Breast milk and in utero transmission of HIV-1 select for envelope variants with unique molecular signatures.

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.

A Conserved Glycan in the C2 Domain of HIV-1 Envelope Acts as a Molecular Switch to Control X4 Utilization by Clonal Variants with Identical V3 Loops.

Nearly all persons newly infected with HIV-1 harbor exclusively CCR5-using virus. CXCR4-using variants eventually arise in up to 50% of patients infected with subtypes B or D. This transition to efficient CXCR4 utilization is often co-incident with progression to AIDS.

Coverage of primary mother-to-child HIV transmission isolates by second-generation broadly neutralizing antibodies.

Objectives And Design: A vaccine capable of providing cross-clade, sterilizing protection has been the holy grail of HIV-1 prevention and control since the beginning of the pandemic. A major component of this effort has been the identification and characterization of broadly neutralizing antibodies (bNAbs). Recent advances in bNAb isolation, structure-based engineering, and vector-mediated gene transfer have led to increased interest in bypassing the immune system by expressing neutralizing antibodies directly in muscle.