MAIDS resistance-associated gene expression patterns in secondary lymphoid organs.
Murine acquired immunodeficiency syndrome (MAIDS) is caused by exposure to murine leukemia virus and serves as a model to study human AIDS. In MAIDS-susceptible C57BL/6 mice, virus exposure leads to progressive immune deficiency, while resistant strains such as BALB/c recover from infection and develop protective immunity. The goal of this study was to identify early gene expression patterns that may be important in establishing this strain-specific differential response. Total RNA was isolated from spleens and pooled lymph nodes of both mouse strains at 3 and 7 days post virus infection. The complementary DNA generated from this RNA was hybridized to mouse oligonucleotide DNA microarrays using a strategy that controlled for inherent variability and highlighted only virus-induced changes. Fluorescent intensities were normalized and analyzed for statistically significant differential expression between strains across both time points and lymphoid organs. The majority of the resistance-associated genes was identified at day 3 post-infection and demonstrated the highest fold differences between strains, while more susceptibility-associated sequences were seen at 7 days post-infection. Among the most highly differentially expressed sequences seen at the earlier time point were genes related to protein metabolism, especially serine proteases. Differential patterns of chemokine-related genes were observed at the later time point. The overall pattern of expression suggests strain-specific differences in proteases and chemokines within secondary lymphoid organs shortly after infection influence the likelihood of disease progression.
Tepsuporn
Suprawee
S
Department of Biological Sciences, Mount Holyoke College, South Hadley, MA 01075, USA.
Horwitt
Jedediah N
JN
Cobb
George W
GW
Stranford
Sharon A
SA
D000818:Animals; D020869:Gene Expression Profiling; D009052:Leukemia Virus, Murine / Q000276:immunology / Q000502:physiology*; D008198:Lymph Nodes / Q000378:metabolism; D008208:Lymphatic System / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016183:Murine Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000378:metabolism* / Q000821:virology; D020411:Oligonucleotide Array Sequence Analysis; D013045:Species Specificity; D013154:Spleen / Q000378:metabolism; D013997:Time Factors; D014779:Virus Replication