Trichophyton benhamiae and T. mentagrophytes target guinea pigs in a mixed small animal stock

Lassa virus (LASV) is a mammarenavirus (arenavirus) that causes zoonotic infection in humans that can lead to fatal hemorrhagic Lassa fever (LF) disease. Currently, there are no FDA-approved vaccines or therapeutics against LASV. Development of treatments against LF and other related arenavirus-induced hemorrhagic fevers (AHFs) requires relevant animal models that can recapitulate clinical and pathological features of AHF diseases in humans. Laboratory mice are generally resistant to LASV infection, and non-human primates, while being a good animal model for LF, are limited by their high cost. Here, we describe a small, affordable, and convenient animal model that is based on outbred Hartley guinea pigs infected with Pichinde virus (PICV), a mammarenavirus that is non-pathogenic in humans, for use as a surrogate model of human LF. We conducted a detailed analysis of tissue histopathology and immunohistochemical analysis of different organs of outbred Hartley guinea pigs infected with different PICV strains that show differential disease phenotypes and pathologies. Comparing to infection with the avirulent PICV strain (P2 or rP2), animals infected with the virulent strain (P18 or rP18) show extensive pathological changes in different organs that sustain high levels of virus replication. The similarity of tissue pathology and viral antigen distribution between the virulent PICV–guinea pig model and lethal human LASV infection supports a role of this small animal model as a surrogate model of studying human LF in order to understand its pathogenesis and for evaluating potential preventative and therapeutic options against AHFs.

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Development and Characterization of a Guinea Pig-Adapted Sudan Virus

Journal of Virology ◽

10.1128/jvi.02331-15 ◽

2015 ◽

Vol 90 (1) ◽

pp. 392-399 ◽

Cited By ~ 23

Author(s):

Gary Wong ◽

Shihua He ◽

Haiyan Wei ◽

Andrea Kroeker ◽

Jonathan Audet ◽

...

Keyword(s):

Animal Model ◽

Guinea Pig ◽

Guinea Pigs ◽

Lethal Dose ◽

Fatal Outcome ◽

Small Animal ◽

Disease Outbreak ◽

Small Animal Model ◽

Content Type

ABSTRACT Infections with Sudan virus (SUDV), a member of the genus Ebolavirus , result in a severe hemorrhagic fever with a fatal outcome in over 50% of human cases. The paucity of prophylactics and therapeutics against SUDV is attributed to the lack of a small-animal model to screen promising compounds. By repeatedly passaging SUDV within the livers and spleens of guinea pigs in vivo , a guinea pig-adapted SUDV variant (SUDV-GA) uniformly lethal to these animals, with a 50% lethal dose (LD 50 ) of 5.3 × 10 −2 50% tissue culture infective doses (TCID 50 ), was developed. Animals infected with SUDV-GA developed high viremia and died between 9 and 14 days postinfection. Several hallmarks of SUDV infection, including lymphadenopathy, increased liver enzyme activities, and coagulation abnormalities, were observed. Virological analyses and gross pathology, histopathology, and immunohistochemistry findings indicate that SUDV-GA replicates in the livers and spleens of infected animals similarly to SUDV infections in nonhuman primates. These developments will accelerate the development of specific medical countermeasures in preparation for a future disease outbreak due to SUDV. IMPORTANCE A disease outbreak due to Ebola virus (EBOV), suspected to have emerged during December 2013 in Guinea, with over 11,000 dead and 28,000 infected, is finally winding down. Experimental EBOV vaccines and treatments were administered to patients under compassionate circumstances with promising results, and availability of an approved countermeasure appears to be close. However, the same range of experimental candidates against a potential disease outbreak caused by other members of the genus Ebolavirus , such as Sudan virus (SUDV), is not readily available. One bottleneck contributing to this situation is the lack of a small-animal model to screen promising drugs in an efficient and economical manner. To address this, we have generated a SUDV variant (SUDV-GA) that is uniformly lethal to guinea pigs. Animals infected with SUDV-GA develop disease similar to that of SUDV-infected humans and monkeys. We believe that this model will significantly accelerate the development of life-saving measures against SUDV infections.

