Studying the immunomodulatory effects of SARS-CoV-2 viral proteins in human lung epithelial cell lines

The novel coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), presents a wide spectrum of clinical manifestations which range from asymptomatic or cold-like symptoms to severe pneumonia and multisystem failure with fatal outcome. Disease severity correlates with dysregulated host immune responses, characterized by delayed or missing antiviral type I and III interferon (IFN) responses and excessive inflammatory responses. Several viral proteins are proposed to inhibit IFN production, among these SARS-CoV-2 Orf3a, Orf6 and Orf9b. However, most studies have so far focused on viral protein inhibition of type I IFN (IFNα/β) responses in cell types that are of low relevance, and most mechanisms are not yet fully characterized. Here, we studied immunomodulatory effects of SARS-CoV-2 Orf3a, Orf6 and Orf9b proteins in human lung epithelial cell lines (A549, Calu-3) as a relevant cell model for SARS-CoV-2 infection and focused on effects on type III IFN (IFN-λ1/2/3) induction. For this, we used lentiviral transduction to generate cell lines stably expressing the viral proteins upon doxycycline treatment. We demonstrate that A549 and Calu-3 cells respond to transfection of poly(I:C), a dsRNA mimic and common RIG-I/MDA5 agonist, by inducing antiviral and inflammatory immune responses. Inflammatory cytokine and chemokine production was not found altered in lung epithelial cells expressing viral proteins. But interestingly we found a slight reduction in IFN-λ2 secretion from A549 cells expressing Orf3a, Orf6 or Orf9b compared to wildtype cells. Combined, our findings suggest exclusive anti-IFN activity by SARS-CoV-2 Orf3a, Orf6 and Orf9b, but lower type III IFN antagonistic effects compared to what has previously been proposed for type I IFNs. This highlights the distinct role of type III IFNs in maintaining antiviral immunity at the airway epithelium, and the importance of further in-depth studies. Deeper understanding of the immune responses in severe COVID-19 is strongly needed to develop effective therapeutic approaches and to prepare us with knowledge for future pandemic coronavirus outbreaks

Der Brasil-Strom im Spatquartär: Rekonstruktion der oberflächennahen Hydrographie wahrend der letzten400000 Jahre

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Stable isotope data of sediment cores in the western equatorial Atlantic

In order to reconstruct hydrographic changes during glacial-interglacial cycles for a transequatorial transect we analyzed oxygen isotopes of Globigerinoides sacculifer (without sac-like chamber) and abundances of Globorotalia truncatulinoides (dextral) from FS Meteor cores GeoB 2204-2 (Brazilian continental slope) and GeoB 1523-1 (Ceara Rise). Delta d18O values of G. sacculifer between the two cores were calculated. Modern Delta d18O (G. sacculifer) is ~0.2 per mill between the two core positions, reflecting differences in sea surface salinity (SSS). Higher SSS at GeoB 1523-1 (Ceara Rise) is the result of increased precipitation in the region of the Intertropical Convergence Zone. During glacials the ?18O records from the two cores converge to the same absolute value, resulting in ??18O values of around 0 per mill. Maximum abundances of G. truncatulinoides (dex) correlate with minimum Delta d18O, suggesting a possible increase of SSS at GeoB 1523-1 during stages 2, 3, 4, and 6, which is related to a glacial weakening of the tropical Hadley Cell [Gates, 1976]. Variations in tropical sea surface temperatures are assumed to be low [Climate: Long-Range Investigation, Mapping, and Prediction (CLIMAP), 1981]