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Using an animal model they developed, researchers have identified a pathway that inhibits replication of the adenovirus.
The team generated a new strain of Syrian hamster, a model in which human adenovirus replicates and causes illness similar to that observed in humans.
Experiments with this model suggested the Type I interferon pathway plays a key role in inhibiting adenovirus replication.
“[L]ike many other viruses, adenovirus can replicate at will when a patient’s immune system is suppressed,” said William Wold, PhD, of Saint Louis University in Missouri.
“Adenovirus can become very dangerous, such as for a child who is undergoing a bone marrow transplant to treat leukemia.”
Previously, Dr Wold led a research team that identified the Syrian hamster as an appropriate animal model to study adenovirus because species C human adenoviruses replicate in these animals.
For the current study, which was published in PLOS Pathogens, Dr Wold and his colleagues conducted experiments with a new Syrian hamster strain. In these animals, the STAT2 gene was functionally knocked out by site-specific gene targeting.
The researchers found that STAT2-knockout hamsters were extremely sensitive to infection with type 5 human adenovirus (Ad5).
The team infected both STAT2-knockout hamsters and wild-type controls with Ad5. Knockout hamsters had 100 to 1000 times the viral load of controls.
The knockout hamsters also had pathology characteristic of advanced adenovirus infection—yellow, mottled livers and enlarged gall bladders—whereas controls did not.
The adaptive immune response to Ad5 remained intact in the STAT2-knockout hamsters, as surviving animals were able to clear the virus.
However, the Type 1 interferon response was hampered in these animals. Knocking out STAT2 disrupted the Type 1 interferon pathway by interrupting the cascade of cell signaling.
The researchers said their findings suggest the disrupted Type I interferon pathway contributed to the increased Ad5 replication in the STAT2-knockout hamsters.
“Besides providing an insight into adenovirus infection in humans, our results are also interesting from the perspective of the animal model,” Dr Wold said. “The STAT2-knockout Syrian hamster may also be an important animal model for studying other viral infections, including Ebola, hanta, and dengue viruses.”
The model was created by Zhongde Wang, PhD, and his colleagues at Utah State University in Logan, Utah. Dr Wang’s lab is the first to develop gene-targeting technologies in the Syrian hamster.
“The success we achieved in conducting gene-targeting in the Syrian hamster has provided the opportunity to create models for many of the human diseases for which there are either no existent animal models or severe limitations in the available animal models,” Dr Wang said. 
Using an animal model they developed, researchers have identified a pathway that inhibits replication of the adenovirus.
The team generated a new strain of Syrian hamster, a model in which human adenovirus replicates and causes illness similar to that observed in humans.
Experiments with this model suggested the Type I interferon pathway plays a key role in inhibiting adenovirus replication.
“[L]ike many other viruses, adenovirus can replicate at will when a patient’s immune system is suppressed,” said William Wold, PhD, of Saint Louis University in Missouri.
“Adenovirus can become very dangerous, such as for a child who is undergoing a bone marrow transplant to treat leukemia.”
Previously, Dr Wold led a research team that identified the Syrian hamster as an appropriate animal model to study adenovirus because species C human adenoviruses replicate in these animals.
For the current study, which was published in PLOS Pathogens, Dr Wold and his colleagues conducted experiments with a new Syrian hamster strain. In these animals, the STAT2 gene was functionally knocked out by site-specific gene targeting.
The researchers found that STAT2-knockout hamsters were extremely sensitive to infection with type 5 human adenovirus (Ad5).
The team infected both STAT2-knockout hamsters and wild-type controls with Ad5. Knockout hamsters had 100 to 1000 times the viral load of controls.
The knockout hamsters also had pathology characteristic of advanced adenovirus infection—yellow, mottled livers and enlarged gall bladders—whereas controls did not.
The adaptive immune response to Ad5 remained intact in the STAT2-knockout hamsters, as surviving animals were able to clear the virus.
However, the Type 1 interferon response was hampered in these animals. Knocking out STAT2 disrupted the Type 1 interferon pathway by interrupting the cascade of cell signaling.
The researchers said their findings suggest the disrupted Type I interferon pathway contributed to the increased Ad5 replication in the STAT2-knockout hamsters.
“Besides providing an insight into adenovirus infection in humans, our results are also interesting from the perspective of the animal model,” Dr Wold said. “The STAT2-knockout Syrian hamster may also be an important animal model for studying other viral infections, including Ebola, hanta, and dengue viruses.”
The model was created by Zhongde Wang, PhD, and his colleagues at Utah State University in Logan, Utah. Dr Wang’s lab is the first to develop gene-targeting technologies in the Syrian hamster.
“The success we achieved in conducting gene-targeting in the Syrian hamster has provided the opportunity to create models for many of the human diseases for which there are either no existent animal models or severe limitations in the available animal models,” Dr Wang said.
Using an animal model they developed, researchers have identified a pathway that inhibits replication of the adenovirus.
The team generated a new strain of Syrian hamster, a model in which human adenovirus replicates and causes illness similar to that observed in humans.
Experiments with this model suggested the Type I interferon pathway plays a key role in inhibiting adenovirus replication.
“[L]ike many other viruses, adenovirus can replicate at will when a patient’s immune system is suppressed,” said William Wold, PhD, of Saint Louis University in Missouri.
“Adenovirus can become very dangerous, such as for a child who is undergoing a bone marrow transplant to treat leukemia.”
Previously, Dr Wold led a research team that identified the Syrian hamster as an appropriate animal model to study adenovirus because species C human adenoviruses replicate in these animals.
For the current study, which was published in PLOS Pathogens, Dr Wold and his colleagues conducted experiments with a new Syrian hamster strain. In these animals, the STAT2 gene was functionally knocked out by site-specific gene targeting.
The researchers found that STAT2-knockout hamsters were extremely sensitive to infection with type 5 human adenovirus (Ad5).
The team infected both STAT2-knockout hamsters and wild-type controls with Ad5. Knockout hamsters had 100 to 1000 times the viral load of controls.
The knockout hamsters also had pathology characteristic of advanced adenovirus infection—yellow, mottled livers and enlarged gall bladders—whereas controls did not.
The adaptive immune response to Ad5 remained intact in the STAT2-knockout hamsters, as surviving animals were able to clear the virus.
However, the Type 1 interferon response was hampered in these animals. Knocking out STAT2 disrupted the Type 1 interferon pathway by interrupting the cascade of cell signaling.
The researchers said their findings suggest the disrupted Type I interferon pathway contributed to the increased Ad5 replication in the STAT2-knockout hamsters.
“Besides providing an insight into adenovirus infection in humans, our results are also interesting from the perspective of the animal model,” Dr Wold said. “The STAT2-knockout Syrian hamster may also be an important animal model for studying other viral infections, including Ebola, hanta, and dengue viruses.”
The model was created by Zhongde Wang, PhD, and his colleagues at Utah State University in Logan, Utah. Dr Wang’s lab is the first to develop gene-targeting technologies in the Syrian hamster.
“The success we achieved in conducting gene-targeting in the Syrian hamster has provided the opportunity to create models for many of the human diseases for which there are either no existent animal models or severe limitations in the available animal models,” Dr Wang said.