Biology subjects

Eray, E.

Publications and source records attributed to Eray, E..

4 recordsLinked to original sources

bioRxiv2026

Distinct mechanisms of neutralization by antibodies targeting a conserved pneumovirus F epitope

Pneumoviruses cause seasonal outbreaks leading to hospitalizations of vulnerable populations such as infants and the elderly. Cross-neutralizing antibodies targeting viral fusion have been isolated from infected individuals, but their elicitation and mechanisms of action remain understudied. Here, we describe two vaccine-elicited antibody classes, LOR24 and LOR69, that bind an overlapping epitope, and identify the somatic mutations that endow their breadth and potency, respectively. Cryo-electron microscopy structures of both antibodies bound to the HRSV fusion (F) protein show binding modes distinct from each other and from the previously described cross-neutralizing antibody MPE8, yet they all use similar motifs for binding. Complementary in vitro and electron microscopy experiments show that these antibodies either lock prefusion F as a trimer, arrest F in a monomeric or intermediate state, or promote the transition to the postfusion conformation. This work sheds light on mechanisms of pneumovirus neutralization and the elicitation of cross-neutralizing antibody responses.

immunology↗

bioRxiv2026

Antigenic landscape of a highly mutated SARS-CoV-2 Spike in ongoing viral evolution

The ongoing emergence of SARS-CoV-2 variants in an increasingly immune-experienced population is largely enabled by the plasticity of the Spike protein, which lies at the frontline of host immune pressure. Here, we investigated how extensive remodeling of the N-terminal domain (NTD) in Spike influences its antigenic properties. Using BA.2.87.1, a variant heavily mutated in this domain, we found that even large deletions do not substantially disrupt overall Spike structure or pseudovirus infectivity. However, our structural and binding analyses revealed that the NTD exhibits increased flexibility and that interaction with a heme-metabolite, contributing to assembly of an immunodominant epitope, is lost. These conformational effectscoupled with mutations, compromised the ability of human convalescent antibodies to engage this domain, contributing to their reduced neutralizing capacity. Consequently, BA.2.87.1-like variants may escape recognition by the pre-existing NTD-targeting antibodies, potentially reducing protection. Together, our results highlight the intrinsic adaptability of the Spike beyond the receptor-binding domain, with important implications for immune escape during viral evolution. TeaserStructural flexibility of the Spike and immune escape of a SARS-CoV-2 variant with public health implications.

immunology↗

bioRxiv2024

Dual CRISPRi-Seq for genome-wide genetic interaction studies identifies key genes involved in the pneumococcal cell cycle

A major goal in biology is to uncover the relationship between genotype and phenotype. However, identifying gene function is often hampered by genetic redundancy. For example, under standard laboratory conditions, three-quarters of the genes in the human pathogen Streptococcus pneumoniae are non-essential. A powerful approach to unravel genetic redundancy is by identifying gene-gene interactions. To uncover genetic interactions (GIs) in S. pneumoniae on a genome-wide scale, a generally applicable dual CRISPRi-Seq method and associated analysis pipeline was developed. Specifically, we created a library of 869 dual sgRNAs targeting high-confidence operons that encode essential and non-essential genes, covering over 70% of the genetic elements in the pneumococcal genome. Testing these 378,015 unique combinations, 4,026 significant GIs were identified, including 1,935 negative and 2,091 positive interactions. Besides known GIs, we found and confirmed previously unknown interactions involving genes responsible for fundamental cellular processes such as cell division, cell shape maintenance, and chromosome segregation. The presented methods and bioinformatic approaches can serve as a roadmap for genome-wide gene interaction studies in other organisms. Lastly, all interactions are available for exploration via the Pneumococcal Genetic Interaction Network (PneumoGIN) at https://veeninglab.shinyapps.io/PneumoGIN, which can serve as a starting point for new biological discoveries and translational research.

microbiology↗

bioRxiv2020

Diverse natural variants suppress mutations in hundreds of essential genes

The consequence of a mutation can be influenced by the context in which it operates. For example, loss of gene function may be tolerated in one genetic background, but lead to lethality in another. The extent to which mutant phenotypes are malleable, the complexity of the architecture of modifiers, and the identities of causal genes and pathways remain largely unknown. Here, we measure the fitness effects of ~1,500 temperature sensitive alleles of yeast essential genes in the context of variation from ten different natural genetic backgrounds, and map the modifiers for 19 combinations. Altogether, fitness defects for 183 of the 530 tested genes (35%) could be suppressed by standing genetic variation in at least one wild strain. Suppression was generally driven by gain-of-function of a single, strong modifier gene. The validated causes included both variants in protein interaction partners or pathway members suppressing specific genes, as well as general modifiers altering the effect of many temperature sensitive alleles. The emerging frequency of suppression and range of possible suppression mechanisms suggest that a substantial fraction of monogenic diseases could be repressed by modulating other gene products.

genetics↗