Ectromelia virus (ECTV) is a mouse-specific orthopoxvirus that is related closely to Variola virus and Monkeypox virus,the causative agent of smallpox and monkeypox,respectively.ECTV has emerged as a valuable model to investigate the host-orthopoxvirus relationship as it relates to pathogenesis and the immune response.ECTV causes mousepox in most strains of mice,such as BALB/c and DBA/2 strains,which are classified as susceptible mice,while C57BL/6 and certain 129 strains have very low mortality and limited pathology and are classified as resistant mice.To understand the host genetic factors of different mice strains response to ECTV infection,we carried out a microarray analysis with Affymetrix Gene-Chip Mouse Genome Arrays in spleen tissues of BALB/e and C57BL/6 mice at 72 h and 10 d post ECTV-infection.Differential Expression of Genes (DEGs) analysis showed that distinct differences exist in gene profiles expressed in resistant and susceptible mice infected with ECTV.Susceptible BALB/c mice generate more DEGs (743 DEGs at 72 hpi and 2184 DEGs at 10 dpi) than resistant C57BL/6 mice (361 DEGs at 72 hpi and 1619 DEGs at 10 dpi) during the ECTV infection.In addition,gene ontology and KEGG pathway analysis showed that DEGs of susceptible mice were mainly involved in immunity,apoptosis,spliceosome and pathway in cancer,while fewer DEGs of resistant mice were mainly involved in MAPK signaling pathway and leukocyte transendothelial migration,suggesting BALB/c mice have a stronger response to the ECTV infection.