During the course of a large-scale HIV-1 vaccine field trial (VAX004), full-length gp120 sequences were determined for 349 new HIV-1 infections. The data collected represent the largest survey of full-length gp120 sequences from new HIV-1 infections ever assembled. Previous studies have shown that subtype B viruses typically possess 18 cysteine residues that are covalently linked to form 9 conserved disulfide bridges. However, in this study we found that approximately 20% of the trial participants possessed envelope proteins with an unusual number of cysteine residues that could very likely result in unusual protein structures. One class of variants included envelope proteins with two additional cysteine residues in close proximity, potentially yielding additional disulfide-bonded loops. Other classes of variants included envelope proteins where amino acid replacements increased or decreased the number of cysteine residues by one, resulting in molecules with either 19 or 17 cysteines, respectively. Initial functional analysis demonstrated that envelope proteins with 19 cysteine residues bind to CD4 and the CCR5 chemokine coreceptor, and are infectious. These results suggest that the protein structure of gp120 in newly transmitted viruses may be more heterogeneous than previously appreciated and potentially represent a new mechanism of virus variation. The disulfide variation that we report here may have important implications for HIV vaccine and drug development efforts.

This study documents a case of coinfection (simultaneous infection of an individual with two or more strains) of two HIV-1 subtype B strains in an individual from a Phase 3 HIV-1 vaccine efficacy trial, conducted in North American and the Netherlands. We examined 86 full-length gp120 (env) gene sequences from this individual collected from nine different time points over a 20-month period. We estimated evolutionary relationships using maximum likelihood and Bayesian methods and inferred recombination breakpoints and recombinant sequences using phylogenetic and substitutional methods. These analyses identified two strongly supported monophyletic clades (clades A and B) of 14 and 69 sequences each and a small paraphyletic recombinant clade of three sequences. We then studied the genetic characteristics of these lineages by comparing estimates of genetic diversity generated by mutation and recombination and adaptive selection within a coalescent and maximum likelihood framework. Our results suggest significant differences on the evolutionary dynamics of these strains. We then discuss the implications of these results for vaccine development.

In this paper, we draw upon a narrative inquiry alongside two creators of an out-of-doors Nipugtugewei Kindergarten program within a Mi’gmaw community, in northeastern Canada. Our intention was to understand their schooling, educational, and communal experiences over time. Diverse field texts were composed and interpreted alongside participants. We turned towards narrative conceptions of knowledge to show how attending to teachers’ personal practical knowledge and stories to live by on their professional knowledge landscape is sustaining who they are as teachers and people. It is also a way for teachers to live their responsibility to Indigenous communities and students.

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