Induction of protective immunity in a syrian hamster model against a cytopathogenic strain of andes virus

We investigated whether chloroquine can prevent hantavirus infection and disease in vitro and in vivo, using the Hantaan virus newborn C57BL/6 mice model and the Syrian hamster model for Andes virus. In vitro antiviral experiments were performed using Vero E6 cells, and Old World and New World hantavirus species. Hantavirus RNA was detected using quantitative RT-PCR. For all hantavirus species tested, results indicate that the IC50 of chloroquine (mean 10.2 ± 1.43 μM) is significantly lower than the CC50 (mean 260 ± 2.52 μM) yielding an overall selectivity index of 25.5. We also investigated the potential of chloroquine to prevent death in newborn mice after Hantaan virus infection and its antiviral effect in the hantavirus Syrian hamster model. For this purpose, C57Bl/6 mother mice were treated subcutaneously with daily doses of chloroquine. Subsequently, 1-day-old suckling mice were inoculated intracerebrally with 5 x 102 Hantaan virus particles. In litters of untreated mothers, none of the pups survived challenge. The highest survival rate (72.7% of pups) was found when mother mice were administered a concentration of 10 mg/kg chloroquine. Survival rates declined in a dose-dependent manner, with 47.6% survival when treated with 5 mg/kg chloroquine, and 4.2% when treated with 1 mg/kg chloroquine. Assessing the antiviral therapeutic and prophylactic effect of chloroquine in the Syrian hamster model was done using two different administration routes (intraperitoneally and subcutaneously using an osmotic pump system). Evaluating the prophylactic effect, a delay in onset of disease was noted and for the osmotic pump, 60% survival was observed. Our results show that chloroquine can be highly effective against Hantaan virus infection in newborn mice and against Andes virus in Syrian hamsters.

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Andes Virus Recognition of Human and Syrian Hamster β3 Integrins Is Determined by an L33P Substitution in the PSI Domain

Journal of Virology ◽

10.1128/jvi.01013-09 ◽

2009 ◽

Vol 84 (1) ◽

pp. 352-360 ◽

Cited By ~ 34

Author(s):

Valery S. Matthys ◽

Elena E. Gorbunova ◽

Irina N. Gavrilovskaya ◽

Erich R. Mackow

Keyword(s):

Endothelial Cells ◽

Syrian Hamster ◽

Hantavirus Infection ◽

Human Endothelial Cells ◽

Hamster Model ◽

High Affinity ◽

Naturally Occurring ◽

Andes Virus ◽

Integrin Ligand

ABSTRACT Andes virus (ANDV) causes a fatal hantavirus pulmonary syndrome (HPS) in humans and Syrian hamsters. Human αvβ3 integrins are receptors for several pathogenic hantaviruses, and the function of αvβ3 integrins on endothelial cells suggests a role for αvβ3 in hantavirus directed vascular permeability. We determined here that ANDV infection of human endothelial cells or Syrian hamster-derived BHK-21 cells was selectively inhibited by the high-affinity αvβ3 integrin ligand vitronectin and by antibodies to αvβ3 integrins. Further, antibodies to the β3 integrin PSI domain, as well as PSI domain polypeptides derived from human and Syrian hamster β3 subunits, but not murine or bovine β3, inhibited ANDV infection of both BHK-21 and human endothelial cells. These findings suggest that ANDV interacts with β3 subunits through PSI domain residues conserved in both Syrian hamster and human β3 integrins. Sequencing the Syrian hamster β3 integrin PSI domain revealed eight differences between Syrian hamster and human β3 integrins. Analysis of residues within the PSI domains of human, Syrian hamster, murine, and bovine β3 integrins identified unique proline substitutions at residues 32 and 33 of murine and bovine PSI domains that could determine ANDV recognition. Mutagenizing the human β3 PSI domain to contain the L33P substitution present in bovine β3 integrin abolished the ability of the PSI domain to inhibit ANDV infectivity. Conversely, mutagenizing either the bovine PSI domain, P33L, or the murine PSI domain, S32P, to the residue present human β3 permitted PSI mutants to inhibit ANDV infection. Similarly, CHO cells transfected with the full-length bovine β3 integrin containing the P33L mutation permitted infection by ANDV. These findings indicate that human and Syrian hamster αvβ3 integrins are key receptors for ANDV and that specific residues within the β3 integrin PSI domain are required for ANDV infection. Since L33P is a naturally occurring human β3 polymorphism, these findings further suggest the importance of specific β3 integrin residues in hantavirus infection. These findings rationalize determining the role of β3 integrins in hantavirus pathogenesis in the Syrian hamster model.

