The Experts below are selected from a list of 270 Experts worldwide ranked by ideXlab platform
William S. M. Wold - One of the best experts on this subject based on the ideXlab platform.
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16 stat2 knockout syrian Hamsters support enhanced replication and pathogenicity of human adenovirus type 5 revealing an important role of type i interferon response in viral control
Molecular Therapy, 2016Co-Authors: Karoly Toth, Jacqueline F. Spencer, Ann E. Tollefson, Baoling Ying, Zhongde Wang, John E Sagartz, Ilkeun Kong, William S. M. WoldAbstract:Oncolytic vectors based on human species C adenovirus type 5 (Ad5) are being developed for cancer gene therapy. Studies on wild-type Ad5 in animal models are likely to provide important insights into the behavior of these vectors in patients. The most frequently used permissive immunocompetent animal model for Ad5 infection is the Syrian Hamster. Ad5 (and Ad6) replicates in these animals and causes pathology that is similar to that seen with humans. Here, we report findings with a new Syrian Hamster strain in which the STAT2 gene was functionally knocked out (KO) by site-specific CRISPR/Cas9-mediated gene targeting. STAT2 is a critical element of the Type I and Type III interferon signal transduction pathways. STAT2 KO Hamsters infected intravenously with Ad5 demonstrated an accentuated pathology compared to the wild-type control animals, and the virus load in the organs (liver, lung, kidney) of STAT2 KO animals was 100- to 1000-fold higher than that in wild-type Hamsters. We show that the Type I interferon pathway is disrupted in these Hamsters, inasmuch as the interferon response genes PKR, OAS, and Mx2 were induced by Ad5 in the liver of wild-type but not STAT2 KO Hamsters, revealing a critical role of interferon-stimulated genes in controlling Ad5 infection. Notably, the adaptive immune response to Ad5 is not adversely affected in STAT2 KO Hamsters, and surviving Hamsters cleared the infection by 7 to 10 days post challenge. In fact, anti-Ad5 neutralizing antibodies were 10-fold higher at 7 days postinfection in the STAT2 KO Hamsters than in wild-type Hamsters. T cell infiltration into the liver was similar at 3 and 7 days in the STAT2 KO and wild-type Hamsters. Treatment of Ad5-infected STAT2 KO Hamsters with high dose cyclophosphamide resulted in markedly increased mortality, pathogenesis, and virus replication in the liver (~1011 TCID50/g liver) at 10 days postinfection, likely because the adaptive immune response as well as other aspects of the innate response were abolished. This is the first study to report findings with a genetically modified Syrian Hamster infected with human adenovirus. Further, this is the first study to show that the Type I interferon pathway plays a role in inhibiting Ad5 replication in a permissive animal model. This conclusion is in accord with a previous study in which we showed using a custom microarray platform that there is a robust up-regulation of genes involved in the innate immune response (e.g. OAS, PKR, IFN-inducible protein 10) in the liver at 18 h post-intravenous infection of wild-type Syrian Hamsters with Ad5 (Ying, B. et al., Virology 485, 305, 2015). Besides providing an insight into adenovirus infection in humans, our results underscore the usefulness of Syrian Hamsters as a permissive model for the study of species C human adenovirus and adenovirus-based vectors. In future studies, STAT2 KO Hamsters bearing tumors could be used to explore the role of Type I and Type III interferon signaling on the efficacy of oncolytic adenovirus vectors.
