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COVID changes the DNA landscape Healthy cells have an organized system for storing their DNA instructions. DNA is wrapped tightly around his- tone proteins to form chromatin, which is packaged into compartments based on transcriptional activity. The A compartment contains actively transcribed genes, and the B compartment includes silenced genes. Each compart- ment has progressive folding and looping, with many loops in the A compartment held in place by cohesion proteins.

Cohesion proteins lock DNA into loops called topologically active domains (TADs). Within TADs, transcription machinery churns out RNA for heavily expressed genes. (see pages 16-17 about Gene Expression) Researchers found that cul- tured human lung cells infected with SARS-CoV-2 had disrupt- ed DNA organization. Some domains had wholly lost shape,

Vampire virus attaches to the neck of a bacteriophage to highjack its ability to infect cells.

and cohesion proteins were often missing, reducing tran- scription in those regions. More importantly, the impacted areas hold genes activated in immune system responses to viruses, including interferon production. A healthy immune response to viral infection involves producing a flood of interferons. Yet COVID-infected patients only make a dribble. The infection’s reshaping of the chromatin architecture could account for this difference. It seems COVID messes with the chemical tags on DNA, making it harder for the cell to "read" and follow the instructions. The loss of an acetyl group on a key histone connected to activating transcription leads to the DNA wrapping tighter around the histone, making it harder for RNA polymerase to bind there. The virus also disguises itself as part of the system, further confusing the cell's machinery. These changes persist even after the infection clears, potentially contributing to the lingering symptoms some patients experience in Long COVID. n REFERENCE: Wang, R., Lee, JH., Kim, J. et al. SARS-CoV-2 restructures host chromatin architecture. Nat Microbiology (2023), 8: 679–694. doi.org/10.1038/s41564-023-01344-8

Vampire virus Scientists recently discovered an interesting new virus in a soil sample from Maryland. Soil typically contains millions of bacte- riophages per gram. These viruses infect bacterial cells and are a significant component of a healthy soil microbiome. Under- graduate students investigating this soil sample repeatedly got unusual DNA sequencing results. What should have been pure cultures of a particular bacteriophage yielded DNA results with sequences from another viral family. Was this contamination? Electron microscopy revealed the answer. Images show a set of phages with an even smaller virus attached to their necks. This tiny virus, found linked to another

virus, may exhibit charac- teristics associated with parasitic behavior. Research- ers hypothesize that the tiny

vampire viruses have lost the ability to make copies of themselves inside cells, which is how viruses repro- duce. Attaching to the larger phage gives the virus the opportunity for ‘simultaneous entry’ as the host phage infects a cell.

Representative virus images

Since characterizing the tiny virus, researchers found other examples in older samples of bacteriophages with molecular ‘bite marks’ on their necks, indicating previous infection by the mini-virus. Researchers continue to investigate this new system at the molecular and ecological level. These discoveries collec- tively enhance our understanding of microbial diversity and their roles in various environments. n REFERENCE: deCarvalho, T., Mascolo, E., Caruso, S.M. et al. Simultaneous entry as an adaptation to virulence in a novel satellite-helper system infecting Streptomyces species. ISMEJ (2023) 17: 2381–2388. doi.org/10.1038/s41396-023-01548-0

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SCIENCE FOR LIFE

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