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

Dickover, Ruth; Garratty, Eileen; Plaeger, Susan; Bryson, Yvonne J.

doi:10.1128/jvi.75.5.2194-2203.2001

Cited by 98 publications

(81 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…31 Phylogenetic analyses showed that single-strain infection occurred in five of the eight mother-child pairs, few-strain infection in two, and multiple-strain infection in one during vertical transmission. This finding is consistent with previous studies on MTCT of HIV-1 showing that either single or multiple variants can be transmitted vertically, [42][43][44] but multiple-strain infection during vertical transmission seems to be less frequent than infection initiated by a single or a few closely related maternal variants. [41][42][43][44][45][46][47] Phylogenetic analyses also showed relatively longer genetic distances between the viral populations of mothers and their children in all pairs, except for HP13, which could be due to the transmission of a minor variant from the mother to her child.…”

Section: Discussionsupporting

confidence: 82%

Genetic Analyses of HIV-1 Strains Transmitted from Mother to Child in Northern Vietnam

Phan

Pham

et al. 2015

AIDS Research and Human Retroviruses

View full text Add to dashboard Cite

We previously reported mother-to-child transmission of HIV-1 in nine (6.7%) of 135 children on nevirapine prophylaxis in Vietnam. In the current study, we investigated the appearance and profile of antiretroviral drug (ARV) resistance mutations, the predicted coreceptor usage, and the genetic diversity of HIV-1 strains isolated from the eight pairs of HIV-1-infected mothers and their children, who were followed up to 12 months after birth. Portions of the pol and env C2V3 regions of the HIV-1 strains were analyzed genetically. HIV-1 CRF01_AE RNA was detected in four (50%) children at delivery. Y181C, a nevirapine resistance mutation, appeared in two (25%) children 1 and 3 months after birth, respectively. No ARV resistance mutation was detected in the mothers, though three mothers were on ARV prophylaxis. Five mothers and their children harbored CCR5-tropic (R5) viruses. Two mothers harbored both R5 and CXCR4-tropic (X4) viruses, but their children harbored only R5 viruses even though the X4 viruses were dominant in the mothers. In the remaining one mother, HIV-1 RNA was not amplified and her child harbored both R5 and X4 viruses at birth, but only X4 virus 12 months after delivery. The infants' viruses were more homogeneous than their mothers' viruses (mean distance: 0.5% vs.

show abstract

Section: Discussionsupporting

confidence: 82%

Genetic Analyses of HIV-1 Strains Transmitted from Mother to Child in Northern Vietnam

Phan

Pham

et al. 2015

AIDS Research and Human Retroviruses

View full text Add to dashboard Cite

show abstract

“…36 This similarity between variants could be stochastic or it could suggest selection for certain characteristics (in breast milk, during transmission, or through selective amplification in the infant). [37][38][39] Other studies have presented conflicting results testing the hypothesis that selection is influenced by neutralizing antibodies, and 512 RUSSELL ET AL.…”

mentioning

confidence: 97%

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

View full text Add to dashboard Cite

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 ...

show abstract

“…One study suggested HIV-1C viruses newly transmitted from mother-to-child were more fit, had significantly fewer PNG sites, and were more resistant to autologous maternal serum than nontransmitted viruses (60). For studies that analyzed vertical transmission stratified by timing, viral populations have been reported to have different properties if transmitted in utero (IU) or intrapartum (IP) (3,11,30).…”

Section: Subtype C Human Immunodeficiency Virus Type 1 (Hiv-1c) Contimentioning

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

View full text Add to dashboard Cite

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.

show abstract

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

Cited by 98 publications

References 42 publications

Genetic Analyses of HIV-1 Strains Transmitted from Mother to Child in Northern Vietnam

Genetic Analyses of HIV-1 Strains Transmitted from Mother to Child in Northern Vietnam

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

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

Contact Info

Product

Resources

About