Biology subjects

Terebiznik, M.

Publications and source records attributed to Terebiznik, M..

4 recordsLinked to original sources

bioRxiv2026

A dsRNA Virus Converts Early Endosomes into Stable Replication Organelles Through Maturation Arrest and Retrograde Transport

Infectious bursal disease virus (IBDV) and infectious pancreatic necrosis virus (IPNV) are major animal pathogens that impose a heavy burden on the poultry and aquaculture industries. Yet, major aspects of their unique replication program remain unknown. IBDV is unusual among double-stranded RNA viruses in that it replicates in association with host endosomes. We previously demonstrated this association to be orchestrated by the viral protein VP3 and the early endosomal lipid phosphatidylinositol 3-phosphate [PtdIns(3)P], suggesting an essential role for VP3 in forming birnaviruses specialized replication compartments. Here, combining high-resolution fluorescence and correlative light-electron microscopy with diverse molecular and biochemical analyses, we define how the IBDV protein VP3 targets and remodels host endosomes, and establish that endosome-associated replication is conserved in members of the Birnaviridae family. We show that IBDV VP3 targets early endosomes via the PtdIns(3)P effector Early Endosomal Antigen 1 (EEA1) to arrest their maturation and prompt their association with the Golgi complex via ESCPE-1-mediated retrograde transport. We further show that IPNV also exploits endosomal membranes for replication in a PtdIns(3)P dependent manner, although for this virus VP3 engages endosomes through an EEA1-independent mechanism yet to be determined. This work uncovers how birnaviruses exploit a single viral protein to orchestrate endosome remodeling and intracellular trafficking to establish specialized replication compartments while revealing both conserved and host-adapted features of birnaviruses replication.

cell biology↗

bioRxiv2026

3' Plasma Membrane Phosphoinositides Sustain ROS Production at Persistent Non-canonical Phagocytic Cups that Promote Macrophage Control of Aspergillus fumigatus Hyphae

Aspergillus fumigatus is the leading cause of aspergillosis in immunocompromised individuals. Because A. fumigatus hyphae rapidly outgrow macrophages, they are generally thought to evade macrophage-mediated control once they exceed the size limits of phagocytosis, enabling invasive growth within host tissues. Here, we show that macrophages circumvent this limitation by capturing hyphal tips within persistent tubular phagocytic cups. Rather than resolving into complete phagosomes or disengaging from their targets, these long-lived open compartments maintain key features of phagocytic cups while progressively acquiring characteristics of maturing phagosomes. Their persistence sustains localized NOX2-dependent reactive oxygen species production, leading to hyphal-tip damage and restriction of fungal growth. Sustained PI(3,4)P2 signaling downstream of class I PI3K promotes prolonged NOX2 activity and is required for efficient hyphal restriction. Together, our findings reveal a previously unrecognized antifungal mechanism in which persistent phagocytic cups transform incomplete phagocytosis into sustained antimicrobial activity, extending macrophage control beyond the physical limits of engulfment.

cell biology↗

bioRxiv2024

Depletion of endomembrane reservoirs drives phagocytic appetite exhaustion in macrophages

During phagocytosis, a phagocytic cup grows via F-actin remodelling and localized secretion to entrap a particle within a phagosome, which then fuses with endosomes and lysosomes to digest the particle, followed by phagosome resolution. As spatially limited systems, phagocytes have a maximal phagocytic capacity, at which point further uptake must be blunted. However, the processes responsible for phagocytic appetite exhaustion as phagocytes reach their maximal phagocytic capacity are poorly defined. We found that macrophages at their capacity have lower surface levels of Fc{gamma} receptors but overexpression of these receptors did not increase their capacity, suggesting that receptor levels are not limiting. Instead, surface membrane in-folding, membrane tension, and cortical F-actin were all reduced in exhausted macrophages. While this might contribute to appetite suppression, we also found that "free" endosomes and lysosomes were severely depleted in exhausted macrophages. Consequently, focal exocytosis at sites of externally bound particles was blunted. In comparison, macrophages recovered their appetite if phagosome resolution was permitted. We propose that depletion of the endomembrane pools is a major determinant of phagocytic fatigue as macrophages reach their phagocytic capacity. Summary statementMacrophages that reach their maximal phagocytic capacity lose their appetite for further uptake. This appetite exhaustion is driven partly by depletion of endosomes and lysosomes, preventing growth of additional phagocytic cups.

cell biology↗

bioRxiv2020

Phagosome resolution regenerates lysosomes and maintains the degradative capacity in phagocytes

Phagocytes engulf unwanted particles into phagosomes that then fuse with lysosomes to degrade the enclosed particles. Ultimately, phagosomes must be recycled to help recover membrane resources that were consumed during phagocytosis and phagosome maturation, a process referred to as phagosome resolution. Little is known about phagosome resolution, which may proceed through exocytosis or membrane fission. Here, we show that bacteria-containing phagolysosomes in macrophages undergo fragmentation through vesicle budding, tubulation, and constriction. Phagosome fragmentation requires cargo degradation, the actin and microtubule cytoskeletons, and clathrin. We provide evidence that lysosome reformation occurs during phagosome resolution since the majority of phagosome-derived vesicles displayed lysosomal properties. Importantly, we show that clathrin-dependent phagosome resolution is important to maintain the degradative capacity of macrophages challenged with two waves of phagocytosis. Overall, our work suggests that phagosome resolution contributes to lysosome recovery and to maintain the degradative power of macrophages to handle multiple waves of phagocytosis. SummaryPhagocytes engulf particles into phagolysosomes for degradation. However, the ultimate fate of phagolysosomes is undefined. Lancaster, Fountain et al. show that phagosomes fragment to reform lysosomes in a clathrin-dependent manner. This process helps maintain the degradative capacity of phagocytes for subsequent rounds of phagocytosis.

cell biology↗