Vertical transmission of human immunodeficiency virus type 1: Autologous neutralizing antibody, virus load, and virus phenotype

Husson, Robert N.; Lan, Yan; Kojima, Eiji; Venzon, David; Mitsuya, Hiroaki; McIntosh, Kenneth

doi:10.1016/s0022-3476(95)70198-2

Cited by 50 publications

(30 citation statements)

References 43 publications

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“…Possible selective pressures influencing perinatal HIV-1 transmission include maternal viral phenotype, tropism, coreceptor usage, maternal neutralizing antibody, and/or other immune pressures (19,24,27,38). In the present study, low maternal CD4 counts and low rates of HIV-1 env gene diversity were observed primarily in mothers transmitting major env variants to their infants in utero.…”

Section: Discussionmentioning

confidence: 99%

Perinatal Transmission of Major, Minor, and Multiple Maternal Human Immunodeficiency Virus Type 1 Variants In Utero and Intrapartum

Dickover

Garratty

Plaeger

et al. 2001

J Virol

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Previous studies have provided conflicting data on the presence of selective pressures in the transmission of a homogeneous maternal viral subpopulation to the infant. Therefore, the purpose of this study was to definitively characterize the human immunodeficiency virus type 1 (HIV-1) quasispecies transmitted in utero and intrapartum. HIV-1 envelope gene diversity from peripheral blood mononuclear cells and plasma was measured during gestation and at delivery in mothers who did and did not transmit HIV perinatally by using a DNA heteroduplex mobility assay. Children were defined as infected in utero or intrapartum based on the timing of the first detection of HIV. Untreated transmitting mothers (n ‫؍‬ 19) had significantly lower HIV-1 quasispecies diversity at delivery than untreated nontransmittting mothers (n ‫؍‬ 18

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Section: Discussionmentioning

confidence: 99%

Perinatal Transmission of Major, Minor, and Multiple Maternal Human Immunodeficiency Virus Type 1 Variants In Utero and Intrapartum

Dickover

Garratty

Plaeger

et al. 2001

J Virol

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“…However, the results of studies of the effect of maternal NAb on transmission have reached divergent conclusions as to whether NAbs are important during all stages of mother-to-child transmission (in utero, intrapartum, and breastfeeding); for example, one study suggested a protective effect of NAb only for intrapartum transmission (Barin et al 2006;Samleerat et al 2009), whereas two others suggest NAb protection only in utero transmission (Dickover et al 2006). Moreover, some studies have reported no association of maternal NAbs and infant infection (Husson et al 1995;Hengel et al 1998). These divergent findings could reflect methodological differences, such as the relative timing of the NAb and viruses studied, which is critical given the rapid evolution of both virus and antibody responses (Burton et al 2005), whether the study examined autologous or heterologous responses and the assays used, as well as the sample size of the study, which in the earliest studies was typically small.…”

Section: Because Effective Protection Afforded By Most Vaccines Corrementioning

confidence: 99%

The Antibody Response against HIV-1

Overbaugh

Morris²

2011

Cold Spring Harbor Perspectives in Medicine

156

113

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“…Indeed, some studies have shown that mothers who transmitted to their infants had lower titers of NAb against autologous viruses than did nontransmitting mothers (13,27,30,62), although not all studies have shown this association (18,20,23). Some of the differences in these findings could reflect inconsistencies in sampling viruses and antibodies near the window of transmission.…”

mentioning

confidence: 99%

Neutralizing Antibody Escape during HIV-1 Mother-to-Child Transmission Involves Conformational Masking of Distal Epitopes in Envelope

Goo

Milligan

Simonich

et al. 2012

J Virol

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HIV-1 variants transmitted to infants are often resistant to maternal neutralizing antibodies (NAbs), suggesting that they have escaped maternal NAb pressure. To define the molecular basis of NAb escape that contributes to selection of transmitted variants, we analyzed 5 viruses from 2 mother-to-child transmission pairs, in which the infant virus, but not the maternal virus, was resistant to neutralization by maternal plasma near transmission. We generated chimeric viruses between maternal and infant envelope clones obtained near transmission and examined neutralization by maternal plasma. The molecular determinants of NAb escape were distinct, even when comparing two maternal variants to the transmitted infant virus within one pair, in which insertions in V4 of gp120 and substitutions in HR2 of gp41 conferred neutralization resistance. In another pair, deletions and substitutions in V1 to V3 conferred resistance, but neither V1/V2 nor V3 alone was sufficient. Although the sequence determinants of escape were distinct, all of them involved modifications of potential N-linked glycosylation sites. None of the regions that mediated escape were major linear targets of maternal NAbs because corresponding peptides failed to compete for neutralization. Instead, these regions disrupted multiple distal epitopes targeted by HIV-1-specific monoclonal antibodies, suggesting that escape from maternal NAbs occurred through conformational masking of distal epitopes. This strategy likely allows HIV-1 to utilize relatively limited changes in the envelope to preserve the ability to infect a new host while simultaneously evading multiple NAb specificities present in maternal plasma.

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Vertical transmission of human immunodeficiency virus type 1: Autologous neutralizing antibody, virus load, and virus phenotype

Cited by 50 publications

References 43 publications

Perinatal Transmission of Major, Minor, and Multiple Maternal Human Immunodeficiency Virus Type 1 Variants In Utero and Intrapartum

Perinatal Transmission of Major, Minor, and Multiple Maternal Human Immunodeficiency Virus Type 1 Variants In Utero and Intrapartum

The Antibody Response against HIV-1

Neutralizing Antibody Escape during HIV-1 Mother-to-Child Transmission Involves Conformational Masking of Distal Epitopes in Envelope

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