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

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.

SUBMITTER: Xu S

PROVIDER: S-EPMC6933948 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:H5N1 highly pathogenic avian influenza (HPAI) was one of the most important avian diseases in poultry production of China, especially in Guangdong province. In recent years, new H5N1 highly pathogenic avian influenza viruses (HPAIV) still emerged constantly, although all poultry in China were immunized with H5N1 vaccinations compulsorily. To better understand the pathogenicity and transmission of dominant clades of the H5N1 HPAIVs in chicken from Guangdong in 2012, we chose a clade 7.2 avian influenza virus named A/Chicken/China/G2/2012(H5N1) (G2) and a clade 2.3.2.1 avian influenza virus named A/Duck/China/G3/2012(H5N1) (G3) in our study. Our results showed that the chickens inoculated with 10(3) EID50 of G2 or G3 viruses all died, and the titers of virus replication detected in several visceral organs were high but different. In the naive contact groups, virus shedding was not detected in G2 group and all chickens survived, but virus shedding was detected in G3 group and all chickens died. These results showed that the two clades of H5N1 HPAIVs had high pathogenicity in chickens and the contact transmission of them was different in chickens. The results of cross reactive HI assay showed that antigens of G2 and G3 were very different from those of current commercial vaccines isolates (Re-4, Re-6, and D7). And to evaluate the protective efficacy of three vaccines against most isolates form Guangdong belonging to clade 2.3.2.1 in 2012, G3 was chosen to challenge the three vaccines such as Re-4, Re-6, and D7. First, chickens were immunized with 0.3 ml Re-4, Re-6, and D7 inactivated vaccines by intramuscular injection, respectively, and then challenged with 10(6) EID50 of G3 on day 28 post-vaccination. The D7 vaccine had 100% protection against G3 for chickens, the Re-6 vaccine had 88.9%, and the Re-4 vaccine only had 66.7%. Our results suggested that the D7 vaccine could prevent and control H5N1 virus outbreaks more effectively in Guangdong. From the above, it was necessary to conduct continuously epidemiological survey and study the pathogenicity and antigenic variation of avian influenza in Southern China.

Dataset Information

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

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