Herpesviridae is a large family of DNA viruses divided into three subfamilies: Alpha-, Beta- and Gammaherpesvirinae. The process of herpesvirus transmission is mediated by a range of proteins, one of which is glycoprotein L (gL). Based on our analysis of the solved structures of HSV2 and EBV gH/gL complexes, we propose that Alphaherpesvirinae and Gammaherpesvirinae glycoprotein L and Betaherpesvirinae UL130 originate from chemokines. Herpes simplex virus type 2 gL and human cytomegalovirus homolog (UL130) adopt a novel C chemokine-like fold, while Epstein-Barr virus gL mimics a CC chemokine structure. Hence, it is possible that gL interface with specific chemokine receptors during the transmission of Herpesviridae. We conclude that the further understanding of the function of viral chemokine-like proteins in Herpesviridae infection may lead to development of novel prophylactic and therapeutic treatment.

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SCO2 mutations cause recessively inherited cytochrome c oxidase deficiency. Recently Tran-Viet et al. proposed that heterozygosity for pathogenic SCO2 variants, including the common E140K variant, causes high-grade myopia. To investigate the association of SCO2 mutations with myopia, ophthalmic examinations were performed on 35 E140K carriers, one homozygous infant, and on a mouse model of Sco2 deficiency. Additionally, a screen for other putative effects of SCO2 heterozygosity was carried out by comparing the prevalence of the common E140K variant in a population of patients with undiagnosed diseases compatible with SCO2-related pathogenesis to that in a general population sample. High-grade myopia was not identified in any of the studied individuals. Of the carriers, 17 were emmetropic, and 18 possessed refractive errors. Additionally, no significant axial elongation indicative of high-grade myopia was found in mice carrying E129K (corresponding to E140K in humans) knock-in mutations. The prevalence of E140K carriers in the symptomatic cohort was evaluated as 1:103 (CI: 0.44-2.09) and did not differ significantly from the population prevalence (1:147, CI: 0.45-1.04).Our study demonstrates that heterozygosity for pathogenic SCO2 variants is not associated with high-grade myopia in either human patients or in mice.

Motivation: The identification of functional sequence variations in regulatory DNA regions is one of the major challenges of modern genetics. Here, we report results of a combined multifactor analysis of properties characterizing functional sequence variants located in promoter regions of genes. Results: We demonstrate that GC-content of the local sequence fragments and local DNA shape features play significant role in prioritization of functional variants and outscore features related to histone modifications, transcription factors binding sites, or evolutionary conservation descriptors. Those observations allowed us to build specialized machine learning classifier identifying functional SNPs within promoter regions – ShapeGTB. We compared our method with more general tools predicting pathogenicity of all non-coding variants. ShapeGTB outperformed them by a wide margin (AUC ROC 0.97 vs. 0.57-0.59). On the external validation set based on ClinVar database it displayed only slightly worse performance (AUC ROC 0.92 vs. 0.74-0.81). Such results suggest unique characteristics of mutations located within promoter regions and are a promising signal for the development of more accurate variant prioritization tools in the future. Availability and implementation: The datasets and source code are publicly available at: https://github.com/zubekj/ShapeGTB.