scholarly journals Characterization of an N-Terminal Non-Core Domain of RAG1 Gene Disrupted Syrian Hamster Model Generated by CRISPR Cas9

Viruses ◽  
2018 ◽  
Vol 10 (5) ◽  
pp. 243 ◽  
Author(s):  
Jinxin Miao ◽  
Baoling Ying ◽  
Rong Li ◽  
Ann Tollefson ◽  
Jacqueline Spencer ◽  
...  
2020 ◽  
Vol 13 (8) ◽  
pp. dmm044602 ◽  
Author(s):  
Rong Li ◽  
Baoling Ying ◽  
Yanan Liu ◽  
Jacqueline F. Spencer ◽  
Jinxin Miao ◽  
...  

ABSTRACTModel animals are indispensable for the study of human diseases, and in general, of complex biological processes. The Syrian hamster is an important model animal for infectious diseases, behavioral science and metabolic science, for which more experimental tools are becoming available. Here, we describe the generation and characterization of an interleukin-2 receptor subunit gamma (Il2rg) knockout (KO) Syrian hamster strain. In humans, mutations in IL2RG can result in a total failure of T and natural killer (NK) lymphocyte development and nonfunctional B lymphocytes (X-linked severe combined immunodeficiency; XSCID). Therefore, we sought to develop a non-murine model to study XSCID and the infectious diseases associated with IL2RG deficiency. We demonstrated that the Il2rg KO hamsters have a lymphoid compartment that is greatly reduced in size and diversity, and is impaired in function. As a result of the defective adaptive immune response, Il2rg KO hamsters developed a more severe human adenovirus infection and cleared virus less efficiently than immune competent wild-type hamsters. Because of this enhanced virus replication, Il2rg KO hamsters developed more severe adenovirus-induced liver pathology than wild-type hamsters. This novel hamster strain will provide researchers with a new tool to investigate human XSCID and its related infections.


2001 ◽  
Vol 120 (5) ◽  
pp. A613-A613
Author(s):  
T IKEGAMI ◽  
P LATHAM ◽  
K KOBAYASHI ◽  
K ARIMORI ◽  
B BOUSCAREL

2022 ◽  
Author(s):  
Shuofeng Yuan ◽  
Zi-Wei Ye ◽  
Ronghui Liang ◽  
Kaiming Tang ◽  
Anna Jinxia Zhang ◽  
...  

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.


2021 ◽  
Vol 12 ◽  
Author(s):  
Kathrin Becker ◽  
Georg Beythien ◽  
Nicole de Buhr ◽  
Stephanie Stanelle-Bertram ◽  
Berfin Tuku ◽  
...  

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.


2019 ◽  
Vol 43 (4) ◽  
pp. 380-388 ◽  
Author(s):  
William S M Wold ◽  
Ann E Tollefson ◽  
Baoling Ying ◽  
Jacqueline F Spencer ◽  
Karoly Toth

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.


2019 ◽  
Vol 222 (2) ◽  
pp. 340-340
Author(s):  
Stephen R Welch ◽  
Florine E M Scholte ◽  
Jessica R Harmon ◽  
Joann D Coleman-Mccray ◽  
Michael K Lo ◽  
...  

1977 ◽  
Vol 52 (2) ◽  
pp. 133-147
Author(s):  
YUKIAKI KURODA ◽  
AKIKO YOKOIYAMA ◽  
TSUNEO KADA

2016 ◽  
Vol 6 (4) ◽  
pp. 454-462 ◽  
Author(s):  
G. A. Maksimova ◽  
M. Y. Pakharukova ◽  
E. V. Kashina ◽  
N. A. Zhukova ◽  
M. N. Lvova ◽  
...  

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