Abstract
The HIV-1 characteristics associated with mother to child transmission (MTCT) are still poorly understood and if known would indicate where intervention strategies should be targeted. In contrast to horizontally infected individuals, exposed infants possess inherited antibodies (Abs) from their mother with the potential to protect against infection. We investigated the HIV-1 gp160 envelope proteins from seven transmitting mothers (TM) whose children were infected either during gestation or soon after delivery and from four non-transmitting mothers (NTM) with similar viral loads and CD4 counts. Using pseudo-typed viruses we tested gp160 envelope glycoproteins for TZM-bl infectivity, CD4 and CCR5 interactions, DC-SIGN capture and transfer and neutralization with an array of common neutralizing Abs (NAbs) (2F5, 2G12, 4E10 and b12) as well as mother and infant plasma. We found no viral correlates associated with HIV-1 MTCT nor did we find differences in neutralization with the panel of NAbs. We did, however, find that TM possessed significantly higher plasma neutralization capacities than NTM (P = 0.002). Furthermore, we found that in utero (IU) TM had a higher neutralization capacity than mothers transmitting either peri - partum (PP) or via breastfeeding (BF) (P = 0.002). Plasma from children infected IU neutralized viruses carrying autologous gp160 viral envelopes as well as those from their corresponding mothers whilst plasma from children infected PP and/or BF demonstrated poor neutralizing capacity. Our results demonstrate heightened autologous NAb responses against gp120/gp41 can associate with a greater risk of HIV-1 MTCT and more specifically in those infants infected IU. Although the number of HIV-1 transmitting pairs is low our results indicate that autologous NAb responses in mothers and infants do not protect against MTCT and may in fact be detrimental when considering IU HIV-1 transmissions.
Highlights
According to the 2011 UNAIDS Progress report an estimated 2.7 million people worldwide were newly infected with HIV-1 in 2010
We investigated the constructed envelope glycoprotein (Env) pseudo-typed viruses from non-transmitting mothers (NTM), transmitting mothers (TM) and IC for properties such as entry, receptor and coreceptor usage, interaction with dendritic cells (DCs)-SIGN as well as neutralization sensitivity
Since DC-SIGN binding is influenced by the gp120 glycan composition we investigated the correlation between the number of potential N-linked glycosylation sites (PNGS) in the V1V5 region of the pseudo-typed viruses and the levels of capsid p24 (CA-p24) captured by DC-SIGN (Fig. 4C and 4D)
Summary
According to the 2011 UNAIDS Progress report an estimated 2.7 million people worldwide were newly infected with HIV-1 in 2010. Of this 390,000 were infants with the majority resulting from mother-to-child transmission (MTCT). Known maternal risk factors associated with MTCT are high plasma viral loads, low CD4 T-cell numbers coinciding with advanced maternal immune deficiency and prolonged labor [1]. The majority of transmissions are found in regions where antiretroviral therapy availability is limited, such as sub-Saharan Africa (UNAIDS Progress report 2011) and regions where HIV-1 subtype A and C predominate, including the growing number of infections in Russia [3]. Little is known regarding mechanisms determining risk of MTCT but better understanding of such events will be critical in designing effective means to limit transmissions
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