Reverse-transcribed SARS-CoV-2 RNA can integrate into the genome of cultured human cells and can be expressed in patient-derived tissues from Proceedings of the National Academy of Sciences of the United States of America.
We show here that SARS-CoV-2 RNA can be reverse-transcribed and integrated into the genome of the infected cell and be expressed as chimeric transcripts fusing viral with cellular sequences. Importantly, such chimeric transcripts are detected in patient-derived tissues. Our data suggest that, in some patient tissues, the majority of all viral transcripts are derived from integrated sequences.An angry letter from other scientists tries to cast shade but the authors hold their ground.
Parry et al. state that “SARS-CoV-2 integration into the host genome is unlikely.” Our response is that the “percent of library” calculation is not an estimate of integration frequency, which requires consideration of whole-genome sequencing (WGS) coverage. We identified integration events and observed two to five integrations per 10,000 cells at the current sequencing depth (Table 1). This is similar to the estimated integration frequency of lymphocytic choriomeningitis virus after acute infection (3). “Low frequency” of integration events cannot be interpreted as “unlikely.”