Current Animal Models for Understanding the Pathology Caused by the Respiratory Syncytial Virus

Abstract

The human respiratory syncytial virus (hRSV) is the main etiologic agent of severe lower respiratory tract infections that affect young children throughout the world, associated with significant morbidity and mortality, becoming a serious public health problem globally. Up to date, no licensed vaccines are available to prevent severe hRSV-induced disease, and the generation of safe-effective vaccines has been a challenging task, requiring constant biomedical research aimed to overcome this ailment. Among the difficulties presented by the study of this pathogen, it arises the fact that there is no single animal model that resembles all aspects of the human pathology, which is due to the specificity that this pathogen has for the human host. Thus, for the study of hRSV, different animal models might be employed, depending on the goal of the study. Of all the existing models, the murine model has been the most frequent model of choice for biomedical studies worldwide and has been of great importance at contributing to the development and understanding of vaccines and therapies against hRSV. The most notable use of the murine model is that it is very useful as a first approach in the development of vaccines or therapies such as monoclonal antibodies, suggesting in this way the direction that research could have in other preclinical models that have higher maintenance costs and more complex requirements in its management. However, several additional different models for studying hRSV, such as other rodents, mustelids, ruminants, and non-human primates, have been explored, offering advantages over the murine model. In this review, we discuss the various applications of animal models to the study of hRSV-induced disease and the advantages and disadvantages of each model, highlighting the potential of each model to elucidate different features of the pathology caused by the hRSV infection.

In vivo comparison of a laboratory-adapted and clinical-isolate-based recombinant human respiratory syncytial virus

“…Cotton rats (n=36, 3-5-week-old females) were inoculated intranasally with 10 4 TCID 50 rHRSV-A2 or rHRSV-A11 in a high volume (100 µl) to ensure deposition in the URT and LRT [16,20]. Over the course of the experiment, the cotton rats showed no clinical signs or weight loss (data not shown).…”

“…These symptoms have not been properly reproduced in any animal model, except in the chimpanzee. Naturally infected chimpanzees have been reported to develop severe LRT disease, but using chimpanzees has practical restrictions and now has been banned for ethical reasons [16,17]. Other non-human primates, such as baboons (Papio anubis) and macaques (Macaca fascicularis), have limited permissiveness to HRSV.…”

“…Another animal model used for studying HRSV disease is the ferret model. In ferrets, HRSV replicated in the upper respiratory tract (URT) and LRT; however, ferrets do not show clinical signs upon infection, and the tools for immunological and molecular studies are limited [16,17,20,21].…”

“…Sporadically infected cells, presumably pneumocytes, can be found in the alveoli [22]. The tropism of HRSV in cotton rats and humans is similar, but cotton rats lack signs of respiratory disease or symptoms [16,23]. The animals are also not easy to handle, and tools for immunological and genetic studies are limited [16,17].…”

“…BALB/cJ mice are used more often than C57BL/6 mice as they are slightly more permissive to HRSV, reflected by higher viral loads in the URT and LRT. However, C57BL/6 mice are potentially more informative for future studies due to the wide availability of transgenic strains [16,17].…”