Maternal Envelope gp41 Ectodomain-Specific Antibodies Are Associated With Increased Mother-to-Child Transmission of Human Immunodeficiency Virus-1.
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ABSTRACT:
SUBMITTER: Naiman NE
PROVIDER: S-EPMC6935999 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Trimerization of the human immunodeficiency virus (HIV-1) envelope glycoproteins is mediated by the ectodomain of the gp41 transmembrane glycoprotein. Here we investigate oligomer-specific conformations of gp41 by using monoclonal antibodies (MAbs) from HIV-1-infected humans. Human MAbs directed against the cluster I region of gp41 recognized trimeric, dimeric, and monomeric forms of soluble envelope glycoproteins; thus, the integrity of the cluster I epitopes is minimally affected by the oligomeric state. In contrast, human MAbs to the cluster II region were all oligomers specific. One cluster II MAb, 126-6, recognized exclusively the trimeric form of envelope glycoproteins, whereas the others recognized both trimeric and dimeric forms. Thus, a distinct trimer-specific conformation exists in the cluster II region of gp41. Analysis of soluble envelope glycoprotein mutants revealed that gp41 sequences immediately N-terminal to isoleucine 646 contribute to the formation of both the trimer and the trimer-specific conformational epitope.
| S-EPMC2853836 | biostudies-literature
Project description:This study contrasts the expression profiles of peripheral blood leukocytes from third trimester pregnant mothers, with cord blood leukocytes from their newborn children. It is a companion to (GSE21311). After normalization for RNA integrity, major principal components of the variation were found to distinguish individuals. Transmission of gene expression profiles from mother to child was documented, along with differences between gestational diabetic, obese, and normal weight mothers and their children.
2011-01-01 | GSE21342 | GEO
Project description:This study contrasts the expression profiles of peripheral blood leukocytes from third trimester pregnant mothers, with cord blood leukocytes from their newborn children. It is a companion to (GSE21311). After normalization for RNA integrity, major principal components of the variation were found to distinguish individuals. Transmission of gene expression profiles from mother to child was documented, along with differences between gestational diabetic, obese, and normal weight mothers and their children. 56 individulas (Brisbane, Australia) were sampled for the mother-newborn study, under informed consent. 19 mothers sample were collected in the last month of pregnancy (between 30th and 36th week of pregnancy) and 37 cord blood samples were obtained at birth from newborn babies. Mothers having BMI values over 30 before pregnancy were classified as obese. From the 37 newborn babies, 10 were born to obese mothers, 8 to gestational diabetic mothers (with a wide range of body mass indices), and 19 to normal-weight mothers. There were 16 mother-newborn pairs in the dataset. RNA from each was hybridized to an Illumina HT12 array.
2011-01-01 | E-GEOD-21342 | biostudies-arrayexpress
Project description:In order to elucidate the molecular mechanisms involved in human immunodeficiency virus type 1 (HIV-1) mother-to-child transmission, we have analyzed the genetic variation within the V3 hypervariable domain and flanking regions of the HIV-1 envelope gene in four mother-child transmission pairs. Phylogenetic analysis and amino acid sequence comparison were performed on cell-associated viral sequences derived from maternal samples collected at different time points during pregnancy, after delivery, and from child samples collected from the time of birth until the child was approximately 1 year of age. Heterogeneous sequence populations were observed to be present in all maternal samples collected during pregnancy and postdelivery. In three newborns, viral sequence populations obtained within 2 weeks after birth revealed a high level of V3 sequence variability. In contrast, V3 sequences obtained from the fourth child (diagnosed at the age of 1 month) displayed a more restricted heterogeneity. The phylogenetic analysis performed for each mother-child sequence set suggested that several mechanisms may potentially be involved in HIV-1 vertical transmission. For one pair, child sequences were homogeneous and clustered in a single branch within the phylogenetic tree, consistent with selective transmission of a single maternal variant. For the other three pairs, the child sequences were more heterogeneous and clustered in several separate branches within the tree. In these cases, it appeared likely that more than one maternal variant was responsible for infection of the child. In conclusion, no single mechanism can account for mother-to-child HIV-1 transmission; both the selective transmission of a single maternal variant and multiple transmission events may occur.
