Sequence analysis of the 5′ third of glycoprotein C gene of South American bovine herpesviruses 1 and 5

Bovine herpesviruses 1 (BoHV-1) and 5 (BoHV-5) share high genetic and antigenic similarities, but exhibit marked differences in tissue tropism and neurovirulence. The amino-terminal region of glycoprotein C (gC), which is markedly different in each of the viruses, is involved in virus binding to cellular receptors and in interactions with the immune system. This study investigated the genetic and antigenic differences of the 5′ region of the gC (5′ gC) gene (amino-terminal) of South American BoHV-1 (n=19) and BoHV-5 (n=25) isolates. Sequence alignments of 374 nucleotides (104 amino acids) revealed mean similarity levels of 97.3 and 94.2% among BoHV-1 gC (gC1), respectively, 96.8 and 95.6% among BoHV-5 gC (gC5), and 62 and 53.3% between gC1 and gC5. Differences included the absence of 40 amino acid residues (27 encompassing predicted linear epitopes) scattered throughout 5′ gC1 compared to 5′ gC5. Virus neutralizing assays testing BoHV-1 and BoHV-5 antisera against each isolate revealed a high degree of cross-neutralization between the viruses, yet some isolates were neutralized at very low titers by heterologous sera, and a few BoHV-5 isolates reacted weakly with either sera. The virus neutralization differences observed within the same viral species, and more pronounced between BoHV-1 and BoHV-5, likely reflect sequence differences in neutralizing epitopes. These results demonstrate that the 5′ gC region is well conserved within each viral species but is divergent between BoHV-1 and BoHV-5, likely contributing to their biological and antigenic differences.

牛疱疹病毒1型（Bovine herpesvirus 1, BoHV-1）与牛疱疹病毒5型（BoHV-5）具有高度的遗传与抗原相似性，但在组织嗜性和神经毒力方面存在显著差异。糖蛋白C（glycoprotein C, gC）的氨基末端区域在两种病毒中差异显著，该区域参与病毒结合细胞受体以及与免疫系统的相互作用。本研究针对南美来源的19株BoHV-1分离株与25株BoHV-5分离株的gC基因5'端区域（即氨基末端区域，5' gC）的遗传与抗原差异展开了研究。对374个核苷酸（对应104个氨基酸）的序列进行比对后发现：BoHV-1 gC（gC1）组内的核苷酸与氨基酸平均相似性分别为97.3%和94.2%；BoHV-5 gC（gC5）组内的核苷酸与氨基酸平均相似性分别为96.8%和95.6%；而gC1与gC5之间的核苷酸与氨基酸相似性分别为62%和53.3%。序列差异具体表现为：与5' gC5相比，5' gC1中散在缺失了40个氨基酸残基，其中27个位于预测的线性表位范围内。采用BoHV-1与BoHV-5的抗血清分别对各分离株开展病毒中和实验，结果显示两种病毒间存在较高程度的交叉中和反应，但部分分离株仅能被异源抗血清以极低滴度中和，且少数BoHV-5分离株与两种抗血清的反应均较弱。同一病毒物种内观察到的中和反应差异，以及BoHV-1与BoHV-5之间更为显著的差异，大概率反映了中和表位的序列差异。本研究结果表明，5' gC区域在各病毒物种内保守性良好，但在BoHV-1与BoHV-5之间存在显著分化，这可能是导致二者生物学特性与抗原特性差异的重要原因。