The tree shrew provides a useful alternative model for the study of influenza H1N1 virus

Abstract

BackgroundThe influenza pandemics have resulted in significant morbidity and mortality worldwide. Animal models are useful in the study of influenza virus pathogenesis. Because of various limitations in current laboratory animal models, it is essential to develop new alternative animal models for influenza virus research aimed at understanding the viral and host factors that contribute to virus infection in human.MethodWe investigated the replicative efficiency of influenza H1N1 virus (classic strain (Influenza A/PR/8/34), seasonal influenza isolate (A/Guangzhou/GIRD/02/09) and swine-origin human influenza virus (A/Guangzhou/GIRD/07/09)) at Day1,2,4,6 and 9 p.i. using TCID50 and qPCR assay in tree shrew model. Body temperature was monitored in the morning and evening for 3 days before infection and for 14 days. Seroconversion was detected by determining the neutralizing antibody titers against the challenge viruses in the pre- and exposure serum samples collected before infection and at 14 days p.i., respectively. Lungs and tracheas of tree shews were collected at day 14 post p.i. for histopathological analysis. Lectinhistochemistry analysis was conducted to identify the distribution of SAα2,3 Gal and SAα2,6 Gal receptors in the lung and trachea.ResultsThe infected tree shrew displayed mild or moderate systemic and respiratory symptoms and pathological changes in respiratory tracts. The human H1N1 influenza virus may replicate in the upper respiratory tract of tree shrews. Analysis of the receptors distribution in the respiratory tract of tree shrews by lectinhistochemistry showed that sialic acid (SA)α2,6-Gal receptors were widely distributed in the trachea and nasal mucosa, whereas (SA)α2,3-Gal receptor was the main receptor in the lung tissue.ConclusionsBased on these findings, tree shrew seemed to mimic well influenza virus infection in humans. We propose that tree shrews could be a useful alternative mammalian model to study pathogenesis of influenza H1N1 virus.

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 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).…”

The tree shrew cerebellum atlas: Systematic nomenclature, neurochemical characterization, and afferent projections

“…The Chinese tree shrew has been widely used to establish human disease models, such as virus infection (Yang et al, ), breast tumor (Xia et al, ), nonalcoholic fatty liver (Zhang et al, ), acute hyperuricemia (Tang et al, ), depression (Wang et al, ), Alzheimer's Disease (Fan et al, ), and so on. Findings suggest that cerebellar morphology in tree shrews more closely resembles that of primates than it does rodents (Sillitoe, Malz, Rockland, & Hawkes, ).…”