| S-EPMC189095 | biostudies-other
Project description:Background. ?Fc-mediated effector functions have been suggested to influence human immunodeficiency virus (HIV) acquisition and disease progression. Analyzing the role of host Fc gamma receptor (Fc?R) polymorphisms on HIV outcome in mother-to-child transmission (MTCT) will increase our understanding of how host genetics may alter immune responses in prevention, therapy, and disease. This study analyzed the impact of FCGR2A and FCGR3A genotypes on MTCT in a cohort in which Fc-mediated antibody functions are predictive of infant HIV outcome. Methods. ?Human immunodeficiency virus-positive mothers and their infants from a historical MTCT cohort were genotyped for FCGR2A and FCGR3A. We assessed the impact of these genotypes on transmission and acquisition of HIV and disease progression using ?(2) tests, survival analyses, and logistic regression. Results. ?Among 379 mother-infant pairs, infant FCGR2A and FCGR3A genotypes were not associated with infant HIV infection or disease progression. Maternal FCGR2A was not associated with transmission, but there was a trend between maternal FCGR3A genotype and transmission (P = .07). When dichotomizing mothers into FCGR3A homozygotes and heterozygotes, heterozygotes had a 64.5% higher risk of transmission compared with homozygotes (P = .02). This risk was most evident in the early breastfeeding window, but a trend was only observed when restricting analyses to breastfeeding mothers (hazards ratio, 1.64; P = .064). Conclusions. ?Infant FCGR2A and FCGR3A genotypes were not associated with HIV infection or disease progression, and, thus, host Fc?R genotype may not significantly impact vaccination or therapeutic regimens that depend on Fc-mediated antibody functions. Maternal FCGR3A genotype may influence early breastfeeding transmission risk, but more studies should be conducted to clarify this association and its mechanism.
| S-EPMC4653957 | biostudies-literature
Project description:OBJECTIVE:To identify missed opportunities for prevention of mother-to-child transmission of human immunodeficiency virus (HIV). METHODS:Data regarding HIV-infected children born between 2002 and 2009 to HIV-infected women enrolled in the U.S. International Maternal Pediatric Adolescent AIDS Clinical Trials prospective cohort study (protocol P1025) were reviewed. The characteristics of the HIV-infected infants and their mothers and the mothers' clinical management are described. RESULTS:Twelve cases of mother-to-child transmission of HIV occurred among 1,857 liveborn neonates, for a prevalence of 0.65 per 100 live births to HIV-infected women (95% confidence interval 0.33-1.13). Four transmissions occurred in utero, three were peripartum transmissions, and the timing of transmission for five neonates was unable to be determined. None were breastfed. Seven women had plasma viral loads greater than 400 copies/mL near delivery. Six women had less than 11 weeks of antiretroviral therapy during pregnancy; three of these women had premature deliveries. One woman received no antiretroviral therapy during pregnancy because she was diagnosed with HIV postpartum. Six had poor to moderate adherence to antiretroviral therapy. Four of the five mothers with viral loads greater than 1,000 copies/mL delivered preterm neonates. There were five women who delivered by cesarean; four were nonelective cesarean deliveries and only one was an elective cesarean delivery for HIV prevention. CONCLUSION:Despite access to high-level care and follow-up, a small proportion of HIV-infected women transmitted the virus to their neonates. This case series provides insight into factors contributing to HIV perinatal transmission and can inform the development of new strategies for prevention of mother-to-child transmission of HIV. CLINICAL TRIAL REGISTRATION:ClinicalTrials.gov, https://clinicaltrials.gov, NCT00028145.
