Synthetic virions reveal fatty acid-coupled adaptive immunogenicity of SARS-CoV-2 spike glycoprotein.

SARS-CoV-2 infection is a major global public health concern with incompletely understood pathogenesis. The SARS-CoV-2 spike (S) glycoprotein comprises a highly conserved free fatty acid binding pocket (FABP) with unknown function and evolutionary selection advantage1,2. Deciphering FABP impact on COVID-19 progression is challenged by the heterogenous nature and large molecular variability of live virus. Here we create synthetic minimal virions (MiniVs) of wild-type and mutant SARS-CoV-2 with precise molecular composition and programmable complexity by bottom-up assembly. MiniV-based systematic assessment of S free fatty acid (FFA) binding reveals that FABP functions as an allosteric regulatory site enabling adaptation of SARS-CoV-2 immunogenicity to inflammation states via binding of pro-inflammatory FFAs. This is achieved by regulation of the S open-to-close equilibrium and the exposure of both, the receptor binding domain (RBD) and the SARS-CoV-2 RGD motif that is responsible for integrin co-receptor engagement. We find that the FDA-approved drugs vitamin K and dexamethasone modulate S-based cell binding in an FABP-like manner. In inflammatory FFA environments, neutralizing immunoglobulins from human convalescent COVID-19 donors lose neutralization activity. Empowered by our MiniV technology, we suggest a conserved mechanism by which SARS-CoV-2 dynamically couples its immunogenicity to the host immune response.

Analysis of the impact of the absence of RAD51 strand exchange activity in Arabidopsis meiosis.

The ploidy of eukaryote gametes must be halved to avoid doubling of numbers of chromosomes with each generation and this is carried out by meiosis, a specialized cell division in which a single chromosomal replication phase is followed by two successive nuclear divisions. With some exceptions, programmed recombination ensures the proper pairing and distribution of homologous pairs of chromosomes in meiosis and recombination defects thus lead to sterility. Two highly related recombinases are required to catalyse the key strand-invasion step of meiotic recombination and it is the meiosis-specific DMC1 which is generally believed to catalyse the essential non-sister chromatid crossing-over, with RAD51 catalysing sister-chromatid and non-cross-over events. Recent work in yeast and plants has however shown that in the absence of RAD51 strand-exchange activity, DMC1 is able to repair all meiotic DNA breaks and surprisingly, that this does not appear to affect numbers of meiotic cross-overs. In this work we confirm and extend this conclusion. Given that more than 95% of meiotic homologous recombination in Arabidopsis does not result in inter-homologue crossovers, Arabidopsis is a particularly sensitive model for testing the relative importance of the two proteins-even minor effects on the non-crossover event population should produce detectable effects on crossing-over. Although the presence of RAD51 protein provides essential support for the action of DMC1, our results show no significant effect of the absence of RAD51 strand-exchange activity on meiotic crossing-over rates or patterns in different chromosomal regions or across the whole genome of Arabidopsis, strongly supporting the argument that DMC1 catalyses repair of all meiotic DNA breaks, not only non-sister cross-overs.

Transcriptome dynamics during fibre development in contrasting genotypes of Gossypium hirsutum L.

Understanding the contribution of genetic background in fibre quality traits is important for the development of future cotton varieties with superior fibre quality. We used Affymetrix microarray (Santa Clara, CA) and Roche 454 GSFLX (Branford, CT) for comparative transcriptome analysis between two superior and three inferior genotypes at six fibre developmental stages. Microarray-based analysis of variance (ANOVA) for 89 microarrays encompassing five contrasting genotypes and six developmental stages suggests that the stages of the fibre development have a more pronounced effect on the differentially expressed genes (DEGs) than the genetic background of genotypes. Superior genotypes showed enriched activity of cell wall enzymes, such as pectin methyl esterase, at early elongation stage, enriched metabolic activities such as lipid, amino acid and ribosomal protein subunits at peak elongation, and prolonged combinatorial regulation of brassinosteroid and auxin at later stages. Our efforts on transcriptome sequencing were focused on changes in gene expression at 25 DPA. Transcriptome sequencing resulted in the generation of 475 658 and 429 408 high-quality reads from superior and inferior genotypes, respectively. A total of 24 609 novel transcripts were identified manually for Gossypium hirsutum with no hits in NCBI 'nr' database. Gene ontology analyses showed that the genes for ribosome biogenesis, protein transport and fatty acid biosynthesis were over-represented in superior genotype, whereas salt stress, abscisic acid stimuli and water deprivation leading to the increased proteolytic activity were more pronounced in inferior genotype.