Upregulation of innate antiviral restricting factor expression in the cord blood and decidual tissue of HIV-infected mothers

• Published in: PloS one 2013-12, Vol.8 (12), p.e84917-e84917
• Main Authors: Pereira, Nátalli Zanete, Cardoso, Elaine Cristina, Oliveira, Luanda Mara da Silva, de Lima, Josenilson Feitosa, Branco, Anna Cláudia Calvielli Castelo, Ruocco, Rosa Maria de Souza Aveiro, Zugaib, Marcelo, de Oliveira Filho, João Bosco, Duarte, Alberto José da Silva, Sato, Maria Notomi
• Format: Article
• Language: English
• Subjects: Antiretroviral agents; Antiretroviral therapy; APOBEC-3G Deaminase; Apolipoprotein B; Apolipoproteins; Biological response modifiers; Blood; Blotting, Western; Brazil; Carrier Proteins - metabolism; Cesarean section; Chemokines; Children & youth; Chorionic Villi - metabolism; Colostrum; Colostrum - metabolism; Cord blood; CXCL9 protein; Cytidine Deaminase - metabolism; Cytokines; Decidua; Decidua - metabolism; Dendritic cells; Dermatology; Disease transmission; DNA Primers - genetics; Enzymes; Female; Fetal Blood - metabolism; Fetuses; Gene expression; Gene Expression Profiling; Gene Expression Regulation - immunology; Genes; Gynecology; Health aspects; Highly active antiretroviral therapy; HIV; HIV infections; HIV Infections - blood; HIV Infections - immunology; HIV patients; Human immunodeficiency virus; Humans; Immunity; Immunity, Innate - immunology; Infants; Infection; Infections; Interferon; Interferon-beta - economics; Interferon-beta - metabolism; Laboratories; Leukocytes (mononuclear); Leukocytes, Mononuclear - metabolism; Medical schools; Medicine; Membrane Proteins - metabolism; Minor Histocompatibility Antigens; Mothers; Myxovirus resistance proteins; Myxovirus Resistance Proteins - metabolism; Neonates; Newborn babies; Obstetrics; Placenta; Polypeptides; Pregnancy; Pregnant women; Protein A; Proteins; Real-Time Polymerase Chain Reaction; Repressor Proteins - metabolism; RNA; RNA editing; Statistics, Nonparametric; Tissues; Transcription; Tripartite Motif Proteins; Ubiquitin-Protein Ligases; Up-regulation; Villus; Viremia - metabolism; Viremia - prevention & control; Viruses; α-Interferon
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0084917

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.