| S-EPMC6122962 | biostudies-literature
Project description:Genetic analysis of human immunodeficiency virus type 1 (HIV-1) from cases of mother-to-infant transmission were analyzed in an effort to provide insights into the viral selection that may occur during transmission, as well as the timing and source of transmitted viruses. HIV-1 env genes obtained from seven mothers and their perinatally infected infants in Sweden were studied. Five envelope sequence clades (A to E) were found to be represented. We used a heteroduplex tracking assay (HTA) to assess the genetic relatedness between early viral isolates from the infants and serial maternal virus populations taken during pregnancy and at delivery. HTA findings were used to select for DNA sequence analysis maternal virus populations that were either closely or more distantly related to the infant virus. In each case, nucleotide sequence analysis confirmed the genetic relationships inferred by the HTA. Only maternal peripheral blood was sampled, and large sets of maternal specimens throughout pregnancy were generally not available. However, no consistent correlation was found to support the hypothesis that infant viruses should match blood-derived maternal virus genotypes found early in pregnancy if infants were found to be infected at birth or, conversely, that infant viruses should match blood-derived maternal virus genotypes found at delivery if infants were found to be infected only some time later.
| S-EPMC191184 | biostudies-other
Project description:Understanding the properties of viruses capable of establishing infection during perinatal transmission of HIV-1 is critical for designing effective means of limiting transmission. We previously demonstrated that the newly transmitted viruses (in infant) were more fit in growth, as imparted by their envelope glycoproteins, than those in their corresponding mothers. Here, we further characterized the viral envelope glycoproteins from six mother-infant transmission pairs and determined whether any specific envelope functions correlate with HIV-1 subtype C perinatal transmission. We found that most newly transmitted viruses were less susceptible to neutralization by their maternal plasma compared to contemporaneous maternal viruses. However, the newly transmitted variants were sensitive to neutralization by pooled heterologous plasma but in general were resistant to IgG1 b12. Neither Env processing nor incorporation efficiency was predictive of viral transmissibility. These findings provide further insight into the characteristics of perinatally transmissible HIV-1 and may have implications for intervention approaches.
| S-EPMC2844456 | biostudies-literature
Project description:Widespread availability of antiretroviral therapy among pregnant women living with HIV has greatly reduced the rate of mother-to-child transmission (MTCT) of HIV across the globe. However, while Joint United Nations Programme on HIV/AIDS has set targets to reduce the annual number of new pediatric HIV infections to fewer than 40,000 in 2018 and fewer than 20,000 in 2020, progress towards these targets has plateaued at an unacceptably high global estimate of greater than 160,000 children newly infected with HIV in 2018. Moreover, it has become clear that expansion of maternal antiretroviral therapy alone will not be sufficient to close the remaining gap and eliminate MTCT of HIV. Additional strategies such as maternal or infant passive and/or active immunization that synergize with maternal antiretroviral therapy will be required to end the pediatric HIV epidemic. In this review, we outline the landscape of existing maternal interventions and emerging maternal immune-based approaches to prevent MTCT of HIV.
| S-EPMC9215267 | biostudies-literature
Project description:BACKGROUND: Toll-like receptors (TLRs) recognize pathogen-associated molecular patterns and play a crucial role in the host's innate immune response. Genetic variations in TLR genes may influence host-viral interactions and might impact upon the risk of mother-to-child transmission (MTCT) of Human Immunodeficiency Virus type 1 (HIV-1). The aim of this study was to investigate the influence of genetic variants of TLR 9 gene on MTCT. METHODS: Three hundred children (118 HIV-1-infected and 182 HIV-1-uninfected) born to HIV-1-infected mothers were studied. Single nucleotide polymorphisms (SNPs) NM_017442.2: c.4-44G > A (rs352139) and c.1635A > G (rs352140) of the TLR9 gene were genotyped by TaqMan allelic discrimination assay. Statistical analyses were performed using SNPStats program. RESULTS: When considered separately, neither of the two SNPs was significantly associated with risk of HIV-1 infection. However, the [A;A] and [G;G] haplotypes were associated with a higher risk of HIV-1 infection compared to the prevalent [G;A] haplotype [odds ratio (OR) = 3.16, 95% confidence interval (CI) 1.24-8.03, p = 0.016, and OR = 5.54, 95% CI 1.76-17.50, p = 0.004, respectively]. CONCLUSIONS: Overall, results demonstrate a significant correlation between specific genetic variants of the TLR9 gene and risk of MTCT of HIV-1, thus confirming a critical role of innate immunity in perinatal HIV-1 infection. Strategies aimed at modulating innate immunity might be useful for future treatment of pediatric HIV-1 infection and AIDS.
| S-EPMC2887426 | biostudies-literature