Us3 protein is a serine/threonine kinase conserved within the Alphaherpesvirinae subfamily of herpesviruses. The Us3 homologs of herpes simplex virus, pseudorabies virus, and bovine herpesvirus type 5 have been shown to block apoptosis triggered by viral infection or exogenous inducers.

To determine whether these characteristics are shared by bovine herpesvirus type 1 Us3, we constructed two viral mutants: BHV-1 Us3 deletion mutant (BHV-1ΔUs3) and a kinase-dead mutant (BHV-1KD). Flow cytometry analysis and TUNEL assay clearly demonstrated, that only BHV-1 wild type virus suppressed infection-induced apoptosis and protected cells from apoptosis triggered by exogenous factors: sorbitol or staurosporine. Us3 of BHV-1 was directly capable of blocking apoptosis without the presence of other viral proteins. The presence of Us3 correlated with phosphorylation of BAD, a pro-apoptotic Bcl-2 family member. Our results clearly indicate that BHV-1 Us3 is necessary for efficient blocking of apoptosis triggered by viral infection and exogenous factors.

Us3蛋白是在疱疹病毒的Alphaherpesvirinae亚科中保守的丝氨酸/苏氨酸激酶。单纯疱疹病毒，伪狂犬病病毒和5型牛疱疹病毒的Us3同源物已显示可阻断病毒感染或外源性诱导物触发的细胞凋亡。

为了确定1型牛疱疹病毒是否具有这些特征，我们构建了两个病毒突变体：BHV-1 Us3缺失突变体（BHV-1ΔUs3）和激酶死亡突变体（BHV-1KD）。流式细胞仪分析和TUNEL分析清楚地表明，只有BHV-1野生型病毒抑制感染诱导的细胞凋亡，并保护细胞免受外源因素（山梨糖醇或星形孢菌素）触发的细胞凋亡。BHV-1的Us3在没有其他病毒蛋白的情况下直接能够阻止细胞凋亡。Us3的存在与促凋亡Bcl-2家族成员BAD的磷酸化有关。我们的结果清楚地表明，BHV-1 Us3对于有效阻断由病毒感染和外源因素触发的凋亡是必要的。