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: Song Wang, Chao Chen, Zhou Yang, Xiaojuan Chi, Jing Zhang, Ji-Long Chen
• Journal: Scientific reports (Sci Rep) Vol. 6 Pg. 23746 (Apr 01 2016) ISSN: 2045-2322 [Electronic] England
• PMID: 27033724 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Hemagglutinin Glycoproteins, Influenza Virus
• RNA, Small Interfering
• hemagglutinin, human influenza A virus

Topics

• Animals
• Cell Line
• Female
• Gene Expression Regulation, Viral
• Gene Knockdown Techniques
• Genetic Vectors (genetics)
• Hemagglutinin Glycoproteins, Influenza Virus (genetics)
• Influenza A Virus, H1N1 Subtype (genetics, physiology)
• Leukopenia (etiology)
• Lung (pathology, virology)
• Mice
• Mice, Inbred BALB C
• Mice, Transgenic
• Orthomyxoviridae Infections (blood, pathology, prevention & control, virology)
• RNA Interference
• RNA, Small Interfering (genetics)
• Spleen (pathology)
• Thymus Gland (pathology)
• Virus Replication