Ferret animal model of severe fever with thrombocytopenia syndrome phlebovirus for human lethal infection and pathogenesis

A novel tick-borne bunyavirus (Huaiyangshan virus, HYSV), which causes haemorrhagic fever-like disease, has recently been reported in China. So far no animal experiments have been performed to study its pathogenesis. Towards developing an animal model for HYSV fever, newborn and adult mice and rats and golden hamsters were inoculated intracerebrally or intraperitoneally with HYSV. Newborn rats and newborn mice, especially Kunming (KM) mice, appeared highly susceptible. Remarkably, the KM mice that died of the HYSV infection developed large necrotic areas in the liver, while no obvious pathological changes were observed within the other organs. PCR and immunohistochemical analyses of the post-mortem material detected both HYSV antigen and RNA in almost all organs, indicating a systemic infection. Our data demonstrate that HYSV can cause a lethal infection of both newborn mice and newborn rats with apparent pathological damage of the liver. This animal model may help to understand the pathogenesis of the HYSV infection in humans.

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An Alternative Animal Model for Comparison of Treatments for Cryptococcal Meningitis

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.43.2.413 ◽

1999 ◽

Vol 43 (2) ◽

pp. 413-414 ◽

Cited By ~ 8

Author(s):

Laura K. Najvar ◽

Rosie Bocanegra ◽

John R. Graybill

Keyword(s):

Central Nervous System ◽

Animal Model ◽

Nervous System ◽

Antifungal Activity ◽

Brain Tissue ◽

Cryptococcal Meningitis ◽

Central Nervous System Infection ◽

Lethal Infection ◽

Weanling Rats ◽

Acceptable Model

ABSTRACT Weanling outbred rats were infected with Cryptococcus neoformans by direct percranial puncture and inoculation into the cranium. A lethal infection ensued. Treatment with LY295337, a depsipeptide with antifungal activity, was effective in prolonging survival and reducing fungal counts in brain tissue. Weanling rats are an acceptable model for the study of central nervous system infection with C. neoformans.

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Effect of mutS and recDMutations on Salmonella Virulence

Infection and Immunity ◽

10.1128/iai.67.11.6168-6172.1999 ◽

1999 ◽

Vol 67 (11) ◽

pp. 6168-6172 ◽

Cited By ~ 21

Author(s):

Thomas C. Zahrt ◽

Nancy Buchmeier ◽

Stanley Maloy

Keyword(s):

Animal Model ◽

Salmonella Typhimurium ◽

Dna Sequences ◽

Time Course ◽

Lethal Dose ◽

Lethal Infection ◽

Salmonella Virulence ◽

Time Required ◽

Derivatives Of ◽

Synthetic Phenotype

ABSTRACT Hybrid derivatives of closely related bacteria may be used to dissect strain-specific functions that contribute to virulence within a host. However, mismatches between DNA sequences are a potent barrier to recombination. Recipients with mutS and recDmutations overcome this barrier, allowing construction of genetic hybrids. To determine whether Salmonella hybrids constructed in a mutS recD host can be used to study virulence, we assayed the effect of mutS andrecD mutations on the virulence of Salmonella typhimurium 14028s in mice. Mutants defective in eithermutS or recD do not affect the time course or the 50% lethal dose (LD50) of the infection. In contrast, the inactivation of both mutS and recD results in a synthetic phenotype which substantially increases the time required to cause a lethal infection without changing the LD50. This phenotype results from an inability ofmutS recD double mutants to rapidly adapt to purine-limiting conditions present within macrophages. Although the disease progression is slower, S. typhimurium mutS recDmutants retain the ability to cause lethal infections, and, thus, hybrids constructed in mutS recD hosts may permit the analysis of virulence factors in a surrogate animal model.

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Passive transfer of poly-(1-6)-beta-glucotriosyl-(1-3)-beta-glucopyranose glucan protection against lethal infection in an animal model of intra-abdominal sepsis.

Infection and Immunity ◽

10.1128/iai.64.6.2201-2205.1996 ◽

1996 ◽

Vol 64 (6) ◽

pp. 2201-2205 ◽

Cited By ~ 28

Author(s):

R L Cisneros ◽

F C Gibson ◽

A O Tzianabos

Keyword(s):

Animal Model ◽

Abdominal Sepsis ◽

Passive Transfer ◽

Lethal Infection

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A Lethal Murine Infection Model for Dengue Virus 3 in AG129 Mice Deficient in Type I and II Interferon Receptors Leads to Systemic Disease

Journal of Virology ◽

10.1128/jvi.01320-14 ◽

2014 ◽

Vol 89 (2) ◽

pp. 1254-1266 ◽

Cited By ~ 45

Author(s):

Vanessa V. Sarathy ◽

Mellodee White ◽

Li Li ◽

Summer R. Gorder ◽

Richard B. Pyles ◽

...

