Animal Models in Human Adenovirus Research

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.

Keywords: (humanized) mice; Syrian hamsters; cotton rats; experimental infection; human adenovirus (HAdV); in vivo model; pigs; rabbits; susceptibility; tree shrews.

Figure 1

Landmark publications on animal models in HAdV research. HAdV research in small animal models was pioneered by Rowe et al. in 1955 at the NIH in Bethesda, MD (USA) [21]. That work laid the foundation for various follow-up studies and novel approaches to establish a suitable animal model to study HAdV infection, including HAdV-induced pathogenesis and cancer development in vivo. The most relevant models are Syrian hamsters [28], mice [32,33], cotton rats [37], New Zealand (NZ) rabbits [38], STAT2 knockout (KO) Syrian hamsters [39], humanized mice [40], and Chinese tree shrews [41] (sorted by publication date of the first report on the respective animal model).