Health
SARS-CoV-2 virus turns out to mimic protein that packages DNA and prevents transcription
ORF8 associates with chromatin. aORF8 contains an ARKS motif at amino acid 50, consistent with the histone H3 tail. bLamin A/C staining of HEK293T cells transfected to express Strep-ORF8. cORF8 and Lamin A/C staining of SARS-CoV-2-infected A549ACE2 MOI = 1, cells 48 hours post-infection. dsequential salt extraction of ORF8 or HEK293T cells expressing ORF8ΔARK SAP. egene tracks of ORF8 ChIP–seq normalized to the input control. What, Targeted mass spectrometry analysis of trypsin-digested ORF8, showing that ORF8 is acetylated at lysine 52. intact peptide or precursor of 879.9508meters/ Ze The one with 2+ charge was isolated and fragmented. The tandem mass spectrometry spectrum shows the unfragmented precursor (green) with matching product ions within 10 ppm mass error. Fragment intensities are relative to the intensity of the ion with the highest intensity over the entire region.meters/ Ze range. The color, letter, and number of each fragment indicate the sequence in which the fragment is contained within a larger peptide (top). The y (red) and b (blue) fragments indicate fragments with matching C- and N-termini, respectively. g, ORF8 expression reduces the level of KAT2A. Scale bar, 10 μm. credit: Nature (2022). DOI: 10.1038/s41586-022-05282-z
A team of researchers at the University of Pennsylvania, working with colleagues at the University of Texas Medical School and another at Boston University and Boston Medical Center, discovered that the SARS-CoV-2 virus produces proteins that mimic proteins. Prevents transcription of DNA, which normally plays a role in the immune response.
In their paper published in Naturethe group describes how they compared the proteins that package human DNA with those produced by the SARS-CoV-2 virus, and what that showed them. Lisa Thomann and Volker Thiel from the Institutes of Science (Bern and Mittelheisern) published a News & Views article in the same journal issue describing the work the team has done on this new initiative.
As the pandemic drags on and weakens, medical researcher They continue to study the virus behind it, and one of their areas of focus is its amazing ability to suppress responses by infected host cells. probed the relationships between the proteins that package DNA. human cells A protein produced by the SARS-CoV-2 virus.
Previous studies have shown that the SARS-CoV-2 virus produces three main types of proteins. Those involved in replication, those involved in structural processes, and a third known as accessory proteins.
The third type is involved in a wide range of activities. Previous studies have also shown that human DNA is packaged into proteins known as histones. Histones act as gatekeepers for substances that hold DNA strands in place, read the strands, and use that information to engage in activities such as signaling to other bodies. parts. When a host is infected, such signaling is involved to prompt defense mechanisms to combat intruding agents.
In this new effort, researchers found evidence suggesting that one of the accessory proteins (ORF8) produced by the SARS-CoV-2 virus can mimic at least one type of histone. protein Package (KAT2A) DNA. By doing so, it weakens the type of signaling that should occur when the host is infected, reducing the immune response.
John Kee et al., SARS-CoV-2 disrupts host epigenetic regulation via histone mimicry. Nature (2022). DOI: 10.1038/s41586-022-05282-z
Lisa Thomann et al., SARS-CoV-2 mimics host proteins to evade defenses,Nature (2022). DOI: 10.1038/d41586-022-02930-2
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