Because our data consists of multiple sequences from each mother-infant pair, ignoring this phylogenetic correction could potentially yield to spurious associations driven by within-subject correlations. For this analysis, maternal plasma neutralization sensitivity (above or below neutralization threshold of 1 1:50) and transmission status were treated as dichotomous variables, whereas PG9, DH429, DH512 and VRC01 IC50s were considered multiple ways (upper quartile vs. transmitting and non-transmitting mothers (Table 2). Each stack shows the different amino acids at a single Env position, with letters proportional to the frequencies at which they were found in the sequence sample. Red indicates residues associated with resistance, and O indicates an N-linked glycosylation site. Top: Logo plot of all infant TF and paired closest maternal sequences, combined. Middle: infant TF sequences only. Bottom: maternal sequences closest to infant TFs. All logo plots were obtained using the AnalyzeAlign tool available on the LANL database (https://www.hiv.lanl.gov/content/sequence/ANALYZEALIGN/analyze_align.html).(TIFF) ppat.1009478.s004.tiff (2.2M) GUID:?E8E5BBD4-8D27-4802-B812-85104C2C4646 Data Availability StatementAll relevant data (-)-Indolactam V are within the manuscript and its Supporting Information files. Abstract Despite considerable reduction of mother-to-child transmission (MTCT) of HIV through use of maternal and infant antiretroviral therapy (ART), over 150,000 infants continue to become infected with HIV annually, falling far short of the World Health Organization goal of reaching 20,000 annual pediatric HIV cases worldwide by 2020. Prior to the widespread use of ART in the setting of pregnancy, over half of infants born to HIV-infected mothers were protected against HIV acquisition. Yet, the role of maternal immune factors in this protection against vertical transmission is still unclear, hampering the development of synergistic strategies to further reduce MTCT. It has been established that (-)-Indolactam V infant transmitted/founder (T/F) viruses are often resistant to maternal plasma, yet it is unknown if the neutralization resistance profile of circulating viruses predicts the maternal risk of transmission to her infant. In this study, we amplified HIV-1 envelope genes (sequences from transmitting mothers were associated with broadly neutralizing antibody (bnAb) resistance. Altogether, our findings suggest that circulating maternal virus resistance to bnAb-mediated neutralization, but not autologous plasma neutralization, near the time of delivery, predicts increased MTCT risk. These results caution that enhancement of maternal plasma neutralization through passive or active vaccination during pregnancy may potentially drive the evolution of variants fit for vertical transmission. Author summary Despite widespread, effective use of ART among HIV infected pregnant women, new pediatric HIV infections increase by about 150,000 every year. Thus, alternative strategies will be required to reduce MTCT and eliminate pediatric HIV infections. Interestingly, in the absence of ART, less than half of HIV-infected pregnant women will transmit HIV, suggesting natural immune safety of babies from disease acquisition. To understand the effect (-)-Indolactam V of maternal plasma autologous disease neutralization reactions on MTCT, we compared the plasma and bnAb neutralization level of sensitivity of the circulating viral human population present at the time of delivery in untreated, HIV-infected transmitting and non-transmitting mothers. While there was no significant difference in the ability of transmitting and non-transmitting ladies to neutralize their personal circulating disease strains, specific genetic motifs enriched in variants from transmitting mothers were associated with resistance to bnAbs, suggesting that acquired bnAb resistance is definitely a common feature of vertically-transmitted variants. This work suggests that enhancement of plasma neutralization reactions in HIV-infected mothers through passive or active vaccination could further drive (-)-Indolactam V selection of variants that may be vertically transmitted, and cautions the use of passive bnAbs for HIV-1 prophylaxis or therapy during pregnancy. Introduction Mother-to-child transmission (MTCT) of HIV-1 was responsible for approximately 150,000 fresh Rabbit Polyclonal to Catenin-gamma pediatric infections worldwide in 2019 [1], despite wide availability of maternal antiretroviral therapy (ART), which can significantly reduce vertical transmission rates [2]. MTCT happens via three unique routes: gene sequences from transmitting mother-infant pairs and non-transmitting mothers Solitary genome amplicons (SGA) for the HIV-1 gene were from the plasma of transmitting mother-infant pairs as explained previously [16]. A total of 463 and 465 SGAs were from the mother and infant transmitting pairs, respectively. Additionally, plasma from 19 non-transmitting mothers.