Abstract
BackgroundMother-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.ResultsOur 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.ConclusionsThese 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.
Highlights
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
Transmission timing and phylogenetic linkage of HIV strains within mother‐to‐child transmission pairs We examined 22 mother-to-child transmission (MTCT) pairs participating in the Zambia Exclusive Breastfeeding Study (ZEBS) [44]
Six mothers from this cohort transmitted in utero (IUT), as their infants were HIV-positive at birth by polymerase chain reaction (PCR) tests, while 13 mothers transmitted virus through breastfeeding (BMT), since their infants were HIV-negative at birth and at 1 month of age, but HIV-positive after 42 days
Summary
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. Despite focused efforts upon preventative measures, pediatric human immunodeficiency virus-type 1 (HIV1) infections through mother-to-child transmission (MTCT) continue to challenge clinicians and strain healthcare systems, with 1.5 million HIV-positive women giving birth and 240,000 children acquiring the virus in 2013 [1]. A large majority of HIV-1 infections that occur through sexual or vertical transmission are established by a single “founder” variant, with primary infection being characterized by a virus population with significantly less sequence diversity compared to donor viruses [4,5,6,7,8,9,10,11,12,13,14,15,16,17].
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
