Diversity of the Human Immunodeficiency Virus Type 1 (HIV-1)
            <i>env</i>
            Sequence after Vertical Transmission in Mother-Child Pairs Infected with HIV-1 Subtype A

Verhofstede, Chris; Demecheleer, Els; Cabooter, Nancy De; Gaillard, Philippe; Mwanyumba, Fabian; Claeys, Pieter W.; Chohan, Vrasha; Mandaliya, Kishorchandra; Temmerman, Marleen; Plum, Jean

doi:10.1128/jvi.77.5.3050-3057.2003

Cited by 64 publications

(54 citation statements)

References 31 publications

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“…MTCT occurs in utero, during delivery, and through breastfeeding, at a rate of approximately 30% in the absence of antiretroviral therapy (6,19). Previous studies have demonstrated that, despite a complex viral population in the mother, only viruses of a restricted subset were typically transmitted to the infant (1,23,29,40,41,45,48). This suggests that some viruses may be favored for transmission in this setting.…”

mentioning

confidence: 97%

Neutralization Escape Variants of Human Immunodeficiency Virus Type 1 Are Transmitted from Mother to Infant

Wu¹,

Parast²,

Richardson

et al. 2006

J Virol

278

258

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Maternal passive immunity typically plays a critical role in protecting infants from new infections; however, the specific contribution of neutralizing antibodies in limiting mother-to-child transmission of human immunodeficiency virus type 1 is unclear. By examining cloned envelope variants from 12 transmission pairs, we found that vertically transmitted variants were more resistant to neutralization by maternal plasma than were maternal viral variants near the time of transmission. The vertically transmitted envelope variants were poorly neutralized by monoclonal antibodies biz, 2G12, 2F5, and 4E10 individually or in combination. Despite the fact that the infant viruses were among the most neutralization resistant in the mother, they had relatively few glycosylation sites. Moreover, the transmitted variants elicited de novo neutralizing antibodies in the infants, indicating that they were not inherently difficult to neutralize. The neutralization resistance of vertically transmitted viruses is in contrast to the relative neutralization sensitivity of viruses sexually transmitted within discordant couples, suggesting that the antigenic properties of viruses that are favored for transmission may differ depending upon mode of transmission.

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mentioning

confidence: 97%

Neutralization Escape Variants of Human Immunodeficiency Virus Type 1 Are Transmitted from Mother to Infant

Wu¹,

Parast²,

Richardson

et al. 2006

J Virol

278

258

View full text Add to dashboard Cite

show abstract

“…We also found evidence for the transmission of multiple viral variants in 2 of 10 IUinfected infants and 4 of 9 IP-infected infants, 6 of 19 overall. Previous studies of MTCT, using similar methods, found a heterogeneous infant viral population in 7 of 13 infants infected with subtype CRF01_AE (4 of 6 infected IU and 3 of 7 infected IP) and in 3 of 17 infants infected with subtype A (unknown transmission timing) (47,57). Thus, our data for subtype C HIV-1 transmission are in line with previous studies of other subtypes in the frequency of multiple-variant transmission in MTCT, and overall with the conclusion that in a majority of cases the infant is infected with a single variant.…”

Section: Discussionmentioning

confidence: 99%

The Genetic Bottleneck in Vertical Transmission of Subtype C HIV-1 Is Not Driven by Selection of Especially Neutralization-Resistant Virus from the Maternal Viral Population

Russell¹,

Kwiek

Keys

et al. 2011

J Virol

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Subtype C human immunodeficiency virus type 1 (HIV-1C) continues to cause the majority of new cases of mother-to-child transmission (MTCT), and yet there are limited data on HIV-1C transmission. We amplified env from plasma RNA for 19 HIV-1C MTCT pairs, 10 transmitting in utero (IU) and 9 transmitting intrapartum (IP). There was a strong genetic bottleneck between all mother-infant pairs, with a majority of transmission events involving the transmission of a single virus. env genes of viruses transmitted to infants IP, but not IU, encoded Env proteins that were shorter and had fewer putative N-linked glycosylation sites in the V1-V5 region than matched maternal sequences. Viruses pseudotyped with env clones representative of each maternal and infant population were tested for neutralization sensitivity. The 50% inhibitory concentration of autologous serum was similar against both transmitted (infant) and nontransmitted (maternal) viruses in a paired analysis. Mother and infant Env proteins were also similar in sensitivity to soluble CD4, to a panel of monoclonal antibodies, and to heterologous HIV-1C sera. In addition, there was no difference in the breadth or potency of neutralizing antibodies between sera from 50 nontransmitting and 23 IU and 23 IP transmitting HIV-1C-infected women against four Env proteins from heterologous viruses. Thus, while a strong genetic bottleneck was detected during MCTC, with viruses of shorter and fewer glycosylation sites in env present in IP transmission, our data do not support this bottleneck being driven by selective resistance to antibodies.