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Intrathecal Catheterization and Drug Delivery in Guinea Pigs

Anesthesiology ◽

10.1097/aln.0000000000001166 ◽

2016 ◽

Vol 125 (2) ◽

pp. 378-394 ◽

Cited By ~ 9

Author(s):

Kelly A. Eddinger ◽

Eric S. Rondon ◽

Veronica I. Shubayev ◽

Marjorie R. Grafe ◽

Miriam Scadeng ◽

...

Keyword(s):

Animal Model ◽

Guinea Pigs ◽

Ex Vivo ◽

Intrathecal Morphine ◽

Small Animal ◽

Thermal Stimulus ◽

Small Animal Model ◽

Morphine Infusion ◽

Catheter Tip ◽

Intrathecal Infusion

Abstract Background Intrathecal infusion of opioids in dogs, sheep, and humans produces local space-occupying masses. To develop a small-animal model, the authors examined effects of intrathecal catheterization and morphine infusion in guinea pigs. Methods Under isoflurane, polyethylene or polyurethane catheters were advanced from the cisterna magna to the lumbar enlargement. Drugs were delivered as a bolus through the externalized catheter or continuously by subcutaneous minipumps. Hind paw withdrawal to a thermal stimulus was assessed. Spinal histopathology was systematically assessed in a blinded fashion. To assist in determining catheter placement, ex vivo images were obtained using magnetic resonance imaging in several animals. Canine spinal tissue from previous intrathecal morphine studies was analyzed in parallel. Results (1) Polyethylene (n = 30) and polyurethane (n = 25) catheters were implanted in the lumbar intrathecal space. (2) Bolus intrathecal morphine produced a dose-dependent (20 to 40 μg/10 μl) increase in thermal escape latencies. (3) Absent infusion, a catheter-associated distortion of the spinal cord and a fibrotic investment were noted along the catheter tract (polyethylene > polyurethane). (4) Intrathecal morphine infusion (25 mg/ml/0.5 μl/h for 14 days) resulted in intrathecal masses (fibroblasts, interspersed collagen, lymphocytes, and macrophages) arising from meninges proximal to the catheter tip in both polyethylene- and polyurethane-catheterized animals. This closely resembles mass histopathology from intrathecal morphine canine studies. Conclusions Continuous intrathecal infusion of morphine leads to pericatheter masses that morphologically resemble those observed in dogs and humans. This small-animal model may be useful for studying spinal drug toxicology in general and the biology of intrathecal granuloma formation in particular.

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The Cotton Rat (Sigmodon hispidus) Is a Permissive Small Animal Model of Human Metapneumovirus Infection, Pathogenesis, and Protective Immunity

Journal of Virology ◽

10.1128/jvi.79.17.10944-10951.2005 ◽

2005 ◽

Vol 79 (17) ◽

pp. 10944-10951 ◽

Cited By ~ 81

Author(s):

John V. Williams ◽

Sharon J. Tollefson ◽

Joyce E. Johnson ◽

James E. Crowe

Keyword(s):

