Functional genomics analyses of differential macaque peripheral blood mononuclear cell infections by human immunodeficiency virus-1 and simian immunodeficiency virus.
The pathogenicity of the primate lentiviruses, human, and simian immunodeficiency viruses, is host-specific. Previous studies indicated that the highly pathogenic human lentivirus HIV-1 has markedly reduced pathogenicity compared to the pathogenic simian lentivirus SIV in pigtail macaques (Macaca nemestrina). We therefore hypothesized that the pigtail macaque peripheral blood mononuclear cells (mPBMCs) would respond differently to infections of HIV-1 and pathogenic SIV. To elucidate the cellular responses to the infections of HIV-1 and SIV, we infected mPBMC with these two viruses. Like infections in vivo, HIV-1 and SIV demonstrated distinct replication kinetics in mPBMCs, with HIV-1 replicating at significantly lower levels. Similarly, gene expression profiling facilitated by macaque-specific oligonucleotide microarrays also revealed distinct expression patterns of genes between the HIV-1- and SIV-infected mPBMCs; in particular, genes associated with the antigen presentation, T cell receptor, ERK/MAPK signaling, Wnt/beta-catenin signaling, and natural killer cell signaling pathways were differentially regulated between these two viruses. Most interestingly, despite the lower levels of replication, HIV-1 triggered a more robust regulation of immune response genes early after infection; the converse was true in SIV-infected mPBMCs. Our results therefore suggest that macaques may be controlling the infection of HIV-1 at an early stage through coordinated regulation of host defense pathways.
Li
Yu
Y
Department of Microbiology and Washington National Primate Research Center, University of Washington, Box 358070, Seattle, WA 98195-8070, USA.
Chan
Eric Y
EY
Katze
Michael G
MG
D000818:Animals; D015967:Gene Expression Regulation, Viral; D016679:Genome, Viral; D023281:Genomics; D015497:HIV-1 / Q000235:genetics / Q000472:pathogenicity*; D006681:HLA-D Antigens; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D007963:Leukocytes, Mononuclear / Q000821:virology*; D008254:Macaca nemestrina; D020411:Oligonucleotide Array Sequence Analysis; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000472:pathogenicity*; D013045:Species Specificity
D006681:HLA-D Antigens; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D011948:Receptors, Antigen, T-Cell