Treponema pallidum, lipoproteins, and synthetic lipoprotein analogues induce human immunodeficiency virus type 1 gene expression in monocytes via NF-kappaB activation.
Syphilitic genital ulcers are cofactors for the bidirectional transmission of human immunodeficiency virus (HIV). U937 human promonocytic cells chronically infected with HIV-1 (U1 cells) or transiently transfected with wild type or mutant HIV long terminal repeat (LTR) reporter constructs were used to examine mechanisms that likely underlie Treponema pallidum-induced immune cell activation and consequent induction of HIV. Virulent T. pallidum, a representative native treponemal lipoprotein (NTp47), or synthetic lipoprotein analogues (lipopeptides) all induced HIV replication in U1 cells. These stimuli also induced HIV gene expression from a wild type HIV LTR. HIV gene expression correlated with the translocation of NF-kappaB, and mutations within the NF-kappaB binding sites of the HIV LTR abrogated HIV gene expression. This study implicates treponemal lipoproteins as key mediators of immune cell activation and provides insights into the cellular and molecular bases for enhanced HIV transmission in syphilitic persons.
Theus
S A
SA
Department of Microbiology, University of Texas Southwestern Medical Center, Dallas 75235-9048, USA.
Harrich
D A
DA
Gaynor
R
R
Radolf
J D
JD
Norgard
M V
MV
D000818:Animals; D019677:Artificial Gene Fusion; D001483:Base Sequence; D018562:Disease Transmission, Infectious; D015870:Gene Expression; D017930:Genes, Reporter; D016655:HIV Core Protein p24 / Q000032:analysis; D015658:HIV Infections / Q000235:genetics* / Q000276:immunology / Q000635:transmission; D016325:HIV Long Terminal Repeat / Q000235:genetics*; D015497:HIV-1 / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008074:Lipoproteins / Q000138:chemical synthesis / Q000235:genetics / Q000276:immunology*; D008969:Molecular Sequence Data; D009000:Monocytes / Q000276:immunology; D016328:NF-kappa B / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D010957:Plasmids; D011817:Rabbits; D011995:Recombination, Genetic; D014162:Transfection; D014178:Translocation, Genetic / Q000235:genetics / Q000276:immunology; D014210:Treponema pallidum / Q000276:immunology*; D014407:Tumor Cells, Cultured; D014779:Virus Replication / Q000235:genetics / Q000276:immunology
D016655:HIV Core Protein p24; D008074:Lipoproteins; D016328:NF-kappa B