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Breast milk and in utero transmission of HIV-1 select for envelope variants with unique molecular signatures
- Source :
- Retrovirology, vol 14, iss 1, Retrovirology
- Publication Year :
- 2017
- Publisher :
- eScholarship, University of California, 2017.
-
Abstract
- Background Mother-to-child transmission of human immunodeficiency virus-type 1 (HIV-1) poses a serious health threat in developing countries, and adequate interventions are as yet unrealized. HIV-1 infection is frequently initiated by a single founder viral variant, but the factors that influence particular variant selection are poorly understood. Results Our analysis of 647 full-length HIV-1 subtype C and G viral envelope sequences from 22 mother–infant pairs reveals unique genotypic and phenotypic signatures that depend upon transmission route. Relative to maternal strains, intrauterine HIV transmission selects infant variants that have shorter, less-glycosylated V1 loops that are more resistant to soluble CD4 (sCD4) neutralization. Transmission through breastfeeding selects for variants with fewer potential glycosylation sites in gp41, are more sensitive to the broadly neutralizing antibodies PG9 and PG16, and that bind sCD4 with reduced cooperativity. Furthermore, experiments with Affinofile cells indicate that infant viruses, regardless of transmission route, require increased levels of surface CD4 receptor for productive infection. Conclusions These data provide the first evidence for transmission route-specific selection of HIV-1 variants, potentially informing therapeutic strategies and vaccine designs that can be tailored to specific modes of vertical HIV transmission. Electronic supplementary material The online version of this article (doi:10.1186/s12977-017-0331-z) contains supplementary material, which is available to authorized users.
- Subjects :
- 0301 basic medicine
Male
Pediatric AIDS
Glycosylation
Infectious Disease Transmission
HIV Infections
Neutralization
law.invention
env Gene Products
Cohort Studies
law
Pregnancy
Genotype
2.2 Factors relating to the physical environment
Vertical
Aetiology
Maternal-Fetal Exchange
Pediatric
env Gene Products, Human Immunodeficiency Virus
Phenotype
3. Good health
Transmission (mechanics)
Infectious Diseases
Breast Feeding
HIV/AIDS
Female
Antibody
Infection
Sequence Analysis
Human Immunodeficiency Virus
Biotechnology
Clinical Sciences
Biology
Gp41
Vaccine Related
03 medical and health sciences
Viral envelope
Genetic
Envelope
Virology
Humans
Selection, Genetic
Vaccine Related (AIDS)
Broadly neutralizing antibodies
Selection
Selection (genetic algorithm)
Mother-to-child transmission
Prevention
Research
Infant, Newborn
Infant
Sequence Analysis, DNA
DNA
Perinatal Period - Conditions Originating in Perinatal Period
Newborn
Infectious Disease Transmission, Vertical
CD4
Good Health and Well Being
030104 developmental biology
biology.protein
HIV-1
Immunization
Subjects
Details
- Database :
- OpenAIRE
- Journal :
- Retrovirology, vol 14, iss 1, Retrovirology
- Accession number :
- edsair.doi.dedup.....05e4f6f862f48f292f32204af7d12c2a