Mapping evolutionary paradigm of bovine viral diarrhea virus Npro associated with different organizations of nucleotide

牛病毒性腹泻病毒 （BVDV） 的非结构蛋白 （Npro） 是一种关键的毒力因子，可损害宿主的抗病毒免疫反应并促进病毒产生。本研究为理解不同的选择压力如何影响 BVDV Npro 中核苷酸对、同义密码子和环境依赖性密码子偏差 （CDCB） 的形成奠定了基础。与其他基因型相比，BVDV 基因型 1 表现出更多的亚基因型，但其在 Npro 中的总体核苷酸使用偏倚更强。在 Npro 中，某些二核苷酸，特别是 CpG 和 UpA，被显著抑制，而 UpG 在所有基因型中被高频率选择。BVDV Npro 编码序列在同义密码子使用中表现出明显的偏差，并具有区分基因型的遗传能力。与 BVDV 基因分型相关的单核苷酸和同义密码子用法不同，尽管由于 Npro 编码序列中的高突变率，核苷酸对用法和 CDCB 差异很大，但这两种核苷酸结构表现出超越基因型特异性模型的独特进化范式。除了病毒基因组中高突变率带来的核苷酸组成限制外，翻译选择和宿主免疫反应产生的自然选择压力也显着影响 BVDV Npro 编码序列中各种核苷酸结构的形成。通过分析与 Npro 编码序列中不同核苷酸结构相关的遗传特征，核苷酸对、同义密码子和 CDCB 的不同库可能为 BVDV 突变体提供充足的直接适应和驱逐机会，从而克服宿主强大的免疫防御。牛病毒性腹泻病毒 （BVDV） 的非结构蛋白 （Npro） 是一种重要的毒力因子，可损害宿主的抗病毒免疫反应并促进病毒产生。<br>

The nonstructural protein (Npro) of Bovine Viral Diarrhea Virus (BVDV) is a key virulence factor that impairs host antiviral immune responses and promotes viral progeny production. This study lays a foundation for understanding how distinct selective pressures shape the formation of nucleotide pairs, synonymous codons, and context-dependent codon bias (CDCB) within BVDV Npro. Compared to other genotypes, BVDV genotype 1 exhibits a greater number of subtypes, yet displays a stronger overall nucleotide usage bias in its Npro region. Within Npro, certain dinucleotides, particularly CpG and UpA, are significantly suppressed, while UpG is preferentially selected at high frequencies across all genotypes. The coding sequence of BVDV Npro exhibits evident bias in synonymous codon usage and possesses genetic capacity to distinguish between genotypes. Although the usage of mononucleotides and synonymous codons linked to BVDV genotyping differs, and nucleotide pair usage and CDCB vary greatly due to the high mutation rate within the Npro coding sequence, these two nucleotide structural characteristics display unique evolutionary paradigms that go beyond genotype-specific models. In addition to the constraints on nucleotide composition imposed by the high mutation rate in the viral genome, natural selection pressures arising from translational selection and host immune responses also significantly shape the formation of various nucleotide structural features in the BVDV Npro coding sequence. By analyzing the genetic characteristics associated with different nucleotide structural features in the Npro coding sequence, the distinct pools of nucleotide pairs, synonymous codons, and CDCB may provide sufficient opportunities for direct adaptation and evasion for BVDV mutants, enabling them to overcome the host's robust immune defenses. The nonstructural protein (Npro) of Bovine Viral Diarrhea Virus (BVDV) is an important virulence factor that impairs host antiviral immune responses and promotes viral progeny production.<br>