Host-Genome Similarity Characterizes the Adaption of SARS-CoV-2 to Humans.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has a high mutation rate and many variants have emerged in the last 2 years, including Alpha, Beta, Delta, Gamma and Omicron. Studies showed that the host-genome similarity (HGS) of SARS-CoV-2 is higher than SARS-CoV and the HGS of open reading frame (ORF) in coronavirus genome is closely related to suppression of innate immunity. Many works have shown that ORF 6 and ORF 8 of SARS-CoV-2 play an important role in suppressing IFN-β signaling pathway in vivo. However, the relation between HGS and the adaption of SARS-CoV-2 variants is still not clear. This work investigates HGS of SARS-CoV-2 variants based on a dataset containing more than 40,000 viral genomes. The relation between HGS of viral ORFs and the suppression of antivirus response is studied. The results show that ORF 7b, ORF 6 and ORF 8 are the top 3 genes with the highest HGS. In the past 2 years, the HGS values of ORF 8 and ORF 7B of SARS-CoV-2 have increased greatly. A remarkable correlation is discovered between HGS and inhibition of antivirus response of immune system, which suggests that the similarity between coronavirus and host gnome may be an indicator of the suppression of innate immunity. Among the five variants (Alpha, Beta, Delta, Gamma and Omicron), Delta has the highest HGS and Omicron has the lowest HGS. This finding implies that the high HGS in Delta variant may indicate further suppression of host innate immunity. However, the relatively low HGS of Omicron is still a puzzle. By comparing the mutations in genomes of Alpha, Delta and Omicron variants, a commonly shared mutation ACT > ATT is identified in high-HGS strain populations. The high HGS mutations among the three variants are quite different. This finding strongly suggests that mutations in high HGS strains are different in different variants. Only a few common mutations survive, which may play important role in improving the adaptability of SARS-CoV-2. However, the mechanism for how the mutations help SARS-CoV-2 escape immunity is still unclear. HGS analysis is a new method to study virus−host interaction and may provide a way to understand the rapid mutation and adaption of SARS-CoV-2.