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Effect of intestinal alkalinization on irinotecan (CPT-11)-induced diarrhea in the golden Syrian hamster model

Gastroenterology ◽

10.1016/s0016-5085(01)83047-x ◽

2001 ◽

Vol 120 (5) ◽

pp. A613-A613

Author(s):

T IKEGAMI ◽

P LATHAM ◽

K KOBAYASHI ◽

K ARIMORI ◽

B BOUSCAREL

Keyword(s):

Syrian Hamster ◽

Hamster Model ◽

Golden Syrian Hamster

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Immune Serum Produced by DNA Vaccination Protects Hamsters against Lethal Respiratory Challenge with Andes Virus

Journal of Virology ◽

10.1128/jvi.01822-07 ◽

2007 ◽

Vol 82 (3) ◽

pp. 1332-1338 ◽

Cited By ~ 51

Author(s):

Jay W. Hooper ◽

Anthony M. Ferro ◽

Victoria Wahl-Jensen

Keyword(s):

Dna Vaccine ◽

Neutralizing Antibodies ◽

Lethal Dose ◽

Case Fatality ◽

Immune Serum ◽

Human Infection ◽

M Gene ◽

Hamster Model ◽

Highly Pathogenic ◽

Andes Virus

ABSTRACT Hantavirus pulmonary syndrome (HPS) is a highly pathogenic disease (40% case fatality rate) carried by rodents chronically infected with certain viruses within the genus Hantavirus of the family Bunyaviridae. The primary mode of transmission to humans is thought to be inhalation of excreta from infected rodents; however, ingestion of contaminated material and rodent bites are also possible modes of transmission. Person-to-person transmission of HPS caused by one species of hantavirus, Andes virus (ANDV), has been reported. Previously, we reported that ANDV injected intramuscularly causes a disease in Syrian hamsters that closely resembles HPS in humans. Here we tested whether ANDV was lethal in hamsters when it was administered by routes that more accurately model the most common routes of human infection, i.e., the subcutaneous, intranasal, and intragastric routes. We discovered that ANDV was lethal by all three routes. Remarkably, even at very low doses, ANDV was highly pathogenic when it was introduced by the mucosal routes (50% lethal dose [LD50], ∼100 PFU). We performed passive transfer experiments to test the capacity of neutralizing antibodies to protect against lethal intranasal challenge. The neutralizing antibodies used in these experiments were produced in rabbits vaccinated by electroporation with a previously described ANDV M gene-based DNA vaccine, pWRG/AND-M. Hamsters that were administered immune serum on days −1 and +5 relative to challenge were protected against intranasal challenge (21 LD50). These findings demonstrate the utility of using the ANDV hamster model to study transmission across mucosal barriers and provide evidence that neutralizing antibodies produced by DNA vaccine technology can be used to protect against challenge by the respiratory route.

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Pre-existing Immunity and Passive Immunity to Adenovirus 5 Prevents Toxicity Caused by an Oncolytic Adenovirus Vector in the Syrian Hamster Model

Molecular Therapy ◽

10.1038/mt.2009.156 ◽

2009 ◽

Vol 17 (10) ◽

pp. 1724-1732 ◽

Cited By ~ 23

Author(s):

Debanjan Dhar ◽

Jacqueline F Spencer ◽

Karoly Toth ◽

William SM Wold

Keyword(s):

Syrian Hamster ◽

Adenovirus Vector ◽

Oncolytic Adenovirus ◽

Passive Immunity ◽

Hamster Model ◽

Adenovirus 5

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The SARS-CoV-2 Omicron (B.1.1.529) variant exhibits altered pathogenicity, transmissibility, and fitness in the golden Syrian hamster model

10.1101/2022.01.12.476031 ◽

2022 ◽

Author(s):

Shuofeng Yuan ◽

Zi-Wei Ye ◽

Ronghui Liang ◽

Kaiming Tang ◽

Anna Jinxia Zhang ◽

...

Keyword(s):

Syrian Hamster ◽

Neutralizing Antibodies ◽

Selection Pressure ◽

Immune Selection ◽

Hamster Model ◽

Golden Syrian Hamster ◽

New Variant ◽

Contact Transmission

The newly emerging SARS-CoV-2 Omicron (B.1.1.529) variant first identified in South Africa in November 2021 is characterized by an unusual number of amino acid mutations in its spike that renders existing vaccines and therapeutic monoclonal antibodies dramatically less effective. The in vivo pathogenicity, transmissibility, and fitness of this new Variant of Concerns are unknown. We investigated these virological attributes of the Omicron variant in comparison with those of the currently dominant Delta (B.1.617.2) variant in the golden Syrian hamster COVID-19 model. Omicron-infected hamsters developed significantly less body weight losses, clinical scores, respiratory tract viral burdens, cytokine/chemokine dysregulation, and tissue damages than Delta-infected hamsters. The Omicron and Delta variant were both highly transmissible (100% vs 100%) via contact transmission. Importantly, the Omicron variant consistently demonstrated about 10-20% higher transmissibility than the already-highly transmissible Delta variant in repeated non-contact transmission studies (overall: 30/36 vs 24/36, 83.3% vs 66.7%). The Delta variant displayed higher fitness advantage than the Omicron variant without selection pressure in both in vitro and in vivo competition models. However, this scenario drastically changed once immune selection pressure with neutralizing antibodies active against the Delta variant but poorly active against the Omicron variant were introduced, with the Omicron variant significantly outcompeting the Delta variant. Taken together, our findings demonstrated that while the Omicron variant is less pathogenic than the Delta variant, it is highly transmissible and can outcompete the Delta variant under immune selection pressure. Next-generation vaccines and antivirals effective against this new VOC are urgently needed.

