Ovis aries papillomavirus 3 (OaPV3) is an epidermotropic PV reported in sheep cutaneous squamous cell carcinoma (SCC). The presence of OaPV3 DNA and its transcriptional activity in cutaneous SCC, as well as its in vitro transforming properties, suggest a viral etiology for this neoplasm. Nevertheless, the reactome associated with viral-host interaction is still unexplored.

Here, we investigated and compared the proteomic profiles of OaPV3-positive SCCs, OaPV3-negative SCCs, and non-SCC samples by liquid chromatography tandem-mass spectrometry (LC-MS/MS) analysis, bioinformatics tools, and immunohistochemistry (IHC). OaPV3-positive SCCs (n = 3), OaPV3-negative SCCs (n = 3), and non-SCCs samples (n = 3) were subjected to a shotgun proteomic analysis workflow to assess protein abundance differences among the three sample classes. Proteins involved in epithelial cell differentiation, extracellular matrix organization, and apoptotic signaling showed different abundances in OaPV3-positive SCCs tissues (P ≤ 0.05) when compared to the other tissues. Cytokeratin 13 (CK 13) was among the most increased proteins in OaPV3-positive SCC and was validated by immunohistochemistry on 10 samples per class, confirming its potential as a biomarker of OaPV3 infection in SCC.

Collectively, results provide a preliminary insight into the reactome associated with viral-host interaction and pave the way to the development of specific biomarkers for viral-induced sheep SCC.

绵羊白羊乳头瘤病毒3（OaPV3）是羊皮肤鳞状细胞癌（SCC）报告一个表皮性PV。OaPV3 DNA的存在及其在皮肤SCC中的转录活性及其体外转化特性，提示了该肿瘤的病毒病因。然而，与病毒-宿主相互作用相关的反应组仍未开发。

在这里，我们通过液相色谱串联质谱（LC-MS / MS）分析，生物信息学工具和免疫组化（IHC），研究并比较了OaPV3阳性SCC，OaPV3阴性SCC和非SCC样品的蛋白质组学特征。对OaPV3阳性SCC（n  = 3），OaPV3阴性SCC（n = 3）和非SCCs样品（n = 3）进行a弹枪蛋白质组分析工作流程，以评估三个样品类别之间的蛋白质丰度差异。参与上皮细胞分化，细胞外基质组织和凋亡信号转导的蛋白质在OaPV3阳性SCC组织中显示出不同的丰度（P ≤0.05）。细胞角蛋白13（CK 13）是OaPV3阳性SCC中增加最多的蛋白质之一，并通过免疫组织化学法对每类10个样品进行了验证，证实了其作为Sa中OaPV3感染的生物标志物的潜力。

总体而言，结果为与病毒-宿主相互作用相关的反应组提供了初步见识，并为病毒诱导的绵羊SCC的特定生物标记物的开发铺平了道路。