Document Detail


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.
MedLine Citation:
PMID:  23075434     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Elizabeth S Russell; Suany Ojeda; Genevieve G Fouda; Steven R Meshnick; David Montefiori; Sallie R Permar; Ronald Swanstrom
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2013-01-18
Journal Detail:
Title:  AIDS research and human retroviruses     Volume:  29     ISSN:  1931-8405     ISO Abbreviation:  AIDS Res. Hum. Retroviruses     Publication Date:  2013 Mar 
Date Detail:
Created Date:  2013-02-26     Completed Date:  2013-08-02     Revised Date:  2014-03-09    
Medline Journal Info:
Nlm Unique ID:  8709376     Medline TA:  AIDS Res Hum Retroviruses     Country:  United States    
Other Details:
Languages:  eng     Pagination:  511-5     Citation Subset:  IM; X    
Data Bank Information
Bank Name/Acc. No.:
GENBANK/JN983803;  JN983804;  JN983805
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MeSH Terms
Descriptor/Qualifier:
Antibodies, Neutralizing / immunology*
Breast Feeding*
Epitopes / immunology*
Female
HIV Antibodies / immunology*
HIV Infections / immunology,  transmission,  virology*
HIV-1 / immunology*,  isolation & purification
Humans
Infant
Infant, Newborn
Infectious Disease Transmission, Vertical*
Molecular Sequence Data
Pregnancy
Selection, Genetic
Sequence Analysis, DNA
env Gene Products, Human Immunodeficiency Virus / genetics
Grant Support
ID/Acronym/Agency:
P30-AI50410/AI/NIAID NIH HHS; R01 AI044667/AI/NIAID NIH HHS; R21-AI49084/AI/NIAID NIH HHS; R37 AI044667/AI/NIAID NIH HHS; R37-AI44667/AI/NIAID NIH HHS; T32 AI07419/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Antibodies, Neutralizing; 0/Epitopes; 0/HIV Antibodies; 0/env Gene Products, Human Immunodeficiency Virus
Comments/Corrections

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