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“…5 This inefficiency of transmission indicates that anatomical, innate, and/or adaptive mechanisms of protection are able to prevent transmission to a great extent. [6][7][8][9][10][11] Maternal antibodies could prevent infection either through direct binding of virus in the breast milk, or by their systemic and mucosal presence in the infant. This passive maternal immunity in the infant increases in concentration during the last trimester of gestation, and continues to pass into the infant through breastfeeding.…”

mentioning

confidence: 99%

Short Communication: HIV Type 1 Subtype C Variants Transmitted Through the Bottleneck of Breastfeeding Are Sensitive to New Generation Broadly Neutralizing Antibodies Directed Against Quaternary and CD4-Binding Site Epitopes

Russell

Ojeda

Fouda

et al. 2013

AIDS Research and Human Retroviruses

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Mother-to-child transmission of HIV-1 subtype C can occur in utero, intrapartum, or via breast milk exposure. While not well understood, there are putative differences in the mechanisms involved with the distinct routes of vertical HIV transmission. Here, we address the question of whether specific viral characteristics are common to variants transmitted through breastfeeding that may facilitate evasion of innate or adaptive immune responses. We amplified the envelope gene (env) from the plasma of six infants during acute infection who were infected with HIV-1 subtype C through breastfeeding, and from three available matched maternal samples. We sequenced the full-length env genes in these subjects revealing heterogeneous viral populations in the mothers and homogeneous populations in the infants. In five infants, the viral population arose from a single variant, while two variants were detected in the remaining infant. Infant env sequences had fewer N-linked glycosylation sites and shorter sequences than those of the available matched maternal samples. Though the small size of the study precluded our ability to test statistical significance, these results are consistent with selection for virus with shorter variable loops and fewer glycosylation sites during transmission of HIV-1 subtype C in other settings. Transmitted envs were resistant to neutralization by antibodies 2G12 and 2F5, but were generally sensitive to the more broadly neutralizing PG9, PG16, and VRC01, indicating that this new generation of broadly neutralizing monoclonal antibodies could be efficacious in passive immunization strategies.T ransmission of human immunodeficiency virus-1 (HIV-1) through breastfeeding (BF) makes up one-third to one-half of all mother-to-child transmission events.1 The mechanism(s) of transmission, however, are poorly understood. The oral cavity and gastrointestinal tract of breastfed infants are exposed daily to both cell-free and cell-associated HIV-1, 2-4 yet the majority of infants remain uninfected even if neither mother nor baby receive antiretroviral prophylaxis. 5This inefficiency of transmission indicates that anatomical, innate, and/or adaptive mechanisms of protection are able to prevent transmission to a great extent.6-11 Maternal antibodies could prevent infection either through direct binding of virus in the breast milk, or by their systemic and mucosal presence in the infant. This passive maternal immunity in the infant increases in concentration during the last trimester of gestation, and continues to pass into the infant through breastfeeding.Studies of in utero and intrapartum transmission have shown a universal bottleneck in genetic diversity from mother to child, as well as differences in the characteristics of transmitted virus for in utero versus intrapartum transmission. 12,13 Data are very limited for breastfeeding pairs, but one study of three breast milk transmission events found a similar bottleneck for HIV-1 subtype A.14 We previously demonstrated that the viral population found in ...

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Diversity of the Human Immunodeficiency Virus Type 1 (HIV-1) env Sequence after Vertical Transmission in Mother-Child Pairs Infected with HIV-1 Subtype A

Cited by 64 publications

References 31 publications

Neutralization Escape Variants of Human Immunodeficiency Virus Type 1 Are Transmitted from Mother to Infant

Neutralization Escape Variants of Human Immunodeficiency Virus Type 1 Are Transmitted from Mother to Infant

The Genetic Bottleneck in Vertical Transmission of Subtype C HIV-1 Is Not Driven by Selection of Especially Neutralization-Resistant Virus from the Maternal Viral Population

Short Communication: HIV Type 1 Subtype C Variants Transmitted Through the Bottleneck of Breastfeeding Are Sensitive to New Generation Broadly Neutralizing Antibodies Directed Against Quaternary and CD4-Binding Site Epitopes

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