology. In the animals instilled with 200 or 400 µL, inflammation associated with foreign material was detected in the lower respiratory tract indicating that higher volumes may result in aspiration of nasal and/or oropharyngeal material in a subset of animals, resulting in IN instillation-associated histopathology. |
Viral RNA and infectious virus in mucosal specimens from guinea pigs modeling early phases of lethal and non-lethal Lassa fever
Welch SR , Genzer SC , Coleman-McCray JD , Harmon JR , Scholte FEM , Montgomery JM , Spiropoulou CF , Spengler JR . Emerg Microbes Infect 2022 11 (1) 1-17 ABSTRACTLassa fever (LF) is endemic to broad regions of West Africa. Infection with Lassa virus (LASV), the etiologic agent of LF, results in a spectrum of clinical signs in humans, including severe and lethal hemorrhagic disease. Person-to-person transmission occurs through direct contact with body fluids or contaminated bedding and clothing. To investigate transmission risk in acute LASV infection, we evaluated viral RNA and infectious virus obtained from conjunctival, nasal, oral, genital, and rectal swab specimens from guinea pigs modeling lethal and non-lethal LF. Viral RNA and infectious virus were detected in all specimen types beginning 8 days post infection, prior to onset of fever. In the pre-clinical and clinical period, virus was isolated from a subset of nasal, oral, genital, and rectal swabs, and from all conjunctival swabs. Overall, conjunctival and nasal specimens most frequently yielded infectious virus. These findings indicate mucosal transmission risk based on virus isolation from various sites early in infection and support potential utility of minimally invasive specimen evaluation by RT-qPCR for LASV diagnostics. |
Defective Interfering Viral Particle Treatment Reduces Clinical Signs and Protects Hamsters from Lethal Nipah Virus Disease.
Welch SR , Spengler JR , Harmon JR , Coleman-McCray JD , Scholte FEM , Genzer SC , Lo MK , Montgomery JM , Nichol ST , Spiropoulou CF . mBio 2022 13 (2) e0329421 Defective interfering particles (DIs) contain a considerably smaller genome than the parental virus but retain replication competency. As DIs can directly or indirectly alter propagation kinetics of the parental virus, they offer a novel approach to antiviral therapy, capitalizing on knowledge from natural infection. However, efforts to translate in vitro inhibition to in vivo screening models remain limited. We investigated the efficacy of virus-like particles containing DI genomes (therapeutic infectious particles [TIPs]) in the Syrian hamster model of lethal Nipah virus (NiV) disease. We found that coadministering a high dose of TIPs intraperitoneally with virus challenge improved clinical course and reduced lethality. To mimic natural exposure, we also evaluated lower-dose TIP delivery and virus challenge intranasally, finding equally efficacious reduction in disease severity and overall lethality. Eliminating TIP replicative capacity decreased efficacy, suggesting protection via direct inhibition. These data provide evidence that TIP-mediated treatment can confer protection against disease and lethal outcome in a robust animal NiV model, supporting further development of TIP treatment for NiV and other high-consequence pathogens. IMPORTANCE Here, we demonstrate that treatment with defective interfering particles (DIs), a natural by-product of viral infection, can significantly improve the clinical course and outcome of viral disease. When present with their parental virus, DIs can directly or indirectly alter viral propagation kinetics and exert potent inhibitory properties in cell culture. We evaluated the efficacy of a selection of virus-like particles containing DI genomes (TIPs) delivered intranasally in a lethal hamster model of Nipah virus disease. We demonstrate significantly improved clinical outcomes, including reduction in both lethality and the appearance of clinical signs. This work provides key efficacy data in a robust model of Nipah virus disease to support further development of TIP-mediated treatment against high-consequence viral pathogens. |
Screening and Identification of Lujo Virus Inhibitors Using a Recombinant Reporter Virus Platform.
Welch SR , Spengler JR , Genzer SC , Chatterjee P , Flint M , Bergeron É , Montgomery JM , Nichol ST , Albariño CG , Spiropoulou CF . Viruses 2021 13 (7) Lujo virus (LUJV), a highly pathogenic arenavirus, was first identified in 2008 in Zambia. To aid the identification of effective therapeutics for LUJV, we developed a recombinant reporter virus system, confirming reporter LUJV comparability with wild-type virus and its utility in high-throughput antiviral screening assays. Using this system, we evaluated compounds with known and unknown efficacy against related arenaviruses, with the aim of identifying LUJV-specific and potential new pan-arenavirus antivirals. We identified six compounds demonstrating robust anti-LUJV activity, including several compounds with previously reported activity against other arenaviruses. These data provide critical evidence for developing broad-spectrum antivirals against high-consequence arenaviruses. |
Prothrombin time, activated partial thromboplastin time, and fibrinogen reference intervals for inbred strain 13/N guinea pigs (Cavia porcellus) and validation of low volume sample analysis
