Chinese tree shrew: a permissive model for in vitro and in vivo replication of human adenovirus species B

Abstract

Human adenovirus (HAdV) species B can cause severe acute respiratory diseases. However, the researches to combat this infection have been hampered by the lack of an animal model permissive to the virus. Here, we report in vitro and in vivo HAdV species B infections of tree shrews, the closest relative of primates. HAdV-3, -7, -14, and -55 efficiently replicated in primary cell cultures. After intranasal inoculation of tree shrews with HAdV-55, the viral replication in the oropharyngeal region remained high until day 5 post-infection and was still detected until day 12. HAdV-55 in the lung or turbinate bone tissues reached the highest levels between days 3 and 5 post-infection, which indicated viral replication in the upper and lower respiratory tracts. HAdV-55 infection caused severe interstitial pneumonia in the animal. IL-8, IL-10, IL-17A, and IFN-γ expression in the peripheral blood mononuclear cells from infected animals was up-regulated. The pre-vaccination with HAdV-55 cleared the virus faster in the respiratory tract, mitigated lung pathological changes. Finally, HAdV-55 infection was propagated among tree shrews. Our study demonstrated that the tree shrew is a permissive animal model for HAdV species B infection and may serve as a valuable platform for testing multiple anti-viral treatments.

Animal Models in Human Adenovirus Research

“…Li and colleagues infected Chinese tree shrews intranasally, and showed that they were permissive to infection as evidenced by viral replication in the upper and lower airways and the lungs, resulting in severe pneumonia ( Table 1 ). They additionally demonstrated that tree shrews reacted to HAdV-B55 infection with rapid seroconversion, elevated body temperatures, and upregulation of pro-inflammatory cytokines in PBMCs [ 41 ]. The tree shrew therefore poses a promising model for HAdV-induced clinical disease and research on the zoonotic potential of HAdVs that should be followed up upon, especially using other HAdVs for infection.…”

“…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).…”

Tree Shrew as an Emerging Small Animal Model for Human Viral Infection: A Recent Overview

“…A suitable animal model is essential for studying pathogenicity, promoting antiviral and vaccine development, and conducting preclinical efficacy testing of oncolytic adenoviral vectors. Moreover, a permissive animal model for HAdV-B infection is still lacking [ 31 ], which is crucial for a proper understanding of pathogenesis and host response. A recent study by Li et al showed that tree shrews demonstrate susceptibility to HAdV-B infection.…”

“…A recent study by Li et al showed that tree shrews demonstrate susceptibility to HAdV-B infection. They showed that intranasally inoculated HAdV-55 efficiently replicates and produces severe interstitial pneumonia in tree shrews [ 31 ]. However, a pre-existing neutralizing antibody (nAb) was found in 6 tree shrews out of 18 against HAdV-3, and 1 had a preexisting nAb against HAdV-14, suggesting the occurrence of natural infection of HAdV in tree shrews.…”

“…It has been reported that Tupaia adenovirus (TAV) infects the members of Tupaiidae family, and TAV has a genome of 33.5 kb [ 65 ]. However, there were no pre-existing nAbs against HAdV-55 in those tree shrews [ 31 ]. The overall findings of the study demonstrated the tree shrew as a permissive animal model for studying HAdV-B infection which may be useful for antiviral testing.…”