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

Nátalli Zanete Pereira,Alberto José Da Silva Duarte,Marcelo Zugaib,João Bosco De Oliveira Filho,Josenilson Feitosa De Lima,Rosa Maria De Souza Aveiro Ruocco,Elaine Cristina Cardoso,Luanda Mara Da Silva Oliveira,Maria Notomi Sato,Anna Cláudia Calvielli Castelo Branco,Tobias R Kollmann

doi:10.1371/journal.pone.0084917

Nátalli Zanete Pereira, Alberto José Da Silva Duarte + Show 9 more

Open Access

https://doi.org/10.1371/journal.pone.0084917

Copy DOI

Journal: PLoS ONE	Publication Date: Dec 18, 2013
Citations: 59	License type: CC BY 4.0

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.

Highlights

Effective measures for preventing infant HIV infection have reduced the transmission rate of perinatal HIV infection to approximately 2-5%; as a result the population of HIV-exposed uninfected (HEU) infants is growing [1,2]
Antiviral restricting factors were upregulated in the Mononuclear cells (MNCs) of infected vs. uninfected mother and cord blood (CB), and altered patterns of transcription and protein expression were observed in placental tissues of HIV-1 infected vs. uninfected subjects
Upregulation of apolipoprotein B mRNA-editing enzyme 3G (A3G), A3F, tripartite motif family-5α (TRIM-5α), TRIM22, IFN-β, stimulator of interferon (IFN) genes (STING) and myxovirus resistance protein A (MxA) mRNA expression was evident in the MNCs of HIVinfected mothers, and these mRNA gene expression levels were positively correlated with the levels in CB cells

Summary

Introduction

Effective measures for preventing infant HIV infection have reduced the transmission rate of perinatal HIV infection to approximately 2-5%; as a result the population of HIV-exposed uninfected (HEU) infants is growing [1,2]. The vertical transmission of HIV-1 is not an inevitable consequence of exposure; in the absence of treatment, 55-80% of infants exposed to HIV-1 remain uninfected [5] Given that it remains unclear how such a large proportion of HEU children resists infection, this topic warrants further study. These findings highlight the need to understand the mechanisms of natural immunity to HIV-1 infection in the mother-newborn pair. The innate immune response has been correlated with protection from infection during mother-to-child exposure [7], and this response has been proposed to be mediated by extracellular factors, mucosal or systemic IgA [8], α-defensins [9] and CCL3 [10]

Objectives

Methods

Results

Conclusion