Gene expression profiling of the host response to HIV-1 B, C, or A/E infection in monocyte-derived dendritic cells.
Dendritic cells (DC) are among the first targets of human immunodeficiency virus type-1 (HIV-1) infection and in turn play a crucial role in viral transmission to T cells and in the regulation of the immune response. The major group of HIV-1 has diversified genetically based on variation in env sequences and comprise at least 11 subtypes. Because little is known about the host response elicited against different HIV-1 clade isolates in vivo, we sought to use gene expression profiling to identify genes regulated by HIV-1 subtypes B, C, and A/E upon de novo infection of primary immature monocyte-derived DC (iMDDCs). A total of 3700 immune-related genes were subjected to a significance analysis of microarrays (SAM); 656 genes were selected as significant and were further divided into 8 functional categories. Regardless of the time of infection, 20% of the genes affected by HIV-1 were involved in signal transduction, followed by 14% of the genes identified as transcription-related genes, and 7% were classified as playing a role in cell proliferation and cell cycle. Furthermore, 7% of the genes were immune response genes. By 72 h postinfection, genes upregulated by subtype B included the inhibitor of the matrix metalloproteinase TIMP2 and the heat shock protein 40 homolog (Hsp40) DNAJB1, whereas the IFN inducible gene STAT1, the MAPK1/ERK2 kinase regulator ST5, and the chemokine CXCL3 and SHC1 genes were induced by subtypes C and A/E. These analyses distinguish a temporally regulated host response to de novo HIV-1 infection in primary dendritic cells.
Solis
Mayra
M
McGill AIDS Center, Lady Davis Institute for Medical Research, Jewish General Hospital, Department of Microbiology and Immunology, McGill University, 3755 Cote Ste. Catherine, Montreal, Quebec, Canada H3T1E2.
Wilkinson
Peter
P
Romieu
Raphaelle
R
Hernandez
Eduardo
E
Wainberg
Mark A
MA
Hiscott
John
J
D002454:Cell Differentiation; D003713:Dendritic Cells / Q000276:immunology / Q000821:virology*; D020869:Gene Expression Profiling; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000145:classification / Q000472:pathogenicity*; D006801:Humans; D009000:Monocytes / Q000276:immunology / Q000821:virology*; D020411:Oligonucleotide Array Sequence Analysis; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D013045:Species Specificity
D011506:Proteins