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stat2 knockout syrian Hamsters support enhanced replication and pathogenicity of human adenovirus revealing an important role of type i interferon response in viral control
PLOS Pathogens, 2015Co-Authors: Karoly Toth, Jacqueline F. Spencer, Ann E. Tollefson, Baoling Ying, Zhongde Wang, John E Sagartz, Ilkeun Kong, William S. M. WoldAbstract:Human adenoviruses have been studied extensively in cell culture and have been a model for studies in molecular, cellular, and medical biology. However, much less is known about adenovirus replication and pathogenesis in vivo in a permissive host because of the lack of an adequate animal model. Presently, the most frequently used permissive immunocompetent animal model for human adenovirus infection is the Syrian Hamster. Species C human adenoviruses replicate in these animals and cause pathology that is similar to that seen with humans. Here, we report findings with a new Syrian Hamster strain in which the STAT2 gene was functionally knocked out by site-specific gene targeting. Adenovirus-infected STAT2 knockout Hamsters demonstrated an accentuated pathology compared to the wild-type control animals, and the virus load in the organs of STAT2 knockout animals was 100- to 1000-fold higher than that in wild-type Hamsters. Notably, the adaptive immune response to adenovirus is not adversely affected in STAT2 knockout Hamsters, and surviving Hamsters cleared the infection by 7 to 10 days post challenge. We show that the Type I interferon pathway is disrupted in these Hamsters, revealing the critical role of interferon-stimulated genes in controlling adenovirus infection. This is the first study to report findings with a genetically modified Syrian Hamster infected with a virus. Further, this is the first study to show that the Type I interferon pathway plays a role in inhibiting human adenovirus replication in a permissive animal model. Besides providing an insight into adenovirus infection in humans, our results are also interesting from the perspective of the animal model: STAT2 knockout Syrian Hamster may also be an important animal model for studying other viral infections, including Ebola-, hanta-, and dengue viruses, where Type I interferon-mediated innate immunity prevents wild type Hamsters from being effectively infected to be used as animal models.
Jasper F W Chan - One of the best experts on this subject based on the ideXlab platform.
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surgical mask partition reduces the risk of noncontact transmission in a golden syrian Hamster model for coronavirus disease 2019 covid 19
Clinical Infectious Diseases, 2020Co-Authors: Jasper F W Chan, Shuofeng Yuan, Anna Jinxia Zhang, Vincent Kwokman Poon, Chris Chungsing Chan, Andrew C Y Lee, Zhimeng Fan, Ronghui LiangAbstract:Background Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is believed to be mostly transmitted by medium- to large-sized respiratory droplets, although airborne transmission may be possible in healthcare settings involving aerosol-generating procedures. Exposure to respiratory droplets can theoretically be reduced by surgical mask usage. However, there is a lack of experimental evidence supporting surgical mask usage for prevention of COVID-19. Methods We used a well-established golden Syrian Hamster SARS-CoV-2 model. We placed SARS-CoV-2-challenged index Hamsters and naive Hamsters into closed system units each comprising 2 different cages separated by a polyvinyl chloride air porous partition with unidirectional airflow within the isolator. The effect of a surgical mask partition placed between the cages was investigated. Besides clinical scoring, Hamster specimens were tested for viral load, histopathology, and viral nucleocapsid antigen expression. Results Noncontact transmission was found in 66.7% (10/15) of exposed naive Hamsters. Surgical mask partition for challenged index or naive Hamsters significantly reduced transmission to 25% (6/24, P = .018). Surgical mask partition for challenged index Hamsters significantly reduced transmission to only 16.7% (2/12, P = .019) of exposed naive Hamsters. Unlike the severe manifestations of challenged Hamsters, infected naive Hamsters had lower clinical scores, milder histopathological changes, and lower viral nucleocapsid antigen expression in respiratory tract tissues. Conclusions SARS-CoV-2 could be transmitted by respiratory droplets or airborne droplet nuclei which could be reduced by surgical mask partition in the Hamster model. This is the first in vivo experimental evidence to support the possible benefit of surgical mask in prevention of COVID-19 transmission, especially when masks were worn by infected individuals.
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simulation of the clinical and pathological manifestations of coronavirus disease 2019 covid 19 in golden syrian Hamster model implications for disease pathogenesis and transmissibility
Clinical Infectious Diseases, 2020Co-Authors: Jasper F W Chan, Shuofeng Yuan, Anna Jinxia Zhang, Vincent Kwokman Poon, Chris Chungsing Chan, Andrew C Y Lee, Wan Mui Chan, Zhimeng FanAbstract:Background A physiological small-animal model that resembles COVID-19 with low mortality is lacking. Methods Molecular docking on the binding between angiotensin-converting enzyme 2 (ACE2) of common laboratory mammals and the receptor-binding domain of the surface spike protein of SARS-CoV-2 suggested that the golden Syrian Hamster is an option. Virus challenge, contact transmission, and passive immunoprophylaxis studies were performed. Serial organ tissues and blood were harvested for histopathology, viral load and titer, chemokine/cytokine level, and neutralizing antibody titer. Results The Syrian Hamster could be consistently infected by SARS-CoV-2. Maximal clinical signs of rapid breathing, weight loss, histopathological changes from the initial exudative phase of diffuse alveolar damage with extensive apoptosis to the later proliferative phase of tissue repair, airway and intestinal involvement with viral nucleocapsid protein expression, high lung viral load, and spleen and lymphoid atrophy associated with marked chemokine/cytokine activation were observed within the first week of virus challenge. The mean lung virus titer was between 105 and 107 TCID50/g. Challenged index Hamsters consistently infected naive contact Hamsters housed within the same cages, resulting in similar pathology but not weight loss. All infected Hamsters recovered and developed mean serum neutralizing antibody titers ≥1:427 14 days postchallenge. Immunoprophylaxis with early convalescent serum achieved significant decrease in lung viral load but not in lung pathology. No consistent nonsynonymous adaptive mutation of the spike was found in viruses isolated from the infected Hamsters. Conclusions Besides satisfying Koch's postulates, this readily available Hamster model is an important tool for studying transmission, pathogenesis, treatment, and vaccination against SARS-CoV-2.
