| 1. |
- Lee, Yun-Bin, et al.
(författare)
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Super-resolution proximity labeling reveals anti-viral protein network and its structural changes against SARS-CoV-2 viral proteins
- 2023
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Ingår i: Cell Reports. - : CELL PRESS. - 2211-1247. ; 42:8
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Tidskriftsartikel (refereegranskat)abstract
- Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replicates in human cells by interacting with host factors following infection. To understand the virus and host interactome proximity, we introduce a super-resolution proximity labeling (SR-PL) method with a "plug-and-playable"PL enzyme, TurboID-GBP (GFP-binding nanobody protein), and we apply it for interactome mapping of SARS-CoV-2 ORF3a and mem-brane protein (M), which generates highly perturbed endoplasmic reticulum (ER) structures. Through SR-PL analysis of the biotinylated interactome, 224 and 272 peptides are robustly identified as ORF3a and M inter-actomes, respectively. Within the ORF3a interactome, RNF5 co-localizes with ORF3a and generates ubiquitin modifications of ORF3a that can be involved in protein degradation. We also observe that the SARS-CoV-2 infection rate is efficiently reduced by the overexpression of RNF5 in host cells. The interactome data ob-tained using the SR-PL method are presented at https://sarscov2.spatiomics.org. We hope that our method will contribute to revealing virus-host interactions of other viruses in an efficient manner.
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| 2. |
- Yu, Meng, et al.
(författare)
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Delayed generation of functional virus-specific circulating T follicular helper cells correlates with severe COVID-19
- 2023
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Ingår i: Nature Communications. - : NATURE PORTFOLIO. - 2041-1723. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Effective humoral immune responses require well-orchestrated B and T follicular helper (Tfh) cell interactions. Whether these interactions are impaired and associated with COVID-19 disease severity is unclear. Here, longitudinal blood samples across COVID-19 disease severity are analysed. We find that during acute infection SARS-CoV-2-specific circulating Tfh (cTfh) cells expand with disease severity. SARS-CoV-2-specific cTfh cell frequencies correlate with plasmablast frequencies and SARS-CoV-2 antibody titers, avidity and neutralization. Furthermore, cTfh cells but not other memory CD4 T cells, from severe patients better induce plasmablast differentiation and antibody production compared to cTfh cells from mild patients. However, virus-specific cTfh cell development is delayed in patients that display or later develop severe disease compared to those with mild disease, which correlates with delayed induction of high-avidity neutralizing antibodies. Our study suggests that impaired generation of functional virus-specific cTfh cells delays high-quality antibody production at an early stage, potentially enabling progression to severe disease. T follicular helper cells (Tfh) enhance antibody responses and can circulate or be resident in lymph nodes. Here the authors show that during acute SARS-CoV-2 infection, circulating Tfh cells correlate with antibody titres and plasmablast levels but in more severe COVID-19 cases, cTfh generation is delayed.
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