Comparison of Host Gene Expression Profiles in Spleen Tissues of Genetically Susceptible and Resistant Mice during ECTV Infection.

Wen-Yu Cheng,Xiao-Bing He,Chun-Yan Wang,Xiao-Xia Wang,Zhi-Zhong Jing,Guo-Hua Chen,Yuan Feng,Huai-Jie Jia

doi:10.1155/2017/6456180

Abstract

Ectromelia virus (ECTV), the causative agent of mousepox, has emerged as a valuable model for investigating the host-Orthopoxvirus relationship as it relates to pathogenesis and the immune response. ECTV is a mouse-specific virus and causes high mortality in susceptible mice strains, including BALB/c and C3H, whereas C57BL/6 and 129 strains are resistant to the disease. To understand the host genetic factors in different mouse strains during the ECTV infection, we carried out a microarray analysis of spleen tissues derived from BALB/c and C57BL/6 mice, respectively, at 3 and 10 days after ECTV infection. Differential Expression of Genes (DEGs) analyses revealed distinct differences in the gene profiles of susceptible and resistant mice. The susceptible BALB/c mice generated more DEGs than the resistant C57BL/6 mice. Additionally, gene ontology and KEGG pathway analysis showed the DEGs of susceptible mice were involved in innate immunity, apoptosis, metabolism, and cancer-related pathways, while the DEGs of resistant mice were largely involved in MAPK signaling and leukocyte transendothelial migration. Furthermore, the BALB/c mice showed a strong induction of interferon-induced genes, which, however, were weaker in the C57BL/6 mice. Collectively, the differential transcriptome profiles of susceptible and resistant mouse strains with ECTV infection will be crucial for further uncovering the molecular mechanisms of the host-Orthopoxvirus interaction.

Highlights

Poxviruses comprise a diverse family of double-stranded DNA viruses that remain a threat to the human and livestock, despite the fact that naturally circulating variola virus (VARV), the causative agent of smallpox, was eradicated decades ago [1,2,3]
Compared to susceptible BALB/c mice, lower viral loads were detected in resistant C57BL/6 mice at all time points, suggesting that ectromelia virus (ECTV) infects efficiently cells of susceptible BALB/c mice
KLRC1 and KLRK1 were upregulated in both C57BL/6 and BALB/c mice at 10 dpi, but KLRG1 was upregulated only in C57BL/6 mice. These results suggest that a more enhanced innate immune response to ECTV infection occurred in BALB/c mice than in C57BL/6 mice, which may reflect fundamental differences in the genetic background of the host

Summary

Introduction

Poxviruses comprise a diverse family of double-stranded DNA viruses that remain a threat to the human and livestock, despite the fact that naturally circulating variola virus (VARV), the causative agent of smallpox, was eradicated decades ago [1,2,3]. Ly49H ( called resistance to mousepox-1, Rmp-1) maps to the BioMed Research International natural killer gene complex (NKC) and activates NK cells to control early virus replication in C57BL/6 mice, but this is lacking in BALB/c mice [11, 18,19,20] Other loci, such as the Rmp-2 locus that maps near the complement component C5 gene, Rmp-3 locus that is linked to the MHC and is gonad-dependent, and the Rmp-4 locus that maps near the selectin gene complex, are responsible for resistance to ECTV infection [11, 16, 21]. Other components of innate immunity, such as phagocytes, antigen-presenting cells, granzymes A and B, nitric oxide synthase 2, IL-12, and IL-18, play essential roles in inherent resistance to mousepox [31,32,33,34,35,36,37]

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Results

Conclusion