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
- 15 August 2011
- journal article
- Published by American Society for Microbiology in Journal of Virology
- Vol. 85 (16), 8253-8262
- https://doi.org/10.1128/jvi.00197-11
Abstract
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.Keywords
This publication has 59 references indexed in Scilit:
- Functional properties of the HIV-1 subtype C envelope glycoprotein associated with mother-to-child transmissionVirology, 2010
- Acute HIV infection among pregnant women in MalawiDiagnostic Microbiology and Infectious Disease, 2010
- Antibody Specificities Associated with Neutralization Breadth in Plasma from Human Immunodeficiency Virus Type 1 Subtype C-Infected Blood DonorsJournal of Virology, 2009
- Human Immunodeficiency Virus Type 1 Superinfection Occurs despite Relatively Robust Neutralizing Antibody ResponsesJournal of Virology, 2008
- Identification and characterization of transmitted and early founder virus envelopes in primary HIV-1 infectionProceedings of the National Academy of Sciences of the United States of America, 2008
- Env length and N-linked glycosylation following transmission of human immunodeficiency virus Type 1 subtype B virusesVirology, 2008
- The molecular epidemiology of HIV-1 envelope diversity during HIV-1 subtype C vertical transmission in Malawian mother–infant pairsAIDS, 2008
- Genetic and Neutralization Properties of Subtype C Human Immunodeficiency Virus Type 1 Molecular env Clones from Acute and Early Heterosexually Acquired Infections in Southern AfricaJournal of Virology, 2006
- MAFFT version 5: improvement in accuracy of multiple sequence alignmentNucleic Acids Research, 2005
- A simple method for estimating evolutionary rates of base substitutions through comparative studies of nucleotide sequencesJournal of Molecular Evolution, 1980