Keyword(s):

Animal Model ◽

Systemic Disease ◽

Acute Illness ◽

Human Isolate ◽

The Other ◽

Infection Model ◽

Type I ◽

Denv Serotypes ◽

Lethal Infection ◽

Immunocompromised Mice

ABSTRACTThe mosquito-borne disease dengue (DEN) is caused by four serologically and genetically related viruses, termed DENV-1 to DENV-4. Infection with one DENV usually leads to acute illness and results in lifelong homotypic immunity, but individuals remain susceptible to infection by the other three DENVs. The lack of a small-animal model that mimics systemic DEN disease without neurovirulence has been an obstacle, but DENV-2 models that resemble human disease have been recently developed in AG129 mice (deficient in interferon alpha/beta and interferon gamma receptor signaling). However, comparable DENV-1, -3, and -4 models have not been developed. We utilized a non-mouse-adapted DENV-3 Thai human isolate to develop a lethal infection model in AG129 mice. Intraperitoneal inoculation of six to eight-week-old animals with strain C0360/94 led to rapid, fatal disease. Lethal C0360/94 infection resulted in physical signs of illness, high viral loads in the spleen, liver, and large intestine, histological changes in the liver and spleen tissues, and increased serum cytokine levels. Importantly, the animals developed vascular leakage, thrombocytopenia, and leukopenia. Overall, we have developed a lethal DENV-3 murine infection model, with no evidence of neurotropic disease based on a non-mouse-adapted human isolate, which can be used to investigate DEN pathogenesis and to evaluate candidate vaccines and antivirals. This suggests that murine models utilizing non-mouse-adapted isolates can be obtained for all four DENVs.IMPORTANCEDengue (DEN) is a mosquito-borne disease caused by four DENV serotypes (DENV-1, -2, -3, and -4) that have no treatments or vaccines. Primary infection with one DENV usually leads to acute illness followed by lifelong homotypic immunity, but susceptibility to infection by the other three DENVs remains. Therefore, a vaccine needs to protect from all four DENVs simultaneously. To date a suitable animal model to mimic systemic human illness exists only for DENV-2 in immunocompromised mice using passaged viruses; however, models are still needed for the remaining serotypes. This study describes establishment of a lethal systemic DENV-3 infection model with a human isolate in immunocompromised mice and is the first report of lethal infection by a nonadapted clinical DENV isolate without evidence of neurological disease. Our DENV-3 model provides a relevant platform to test DEN vaccines and antivirals.

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Sex Matters: Male Hamsters Are More Susceptible to Lethal Infection with Lower Doses of Pathogenic Leptospira than Female Hamsters

Infection and Immunity ◽

10.1128/iai.00369-18 ◽

2018 ◽

Vol 86 (10) ◽

Cited By ~ 4

Author(s):

Charles K. Gomes ◽

Mariana Guedes ◽

Hari-Hara Potula ◽

Odir A. Dellagostin ◽

Maria Gomes-Solecki

Keyword(s):

Animal Model ◽

Leptospira Interrogans ◽

Pathogenic Leptospira ◽

Male And Female ◽

Transcript Levels ◽

Content Type ◽

Human Leptospirosis ◽

Lethal Infection ◽

Severe Leptospirosis ◽

Higher Doses

ABSTRACT A somewhat contradictory published body of evidence suggests that sex impacts severity outcomes of human leptospirosis. In this study, we used an acute animal model of disease to analyze leptospirosis in male and female hamsters infected side by side with low but increasing doses of Leptospira interrogans serovar Copenhageni. We found that male hamsters were considerably more susceptible to leptospirosis, given that only 6.3% survived infection, whereas 68.7% of the females survived the same infection doses. In contrast to the females, male hamsters had high burdens of L. interrogans in kidney and high histopathological scores after exposure to low infection doses (∼103 bacteria). In hamsters infected with higher doses of L. interrogans (∼104 bacteria), differences in pathogen burdens as well as cytokine and fibrosis transcript levels in kidney were not distinct between sexes. Our results indicate that male hamsters infected with L. interrogans are more susceptible to severe leptospirosis after exposure to lower infectious doses than females.

