Wilson A Douglas, Hicks Chelsea
School of Veterinary Sciences, University of Bristol, Langford, Bristol, BS40 5DU, UK.
Vet Res. 2016 May 9;47(1):55. doi: 10.1186/s13567-016-0339-8.
Bovine papillomavirus (BPV) infections of equine species have a central role in the aetiology of equine sarcoids; a common benign skin tumour of horses, zebras and donkeys. Within the lesions, all of the early papillomavirus genes are expressed and promote the excessive replication of fibroblasts which characterise these tumours. Equine sarcoids differ from BPV induced fibro-papillomas of cattle (the natural host of BPV), in that they do not produce high amounts of virus particles, do not usually regress spontaneously and do not sero-convert to BPV; features which suggest that affected horses lack an effective anti-viral immune response to BPV. Equine sarcoids contain large numbers of CD4+ CD8+ dual positive T-cells which uniformly express FOXP3, the key transcription factor of regulatory T-cells, and FOXP3 is also expressed within the BPV infected fibroblasts. Compared to healthy skin, sarcoids showed increased mRNA transcription for FOXP3 and the regulatory cytokine TGFβ. Transcription of IL17, which has been shown to have a regulatory function in human papillomavirus-associated tumours, was also elevated in equine sarcoids compared to spleen. In contrast, the levels of mRNA transcripts for effector T cell cytokines IL2, IL4 and interferon-gamma (IFNγ) were not elevated in sarcoids compared to healthy skin or spleen. Similarly neither interferon-alpha (IFNα), interferon-beta (IFNβ) nor IL12 family members were elevated in sarcoids compared to normal skin. We suggest that the regulatory cytokine micro-environment within sarcoids enables the persistence of the lesions by preventing an effective anti-viral immune response.
马属动物的牛乳头瘤病毒（BPV）感染在马属肉瘤的病因学中起核心作用；马属肉瘤是马、斑马和驴常见的良性皮肤肿瘤。在病变部位，所有乳头瘤病毒早期基因均表达，并促进成纤维细胞过度增殖，这是这些肿瘤的特征。马属肉瘤与BPV诱导的牛（BPV的自然宿主）纤维乳头瘤不同，在于它们不产生大量病毒颗粒，通常不会自发消退，也不会发生BPV血清转化；这些特征表明患病马匹对BPV缺乏有效的抗病毒免疫反应。马属肉瘤含有大量CD4⁺ CD8⁺双阳性T细胞，这些细胞均一性表达调节性T细胞的关键转录因子FOXP3，并且FOXP3也在被BPV感染的成纤维细胞中表达。与健康皮肤相比，肉瘤中FOXP3和调节性细胞因子TGFβ的mRNA转录增加。与脾脏相比，在马属肉瘤中，已证实在人乳头瘤病毒相关肿瘤中具有调节功能的IL17转录也升高。相反，与健康皮肤或脾脏相比，效应T细胞细胞因子IL2、IL4和干扰素-γ（IFNγ）的mRNA转录水平在肉瘤中并未升高。同样，与正常皮肤相比，肉瘤中干扰素-α（IFNα）、干扰素-β（IFNβ）和IL12家族成员均未升高。我们认为，肉瘤内的调节性细胞因子微环境通过阻止有效的抗病毒免疫反应，使病变得以持续存在。
