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.

Evaluation of Human Mesenchymal Stromal Cells as Carriers for the Delivery of Oncolytic HAdV-5 to Head and Neck Squamous Cell Carcinomas

“…Thus, infection of MSCs from another species with HAdV-5 would not result in the release of viral progeny, disabling the evaluation of oncolytic effects. An intensive effort has been made to find a permissive animal model; however, to date, no really suitable animal model could be identified [ 66 ]. To sum up, this illustrates the complexity of preclinical hMSC-based oncolytic adenovirus therapy and highlights that the establishment of a more suitable in vivo model is indispensable but not yet realizable.…”

Bridging the gap between emerging models and humans by learning from polio animal studies: A systematic review

“…It is interesting to note how research on other viruses like adenoviruses and herpesviruses, which share similar characteristics with poliovirus in terms of host restriction to humans and the absence of an animal reservoir, also use animal models that mimic only certain aspects of human disease. [76][77][78] Similarly, most of the emerging models are being developed as discrimination models, therefore it is essential to view the results from this perspective to prevent drawing overarching conclusions.…”

“…This suggests that animal models for studying poliovirus pathogenesis are almost exclusively discrimination models highlighting the potential that these models have in understanding specific mechanisms in the intricacy of human disease. It is interesting to note how research on other viruses like adenoviruses and herpesviruses, which share similar characteristics with poliovirus in terms of host restriction to humans and the absence of an animal reservoir, also use animal models that mimic only certain aspects of human disease 76–78 . Similarly, most of the emerging models are being developed as discrimination models, therefore it is essential to view the results from this perspective to prevent drawing overarching conclusions.…”

Small DNA tumor viruses and human cancer: Preclinical models of virus infection and disease

“…These natural or engineered virus stocks can then be applied to their natural host at susceptible sites corresponding to those infected in humans. Infection models can be used to study transforming infections, as is the case with the cottontail rabbit papillomavirus model [reviewed in 143 ] and animal models used to study adenovirus [reviewed in [ 48 ]]. The ideal infection model, however, will support the full spectrum of events including productive infection, viral persistence, and neoplastic disease progression.…”

“…However, no definitive etiological link between human adenoviruses and human cancers has been established. Several other articles discuss the prolific transforming and tumorigenic potential of adenoviruses in various model systems [ [37] , [38] , [39] , [46] , [47] , [48] , [49] , [50] , [51] , [52] , [53] ] and clearly justify the classification of human adenoviruses as tumor viruses. However, given the lack of evidence supporting a causal role of adenoviruses in human cancers, animal models of human adenoviruses will not be discussed at length in this review.…”