Animal Models in Human Adenovirus Research

SIMPLE SUMMARY: Animal models are widely used to study various aspects of human diseases and disorders. Likewise, they are indispensable for preclinical testing of medicals and vaccines. Human adenovirus infections are usually self-limiting, and can cause mild respiratory symptoms with fever, eye infection or gastrointestinal symptoms, but occasional local outbreaks with severe disease courses have been reported. In addition, adenovirus infections pose a serious risk for children and patients with a weakened immune system. Human adenovirus research in animal models to study adenovirus-induced disease and tumor development started in the 1950s. Various animal species have been tested for their susceptibility to human adenovirus infection since then, and some have been shown to mimic key characteristics of the infection in humans, including persistent infection. Furthermore, some rodent species have been found to develop tumors upon human adenovirus infection. Our review summarizes the current knowledge on animal models in human adenovirus research, describing the pros and cons along with important findings and future perspectives. ABSTRACT: Human adenovirus (HAdV) infections cause a wide variety of clinical symptoms, ranging from mild upper respiratory tract disease to lethal outcomes, particularly in immunocompromised individuals. To date, neither widely available vaccines nor approved antiadenoviral compounds are available to efficiently deal with HAdV infections. Thus, there is a need to thoroughly understand HAdV-induced disease, and for the development and preclinical evaluation of HAdV therapeutics and/or vaccines, and consequently for suitable standardizable in vitro systems and animal models. Current animal models to study HAdV pathogenesis, persistence, and tumorigenesis include rodents such as Syrian hamsters, mice, and cotton rats, as well as rabbits. In addition, a few recent studies on other species, such as pigs and tree shrews, reported promising data. These models mimic (aspects of) HAdV-induced pathological changes in humans and, although they are relevant, an ideal HAdV animal model has yet to be developed. This review summarizes the available animal models of HAdV infection with comprehensive descriptions of virus-induced pathogenesis in different animal species. We also elaborate on rodent HAdV animal models and how they contributed to insights into adenovirus-induced cell transformation and cancer.