Analysis of envelope sequence variants suggests multiple mechanisms of mother to child transmission of HIV-1

Laboratoire de Virologie, Centre Hospitalo-Universitaire Purpan, Toulouse, France.
Journal of Virology (Impact Factor: 4.44). 07/1995; 69(6):3778-88.
Source: PubMed


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.

Download full-text


Available from: Christopher M. Wade, Apr 08, 2015
  • Source
    • "Phylogenetic analysis of the transmitted genotypes showed that the sequences of these viruses were intermingled with those detected in the mammary gland of the mothers. This indicates that a primary, lactogenic infection with SRLV permits the passage of several viral genotypes between the chronically infected mothers and their kids, a situation reminiscent of the transmission of SIV in acutely infected, lactating monkeys and of some instances of HIV transmission in breastfeeding mothers (Rychert et al., 2006; Briant et al., 1995; Lamers et al., 1994; Mulder-Kampinga et al., 1995; Pasquier et al., 1998; Wade et al., 1998 "
    [Show abstract] [Hide abstract]
    ABSTRACT: Lactogenic transmission plays an important role in the biology of lentiviruses such as HIV and SIV or the small ruminant lentiviruses (SRLV). In this work we analyzed the characteristics of viruses that goats, naturally infected with two strains of SRLV, transmitted to their kids. The spectrum of viral genotypes transmitted was broader and the efficiency of transmission greater compared to their human and simian counterparts. The newly described A10 subgroup of SRLV was more efficiently transmitted than the B1 genotype. The analysis of a particular stretch of the envelope glycoprotein encompassing a potential neutralizing epitope revealed that, as in SIV, the transmitted viruses were positively charged in this region, but, in contrast to SIV, they tended to lack a glycosylation site that might protect against antibody neutralization. We conclude that the physiology of the ruminant neonatal intestine, which permits the adsorption of infected maternal cells, shaped the evolution of these particular lentiviruses that represent a valid model of lactogenic lentivirus transmission.
    Full-text · Article · Nov 2010 · Virology
  • Source
    • "The V3 region may also play an important role in viral pathogenesis, cellular tropism and perinatal transmission (Kuiken et al. 1992). Comparative analysis of V3 sequences derived from mother-infant pairs has shown that the transmitted variant(s) is epidemiologically linked to the mother's viral sequences, but that it is more homogeneous and often represents a minor quasispecies of the mother's total virus population (Wolinsky et al. 1992, Ahmad et al. 1995, Briant et al. 1995). With time, the transmitted sequence(s) usually diversifies, presumably as a result of selective pressure in the infant. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The collection of dried blood spots (DBS) on filter paper provides a powerful approach for the development of large-scale, population-based screening programs. DBS methods are particularly valuable in developing countries and isolated rural regions where resources are limited. Large numbers of field specimens can be economically collected and shipped to centralized reference laboratories for genetic and (or) serological analysis. Alternatively, the dried blood can be stored and used as an archival resource to rapidly establish the frequency and distribution of newly recognized mutations, confirm patient identity or track the origins and emergence of newly identified pathogens. In this report, we describe how PCR-based technologies are beginning to interface with international screening programmes for the diagnosis and genetic characterization of human immunodeficiency virus type 1 (HIV-1). In particular, we review recent progress using DBS specimens to resolve the HIV-1 infection status of neonates, monitor the genetic evolution of HIV-1 during early infancy and establish a sentinel surveillance system for the systematic monitoring of HIV-1 genetic variation in Asia.
    Preview · Article · Jun 1996 · Memórias do Instituto Oswaldo Cruz
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Nevirapine (NVP) is a cheap anti-retroviral drug used in poor countries worldwide, administered to pregnant women at the onset of labour to inhibit HIV enzyme reverse transcriptase. Viruses which may get transmitted to newborns are deficient in this enzyme, and HIV-1 infection cannot be established, thereby preventing mother to child transmission (MTCT). In some cases, babies get infected and positive selection for viruses resistant to nevirapine may be inferred. Positive selection can be inferred from sequence data, when the rate of nonsynonymous substitutions is significantly greater than the rate of synonymous substitutions. Unfortunately, it is found that available positive selection methods should not be used to analyse before- and after- NVP treatment sequence pairs associated with MTCT. Methods which use phylogenetic trees to infer positive selection trace synonymous and nonsynonymous substitutions further back in time than the short time duration during which selection for NVP occurred. The other group of methods for inferring positive selection, the pairwise methods, do not have appreciable power, because they average susbtituion rates over all codons in a sequence pair and not just at single codons. We introduce a simple counting method which we call the Pairwise Homologous Codons (PHoCs) method with which we have inferred positive selection resulting from NVP treatment in longitudinal HIV-1 reverse transcriptase sequences. The PHoCs method estimates rates of substitutions between before- and after- NVP treatment codons, using a simple pairwise method.
    Preview · Article ·
Show more