Tree shrew as a new animal model to study the pathogenesis of avian influenza (H9N2) virus infection

Abstract

Outbreaks of avian influenza virus continue to pose threats to human health. Animal models such as the mouse, ferret, and macaque are used to understand the pathogenesis of avian influenza virus infection in humans. We previously reported that the tree shrew (Tupaia belangeri, family Tupaiidae), which is regarded as a “low-level primate”, has α2,3- and α2,6-linked sialic acid receptor distributions similar to those of humans and is potentially a useful mammalian model for studying mild human influenza (H1N1) virus infection. In this study, we used the tree shrew experimental model to investigate the pathogenesis of avian influenza A (H9N2) virus infection and the effect of the E627K mutation in the PB2 gene, an adaptation to mammalian hosts. Evidence of disease, virus titers in the upper and lower respiratory tract, histopathology and induction of proinflammatory cytokines are described. We also established ex vivo culture models of tree shrew respiratory tissues to study the tropism and replication of the H9N2 virus. Our results demonstrated that the tree shrew is a viable new in vivo experimental model for avian influenza research that provides results comparable to those observed in ferrets. The disease spectrum and pathogenesis in tree shrews correlate well with what is observed in humans.

Susceptibility of tree shrew to SARS-CoV-2 infection

“…Therefore, it is being developed to be an experimental animal that could be an alternative to primates in biomedical research due to its unique characteristics 16 . In fact, tree shrew has been used for several animal models of virus infections, including hepatitis B 17 , influenza virus [18][19][20] , and Zika virus 21 . However, Tupaia model of high pathogenic viruses has not been reported yet, including SARS-CoV-2.…”

Comparative Pathogenicity and Transmissibility of Pandemic H1N1, Avian H5N1, and Human H7N9 Influenza Viruses in Tree Shrews

“…Previous studies have demonstrated that H1N1 and H9N2 influenza viruses replicate in the upper respiratory tract of tree shrews, which showed moderate respiratory symptoms and pathological signs (Yang et al, 2013;Li et al, 2018). Furthermore, while our manuscript was in preparation, Sanada and colleagues documented the pathogenicity of H5N1 and H7N9 IAVs in tree shrews (Sanada et al, 2019).…”

“…Yang and his colleagues demonstrated that H1N1 and H9N2 influenza viruses replicate in the upper respiratory tract of tree shrews, and exhibited moderate respiratory symptoms and pathological signs (Yang et al, 2013;Li et al, 2018).…”

“…In the worst cases, influenza virus may cause pneumonia, respiratory distress syndrome, and even death (Carrat et al, 2008). Previous studies have demonstrated that tree shrews infected with H1N1, H7N9, or H9N2 virus showed moderate respiratory symptoms and pathological signs (Yang et al, 2013;Li et al, 2018;Sanada et al, 2019). Sanada et al reported that H5N1 infection induced severe clinical symptoms including pneumonia, fever, weight loss, and death in tree shrews (Sanada et al, 2019).…”

“…In 2013, Yang et al analyzed the distribution of ɑ2,3 and ɑ2,6 sialic acid receptors in the respiratory tract of tree shrew (Yang et al, 2013), and investigated the pathological change, seroconversion, and cytokine response of tree shrews infected with H1N1, H9N2 IAVs, and influenza B virus (Yang et al, 2013;Li et al, 2018;Yuan et al, 2019). Most recently, Sanada et al assessed the pathogenicity of H5N1 and H7N9 IAVs in tree shrews and found that H5N1 influenza virus infection caused severe diffuse pneumonia with fever and weight loss; in contrast, H7N9 influenza virus infection caused focal pneumonia in this tree shrew model (Sanada et al, 2019).…”