Wild-Type Human Adenovirus (Serotype 7)

Human adenovirus types 3 (HAdV-3) and 7 (HAdV-7) cause significant morbidity in children and cause severe complications and long-term pulmonary sequelae. Here, two strains were tested in vitro for viral quantification, viral growth kinetics, competitive fitness, cytotoxicity, and complement C3a (C3a) assays. A mouse adenovirus model was used to assess acute inflammatory responses. In cell culture, HAdV-7 replicated at higher levels than HAdV-3 and showed significant differences in viral fitness. HAdV-7 also showed higher C3a production and cytotoxic effects, and HAdV-7-infected mice had more severe pathology and higher viral loads in the lungs compared with HAdV-3-infected mice. The number of macrophages in bronchoalveolar lavage fluid (BALF) was significantly increased during infection compared with HAdV-3 infection, and proinflammatory cytokines (TNF-α, IL-1β, IFN-γ, and IL-6) were also increased. These results suggest that HAdV-7 replicates more robustly than HAdV-3 and can exacerbate cytokine responses, leading to more severe airway inflammation.

To better understand the differences in adenovirus-induced respiratory inflammation, the researchers established a human adenovirus mouse respiratory infection model. In this model, lung tissue viral load measurements showed that the number of viral copies in the HAdV-7-infected group was higher than that in the HAdV-3-infected group on days 3, 5, and 7 of infection, especially on day 3, when the number of viral copies in the HAdV-7 group was 1.5 times that in the HAdV-3 group (Figure 1a). Pulmonary inflammation was observed in mice at various time points after HAdV-3 and HAdV-7 infection, and was found to gradually worsen from day 3 to day 5 and to be alleviated on day 7. Lung tissue damage in HAdV-7-infected mice was also higher on all days of infection compared with HAdV-3-infected mice (Figure 1b). Consistent with the morphological changes, the total number of cells in the BALF was higher than that in the control group on all days (Figure 1c-e); importantly, the increase in these cells was significantly greater in the HAdV-7 group compared with the HAdV-3 group (Figure 1d-e). Neutrophils increased only slightly on day 3 and then dropped sharply, while the number of lymphocytes and macrophages continued to increase on days 5 and 7. In addition, after 5 and 7 days of infection, the number of macrophages in the BALF of the HAdV-7 group was significantly higher than that of the HAdV-3 group (Figure 1d-e), while lymphocytes showed significant differences only on day 5 (Figure 1d). At all time points, there was no significant difference in the number of neutrophils in the BALF of the HAdV-7 group compared with the HAdV-3 group (Figure 1c-e). Together, these results indicate that HAdV-7 infection causes relatively more severe acute respiratory inflammation.

Figure 1. Difference of severity of pathology in mouse infected with HAdV-3 and HAdV-7. (Fu Y, et al., 2019)