Animal Model ◽

Respiratory Tract ◽

Guinea Pigs ◽

Small Animal ◽

Human Metapneumovirus ◽

Small Animal Model ◽

Cotton Rat ◽

Nasal Tissue ◽

Hmpv Infection ◽

Cotton Rats

ABSTRACT Human metapneumovirus (hMPV) is a newly described paramyxovirus that is an important cause of acute respiratory tract disease. We undertook to develop a small animal model of hMPV infection, pathogenesis, and protection. Hamsters, guinea pigs, cotton rats, and nine inbred strains of mice were inoculated intranasally with hMPV. The animals were sacrificed, and nasal and lung tissue virus yields were determined by plaque titration. None of the animals exhibited respiratory symptoms. The quantity of virus present in the nasal tissue ranged from 4.6 × 102 PFU/gram tissue (C3H mice) to greater than 105 PFU/gram (hamster). The amount of virus in the lungs was considerably less than in nasal tissue in each species tested, ranging from undetectable (<5 PFU/g; guinea pigs) to 1.8 × 105 PFU/gram (cotton rat). The peak virus titer in cotton rat lungs occurred on day 4 postinfection. hMPV-infected cotton rat lungs examined on day 4 postinfection exhibited histopathological changes consisting of peribronchial inflammatory infiltrates. Immunohistochemical staining detected virus only at the luminal surfaces of respiratory epithelial cells throughout the respiratory tract. hMPV-infected cotton rats mounted virus-neutralizing antibody responses and were partially protected against virus shedding and lung pathology on subsequent rechallenge with hMPV. Viral antigen was undetectable in the lungs on challenge of previously infected animals. This study demonstrates that the cotton rat is a permissive small animal model of hMPV infection that exhibits lung histopathology associated with infection and that primary infection protected animals against subsequent infection. This model will allow further in vivo studies of hMPV pathogenesis and evaluation of vaccine candidates.

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Premature guinea pigs: a new paradigm to investigate the late-effects of preterm birth

Journal of Developmental Origins of Health and Disease ◽

10.1017/s2040174414000592 ◽

2014 ◽

Vol 6 (2) ◽

pp. 143-148 ◽

Cited By ~ 6

Author(s):

M. Berry ◽

C. Gray ◽

K. Wright ◽

R. Dyson ◽

I. Wright

Keyword(s):

Preterm Birth ◽

Animal Models ◽

Guinea Pigs ◽

Small Animal ◽

Large Animal ◽

New Paradigm ◽

Short Term ◽

Human Infants ◽

Caesarean Birth ◽

Large Animal Models

Preterm birth is common and the associated short-term morbidity well described. The adult-onset consequences of preterm birth are less clear, but cardiovascular and metabolic health may be adversely affected. Although large animal models of preterm birth addressing important short-term issues exist, long-term studies are hampered by significant logistical constraints. Current small animal models of prematurity require terminal caesarean section of the mother; both caesarean birth and early maternal care modify offspring adult cardio-metabolic function.We describe a novel method for inducing preterm labour in guinea pigs. With support comparable to that received by moderately preterm human infants, preterm pups are viable. Growth trajectories between preterm and term-born pups differ significantly; between term equivalent age and weaning ex-preterm animals demonstrate increased weight and ponderal index.We believe this novel paradigm will significantly improve our ability to investigate the cardio-metabolic sequelae of preterm birth throughout the life course and into the second generation.

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Three Immunocompetent Small Animal Models That Do Not Support Zika Virus Infection

Pathogens ◽

10.3390/pathogens10080971 ◽

2021 ◽

Vol 10 (8) ◽

pp. 971

Author(s):

Megan R. Miller ◽

Anna C. Fagre ◽

Taylor C. Clarkson ◽

Erin D. Markle ◽

Brian D. Foy

Keyword(s):

Animal Model ◽

New Zealand ◽

Animal Models ◽

Zika Virus ◽

Guinea Pigs ◽

Sexual Transmission ◽

Small Animal ◽

Zikv Infection ◽

Mosquito Bite ◽

Multimammate Mice

Zika virus (ZIKV) is a mosquito-borne flavivirus that is primarily transmitted to humans through the bite of an infected mosquito. ZIKV causes disease in infected humans with added complications of Guillain-Barré syndrome and birth defects in infants born to mothers infected during pregnancy. There are several large immunocompetent animal models for ZIKV including non-human primates (NHPs). NHP models closely reflect human infection; however, due to sample size restrictions, investigations into the effects of transmission route and the impacts on disease dynamics have been understudied. Mice have been widely used for modeling ZIKV infection, yet there are few ZIKV-susceptible immunocompetent mouse models and none of these have been used to investigate sexual transmission. In an effort to identify a small immunocompetent animal model to characterize sexual transmission of ZIKV, we attempt experimental infection of multimammate mice, New Zealand white rabbits, and Hartley guinea pigs. The multimammate mouse is the natural reservoir of Lassa fever virus and has been identified to harbor other human pathogens. Likewise, while NZW rabbits are susceptible to West Nile virus, they have not yet been examined for their susceptibility to infection with ZIKV. Guinea pigs have been successfully used as models for ZIKV infection, but only in immunocompromised life stages (young or pregnant). Here, it was found that the multimammate mouse and New Zealand White (NZW) rabbits are not susceptible ZIKV infection as determined by a lack viral RNA in tissues and fluids collected. Sexually mature male Hartley guinea pigs were inoculated subcutaneously and by mosquito bite, but found to be refractory to ZIKV infection, contrary to findings of other studies in young and pregnant guinea pigs. Interestingly, here it is shown that adult male guinea pigs are not susceptible to ZIKV infection, even when infected by natural route (e.g., mosquito bite). Although a new small animal model for the sexual transmission for ZIKV was not established through this study, these findings provide information on outbred animal species that are not permissive to infection (NZW rabbits and multimammate mice) and new information surrounding limitations of a previously established animal model (guinea pigs).

