Establishment and significance of hDSG2 transgenic mice lung infection model induced by human adenovirus type 55

  Background  Human adenovirus type 55 (HAdV-B55) can cause respiratory tract infection, which may evolve into viral pneumonia and even life-threatening in severe cases. An appropriate model of HAdV-B55 infection would be of great importance for exploring the pathogenesis and the development of drug therapies and multivalent vaccines.

  Objective  To establish an animal model of humanized receptor desmoglein-2 (hDSG2) transgenic mouse with pulmonary infection of HAdV-B55.

  Methods  Totally 25 male hDSG2 transgenic mice and 25 male wild-type C57BL/6 (C57) mice were randomly divided into five groups (5 mice in each group), including 3, 5, 7, 14 days after infection groups and PBS control group. Mice in the infection groups were infected with HAdV-B55 (10⁸ TCID50) by nasal instillation. Mice in the control group were treated with PBS at the same dose by nasal instillation. Animals were weighed daily and their activities were observed. Samples were separately taken on 3, 5, 7 and 14 days after infection, and mice in the control group were killed at 14 days after nasal instillation. Lung coefficient, lung tissue pathology, copy number of HAdV-B55 gene in lung tissues, expression levels of IL-6 and IFN-γ, and sera concentration of IL-6 were detected for each group.

  Results  After infection with HAdV-B55, the hDSG2 transgenic mice recovered slowly and gained weight more slowly than C57 mice (P<0.01), and they developed the symptoms of acute infection such as reduced activity, hunching and huddling. The pathological manifestations in lung tissues of hDSG2 transgenic mice were more severe than those in lung tissues of C57 mice, which included alveolar wall thickening and inflammatory cell infiltration, along with significantly increased lung coefficient (P<0.05), significantly increased copy number of HAdV-B55 gene in lung tissues (P<0.05), and significantly increased expression of IL-6 in lung tissues (P<0.05) and serum IL-6 concentrations (P<0.01).

  Conclusion  An animal model of hDSG2 transgenic mice lung infection is established by using nasal instillation of HAdV-B55. The model features with high stability and persistent pathogenicity, which is useful for further scientific research.