摘要：A new pandemic caused by the betacoronavirus SARS-CoV-2 originated in China in late 2019. Although often asymptomatic, a relevant percentage of affected people can develop severe pneumonia. Initial evidence suggests that dysregulation of the immune response could contribute to the pathogenesis, as previously demonstrated for SARS-CoV. The presence of genome composition features involved in delaying viral recognition is herein investigated for human coronaviruses (HCoVs), with a special emphasis on SARS-CoV-2. A broad collection of HCoVs polyprotein, envelope, matrix, nucleocapsid and spike coding sequences was downloaded and several statistics representative of genome composition and codon bias were investigated. A model able to evaluate and test the presence of a significant under- or over-representation of dinucleotide pairs while accounting for the underlying codon bias and protein sequence was also implemented. The study revealed the significant under-representation of CpG dinucleotide pair in all HcoV, but especially in SARS-CoV and even more in SARS-CoV-2. The presence of forces acting to minimize CpG content was confirmed by relative synonymous codon usage pattern. Codons containing the CpG pair were severely under-represented, primarily in the polyprotein and spike coding sequences of SARS-CoV-2. Additionally, a significant under-representation of the TpA pair was observed in the N and S region of SARS-CoV and SARS-CoV-2. Increasing experimental evidence has proven that CpG and TpA are targeted by innate antiviral host defences, contributing both to RNA degradation and RIG-1 mediated interferon production. The low content of these dinucleotides could contribute to a delayed interferon production, dysregulated immune response, higher viral replication and poor outcome. Significantly, the RIG-1 signalling pathway was proven to be defective in elderlies, suggesting a likely interaction between limited viral recognition and lower responsiveness in interferon production that could justify the higher disease severity and mortality in older patients.
