Gene expression changes in the host response between resistant and susceptible inbred mouse strains after influenza A infection

Abstract

Inbred mouse strains exhibit differences in susceptibility to influenza A infections. However, the molecular mechanisms underlying these differences are unknown. Therefore, we infected a highly susceptible mouse strain (DBA/2J) and a resistant strain (C57BL/6J) with influenza A H1N1 (PR8) and performed genome-wide expression analysis. We found genes expressed in lung epithelium that were specifically downregulated in DBA/2J mice, whereas a cluster of genes on chromosome 3 was only down-regulated in C57BL/6J. In both mouse strains, chemokines, cytokines and interferon-response genes were up-regulated, indicating that the main innate immune defense pathways were activated. However, many immune response genes were up-regulated in DBA/2J much stronger than in C57BL/6J, and several immune response genes were exclusively regulated in DBA/2J. Thus, susceptible DBA/2J mice showed a hyper-inflammatory response. This response is similar to infections with highly pathogenic influenza virus and may serve as a paradigm for a hyper-inflammatory host response to influenza A virus.

Infection with Seasonal Influenza Virus Elicits CD4 T Cells Specific for Genetically Conserved Epitopes That Can Be Rapidly Mobilized for Protective Immunity to Pandemic H1N1 Influenza Virus

“…1B) was analyzed. This result is consistent with recently published work that has evaluated differences in the pathogenicity of H1N1 and other influenza viruses in inbred mice (1,6,58).…”

“…First, our studies revealed that different inbred mouse strains are differentially susceptible to the pathological consequences of infection with the H1N1 strain of the virus: A/J mice are more susceptible than BALB/c and C57BL/10 mice (not shown). Other studies have shown that the mouse genetic background can dramatically impact susceptibility to influenza A virus strains (1,6,7,58). In one particularly systematic study of protective immunity to A/Puerto Rico/8/34 (A/PR8) (58), a mouse-adapted laboratory strain of influenza virus, A/J and DBA/2 mice displayed the most susceptibility to infection, while C57BL/6, BALB/c, CBA, and FVB/NJ mice were among the more resistant strains and ultimately recovered from infection.…”

Distinctive and critical roles for cellular immunity and immune-inflammatory response in the immunopathology of Sendai virus infection in mice

“…A similar conclusion was drawn in a recent study with influenza A virus infection in mice [50]. Nonetheless, our data emphasize the overall complexity of the processes involved, which can be attributed to the participation of many differentially expressed gene products in the anti-inflammatory regulatory circuits.…”

A New Mouse Model Reveals a Critical Role for Host Innate Immunity in Resistance to Rift Valley Fever

“…West Nile virus strain IS-98-ST1 was isolated from a white stork in Israel; it is highly neuroinvasive in adult mice (21). A/Puerto Rico/8/34 (H1N1) PR8 FR 0807 influenza virus is a mouse-adapted strain (22,23). Viral stocks were produced under biosafety level 3 conditions.…”