Karoly Toth - One of the best experts on this subject based on the ideXlab platform.
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16 stat2 knockout syrian Hamsters support enhanced replication and pathogenicity of human adenovirus type 5 revealing an important role of type i interferon response in viral control
Molecular Therapy, 2016Co-Authors: Karoly Toth, Jacqueline F. Spencer, Ann E. Tollefson, Baoling Ying, Zhongde Wang, John E Sagartz, Ilkeun Kong, William S. M. WoldAbstract:Oncolytic vectors based on human species C adenovirus type 5 (Ad5) are being developed for cancer gene therapy. Studies on wild-type Ad5 in animal models are likely to provide important insights into the behavior of these vectors in patients. The most frequently used permissive immunocompetent animal model for Ad5 infection is the Syrian Hamster. Ad5 (and Ad6) replicates in these animals and causes pathology that is similar to that seen with humans. Here, we report findings with a new Syrian Hamster strain in which the STAT2 gene was functionally knocked out (KO) by site-specific CRISPR/Cas9-mediated gene targeting. STAT2 is a critical element of the Type I and Type III interferon signal transduction pathways. STAT2 KO Hamsters infected intravenously with Ad5 demonstrated an accentuated pathology compared to the wild-type control animals, and the virus load in the organs (liver, lung, kidney) of STAT2 KO animals was 100- to 1000-fold higher than that in wild-type Hamsters. We show that the Type I interferon pathway is disrupted in these Hamsters, inasmuch as the interferon response genes PKR, OAS, and Mx2 were induced by Ad5 in the liver of wild-type but not STAT2 KO Hamsters, revealing a critical role of interferon-stimulated genes in controlling Ad5 infection. Notably, the adaptive immune response to Ad5 is not adversely affected in STAT2 KO Hamsters, and surviving Hamsters cleared the infection by 7 to 10 days post challenge. In fact, anti-Ad5 neutralizing antibodies were 10-fold higher at 7 days postinfection in the STAT2 KO Hamsters than in wild-type Hamsters. T cell infiltration into the liver was similar at 3 and 7 days in the STAT2 KO and wild-type Hamsters. Treatment of Ad5-infected STAT2 KO Hamsters with high dose cyclophosphamide resulted in markedly increased mortality, pathogenesis, and virus replication in the liver (~1011 TCID50/g liver) at 10 days postinfection, likely because the adaptive immune response as well as other aspects of the innate response were abolished. This is the first study to report findings with a genetically modified Syrian Hamster infected with human adenovirus. Further, this is the first study to show that the Type I interferon pathway plays a role in inhibiting Ad5 replication in a permissive animal model. This conclusion is in accord with a previous study in which we showed using a custom microarray platform that there is a robust up-regulation of genes involved in the innate immune response (e.g. OAS, PKR, IFN-inducible protein 10) in the liver at 18 h post-intravenous infection of wild-type Syrian Hamsters with Ad5 (Ying, B. et al., Virology 485, 305, 2015). Besides providing an insight into adenovirus infection in humans, our results underscore the usefulness of Syrian Hamsters as a permissive model for the study of species C human adenovirus and adenovirus-based vectors. In future studies, STAT2 KO Hamsters bearing tumors could be used to explore the role of Type I and Type III interferon signaling on the efficacy of oncolytic adenovirus vectors.
