Upregulation of Innate Antiviral Restricting Factor Expression in the Cord Blood and Decidual Tissue of HIV-Infected Mothers

Author(s)

Pereira, Natalli Zanete ^[1] ; Cardoso, Elaine Cristina ^[1] ; da Silva Oliveira, Luanda Mara ^[1] ; de Lima, Josenilson Feitosa ^[1] ; Calvielli Castelo Branco, Anna Claudia ^[1] ; de Souza Aveiro Ruocco, Rosa Maria ^[2] ; Zugaib, Marcelo ^[2] ; de Oliveira Filho, Joao Bosco ^[3] ; da Silva Duarte, Alberto Jose ^[1] ; Sato, Maria Notomi ^[1]

Affiliation

^[1] Univ Sao Paulo, Sch Med, Lab Dermatol & Immunodeficiencies, LIM 56, Dept Dermatol, Trop Med Inst Sao Paulo, Sao Paulo - Brazil

^[2] Univ Sao Paulo, Sch Med, Dept Obstet & Gynecol, Hosp Clin, Sao Paulo - Brazil

^[3] Med Inst Prof Fernando Figueira IMIP, Dept Pediat, Recife, PE - Brazil

• Document type: Journal article
• Source: PLoS One; v. 8, n. 12 DEC 18 2013.
• Web of Science Citations: 9

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-5 alpha (TRIM-5 alpha), TRIM-22, myxovirus resistance protein A (MxA), stimulator of interferon (IFN) genes (STING) and IFN-beta, compared with the levels detected in uninfected (UN) mother-CB pairs. Moreover, A3G transcript and protein levels and alpha-defensin transcript levels were decreased in the decidua of HIV-infected mothers. Decreased TRIM-5 alpha 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-beta 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. (AU)

• FAPESP's process: 12/18837-1 - Expression of antiviral factors and endogenous retroviruses in HIV-1 infected mothers and newborns
• Grantee: Maria Notomi Sato
• Support Opportunities: Regular Research Grants