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Influenza A Virus Studies in a Mouse Model of Infection
Published on: September 7, 2017
Amino Acid Substitutions Associated with Avian H5N6 Influenza A Virus Adaptation to Mice
Chunmao Zhang1, Zongzheng Zhao1, Zhendong Guo1
1Military Veterinary Research Institute, Academy of Military Medical SciencesChangchun, China.
Abstract:
At least 15 cases of human beings infected with H5N6 have been reported since 2014, of which at least nine were fatal. The highly pathogenic avian H5N6 influenza virus may pose a serious threat to both public health and the poultry industry. However, the molecular features promoting the adaptation of avian H5N6 influenza viruses to mammalian hosts is not well understood. Here, we sequentially passaged an avian H5N6 influenza A virus (A/Northern Shoveler/Ningxia/488-53/2015) 10 times in mice to identify the adaptive amino acid substitutions that confer enhanced virulence to H5N6 in mammals. The 1st and 10th passages of the mouse-adapted H5N6 viruses were named P1 and P10, respectively. P1 and P10 displayed higher pathogenicity in mice than their parent strain. P10 showed significantly higher replication capability in vivo and could be detected in the brains of mice, whereas P1 displayed higher replication efficiency in their lungs but was not detectable in the brain. Similar to its parent strain, P10 remained no transmissible between guinea pigs. Using genome sequencing and alignment, multiple amino acid substitutions, including PB2 E627K, PB2 T23I, PA T97I, and HA R239H, were found in the adaptation of H5N6 to mice. In summary, we identified amino acid changes that are associated with H5N6 adaptation to mice.
Insights
Highly pathogenic H5N6 avian influenza virus adaptation to mammals was studied. Mouse adaptation identified key amino acid substitutions, including PB2 E627K, enhancing H5N6 virulence in mammals.
Area of Science:
- Virology
- Molecular Biology
- Public Health
Background:
- The H5N6 influenza virus, a highly pathogenic avian strain, poses a significant threat to public health and the poultry industry.
- Human infections with H5N6 have resulted in a high fatality rate, underscoring the need to understand its mammalian adaptation.
- The molecular mechanisms enabling avian H5N6 influenza viruses to adapt to mammalian hosts remain poorly understood.
Purpose of the Study:
- To identify adaptive amino acid substitutions conferring enhanced virulence of avian H5N6 influenza viruses in mammals.
- To investigate the molecular features associated with H5N6 adaptation to a mammalian host using a mouse model.
Main Methods:
- Sequential passaging of an avian H5N6 influenza A virus in mice for 10 generations.
- Comparative analysis of viral pathogenicity, replication efficiency in vivo, and transmissibility between parent and adapted strains.
- Genome sequencing and alignment to identify amino acid substitutions in adapted viral strains.
Main Results:
- Mouse-adapted H5N6 viruses (P1 and P10) exhibited increased pathogenicity compared to the parent strain.
- P10 demonstrated significantly higher in vivo replication and was detected in mouse brains, unlike P1 which replicated in lungs but not brains.
- Key amino acid substitutions, including PB2 E627K, PB2 T23I, PA T97I, and HA R239H, were identified in the mouse-adapted H5N6 viruses.
Conclusions:
- Specific amino acid substitutions are associated with the adaptation of H5N6 influenza virus to mice.
- These identified mutations may contribute to enhanced H5N6 virulence in mammalian hosts.
- Further research into these adaptive changes is crucial for assessing pandemic potential and informing public health strategies.
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