HIV-1 transcription and virus production are both accentuated by the proinflammatory myeloid-related proteins in human CD4+ T lymphocytes.
S100A8, S100A9, and S100A12, collectively known as myeloid-related proteins (MRPs), are highly expressed by the myeloid cell lineage and are found in the extracellular milieu during infections and inflammatory conditions. Recent data showed high levels of MRPs in the serum of HIV type 1 (HIV-1)-infected patients which correlated with disease progression and low CD4(+) counts. Therefore, we set out to investigate the effect of MRPs on HIV-1 replication. We observed a 4- to 5-fold induction of virus production in J1.1, a human T lymphoid cell line latently infected with HIV-1, following treatment with MRPs. Using luciferase-based reporter gene assays, we demonstrated that MRPs induce a dose- and time-dependent activation of the HIV-1 long terminal repeat promoter region that could be blocked by specific anti-MRP polyclonal Abs and by physical denaturation of these proteins. The MRP-mediated induction was acting through the HIV-1 enhancer sequence and was dependent upon NF-kappaB activity. These latter results were also confirmed by EMSA experiments conducted in Jurkat cells and freshly isolated PBMCs. In conclusion, we demonstrate that MRPs induce HIV-1 transcriptional activity and viral replication in infected CD4(+) T-lymphocytes at concentrations similar to those found in the serum of HIV-1-infected patients.
Ryckman
Carle
C
Centre de Recherche en Infectiologie, Pavillon Centre Hospitalier de l'Université Laval, Centre Hospitalier Universitaire de Québec, and Département de Biologie Médicale, Faculté de Médecine, Université Laval, Québec, Canada.
Robichaud
Gilles A
GA
Roy
Jocelyn
J
Cantin
Réjean
R
Tremblay
Michel J
MJ
Tessier
Philippe A
PA
D000943:Antigens, Differentiation / Q000502:physiology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D002135:Calcium-Binding Proteins / Q000502:physiology*; D040501:Calgranulin A; D040502:Calgranulin B; D016322:HIV Enhancer / Q000276:immunology; D015497:HIV-1 / Q000235:genetics* / Q000276:immunology* / Q000502:physiology; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000821:virology; D019169:Jurkat Cells; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism / Q000821:virology; D022423:Myeloid Cells / Q000276:immunology / Q000473:pathology / Q000821:virology; D016328:NF-kappa B / Q000502:physiology; D009418:S100 Proteins / Q000502:physiology*; D000067616:S100A12 Protein; D014158:Transcription, Genetic / Q000276:immunology*; D014162:Transfection; D014775:Virus Activation / Q000276:immunology; D017735:Virus Latency / Q000276:immunology; D014779:Virus Replication / Q000276:immunology*
D000943:Antigens, Differentiation; D002135:Calcium-Binding Proteins; D040501:Calgranulin A; D040502:Calgranulin B; D016328:NF-kappa B; D009418:S100 Proteins; D000067616:S100A12 Protein; C090441:S100A12 protein, human