Infection and Cancer Program, Division of Viral Transformation Mechanisms, German Cancer Research Centre, Heidelberg, Germany.
J Gen Virol. 2011 Feb;92(Pt 2):383-94. doi: 10.1099/vir.0.023515-0. Epub 2010 Oct 21.
This study used the rodent Mastomys coucha latently infected with Mastomys natalensis papillomavirus (MnPV) and Mastomys coucha PV2 (McPV2), which induce skin papillomas and anogenital condylomas, respectively, to investigate PV antibody responses as serological markers during pathogenesis. In a case-control study (137 animals), virus and tumour prevalence correlated with the seroresponse against the early E2 and late L1 viral proteins. A prospective study (53 animals) revealed for the first time the course of these antibody responses during all stages of a natural PV infection. Numerous tumour entities were observed on the eyelid and in the oral cavity. DNA analyses indicated that McPV2 was not restricted to condylomas but was also present in these mucosa-associated papillomas. The serological survey using a recently established glutathione S-transferase-capture ELISA detected a strong correlation between MnPV L1-specific antibodies and the presence of papillomas on the skin, eye and ear (P<0.001). Notably, extensive antibody responses to MnPV E2 were also detected in these cases. A prospective study revealed that E2 reactivity occurred by the age of 1 month. MnPV L1 antibodies were found at 2.5 months, indicating the initiation of productive viral infection. Thirty-one out of 34 L1-seropositive animals at the age of 4.5 months developed MnPV-associated tumours (positive predictive value=77 %), and none of the seronegative animals developed skin papillomas (negative predictive value=100 %). MnPV E2 and L1 serology thus provides a powerful tool for monitoring early infection and skin tumour progression in M. coucha.
本研究利用潜伏感染 Mastomys natalensis 乳头瘤病毒（MnPV）和 Mastomys coucha PV2（McPV2）的啮齿动物 Mastomys coucha（分别诱导皮肤乳头瘤和肛门生殖器湿疣），研究病毒抗体反应作为发病过程中的血清学标志物。在病例对照研究（137 只动物）中，病毒和肿瘤的流行与针对早期 E2 和晚期 L1 病毒蛋白的血清反应相关。一项前瞻性研究（53 只动物）首次揭示了这些抗体反应在自然 PV 感染的所有阶段的过程。在眼睑和口腔中观察到许多肿瘤实体。DNA 分析表明，McPV2 不仅局限于湿疣，也存在于这些粘膜相关的乳头瘤中。最近建立的谷胱甘肽 S-转移酶捕获 ELISA 的血清学调查检测到 MnPV L1 特异性抗体与皮肤、眼睛和耳朵上的乳头瘤存在之间的强烈相关性（P<0.001）。值得注意的是，在这些病例中还检测到对 MnPV E2 的广泛抗体反应。前瞻性研究表明，E2 反应性在 1 月龄时发生。在 2.5 月龄时发现 MnPV L1 抗体，表明开始发生有性病毒感染。在 4.5 月龄时，31 只 L1 血清阳性动物中有 31 只（阳性预测值=77%）发生了 MnPV 相关肿瘤，而在血清阴性动物中没有发生皮肤乳头瘤（阴性预测值=100%）。MnPV E2 和 L1 血清学因此为监测 Mastomys coucha 中的早期感染和皮肤肿瘤进展提供了有力工具。