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Vasculitis and Neutrophil Extracellular Traps in Lungs of Golden Syrian Hamsters With SARS-CoV-2

Frontiers in Immunology ◽

10.3389/fimmu.2021.640842 ◽

2021 ◽

Vol 12 ◽

Author(s):

Kathrin Becker ◽

Georg Beythien ◽

Nicole de Buhr ◽

Stephanie Stanelle-Bertram ◽

Berfin Tuku ◽

...

Keyword(s):

Animal Models ◽

Syrian Hamster ◽

Neutrophil Extracellular Traps ◽

Virus Antigen ◽

Endothelial Damage ◽

Vascular Lesions ◽

Hamster Model ◽

Golden Syrian Hamster ◽

Pulmonary Lesions ◽

Extracellular Traps

Neutrophil extracellular traps (NETs) have been identified as one pathogenetic trigger in severe COVID-19 cases and therefore well-described animal models to understand the influence of NETs in COVID-19 pathogenesis are needed. SARS-CoV-2 infection causes infection and interstitial pneumonia of varying severity in humans and COVID-19 models. Pulmonary as well as peripheral vascular lesions represent a severe, sometimes fatal, disease complication of unknown pathogenesis in COVID-19 patients. Furthermore, neutrophil extracellular traps (NETs), which are known to contribute to vessel inflammation or endothelial damage, have also been shown as potential driver of COVID-19 in humans. Though most studies in animal models describe the pulmonary lesions characterized by interstitial inflammation, type II pneumocyte hyperplasia, edema, fibrin formation and infiltration of macrophages and neutrophils, detailed pathological description of vascular lesions or NETs in COVID-19 animal models are lacking so far. Here we report different types of pulmonary vascular lesions in the golden Syrian hamster model of COVID-19. Vascular lesions included endothelialitis and vasculitis at 3 and 6 days post infection (dpi), and were almost nearly resolved at 14 dpi. Importantly, virus antigen was present in pulmonary lesions, but lacking in vascular alterations. In good correlation to these data, NETs were detected in the lungs of infected animals at 3 and 6 dpi. Hence, the Syrian hamster seems to represent a useful model to further investigate the role of vascular lesions and NETs in COVID-19 pathogenesis.

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Drug development against human adenoviruses and its advancement by Syrian hamster models

FEMS Microbiology Reviews ◽

10.1093/femsre/fuz008 ◽

2019 ◽

Vol 43 (4) ◽

pp. 380-388 ◽

Cited By ~ 14

Author(s):

William S M Wold ◽

Ann E Tollefson ◽

Baoling Ying ◽

Jacqueline F Spencer ◽

Karoly Toth

Keyword(s):

Syrian Hamster ◽

In Vivo Studies ◽

Current Status ◽

Solid Organ ◽

Cell Transplant ◽

Hamster Model ◽

Hematopoietic Stem ◽

Adenoviral Infection ◽

Human Adenoviruses

ABSTRACTThe symptoms of human adenovirus infections are generally mild and self-limiting. However, these infections have been gaining importance in recent years because of a growing number of immunocompromised patients. Solid organ and hematopoietic stem cell transplant patients are subjected to severe immunosuppressive regimes and cannot efficaciously eliminate virus infections. In these patients, adenovirus infections can develop into deadly multi-organ disseminated disease. Presently, in the absence of approved therapies, physicians rely on drugs developed for other purposes to treat adenovirus infections. As there is a need for anti-adenoviral therapies, researchers have been developing new agents and repurposing existing ones to treat adenovirus infections. There are several small molecule drugs that are being tested for their efficacy against human adenoviruses; some of these have reached clinical trials, while others are still in the preclinical phase. Besides these compounds, research on immunotherapy against adenoviral infection has made significant progress, promising another modality for treatment. The availability of an animal model confirmed the activity of some drugs already in clinical use while proving that others are inactive. This led to the identification of several lead compounds that await further development. In the present article, we review the current status of anti-adenoviral therapies and their advancement by in vivo studies in the Syrian hamster model.

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