Publications by authors named "A Mehle"
ADP-ribosylation is a highly dynamic and fully reversible post-translational modification performed by poly(ADP-ribose) polymerases (PARPs) that modulates protein function, abundance, localization and turnover. Here we show that influenza A virus infection causes a rapid and dramatic upregulation of global ADP-ribosylation that inhibits viral replication. Mass spectrometry defined for the first time the global ADP-ribosylome during infection, creating an infection-specific profile with almost 4,300 modification sites on ~1,080 host proteins, as well as over 100 modification sites on viral proteins.
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- Scientists studied a sensor called STING that helps the body respond to stress and viruses, even when there isn’t typical DNA present.* -
- They found that a special stress response in cells called the unfolded protein response (UPR) can activate STING and help create a certain type of DNA that triggers defense responses.* -
- They discovered that two specific pathways in the UPR, called IRE1 and PERK, play important roles in releasing this DNA and activating immune responses against viruses.*
Article Synopsis
- - The study investigates how endoplasmic reticulum (ER) stress activates the STING pathway, which is involved in immune responses, even in the absence of typical DNA or cyclic di-nucleotide stimuli.
- - Researchers found that the induction of IFN-β (an immune response protein) during ER stress requires both STING and cyclic GMP-AMP synthase (cGAS), involving the release of mitochondrial DNA into the cytoplasm.
- - The study identifies that specific ER stress pathways, particularly the IRE1-XBP1 and PERK pathways, are crucial for generating cytosolic dsDNA and modulating IFN-β production during responses to both viral infections and ER stress.
To streamline standard virological assays, we developed a suite of nine fluorescent or bioluminescent replication competent human species C5 adenovirus reporter viruses that mimic their parental wild-type counterpart. These reporter viruses provide a rapid and quantitative readout of various aspects of viral infection and replication based on EGFP, mCherry, or NanoLuc measurement. Moreover, they permit real-time non-invasive measures of viral load, replication dynamics, and infection kinetics over the entire course of infection, allowing measurements that were not previously possible.
View Article and Find Full Text PDFProductive infections by RNA viruses require faithful replication of the entire genome. Yet many RNA viruses also produce deletion-containing viral genomes (DelVGs), aberrant replication products with large internal deletions. DelVGs interfere with the replication of wild-type virus and their presence in patients is associated with better clinical outcomes.
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