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Virulent infection of outbred Hartley guinea pigs with recombinant Pichinde virus as a surrogate small animal model for human Lassa fever

Virulence ◽

10.1080/21505594.2020.1809328 ◽

2020 ◽

Vol 11 (1) ◽

pp. 1131-1141

Author(s):

Shuiyun Lan ◽

Wun-Ju Shieh ◽

Qinfeng Huang ◽

Sherif R. Zaki ◽

Yuying Liang ◽

...

Keyword(s):

Animal Model ◽

Guinea Pigs ◽

Small Animal ◽

Lassa Fever ◽

Small Animal Model ◽

Pichinde Virus

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Development of Infectious Clones for Virulent and Avirulent Pichinde Viruses: a Model Virus To Study Arenavirus-Induced Hemorrhagic Fevers

Journal of Virology ◽

10.1128/jvi.00019-09 ◽

2009 ◽

Vol 83 (13) ◽

pp. 6357-6362 ◽

Cited By ~ 45

Author(s):

Shuiyun Lan ◽

Lisa McLay Schelde ◽

Jialong Wang ◽

Naveen Kumar ◽

Hinh Ly ◽

...

Keyword(s):

Guinea Pigs ◽

Small Animal ◽

Hemorrhagic Fever ◽

Virulence Determinants ◽

T7 Promoter ◽

Recombinant Viruses ◽

Hemorrhagic Fevers ◽

Infectious Clones

ABSTRACT Several arenaviruses can cause hemorrhagic fever diseases (VHFs) in humans, the pathogenic mechanism of which is poorly understood due to their virulent nature and the lack of molecular clones. A safe, convenient, and economical small animal model of arenavirus hemorrhagic fever is based on guinea pigs infected by the arenavirus Pichinde (PICV). PICV does not cause disease in humans, but an adapted strain of PICV (P18) causes a disease in guinea pigs that mimics arenavirus hemorrhagic fever in humans in many aspects, while a low-passaged strain (P2) remains avirulent in infected animals. In order to identify the virulence determinants within the PICV genome, we developed the molecular clones for both the avirulent P2 and virulent P18 viruses. Recombinant viruses were generated by transfecting plasmids that contain the antigenomic L and S RNA segments of PICV under the control of the T7 promoter into BSRT7-5 cells, which constitutively express T7 RNA polymerase. By analyzing viral growth kinetics in vitro and virulence in vivo, we show that the recombinant viruses accurately recapitulate the replication and virulence natures of their respective parental viruses. Both parental and recombinant virulent viruses led to high levels of viremia and titers in different organs of the infected animals, whereas the avirulent viruses were effectively controlled and cleared by the hosts. These novel infectious clones for the PICV provide essential tools to identify the virulence factors that are responsible for the severe VHF-like disease in infected animals.

