bioRxiv Science⌕ Search

Biology subjects

Kuratli, R.

Publications and source records attributed to Kuratli, R..

3 recordsLinked to original sources

Human antibodies against West Nile and related orthoflaviviruses

West Nile virus (WNV) is a mosquito-borne pathogen of global concern that can cause fatal neuroinvasive disease. No specific prophylaxis or treatment exists for WNV or related orthoflavivirus infections, and the determinants of human disease severity remain poorly understood. Here, we report that neutralizing autoantibodies against type I interferons do not impair antiviral antibody development. Among the fully human monoclonal antibodies with potent neutralizing activity against WNV that were discovered, W010 targets a unique epitope within the envelope protein domain III (EDIII) and confers both pre- and post-exposure protection in a murine WNV model, even when interferon signaling is impaired. A second protective antibody, W014, exhibits broad cross-neutralization of other pathogenic orthoflavivirus members, including Japanese encephalitis virus, Murray Valley encephalitis virus, Saint Louis encephalitis virus, and Usutu virus. These findings identify key neutralizing epitopes on WNV EDIII and provide candidates for the development of antibody-based interventions against encephalitic orthoflavivirus infections.

immunology↗

Tracking eco-evolutionary dynamics among lung pathobiome members from children with cystic fibrosis

Polymicrobial lung infections are common in individuals with cystic fibrosis (CF). Pathogen communities typically follow an ecological succession in which early colonizers such as Haemophilus influenzae and Staphylococcus aureus are later joined by Pseudomonas aeruginosa. Although adaptation to the lung environment is well described for single pathogens in adult people with CF, much less is known about the role of pathogen interactions and how changes in individual pathogens influence community dynamics at the early stages of disease. To address these questions, we combined genome sequencing with phenotypic screens and pathogen interaction assays using longitudinal clinical isolates (19 P. aeruginosa, 44 S. aureus, and 21 H. influenzae) collected from 23 children with CF (0-7.9 years of age) enrolled in the SCILD (Swiss CF Infant Lung Development) cohort. Our analysis revealed that early pathogen communities are characterized by a combination of strain turnover and persistence of isolates undergoing first steps of within-host evolution. Most notably, quorum-sensing-deficient P. aeruginosa variants repeatedly emerged, showing reduced protease production and diminished inhibition of S. aureus and H. influenzae. These changes indicate that P. aeruginosa becomes less antagonistic towards co-occurring pathogens, possibly promoting community stability. Together, our results show that ecological and evolutionary dynamics between pathobiome members may play an underappreciated role in shaping CF lung disease during early childhood.

evolutionary biology↗

Highly-sensitive reporter cell line for detection of interferon types I-III and their neutralization by antibodies

Interferons (IFNs) are a critical component of innate immune defenses and limit viral disease severity. To advance studies on IFNs and their neutralization by pathogenic autoantibodies, we generated a Renilla luciferase-based reporter cell line capable of detecting the activities of IFN-Is, IFN-II, and IFN-IIIs. The reporter cell line exhibits a 125-to 2000-fold higher sensitivity to IFNs than a commonly-used alternative biological reporter system, and allows for a rapid and simple live-cell workflow for detecting low titer amounts of neutralizing anti-IFN antibodies.

immunology↗