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stat2 knockout syrian Hamsters support enhanced replication and pathogenicity of human adenovirus revealing an important role of type i interferon response in viral control
PLOS Pathogens, 2015Co-Authors: Karoly Toth, Jacqueline F. Spencer, Ann E. Tollefson, Baoling Ying, Zhongde Wang, John E Sagartz, Ilkeun Kong, William S. M. WoldAbstract:Human adenoviruses have been studied extensively in cell culture and have been a model for studies in molecular, cellular, and medical biology. However, much less is known about adenovirus replication and pathogenesis in vivo in a permissive host because of the lack of an adequate animal model. Presently, the most frequently used permissive immunocompetent animal model for human adenovirus infection is the Syrian Hamster. Species C human adenoviruses replicate in these animals and cause pathology that is similar to that seen with humans. Here, we report findings with a new Syrian Hamster strain in which the STAT2 gene was functionally knocked out by site-specific gene targeting. Adenovirus-infected STAT2 knockout Hamsters demonstrated an accentuated pathology compared to the wild-type control animals, and the virus load in the organs of STAT2 knockout animals was 100- to 1000-fold higher than that in wild-type Hamsters. Notably, the adaptive immune response to adenovirus is not adversely affected in STAT2 knockout Hamsters, and surviving Hamsters cleared the infection by 7 to 10 days post challenge. We show that the Type I interferon pathway is disrupted in these Hamsters, revealing the critical role of interferon-stimulated genes in controlling adenovirus infection. This is the first study to report findings with a genetically modified Syrian Hamster infected with a virus. Further, this is the first study to show that the Type I interferon pathway plays a role in inhibiting human adenovirus replication in a permissive animal model. Besides providing an insight into adenovirus infection in humans, our results are also interesting from the perspective of the animal model: STAT2 knockout Syrian Hamster may also be an important animal model for studying other viral infections, including Ebola-, hanta-, and dengue viruses, where Type I interferon-mediated innate immunity prevents wild type Hamsters from being effectively infected to be used as animal models.
Norman F Ruby - One of the best experts on this subject based on the ideXlab platform.
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co infection of the siberian Hamster phodopus sungorus with a novel helicobacter sp and campylobacter sp
Journal of Medical Microbiology, 2015Co-Authors: Claude M. Nagamine, Zeli Shen, Richard Luong, Gabriel P. Mckeon, Norman F RubyAbstract:We report the isolation of a novel helicobacter isolated from the caecum of the Siberian Hamster (Phodopus sungorus). Sequence analysis showed 97 % sequence similarity to Helicobacter ganmani. In addition, we report the co-infection of these Siberian Hamsters with a Campylobacter sp. and a second Helicobacter sp. with 99 % sequence similarity to Helicobacter sp. flexispira taxon 8 (Helicobacter bilis), a species isolated previously from patients with bacteraemia. Gross necropsy and histopathology did not reveal any overt pathological lesions of the liver and gastrointestinal tract that could be attributed to the Helicobacter or Campylobacter spp. infections. This is the first helicobacter to be identified in the Siberian Hamster and the first report of co-infection of Helicobacter spp. and Campylobacter sp. in asymptomatic Siberian Hamsters.
Ilkeun Kong - One of the best experts on this subject based on the ideXlab platform.
