Two human deaminase enzymes edit the RNA of the SARS-CoV-2 virus when it enters a patient's body, with implications for the evolution of the virus and the spread of the infection, according to a new study.
The findings provide a first step towards understanding how RNA editing affects the replication of the virus responsible for the current COVID-19 pandemic - a potentially significant process since post-infection viral genome editing in the host is suspected to have influenced the evolution of other viruses, including Rubella.
Salvatore Di Giorgio and colleagues note that by comparing sites in the SARS-CoV-2 genome that are edited with those that are mutated, scientists may be able to identify strategies to target the virus with new therapies.
Mammals express two different deaminase families - ADARs and APOBECs - that alter the basic nucleotide building blocks of viral RNA (or, in the latter case, sometimes DNA intermediates) by removing an amino group from their nucleobase components.
However, it has not been known whether this innate virus-counteracting process operates against coronavirus. To assess whether RNA editing may be involved in the body's response to SARS-CoV-2 infections, Di Giorgio et al. analyzed single-nucleotide variants in RNA sequencing datasets from fluid extracted from the lungs of patients diagnosed with COVID-19.
While they observed low numbers of mutation events, the researchers did identify nucleotide changes (adenosine to inosine, and cytosine to uracil) that may be attributed to RNA editing. To better understand whether RNA editing could be the cause for mutations acquired through evolution, the researchers also compared genomes from SARS-CoV-2, MERS-CoV, and SARS-CoV.
They suggest that a sizable percentage of mutations in each of these coronavirus strains may have been caused by deaminase enzymes. The authors speculate that, if these enzymes are indeed involved in the human response to SARS-CoV-2 infection, a genetic variation that affects two forms of APOBEC - known to be common in the Chinese population - could play a role in the spread of the infection.
Di Giorgio, S., et al. (2020) Evidence for host-dependent RNA editing in the transcriptome of SARS-CoV-2. Science Advances. doi.org/10.1126/sciadv.abb5813.