NDLI: Replication fitness determines high virulence of influenza A virus in mice carrying functional Mx1 resistance gene

Content Provider	PubMed Central
Author	Grimm, Daniel Peter, Staeheli Martin, Hufbauer Koerner, Iris Luis, Martínez-sobrido Alicia, Solórzano Adolfo, García-sastre Haller, Otto Kochs, Georg
Copyright Year	2007
Abstract	The IFN-induced resistance factor Mx1 is a critical component of innate immunity against influenza A viruses (FLUAV) in mice. Animals carrying a wild-type Mx1 gene (Mx1 +/+) differ from regular laboratory mice (Mx1 −/−) in that they are highly resistant to infection with standard FLUAV strains. We identified an extraordinary variant of the FLUAV strain, A/PR/8/34 (H1N1) (designated hvPR8), which is unusually virulent in Mx1 +/+ mice. hvPR8 was well controlled in Mx1 +/+ but not Mx1 −/− mice provided that the animals were treated with IFN before infection, indicating that hvPR8 exhibits normal sensitivity to growth restriction by Mx1. hvPR8 multiplied much faster than standard PR8 early in infection because of highly efficient viral gene expression in infected cells. Studies with reassortant viruses containing defined genome segments of both hvPR8 and standard PR8 demonstrated that the HA, neuraminidase, and polymerase genes of hvPR8 all contributed to virulence, indicating that efficient host cell entry and early gene expression renders hvPR8 highly pathogenic. These results reveal a surprisingly simple concept of how influenza viruses may gain virulence and illustrate that high speed of virus growth can outcompete the antiviral response of the infected host.
Related Links	http://dx.doi.org/10.1073/pnas.0701849104
Ending Page	6811
Page Count	6
Starting Page	6806
File Format	PDF
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	16
Volume Number	104
Language	English
Publisher	National Academy of Sciences
Publisher Date	2007-04-17
Access Restriction	Open
Rights Holder	National Academy of Sciences
Subject Keyword	General Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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