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16 stat2 knockout syrian Hamsters support enhanced replication and pathogenicity of human adenovirus type 5 revealing an important role of type i interferon response in viral control
Molecular Therapy, 2016Co-Authors: Karoly Toth, Jacqueline F. Spencer, Ann E. Tollefson, Baoling Ying, Zhongde Wang, John E Sagartz, Ilkeun Kong, William S. M. WoldAbstract:Oncolytic vectors based on human species C adenovirus type 5 (Ad5) are being developed for cancer gene therapy. Studies on wild-type Ad5 in animal models are likely to provide important insights into the behavior of these vectors in patients. The most frequently used permissive immunocompetent animal model for Ad5 infection is the Syrian Hamster. Ad5 (and Ad6) replicates in these animals and causes pathology that is similar to that seen with humans. Here, we report findings with a new Syrian Hamster strain in which the STAT2 gene was functionally knocked out (KO) by site-specific CRISPR/Cas9-mediated gene targeting. STAT2 is a critical element of the Type I and Type III interferon signal transduction pathways. STAT2 KO Hamsters infected intravenously with Ad5 demonstrated an accentuated pathology compared to the wild-type control animals, and the virus load in the organs (liver, lung, kidney) of STAT2 KO animals was 100- to 1000-fold higher than that in wild-type Hamsters. We show that the Type I interferon pathway is disrupted in these Hamsters, inasmuch as the interferon response genes PKR, OAS, and Mx2 were induced by Ad5 in the liver of wild-type but not STAT2 KO Hamsters, revealing a critical role of interferon-stimulated genes in controlling Ad5 infection. Notably, the adaptive immune response to Ad5 is not adversely affected in STAT2 KO Hamsters, and surviving Hamsters cleared the infection by 7 to 10 days post challenge. In fact, anti-Ad5 neutralizing antibodies were 10-fold higher at 7 days postinfection in the STAT2 KO Hamsters than in wild-type Hamsters. T cell infiltration into the liver was similar at 3 and 7 days in the STAT2 KO and wild-type Hamsters. Treatment of Ad5-infected STAT2 KO Hamsters with high dose cyclophosphamide resulted in markedly increased mortality, pathogenesis, and virus replication in the liver (~1011 TCID50/g liver) at 10 days postinfection, likely because the adaptive immune response as well as other aspects of the innate response were abolished. This is the first study to report findings with a genetically modified Syrian Hamster infected with human adenovirus. Further, this is the first study to show that the Type I interferon pathway plays a role in inhibiting Ad5 replication in a permissive animal model. This conclusion is in accord with a previous study in which we showed using a custom microarray platform that there is a robust up-regulation of genes involved in the innate immune response (e.g. OAS, PKR, IFN-inducible protein 10) in the liver at 18 h post-intravenous infection of wild-type Syrian Hamsters with Ad5 (Ying, B. et al., Virology 485, 305, 2015). Besides providing an insight into adenovirus infection in humans, our results underscore the usefulness of Syrian Hamsters as a permissive model for the study of species C human adenovirus and adenovirus-based vectors. In future studies, STAT2 KO Hamsters bearing tumors could be used to explore the role of Type I and Type III interferon signaling on the efficacy of oncolytic adenovirus vectors.
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stat2 knockout syrian Hamsters support enhanced replication and pathogenicity of human adenovirus revealing an important role of type i interferon response in viral control
PLOS Pathogens, 2015Co-Authors: Karoly Toth, Jacqueline F. Spencer, Ann E. Tollefson, Baoling Ying, Zhongde Wang, John E Sagartz, Ilkeun Kong, William S. M. WoldAbstract:Human adenoviruses have been studied extensively in cell culture and have been a model for studies in molecular, cellular, and medical biology. However, much less is known about adenovirus replication and pathogenesis in vivo in a permissive host because of the lack of an adequate animal model. Presently, the most frequently used permissive immunocompetent animal model for human adenovirus infection is the Syrian Hamster. Species C human adenoviruses replicate in these animals and cause pathology that is similar to that seen with humans. Here, we report findings with a new Syrian Hamster strain in which the STAT2 gene was functionally knocked out by site-specific gene targeting. Adenovirus-infected STAT2 knockout Hamsters demonstrated an accentuated pathology compared to the wild-type control animals, and the virus load in the organs of STAT2 knockout animals was 100- to 1000-fold higher than that in wild-type Hamsters. Notably, the adaptive immune response to adenovirus is not adversely affected in STAT2 knockout Hamsters, and surviving Hamsters cleared the infection by 7 to 10 days post challenge. We show that the Type I interferon pathway is disrupted in these Hamsters, revealing the critical role of interferon-stimulated genes in controlling adenovirus infection. This is the first study to report findings with a genetically modified Syrian Hamster infected with a virus. Further, this is the first study to show that the Type I interferon pathway plays a role in inhibiting human adenovirus replication in a permissive animal model. Besides providing an insight into adenovirus infection in humans, our results are also interesting from the perspective of the animal model: STAT2 knockout Syrian Hamster may also be an important animal model for studying other viral infections, including Ebola-, hanta-, and dengue viruses, where Type I interferon-mediated innate immunity prevents wild type Hamsters from being effectively infected to be used as animal models.
