Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first recognized at the beginning of 2020 and is responsible for the ongoing COVID-19 pandemic.  The persistence of the virus has been partly accredited to its effective suppression of host cell responses.  As such, continued research in elucidating the dynamics of the SARS-CoV-2 life cycle is essential to facilitate the design and development of novel diagnostics and suitable therapies.  Although reports suggest that SARS-CoV-2 can dysregulate the host’s gene expression and innate immune response, the underlying mechanism has remained somewhat elusive, until now.

SARS-CoV-2 consists of a positive-sense single-stranded RNA genome and 4 different types of structural proteins.  The N, or nucleocapsid, protein encapsidates the genome, while the S (spike), E (envelope), and M (membrane) proteins comprise the surrounding lipid bilayer envelope.  Several open reading frames (ORFs) within the SARS-CoV-2 genome have been identified, corresponding to viral structural elements (S, E, M, and N proteins) and accessory genes (ORF1a, 1b, 3a, 6, 7a, 7b, 8, and 10).  In particular, the protein encoded by ORF8 has garnered some attention of late.

The ORF8 viral protein is highly expressed during infection, with a small enough size (15 kDa) to accommodate diffusion into the nucleus.  It was recently shown that ORF8 can modify the epigenome of host cells and disrupt chromatin, consequently impeding the host transcriptional response.  This process is facilitated by