Abstract

Influenza A viruses (IAVs) continuously challenge the poultry industry and human health. Studies of IAVs are still hampered by the availability of suitable animal models. Chinese tree shrews (Tupaia belangeri chinensis) are closely related to primates physiologically and genetically, which make them a potential animal model for human diseases. In this study, we comprehensively evaluated infectivity and transmissibility in Chinese tree shrews by using pandemic H1N1 (A/Sichuan/1/2009, pdmH1N1), avian-origin H5N1 (A/Chicken/Gansu/2/2012, H5N1) and early human-origin H7N9 (A/Suzhou/SZ19/2014, H7N9) IAVs. We found that these viruses replicated efficiently in primary tree shrew cells and tree shrews without prior adaption. Pathological lesions in the lungs of the infected tree shrews were severe on day 3 post-inoculation, although clinic symptoms were self-limiting. The pdmH1N1 and H7N9 viruses, but not the H5N1 virus, transmitted among tree shrews by direct contact. Interestingly, we also observed that unadapted H7N9 virus could transmit from tree shrews to naïve guinea pigs. Virus-inoculated tree shrews generated a strong humoral immune response and were protected from challenge with homologous virus. Taken together, our findings suggest the Chinese tree shrew would be a useful mammalian model to study the pathogenesis and transmission of IAVs.

Highlights

  • Influenza A viruses (IAVs) are segmented, single-stranded, negative-sense RNA viruses, whose genome comprises eight gene segments, including basic polymerase 2 (PB2), basic polymerase 1 (PB1), acidic polymerase (PA), hemagglutinin (HA), nucleoprotein (NP), neuraminidase (NA), matrix (M), and nonstructural protein (NS)

  • Pandemic H1N1, Avian H5N1, and Human H7N9 Influenza Viruses Efficiently Replicate in Primary Tree Shrew Cells. 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)

  • Molecular characterization indicated that the H5N1 virus possesses a polybasic cleavage site motif (PQRERRRKR/GLF), whereas pandemic H1N1 virus A/Sichuan/1/2009 (pdmH1N1) and H7N9 viruses lack this feature (PSIQSR/GLF or PEIPKGR/GLF), suggesting pdmH1N1 and H7N9 viruses may be low pathogenic for chickens (Table 2)

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Summary

Introduction

Influenza A viruses (IAVs) are segmented, single-stranded, negative-sense RNA viruses, whose genome comprises eight gene segments, including basic polymerase 2 (PB2), basic polymerase 1 (PB1), acidic polymerase (PA), hemagglutinin (HA), nucleoprotein (NP), neuraminidase (NA), matrix (M), and nonstructural protein (NS). H1N1, H2N2, and H3N2 viruses caused four influenza pandemics in humans, resulting in widespread disease and severe loss of life (Medina and Garcia-Sastre, 2011; Lipsitch, 2013). In 2009, a novel swine-origin influenza A (H1N1) pandemic. Studies on IAVs in Tree-Shrews caused huge economic losses and casualties (Novel Swine-Origin Influenza A (H1N1) Virus Investigation Team et al, 2009). Since 1997, increasing numbers of humans have been infected with highly pathogenic avian influenza H5N1 viruses, with a mortality rate of about 60% among confirmed cases (WHO, 2017). Avian influenza A (H7N9) viruses have emerged and infected human. The H7N9 avian influenza virus has caused multiple outbreaks of severe disease in humans (Shi et al, 2018; WHO, 2018)

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