title: Differential expression of immunoregulatory genes in male and female Norway rats following infection with Seoul virus.
abstract: Males of many species are more susceptible than females to infections caused by parasites, bacteria, fungi, and viruses. Following inoculation with Seoul virus, male rats have more virus present in target organs and shed virus longer than females. The goal of this study was to test the hypothesis that variation in the expression of genes associated with immune function mediates sex differences in hantavirus infection. Using DNA microarrays, we examined changes in gene expression in lung tissue during the early (when animals are viremic and shedding virus; Day 15 post-inoculation (p.i.)) and late (animals have low levels of infectious virus, but high antibody titers; Day 40 p.i.) phases of infection in adult male and female rats. After normalizing the gene expression levels from infected animals to the gene expression levels from same-sex uninfected controls, our data revealed that 1,813 genes were differentially expressed between the sexes during infection. The expression of key transcriptional factors (e.g., eIF-2 alpha, NF-kappa B, IRF-1, NF-IL-6, and STAT6) and genes that encode for proinflammatory (e.g., TNF alpha R, IL-1R, and IL-1RAcP), antiviral (e.g., IFN gamma R and Mx proteins), T cell (e.g., CD3 and TCR), and Ig superfamily (e.g., IgM, IgG, and MHC class I and II) proteins was higher in females than males. Conversely, males had higher expression of heat shock protein genes (e.g., hsp70) suggesting that cellular stress is elevated in males. These data provide candidate genes and cellular pathways that may underlie sex differences in responses to Seoul virus and possibly other hemorrhagic fever viruses.
authors.affiliation: W. Harry Feinstone Department of Molecular Microbiology and Immunology, The Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland 21205, USA. saklein@jhsph.edu
authors.forename: Sabra L
authors.initials: SL
authors.lastname: Klein
authors.forename: Amy
authors.initials: A
authors.lastname: Cernetich
authors.forename: Sara
authors.initials: S
authors.lastname: Hilmer
authors.forename: Eric P
authors.initials: EP
authors.lastname: Hoffman
authors.forename: Alan L
authors.initials: AL
authors.lastname: Scott
authors.forename: Gregory E
authors.initials: GE
authors.lastname: Glass
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D012739:Gonadal Steroid Hormones / Q000276:immunology; D006360:Heat-Shock Proteins / Q000235:genetics; D006480:Hemorrhagic Fever with Renal Syndrome / Q000235:genetics* / Q000276:immunology* / Q000821:virology; D007155:Immunologic Factors / Q000235:genetics; D008168:Lung / Q000276:immunology; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D051381:Rats; D029263:Seoul virus / Q000276:immunology; D012727:Sex Characteristics; D014157:Transcription Factors / Q000235:genetics; D014158:Transcription, Genetic
chemical_list: D012739:Gonadal Steroid Hormones; D006360:Heat-Shock Proteins; D007155:Immunologic Factors; D014157:Transcription Factors