Previous studies have shown that HSV-1 infection of lymphocytes induces the tyrosine phosphorylation of several proteins that might correspond to viral or host proteins. VP11/12, a viral tegument protein, is the major HSV-induced tyrosine phosphorylated protein identified thus far. In this report, we demonstrated that the cellular adaptor proteins Dok-2 and Dok-1 are tyrosine phosphorylated upon HSV-1 infection. In addition, HSV-1 induced the selective degradation of Dok-2. Finally, we provide evidence that Dok-2 interacts with VP11/12, and that HSV-induced tyrosine phosphorylation and degradation of Dok-2 require VP11/12. Inactivation of either the Src Family Kinases binding motifs or the SHC binding motif of VP11/12 eliminated the interaction of Dok-2 with VP11/12. Elimination of the binding of Dok-2 to VP11/12 prevented Dok-2 phosphorylation and degradation. We propose that HSV-induced Dok phosphorylation and Dok-2 degradation is an immune evasion mechanism to inactivate T cells that might play an important role in HSV pathogenesis.

先前的研究表明，淋巴细胞的HSV-1感染会诱导几种可能与病毒或宿主蛋白质相对应的蛋白质的酪氨酸磷酸化。VP11 / 12是一种病毒外皮蛋白，是迄今为止鉴定出的主要HSV诱导的酪氨酸磷酸化蛋白。在此报告中，我们证明了HSV-1感染后，细胞衔接蛋白Dok-2和Dok-1被酪氨酸磷酸化。另外，HSV-1诱导了Dok-2的选择性降解。最后，我们提供了Dok-2与VP11 / 12相互作用的证据，并且HSV诱导的酪氨酸磷酸化和Dok-2的降解需要VP11 / 12。VP11 / 12的Src家族激酶结合基序或SHC结合基序的失活消除了Dok-2与VP11 / 12的相互作用。消除Dok-2与VP11 / 12的结合可防止Dok-2磷酸化和降解。我们提出，HSV诱导的Dok磷酸化和Dok-2降解是一种免疫逃逸机制，可灭活可能在HSV发病机理中发挥重要作用的T细胞。