title: Targeted disruption of influenza A virus hemagglutinin in genetically modified mice reduces viral replication and improves disease outcome.
abstract: Influenza A virus can cause acute respiratory infection in animals and humans around the globe, and is still a major threat to animal husbandry and public health. Due to antigenic drift and antigenic shift of the virus, development of novel anti-influenza strategies has become an urgent task. Here we generated transgenic (TG) mice stably expressing a short-hairpin RNA specifically targeting hemagglutinin (HA) of influenza A virus, and investigated the susceptibility of the mice to influenza virus infection. We found that HA expression was dramatically disrupted in TG mice infected with WSN or PR8 virus. Importantly, the animals showed reduced virus production in lungs, slower weight loss, attenuated acute organ injury and consequently increased survival rates as compared to wild type (WT) mice after the viral infection. Moreover, TG mice exhibited a normal level of white blood cells following the virus infection, whereas the number of these cells was significantly decreased in WT mice with same challenge. Together, these experiments demonstrate that the TG mice are less permissive for influenza virus replication, and suggest that shRNA-based efficient disruption of viral gene expression in animals may be a useful strategy for prevention and control of a viral zoonosis.
authors.affiliation: College of Animal Sciences, Fujian Agriculture and Forestry University, Fuzhou 350002, Fujian, China.
authors.forename: Song
authors.initials: S
authors.lastname: Wang
authors.affiliation: College of Animal Sciences, Fujian Agriculture and Forestry University, Fuzhou 350002, Fujian, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Chen
authors.affiliation: College of Animal Sciences, Fujian Agriculture and Forestry University, Fuzhou 350002, Fujian, China.
authors.forename: Zhou
authors.initials: Z
authors.lastname: Yang
authors.affiliation: College of Animal Sciences, Fujian Agriculture and Forestry University, Fuzhou 350002, Fujian, China.
authors.forename: Xiaojuan
authors.initials: X
authors.lastname: Chi
authors.affiliation: Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing 100101, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: College of Animal Sciences, Fujian Agriculture and Forestry University, Fuzhou 350002, Fujian, China.|Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing 100101, China.
authors.forename: Ji-Long
authors.initials: JL
authors.lastname: Chen
mesh_terms: D000818:Animals; D002460:Cell Line; D005260:Female; D015967:Gene Expression Regulation, Viral; D055785:Gene Knockdown Techniques; D005822:Genetic Vectors / Q000235:genetics; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics*; D053118:Influenza A Virus, H1N1 Subtype / Q000235:genetics* / Q000502:physiology; D007970:Leukopenia / Q000209:etiology; D008168:Lung / Q000473:pathology / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D009976:Orthomyxoviridae Infections / Q000097:blood / Q000473:pathology / Q000517:prevention & control* / Q000821:virology; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics*; D013154:Spleen / Q000473:pathology; D013950:Thymus Gland / Q000473:pathology; D014779:Virus Replication
chemical_list: D019267:Hemagglutinin Glycoproteins, Influenza Virus; D034741:RNA, Small Interfering; C483468:hemagglutinin, human influenza A virus