Utilizing the codon adaptation index to evaluate the susceptibility to HIV-1 and SARS-CoV-2 related coronaviruses in possible target cells in humans

Abstract

Comprehensive identification of possible target cells for viruses is crucial for understanding the pathological mechanism of virosis. The susceptibility of cells to viruses depends on many factors. Besides the existence of receptors at the cell surface, effective expression of viral genes is also pivotal for viral infection. The regulation of viral gene expression is a multilevel process including transcription, translational initiation and translational elongation. At the translational elongation level, the translational efficiency of viral mRNAs mainly depends on the match between their codon composition and cellular translational machinery (usually referred to as codon adaptation). Thus, codon adaptation for viral ORFs in different cell types may be related to their susceptibility to viruses. In this study, we selected the codon adaptation index (CAI) which is a common codon adaptation-based indicator for assessing the translational efficiency at the translational elongation level to evaluate the susceptibility to two-pandemic viruses (HIV-1 and SARS-CoV-2) of different human cell types. Compared with previous studies that evaluated the infectivity of viruses based on codon adaptation, the main advantage of our study is that our analysis is refined to the cell-type level. At first, we verified the positive correlation between CAI and translational efficiency and strengthened the rationality of our research method. Then we calculated CAI for ORFs of two viruses in various human cell types. We found that compared to high-expression endogenous genes, the CAIs of viral ORFs are relatively low. This phenomenon implied that two kinds of viruses have not been well adapted to translational regulatory machinery in human cells. Also, we indicated that presumptive susceptibility to viruses according to CAI is usually consistent with the results of experimental research. However, there are still some exceptions. Finally, we found that two viruses have different effects on cellular translational mechanisms. HIV-1 decouples CAI and translational efficiency of endogenous genes in host cells and SARS-CoV-2 exhibits increased CAI for its ORFs in infected cells. Our results implied that at least in cases of HIV-1 and SARS-CoV-2, CAI can be regarded as an auxiliary index to assess cells’ susceptibility to viruses but cannot be used as the only evidence to identify viral target cells.

Evolution is All You Need in Promoter Design and Optimization

“…(5) Supporting epidemic control from a promoter standpoint: Recent public health crises such as SARS-CoV-2 have significantly impacted humanity. Various methods are attempting to help address this issue by focusing on diverse genomic elements, such as enhancer analysis [42] and codon adaptation analysis [43]. We can focus on this issue from a promoter standpoint.…”

“…With sufficiently large datasets suitable for deep learning training, our model structure could be further attempted in predicting the strength of eukaryotic core promoters. Supporting epidemic control from a promoter standpoint: Recent public health crises such as SARS-CoV-2 have significantly impacted humanity. Various methods are attempting to help address this issue by focusing on diverse genomic elements, such as enhancer analysis [42] and codon adaptation analysis [43]. We can focus on this issue from a promoter standpoint.…”

Comparative analysis of codon usage patterns of Plasmodium helical interspersed subtelomeric (PHIST) proteins

“…The codon adaptation index (CAI) is a measure used to quantify the similarity between the codon usage of a gene or sequence and the codon usage bias of a reference set, which calculates the frequency of occurrence of each codon in the gene of interest and compares it to the frequency expected based on the codon usage bias observed in a reference set, typically a set of highly expressed genes in the same organism. And the CAI value ranges from zero to one; the larger the value is, the more frequently the CUB ( Zhou et al, 2023 ). The codon bias index (CBI) reflects the components of highly expressed superior codons in a specific gene.…”

Analysis of Codon Usage Bias of Thioredoxin in Apicomplexan Protozoa

“…It ranges from zero to one; the larger the value is, the more frequently the CUB. Thus, CAI is useful for predicting the expression level of a particular gene [53]. The codon bias index (CBI) is used as a standard to evaluate gene expression, which re ects the components of highly expressed superior codons in a speci c gene [54].…”