CBR - Working Papers / Preprints
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Browsing CBR - Working Papers / Preprints by Author "Brás, Daniela"
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- ATG9A facilitates the biogenesis of influenza A virus liquid condensates near the ER by dissociating recycling vesicles from microtubulesPublication . Vale-Costa, Sílvia; Etibor, Temitope Akghibe; Brás, Daniela; Sousa, Ana Laura; Amorim, Maria JoãoMany viruses that threaten public health establish condensates via phase transitions to complete their lifecycles, and knowledge on such processes is key for the design of new antivirals. In the case of influenza A virus, liquid condensates known as viral inclusions are sites dedicated to the assembly of its 8-partite RNA genome. Liquid viral inclusions emerge near the endoplasmic reticulum (ER) exit sites, but we lack the molecular understanding on how the ER contributes to their biogenesis. We show here that viral inclusions develop at remodeled ER sites and display dynamic interactions using the ER, including fusion and fission events and sliding movements. We also uncover a novel role for the host factor, ATG9A, in mediating the exchange of viral inclusions between the ER and microtubules. Depletion of ATG9A arrests viral inclusions at microtubules and prevents their accumulation at the ER, leading to a significantly reduced production of viral genome complexes and infectious virions. In light of our recent findings, we propose that a remodeled ER supports the dynamics of liquid IAV inclusions, with ATG9A acting locally to facilitate their formation. This work advances our current knowledge regarding influenza genome assembly, but also reveals new roles for ATG9A beyond its classical involvement in autophagy.
- Investigation of Trypanosoma-induced vascular damage sheds insights into Trypanosoma vivax sequestrationPublication . Pereira, Sara Silva; Brás, Daniela; Porqueddu, Teresa; Nascimento, Ana M.; Niz, Mariana DeMultiple blood-borne pathogens infecting mammals establish close interactions with the host vascular endothelium as part of their life cycles. In this work, we investigate differences in the interactions of three Trypanosoma species: T. brucei, T. congolense and T. vivax with the blood vasculature. Infection with these species results in vastly different pathologies, including different effects on vascular homeostasis, such as changes in vascular permeability and microhemorrhages. While all three species are extracellular parasites, T. congolense is strictly intravascular, while T. brucei is capable of surviving both extra- and intravascularly. Our knowledge regarding T. vivax tropism and its capacity of migration across the vascular endothelium is unknown. In this work, we show for the first time that T. vivax parasites sequester to the vascular endothelium of most organs, and that, like T. congolense, T. vivax Y486 is largely incapable of extravasation. Infection with this parasite species results in a unique effect on vascular endothelium receptors including general downregulation of ICAM1 and ESAM, and upregulation of VCAM1, CD36 and E-selectin. Our findings on the differences between the two sequestering species (T. congolense and T. vivax) and the non-sequestering, but extravasating, T. brucei raise important questions on the relevance of sequestration to the parasite’s survival in the mammalian host, and the evolutionary relevance of both sequestration and extravasation.