Condrey JA , Flietstra T , Nestor KM , Schlosser EL , Coleman-McCray JD , Genzer SC , Welch SR , Spengler JR . Microorganisms 2020 8 (8) Inbred strain 13/N guinea pigs are used as small animal models for the study of hemorrhagic fever viruses. Coagulation abnormalities, including prolonged clotting times and bleeding, are characteristic of hemorrhagic fever in humans; patients often meet criteria for disseminated intravascular coagulation (DIC). Comprehensively evaluating coagulation function is critical in model development and studies of viral pathogenesis and therapeutic efficacy. Here, using the VetScan VSpro veterinary point-of-care platform, we developed reference intervals in both juvenile and adult strain 13/N guinea pigs for three coagulation parameters: prothrombin time (PT), activated partial thromboplastin time (aPTT), and fibrinogen. In addition, for situations or species with limited availability of blood for clinical analysis, we investigated the validity of a modified collection approach for low-volume (0.1 mL) blood sample analysis of PT and aPTT. |
Pharmacokinetic profiles of gabapentin after oral and subcutaneous administration in black-tailed prairie dogs (Cynomys ludovicianus)
Mills PO , Tansey CO , Genzer SC , Mauldin MR , Howard RA , Kling CA , Jackson FR , Matheny AM , Boothe DM , Lathrop GW , Powell N , Gallardo-Romero N . J Am Assoc Lab Anim Sci 2020 59 (3) 305-309 In veterinary and human medicine, gabapentin (a chemical analog of gamma-aminobutyric acid) is commonly prescribed to treat postoperative and chronic neuropathic pain. This study explored the pharmacokinetics of oral and subcutaneous administration of gabapentin at high (80 mg/kg) and low (30 mg/kg) doses as a potential analgesic in black-tailed prairie dogs (Cynomys ludovicianus; n = 24). The doses (30 and 80 mg/kg) and half maximal effective concentration (1.4 to 16.7 ng/mL) for this study were extrapolated from pharmacokinetic efficacy studies in rats, rabbits, and cats. Gabapentin in plasma was measured by using an immunoassay, and data were evaluated using noncompartmental analysis. The peak plasma concentrations (mean +/-1 SD) were 42.6 +/-14.8 and 115.5 +/-15.2 ng/mL, respectively, after 30 and 80 mg/kg SC and 14.5 +/-3.5 and 20.7 +/-6.1 ng/mL after the low and high oral dosages, respectively. All peak plasma concentrations of gabapentin occurred within 5 h of administration. Disappearance half-lives for the low and high oral doses were 7.4 +/- 6.0 h and 5.0 +/- 0.8 h, respectively. The results of this study demonstrate that oral administration of gabapentin at low (30 mg/kg) doses likely would achieve and maintain plasma concentrations at half maximum effective concentration for 12 h, making it a viable option for an every 12-h treatment. |
Alterations in blood chemistry levels associated with Nipah virus disease in the Syrian hamster model
Genzer SC , Welch SR , Scholte FEM , Harmon JR , Coleman-McCray JD , Lo MK , Montgomery JM , Nichol ST , Spiropoulou CF , Spengler JR . J Infect Dis 2019 221 S454-S459 Nipah virus ([NiV] family Paramyxoviridae, genus Henipavirus) infection can cause severe respiratory and neurological disease in humans. The pathophysiology of disease is not fully understood, and it may vary by presentation and clinical course. In this study, we investigate changes in blood chemistry in NiV-infected Syrian hamsters that survived or succumbed to disease. Increased sodium and magnesium and decreased albumin and lactate levels were detected in animals euthanized with severe clinical disease compared with mock-infected controls. When subjects were grouped by clinical syndrome, additional trends were discernable, highlighting changes associated with either respiratory or neurological disease. |
Suboptimal handling of Piccolo samples or reagent discs for consideration in Ebola response
Spengler JR , Welch SR , Genzer SC , Coleman-McCray J , Harmon JR , Nichol ST , Spiropoulou CF . Emerg Infect Dis 2019 25 (6) 1238-1240 Operating clinical analyzers within recommended parameters can be challenging during outbreak response. Using the Piccolo Xpress point-of-care blood chemistry analyzer on guinea pig blood, we found that values of many analytes are still readily comparable when samples and reagent discs are handled at various conditions outside of manufacturer recommendations. |
Hematology and clinical chemistry reference intervals for inbred strain 13/n guinea pigs (Cavia Porcellus )
Genzer SC , Huynh T , Coleman-Mccray JD , Harmon JR , Welch SR , Spengler JR . J Am Assoc Lab Anim Sci 2019 58 (3) 293-303 Inbred Strain 13/N Guinea Pigs are Frequently Used As Animal Models in Studies of Emerging and High-pathogenicity Viruses. To Date, Clinical Reference Intervals Have Not Been Established for Hematology and Clinical Chemistry Parameters in This Strain. We Obtained Whole-blood Samples from the Cranial Vena Cava of Healthy Strain 13/N Colony Animals for Inhouse Cbc and Clinical Chemistry Analyses. Analyte Values Were Investigated to Determine Subpopulation Differences According to Age and Sex. Glucose, Albumin, Alp, Lymphocyte Percentage, Hgb, and Mchc Decreased with Age, Whereas Neutrophil and Monocyte Percentages, Bun, Creatinine, Calcium, and Amylase Increased with Age. Total Protein and Wbc Counts Increased Over the First 300 D of Life Before Stabilizing. Across All Age Categories, Female Guinea Pigs Consistently Had Lower Rbc, Hct, Hgb, Alt, Alp, and Amylase Levels and Higher Mcv Values Than Males. These Trends Were Strongest in Adults (age, 151 Through 900 D). Most Parameters Stabilized by 300 D; Previous Studies Used 60 D or 120 D As Adult Age and 90 to 120 D As Sexual Maturity. We Recommend Age Group Definitions of 0 Through 150 D for Juveniles, 151 Through 900 D for Adults, and Older Than 900 D for Geriatric Adult Strain 13/N Guinea Pigs. |
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