Kazutomo Yokoya

Human papillomavirus (HPV) variants are classified into lineages and sublineages based upon their genome sequence, but the impact of variation on the function of encoded proteins is unclear. We used a global panel of natural infection sera and relational antigenic maps to assess HPV33 and HPV45 neutralizing antibody specificity. HPV33 A2, A3, B, and C variants were spatially resolved approximately 5-fold distant from the A1 reference, while HPV45 variants were resolved within approximately 2-fold, with differences mapped to residues on the capsid surface. These data inform the degree of lineage and sublineage specificity within the natural infection humoral immune response to oncogenic HPV.

Chlamydia trachomatis (Ct) is a sexually transmitted infection (STI) linked to ectopic pregnancy, infertility, invasive lymphogranuloma venereum (LGV), and the blinding disease trachoma. STI, LGV, and trachoma are associated with disease-specific Ct genovars. Serology is an important surveillance tool for estimating exposure, but the impact of genome variation on the antigenicity of Ct proteins is unclear. Two-dimensional antigenicity profiling of Pgp3 antigens representing LGV, STI, and trachoma demonstrated differential antigenicity using antigen-specific murine sera, but geometric distances were not considered significant (≤2-fold) for human infection sera. Pgp3 should be considered a single serotype for the purposes of Ct serosurveillance.

Human papillomavirus variants are classified into lineages based on their whole genome sequence, but the impact of lineage variation on the structure or function of encoded proteins is unclear. We used a global panel of lineage-specific natural infection sera to assess antibody-binding specificity for lineage-specific L1L2 antigens, and we used these data to create relational antigenic maps. Merging these data with neutralizing antibody data demonstrated similar spatial geometry and revealed dependency on a limited number of amino residues on the capsid surface. These data inform the degree of lineage specificity within the natural infection humoral immune response to oncogenic human papillomaviruses.

Live imaging in the zebrafish embryo using tissue‐specific expression of fluorescent proteins can yield important insights into the mechanisms that drive sensory organ morphogenesis and cell differentiation. Morphogenesis of the semicircular canal ducts of the vertebrate inner ear requires a complex rearrangement of epithelial cells, including outgrowth, adhesion, fusion and perforation of epithelial projections to generate pillars of tissue that form the hubs of each canal. We report the insertion sites and expression patterns of two enhancer trap lines in the developing zebrafish embryo, each of which highlight different aspects of epithelial cell morphogenesis in the inner ear. A membrane‐linked EGFP driven by smad6b regulatory sequences is expressed throughout the otic epithelium, most strongly on the lateral side of the ear and in the sensory cristae. A second enhancer trap line, with cytoplasmic EGFP driven by frizzled1 (fzd1) regulatory sequences, specifically marks cells of the ventral projection and pillar in the developing ear, and marginal cells in the sensory cristae, together with variable expression in the retina and epiphysis, and neurons elsewhere in the developing central nervous system. We have used a combination of methods to identify the insertion sites of these two transgenes, which were generated through random insertion, and show that Targeted Locus Amplification is a rapid and reliable method for the identification of insertion sites of randomly inserted transgenes.