title: Upregulation of innate antiviral restricting factor expression in the cord blood and decidual tissue of HIV-infected mothers.
abstract: Programs for the prevention of mother-to-child transmission of HIV have reduced the transmission rate of perinatal HIV infection and have thereby increased the number of HIV-exposed uninfected (HEU) infants. Natural immunity to HIV-1 infection in both mothers and newborns needs to be further explored. In this study, we compared the expression of antiviral restricting factors in HIV-infected pregnant mothers treated with antiretroviral therapy (ART) in pregnancy (n=23) and in cord blood (CB) (n=16), placental tissues (n=10-13) and colostrum (n=5-6) samples and compared them to expression in samples from uninfected (UN) pregnant mothers (n=21). Mononuclear cells (MNCs) were prepared from maternal and CB samples following deliveries by cesarean section. Maternal (decidua) and fetal (chorionic villus) placental tissues were obtained, and colostrum was collected 24 h after delivery. The mRNA and protein expression levels of antiviral factors were then evaluated. We observed a significant increase in the mRNA expression levels of antiviral factors in MNCs from HIV-infected mothers and CB, including the apolipoprotein B mRNA-editing enzyme 3G (A3G), A3F, tripartite motif family-5α (TRIM-5α), TRIM-22, myxovirus resistance protein A (MxA), stimulator of interferon (IFN) genes (STING) and IFN-β, compared with the levels detected in uninfected (UN) mother-CB pairs. Moreover, A3G transcript and protein levels and α-defensin transcript levels were decreased in the decidua of HIV-infected mothers. Decreased TRIM-5α protein levels in the villi and increased STING mRNA expression in both placental tissues were also observed in HIV-infected mothers compared with uninfected (UN) mothers. Additionally, colostrum cells from infected mothers showed increased tetherin and IFN-β mRNA levels and CXCL9 protein levels. The data presented here indicate that antiviral restricting factor expression can be induced in utero in HIV-infected mothers. Future studies are warranted to determine whether this upregulation of antiviral factors during the perinatal period has a protective effect against HIV-1 infection.
authors.affiliation: Laboratory of Dermatology and Immunodeficiencies, LIM-56, Department of Dermatology, Medical School, Tropical Medicine Institute of São Paulo, University of São Paulo, São Paulo, São Paulo, Brazil.
authors.forename: Nátalli Zanete
authors.initials: NZ
authors.lastname: Pereira
authors.affiliation: Laboratory of Dermatology and Immunodeficiencies, LIM-56, Department of Dermatology, Medical School, Tropical Medicine Institute of São Paulo, University of São Paulo, São Paulo, São Paulo, Brazil.
authors.forename: Elaine Cristina
authors.initials: EC
authors.lastname: Cardoso
authors.affiliation: Laboratory of Dermatology and Immunodeficiencies, LIM-56, Department of Dermatology, Medical School, Tropical Medicine Institute of São Paulo, University of São Paulo, São Paulo, São Paulo, Brazil.
authors.forename: Luanda Mara da Silva
authors.initials: LM
authors.lastname: Oliveira
authors.affiliation: Laboratory of Dermatology and Immunodeficiencies, LIM-56, Department of Dermatology, Medical School, Tropical Medicine Institute of São Paulo, University of São Paulo, São Paulo, São Paulo, Brazil.
authors.forename: Josenilson Feitosa
authors.initials: JF
authors.lastname: de Lima
authors.affiliation: Laboratory of Dermatology and Immunodeficiencies, LIM-56, Department of Dermatology, Medical School, Tropical Medicine Institute of São Paulo, University of São Paulo, São Paulo, São Paulo, Brazil.
authors.forename: Anna Cláudia Calvielli Castelo
authors.initials: AC
authors.lastname: Branco
authors.affiliation: Hospital das Clínicas, Department of Obstetrics and Gynecology, Medical School, University of São Paulo, São Paulo, São Paulo, Brazil.
authors.forename: Rosa Maria de Souza Aveiro
authors.initials: RM
authors.lastname: Ruocco
authors.affiliation: Hospital das Clínicas, Department of Obstetrics and Gynecology, Medical School, University of São Paulo, São Paulo, São Paulo, Brazil.
authors.forename: Marcelo
authors.initials: M
authors.lastname: Zugaib
authors.affiliation: Pediatrics Department, Medical Institute Prof. Fernando Figueira-IMIP, Recife, Pernambuco, Brazil.
authors.forename: João Bosco
authors.initials: JB
authors.lastname: de Oliveira Filho
authors.affiliation: Laboratory of Dermatology and Immunodeficiencies, LIM-56, Department of Dermatology, Medical School, Tropical Medicine Institute of São Paulo, University of São Paulo, São Paulo, São Paulo, Brazil.
authors.forename: Alberto José da Silva
authors.initials: AJ
authors.lastname: Duarte
authors.affiliation: Laboratory of Dermatology and Immunodeficiencies, LIM-56, Department of Dermatology, Medical School, Tropical Medicine Institute of São Paulo, University of São Paulo, São Paulo, São Paulo, Brazil.
authors.forename: Maria Notomi
authors.initials: MN
authors.lastname: Sato
mesh_terms: D000071480:APOBEC-3G Deaminase; D000090103:Antiviral Restriction Factors; D015153:Blotting, Western; D001938:Brazil; D002352:Carrier Proteins / Q000378:metabolism; D002824:Chorionic Villi / Q000378:metabolism; D003126:Colostrum / Q000378:metabolism; D003564:Cytidine Deaminase / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D003656:Decidua / Q000378:metabolism; D005260:Female; D005312:Fetal Blood / Q000378:metabolism*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000276:immunology*; D015658:HIV Infections / Q000097:blood* / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology*; D016899:Interferon-beta / Q000191:economics / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D015778:Minor Histocompatibility Antigens; D009035:Mothers; D064547:Myxovirus Resistance Proteins / Q000378:metabolism; D011247:Pregnancy; D060888:Real-Time Polymerase Chain Reaction; D012097:Repressor Proteins / Q000378:metabolism; D018709:Statistics, Nonparametric; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases; D014766:Viremia / Q000378:metabolism / Q000517:prevention & control*; D000099197:STING Protein
chemical_list: D000071480:APOBEC-3G Deaminase; D000090103:Antiviral Restriction Factors; D002352:Carrier Proteins; D003564:Cytidine Deaminase; D017931:DNA Primers; D016899:Interferon-beta; D008565:Membrane Proteins; D015778:Minor Histocompatibility Antigens; D064547:Myxovirus Resistance Proteins; D012097:Repressor Proteins; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases; C532857:STING1 protein, human; D000099197:STING Protein; C094314:TRIM22 protein, human; C477346:TRIM5 protein, human; C464924:APOBEC3G protein, human