The effect of allogeneic in vitro stimulation and in vivo immunization on memory CD4(+) T-cell APOBEC3G expression and HIV-1 infectivity.
Allogeneic immunity is one of the most potent natural immune responses. APOBEC3G (A3G) is an intracellular anti-viral factor that deaminates cytidine to uridine. Allogeneic stimulation of human CD4(+) T cells in vitro upregulated A3G mRNA and a significant correlation was found between the mixed leukocyte reaction and A3G mRNA. The mechanism of upregulation of A3G mRNA involves interaction between HLA on DC and TCR of CD4(+) T cells, which is ZAP70 and downstream ERK phosphokinase signalling dependent and induces CD40L and A3G mRNA expression in CD4(+) T cells. Alloimmune-induced A3G was found to be significantly increased in CD45RA(-), CCR5(+) and CD45RA(-)CCR7(-) subsets of effector memory T cells. In vivo studies of women alloimmunized with their partners' PBMC also showed a significant increase in A3G protein in CD4(+) T cells, CD45RO(+) memory and CCR7(-) effector memory T cells. The functional effect of allostimulation upregulating A3G mRNA was demonstrated by a significant decrease in in vitro infectivity, using GFP-labelled pseudovirus and confirmed by a decrease in HIV-1 (BaL) infection of primary CD4(+) T cells. The results suggest that alloimmunization offers an alternative or complementary strategy in inducing an innate anti-viral factor that inhibits HIV-1 infection.
Pido-Lopez
Jeffrey
J
Kings College London, Guy's Hospital, London, UK.
Jeffrey
Pido-Lopez
PL
Wang
Yufei
Y
Seidl
Thomas
T
Babaahmady
Kaboutar
K
Vaughan
Robert
R
Lehner
Thomas
T
D000071480:APOBEC-3G Deaminase; D015153:Blotting, Western; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D023201:CD40 Ligand / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D002478:Cells, Cultured; D003564:Cytidine Deaminase / Q000235:genetics / Q000378:metabolism*; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D005260:Female; D005455:Fluorescent Antibody Technique; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D015497:HIV-1 / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism; D006801:Humans; D007114:Immunization; D007156:Immunologic Memory / Q000276:immunology*; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D034741:RNA, Small Interfering / Q000235:genetics; D019713:Receptors, CCR5 / Q000378:metabolism; D054400:Receptors, CCR7 / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000037:antagonists & inhibitors / Q000378:metabolism
C515370:CCR7 protein, human; D004791:Enzyme Inhibitors; D034741:RNA, Small Interfering; D019713:Receptors, CCR5; D054400:Receptors, CCR7; D023201:CD40 Ligand; D049452:Green Fluorescent Proteins; D051746:ZAP-70 Protein-Tyrosine Kinase; C497261:ZAP70 protein, human; D048049:Extracellular Signal-Regulated MAP Kinases; D017493:Leukocyte Common Antigens; D000071480:APOBEC-3G Deaminase; C464924:APOBEC3G protein, human; D003564:Cytidine Deaminase