Genomic analysis reveals age-dependent innate immune responses to severe acute respiratory syndrome coronavirus.
The relationship between immunosenescence and the host response to virus infection is poorly understood at the molecular level. Two different patterns of pulmonary host responses to virus were observed when gene expression profiles from severe acute respiratory syndrome coronavirus (SARS-CoV)-infected young mice that show minimal disease were compared to those from SARS-CoV-infected aged mice that develop pneumonitis. In young mice, genes related to cellular development, cell growth, and cell cycle were downregulated during peak viral replication, and these transcripts returned to basal levels as virus was cleared. In contrast, aged mice had a greater number of upregulated immune response and cell-to-cell signaling genes, and the expression of many genes was sustained even after viral clearance, suggesting an exacerbated host response to virus. Interestingly, in SARS-CoV-infected aged mice, a subset of genes, including Tnfa, Il6, Ccl2, Ccl3, Cxcl10, and Ifng, was induced in a biphasic pattern that correlated with peak viral replication and a subsequent influx of lymphocytes and severe histopathologic changes in the lungs. We provide insight into gene expression profiles and molecular signatures underlying immunosenescence in the context of the host response to viral infection.
Baas
Tracey
T
Department of Microbiology, Box 358070, University of Washington, Seattle, WA 98195-8070, USA. traceybaas@gmail.com
Roberts
Anjeanette
A
Teal
Thomas H
TH
Vogel
Leatrice
L
Chen
Jun
J
Tumpey
Terrence M
TM
Katze
Michael G
MG
Subbarao
Kanta
K
D000818:Animals; D004797:Enzyme-Linked Immunosorbent Assay; D016678:Genome; D023281:Genomics; D007107:Immune System / Q000821:virology*; D007113:Immunity, Innate; D008214:Lymphocytes / Q000378:metabolism / Q000821:virology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008954:Models, Biological; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000378:metabolism; D045473:Severe acute respiratory syndrome-related coronavirus / Q000235:genetics* / Q000378:metabolism; D013997:Time Factors; D014779:Virus Replication
D012333:RNA, Messenger