RNAseq expression analysis of resistant and susceptible mice after influenza A virus infection identifies novel genes associated with virus replication and important for host resistance to infection.
BACKGROUND
The host response to influenza A infections is strongly influenced by host genetic factors. Animal models of genetically diverse mouse strains are well suited to identify host genes involved in severe pathology, viral replication and immune responses. Here, we have utilized a dual RNAseq approach that allowed us to investigate both viral and host gene expression in the same individual mouse after H1N1 infection.


RESULTS
We performed a detailed expression analysis to identify (i) correlations between changes in expression of host and virus genes, (ii) host genes involved in viral replication, and (iii) genes showing differential expression between two mouse strains that strongly differ in resistance to influenza infections. These genes may be key players involved in regulating the differences in pathogenesis and host defense mechanisms after influenza A infections. Expression levels of influenza segments correlated well with the viral load and may thus be used as surrogates for conventional viral load measurements. Furthermore, we investigated the functional role of two genes, Reg3g and Irf7, in knock-out mice and found that deletion of the Irf7 gene renders the host highly susceptible to H1N1 infection.


CONCLUSIONS
Using RNAseq analysis we identified novel genes important for viral replication or the host defense. This study adds further important knowledge to host-pathogen-interactions and suggests additional candidates that are crucial for host susceptibility or survival during influenza A infections.
Department of Infection Genetics, Helmholtz Centre for Infection Research and University of Veterinary Medicine Hannover, Inhoffenstr. 7, 38124, Braunschweig, Germany.
Esther
E
Wilk
Department of Genetics, Genomics and Informatics, Center for Integrative and Translational Genomics, University of Tennessee Health Science Center, 855 Madison Avenue, Memphis, TN, 38163, USA.
Ashutosh K
AK
Pandey
Department of Infection Genetics, Helmholtz Centre for Infection Research and University of Veterinary Medicine Hannover, Inhoffenstr. 7, 38124, Braunschweig, Germany.
Sarah Rebecca
SR
Leist
Department of Infection Genetics, Helmholtz Centre for Infection Research and University of Veterinary Medicine Hannover, Inhoffenstr. 7, 38124, Braunschweig, Germany.
Bastian
B
Hatesuer
Institute for Experimental Infection Research, TWINCORE Centre for Experimental and Clinical Infection Research, Hannover, Germany.|Department of Molecular Bacteriology, Helmholtz Centre for Infection Research, Braunschweig, Germany.
Matthias
M
Preusse
Leibniz-Institut DSMZ-Deutsche Sammlung von Mikroorganismen und Zellkulturen GmbH, Inhoffenstr. 7B, 38124, Braunschweig, Germany.
Claudia
C
Pommerenke
Bioinformatics and Statistics, Helmholtz Centre for Infection Research, Braunschweig, Germany.
Junxi
J
Wang
Department of Infection Genetics, Helmholtz Centre for Infection Research and University of Veterinary Medicine Hannover, Inhoffenstr. 7, 38124, Braunschweig, Germany. kls@helmholtz-hzi.de.|Department of Microbiology, Immunology and Biochemistry, University of Tennessee Health Science Center, Memphis, USA. kls@helmholtz-hzi.de.
Klaus
K
Schughart
D000818:Animals; D001835:Body Weight; D060467:Disease Resistance / Q000235:genetics*; D004198:Disease Susceptibility; D020869:Gene Expression Profiling; D015967:Gene Expression Regulation, Viral; D005814:Genes, Viral; D054884:Host-Pathogen Interactions / Q000235:genetics*; D007113:Immunity, Innate / Q000235:genetics; D009980:Influenza A virus / Q000235:genetics*; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D009976:Orthomyxoviridae Infections / Q000235:genetics* / Q000821:virology*; D025341:Principal Component Analysis; D034741:RNA, Small Interfering / Q000378:metabolism; D017423:Sequence Analysis, RNA / Q000379:methods*; D015854:Up-Regulation / Q000235:genetics; D019562:Viral Load / Q000235:genetics; D014779:Virus Replication / Q000235:genetics*
D034741:RNA, Small Interfering