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Comparative respiratory system mechanics in rodents

Journal of Applied Physiology ◽

10.1152/jappl.2000.89.3.908 ◽

2000 ◽

Vol 89 (3) ◽

pp. 908-916 ◽

Cited By ~ 128

Author(s):

R. F. M. Gomes ◽

X. Shen ◽

R. Ramchandani ◽

R. S. Tepper ◽

J. H. T. Bates

Keyword(s):

Respiratory System ◽

Guinea Pigs ◽

Scaling Laws ◽

Small Animal ◽

Limited Data ◽

Respiratory System Mechanics ◽

In Series ◽

Computer Controlled ◽

Animal Size ◽

Different Levels

Because of the wide utilization of rodents as animal models in respiratory research and the limited data on measurements of respiratory input impedance (Zrs) in small animals, we measured Zrs between 0.25 and 9.125 Hz at different levels (0–7 hPa) of positive end-expiratory pressure (PEEP) in mice, rats, guinea pigs, and rabbits using a computer-controlled small-animal ventilator (Schuessler TF and Bates JHT, IEEE Trans Biomed Eng 42: 860–866, 1995). Zrs was fitted with a model, including a Newtonian resistance (R) and inertance in series with a constant-phase tissue compartment characterized by tissue damping (Gti) and elastance (Hti) parameters. Inertance was negligible in all cases. R, Gti, and Hti were normalized to body weight, yielding normalized R, Gti, and Hti (NHti), respectively. Normalized R tended to decrease slightly with PEEP and increased with animal size. Normalized Gti had a minimal dependence on PEEP. NHti decreased with increasing PEEP, reaching a minimum at ∼5 hPa in all species except mice. NHti was also higher in mice and rabbits compared with guinea pigs and rats at low PEEPs, which we conclude is probably due to a relatively smaller air space volume in mice and rabbits. Our data also suggest that smaller rodents have proportionately wider airways than do larger animals. We conclude that a detailed, comparative study of respiratory system mechanics shows some evidence of structural differences among the lungs of various species but that, in general, rodent lungs obey scaling laws similar to those described in other species.

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Preliminary Evaluation of a Novel Fetal Guinea Pig Myelomeningocele Model

BioMed Research International ◽

10.1155/2021/2180883 ◽

2021 ◽

Vol 2021 ◽

pp. 1-8

Author(s):

Sarah C. Stokes ◽

Kaeli J. Yamashiro ◽

Melissa A. Vanover ◽

Laura A. Galganski ◽

Jordan E. Jackson ◽

...

Keyword(s):

Animal Model ◽

Guinea Pig ◽

Guinea Pigs ◽

Low Cost ◽

Small Animal ◽

Preliminary Evaluation ◽

Locomotor Function ◽

Surgical Model ◽

Gestation Age ◽

Near Term

Introduction. Translational models of myelomeningocele (MMC) are needed to test novel in utero interventions. An ideal animal model for MMC has locomotor function at birth and is low cost enough to allow for high throughput. The rat MMC model is limited by immature locomotor function at birth. The ovine MMC model is a costly surgical model. Guinea pigs are uniquely suited for an MMC model being a small animal model with locomotor function at birth. We aimed to develop a retinoic acid (RA) model of MMC in the guinea pig and to evaluate if pregnant guinea pigs could tolerate uterine manipulation. Methods. Time-mated Dunkin Hartley guinea pig dams were dosed with 60 mg/kg of RA between gestation age (GA) 12 and 15 days in the development of an RA model. Fetuses were grossly evaluated for MMC lesions at Cesarean section after GA 31 days. Evaluation of the ability of pregnant guinea pig dams to tolerate uterine surgical intervention was performed by hysterotomy of a separated group of time-mated guinea pigs at GA 45, 50, and 55. Results. Forty-two pregnant guinea pigs were dosed with RA, with a total of 189 fetuses. The fetal demise rate was 38% ( n = 71 ). A total of 118 fetuses were viable, 83% ( n = 98 ) were normal fetuses, 8% ( n = 10 ) had a neural tube defect, and 8% ( n = 10 ) had a hematoma or other anomalies. No fetuses developed an MMC defect. None of the fetuses that underwent hysterotomy survived to term. Conclusion. RA dosed at 60 mg/kg in guinea pigs between GA 12 and 15 did not result in MMC. Dunkin Hartley guinea pigs did not tolerate a hysterotomy near term in our surgical model. Further work is needed to determine if MMC can be induced in guinea pigs with alternate RA dosing.

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