STAT2 Knockout Syrian Hamsters Support Enhanced Replication and Pathogenicity of Human Adenovirus, Revealing an Important Role of Type I Interferon Response in Viral Control
The biology of human adenoviruses has been studied extensively; however, much less is known about the replication and pathogenesis of the virus in a permissive host. Our laboratory pioneered the use of Syrian hamsters to study the pathogenesis of human adenoviruses. Syrian hamsters are permissive for species C human adenoviruses, which replicate in these animals and cause illness akin to that in humans. Hereby, we report findings with a new Syrian hamster strain (STAT2 KO hamsters), in which the Type I interferon pathway, an important part of the innate immune response to virus infection, is disrupted. This is the first genetically modified Syrian hamster strain ever reported. We show that these animals are very sensitive to infection with type 5 human adenovirus (Ad5). Ad5 replicates to 100- to 1000-fold higher titers in STAT2 KO hamsters than in wild-type ones, and this increased infection causes enhanced pathology. However, the adaptive immune response to the virus infection seems to be intact with the STAT2 KO hamsters, and surviving animals clear the virus effectively. The data reported here may be of interest to researchers focusing on adenoviruses, and also to those who utilize the Syrian hamster as their animal model for other purposes.
Vyšlo v časopise:
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 Pathog 11(8): e32767. doi:10.1371/journal.ppat.1005084
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.ppat.1005084
Souhrn
The biology of human adenoviruses has been studied extensively; however, much less is known about the replication and pathogenesis of the virus in a permissive host. Our laboratory pioneered the use of Syrian hamsters to study the pathogenesis of human adenoviruses. Syrian hamsters are permissive for species C human adenoviruses, which replicate in these animals and cause illness akin to that in humans. Hereby, we report findings with a new Syrian hamster strain (STAT2 KO hamsters), in which the Type I interferon pathway, an important part of the innate immune response to virus infection, is disrupted. This is the first genetically modified Syrian hamster strain ever reported. We show that these animals are very sensitive to infection with type 5 human adenovirus (Ad5). Ad5 replicates to 100- to 1000-fold higher titers in STAT2 KO hamsters than in wild-type ones, and this increased infection causes enhanced pathology. However, the adaptive immune response to the virus infection seems to be intact with the STAT2 KO hamsters, and surviving animals clear the virus effectively. The data reported here may be of interest to researchers focusing on adenoviruses, and also to those who utilize the Syrian hamster as their animal model for other purposes.
Zdroje
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