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Questionable Efficacy of Therapeutic Antibodies in the Treatment of Anthrax

mSphere ◽

10.1128/msphere.00282-19 ◽

2019 ◽

Vol 4 (3) ◽

Cited By ~ 5

Author(s):

Jean-Nicolas Tournier ◽

Clémence Rougeaux ◽

Fabrice V. Biot ◽

Pierre L. Goossens

Keyword(s):

Animal Model ◽

Protective Antigen ◽

Inductive Reasoning ◽

Conclusive Evidence ◽

Therapeutic Antibodies ◽

Rational Basis ◽

Positive Bacterium ◽

Content Type ◽

Lethal Infection ◽

Binding Component

ABSTRACTInhalational anthrax caused byBacillus anthracis, a spore-forming Gram-positive bacterium, is a highly lethal infection. Antibodies targeting the protective antigen (PA) binding component of the toxins have recently been authorized as an adjunct to antibiotics, although no conclusive evidence demonstrates that anthrax antitoxin therapy has any significant benefit. We discuss here the rational basis of anti-PA development regarding the pathogenesis of the disease. We argue that inductive reasoning may induce therapeutic bias. We identified anthrax animal model analysis as another bias. Further studies are needed to assess the benefit of anti-PA antibodies in the treatment of inhalational anthrax, while a clearer consensus should be established around what evidence should be proven in an anthrax model.

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Ultrastructural investigation of spontaneous pituitary gonadotroph cell adenomas in aging Sprague-Dawley rats

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100077086 ◽

1983 ◽

Vol 41 ◽

pp. 702-703

Author(s):

D. J. McComb ◽

J. Beri ◽

F. Zak ◽

K. Kovacs

Keyword(s):

Electron Microscopy ◽

Animal Model ◽

Epoxy Resin ◽

Immunoelectron Microscopy ◽

Tumor Type ◽

Gonadal Function ◽

Sprague Dawley ◽

Male And Female ◽

Reticulin Fibers ◽

Sprague Dawley Rats

Gonadotroph cell adenomas of the pituitary are infrequent in human patients and are not invariably associated with altered gonadal function. To date, no animal model of this tumor type exists. Herein, we describe spontaneous gonadotroph cell adenomas in old male and female Sprague-Dawley rats by histology, immunocytology and electron microscopy.The material consisted of the pituitaries of 27 male and 38 female Sprague Dawley rats, all 26 months of age or older, removed at routine autopsy. Sections of formal in-fixed, paraffin-embedded tissue were stained with hematoxylin-phloxine-saffron (HPS), the PAS method and the Gordon-Sweet technique for the demonstration of reticulin fibers. For immunostaining, sections were exposed to anti-rat β-LH, anti-ratβ-TSH, anti-rat PRL, anti-rat GH and anti-rat ACTH 1-39. For electron microscopy, tissue was fixed in 2.5% glutaraldehyde, postfixed in 1% OsO4 and embedded in epoxy-resin. Tissue fixed in 10% formalin, embedded in epoxy resin without osmification, was used for immunoelectron microscopy.

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Electron Microscopic Detection and Characterization of Nonhuman Primate Enteric Viruses

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100054145 ◽

1982 ◽

Vol 40 ◽

pp. 306-307

Author(s):

G. C. Smith ◽

R. L. Heberling ◽

S. S. Kalter

Keyword(s):

Electron Microscopy ◽

Animal Model ◽

Nonhuman Primate ◽

Clinical Condition ◽

Intestinal Tract ◽

Enteric Viruses ◽

Electron Microscopic ◽

Microscopic Detection

A number of viral agents are recognized as and suspected of causing the clinical condition “gastroenteritis.” In our attempts to establish an animal model for studies of this entity, we have been examining the nonhuman primate to ascertain what viruses may be found in the intestinal tract of “normal” animals as well as animals with diarrhea. Several virus types including coronavirus, adenovirus, herpesvirus, and picornavirus (Table I) were detected in our colony; however, rotavirus, astrovirus, and calicivirus have not yet been observed. Fecal specimens were prepared for electron microscopy by procedures reported previously.

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Neurofilaments and Paired Helical Filaments

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100120357 ◽

1985 ◽

Vol 43 ◽

pp. 740-743

Author(s):

J. Metuzals

Keyword(s):

Animal Model ◽

Posttranslational Modifications ◽

Posttranslational Modification ◽

Giant Axon ◽

Paired Helical Filaments ◽

Squid Giant Axon ◽

In Vitro Experiments ◽

Thin Sections ◽

Structural Relationships

It has been demonstrated that the neurofibrillary tangles in biopsies of Alzheimer patients, composed of typical paired helical filaments (PHF), consist also of typical neurofilaments (NF) and 15nm wide filaments. Close structural relationships, and even continuity between NF and PHF, have been observed. In this paper, such relationships are investigated from the standpoint that the PHF are formed through posttranslational modifications of NF. To investigate the validity of the posttranslational modification hypothesis of PHF formation, we have identified in thin sections from frontal lobe biopsies of Alzheimer patients all existing conformations of NF and PHF and ordered these conformations in a hypothetical sequence. However, only experiments with animal model preparations will prove or disprove the validity of the interpretations of static structural observations made on patients. For this purpose, the results of in vitro experiments with the squid giant axon preparations are compared with those obtained from human patients. This approach is essential in discovering etiological factors of Alzheimer's disease and its early diagnosis.

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