title: In utero activation of fetal memory T cells alters host regulatory gene expression and affects HIV susceptibility.
abstract: In utero priming to malaria antigens renders cord blood mononuclear cells (CBMC) more susceptible to productive HIV infection in vitro in the absence of exogenous stimulation. This provides a unique model to better understand mechanisms affecting lymphocyte susceptibility to HIV infection in vivo. Effector memory CD3(+)CD4(+) T cells (T(EM)) were the exclusive initial targets of HIV with rapid spread to central memory cells. HIV susceptibility correlated with increased expression of CD25 and HLA-DR on T(EM). Virus entered all samples equally, however gag/pol RNA was only detected in HIV susceptible samples, suggesting regulation of proviral gene transcription. Targeted analysis of human genes in memory T cells showed greater expression of IFNG, NFATc1, IRF1, FOS, and PPIA and decreased expression YY1 and TFCP2 in HIV susceptible samples. Thus fetal priming to exogenous antigens enhances specific proviral gene transcription pathways in effector memory cells that may increase risk of vertical transmission of HIV.
authors.affiliation: Center for Global Health and Diseases, Case Western Reserve University, Cleveland, OH 44106-7286, USA.
authors.forename: Kevin L
authors.initials: KL
authors.lastname: Steiner
authors.forename: Indu
authors.initials: I
authors.lastname: Malhotra
authors.forename: Peter L
authors.initials: PL
authors.lastname: Mungai
authors.forename: Eric M
authors.initials: EM
authors.lastname: Muchiri
authors.forename: Arlene E
authors.initials: AE
authors.lastname: Dent
authors.forename: Christopher L
authors.initials: CL
authors.lastname: King
mesh_terms: D017252:CD3 Complex / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D004198:Disease Susceptibility / Q000276:immunology; D005260:Female; D005312:Fetal Blood / Q000276:immunology*; D005786:Gene Expression Regulation; D015658:HIV Infections / Q000276:immunology / Q000635:transmission* / Q000821:virology; D015497:HIV-1 / Q000276:immunology*; D006684:HLA-DR Antigens / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology*; D018445:Infectious Disease Transmission, Vertical; D053645:Interleukin-2 Receptor alpha Subunit / Q000235:genetics / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology*; D011247:Pregnancy
chemical_list: D017252:CD3 Complex; D006684:HLA-DR Antigens; D053645:Interleukin-2 Receptor alpha Subunit