Papillomavirus can be transmitted through the blood and produce infections in blood recipients: Evidence from two animal models

Human papillomaviruses (HPV) contribute to most cervical cancers and are considered to be sexually transmitted. However, papillomaviruses are often found in cancers of internal organs, including the stomach, raising the question as to how the viruses gain access to these sites. A possible connection between blood transfusion and HPV-associated disease has not received much attention. Here we show, in rabbit and mouse models, that blood infected with papillomavirus yields infections at permissive sites with detectable viral DNA, RNA transcripts, and protein products. The rabbit skin tumours induced via blood infection displayed decreased expression of SLN, TAC1, MYH8, PGAM2, and APOBEC2 and increased expression of SDRC7, KRT16, S100A9, IL36G, and FABP9, as seen in tumours induced by local infections. Furthermore, we demonstrate that blood from infected mice can transmit the infection to uninfected animals. Finally, we demonstrate the presence of papillomavirus infections and virus-induced hyperplasia in the stomach tissues of animals infected via the blood. These results indicate that blood transmission could be another route for papillomavirus infection, implying that the human blood supply, which is not screened for papillomaviruses, could be a potential source of HPV infection as well as subsequent cancers in tissues not normally associated with the viruses.

人乳头瘤病毒（Human papillomaviruses, HPV）是导致绝大多数宫颈癌的致病原，且被认为是性传播病原体。然而，乳头瘤病毒也常被检出于包括胃部在内的多种内脏器官恶性肿瘤中，这引发了一个关键科学问题：这类病毒是如何侵入这些原本非典型的组织位点的？输血与HPV相关疾病之间的潜在关联尚未得到广泛关注。本研究在兔与小鼠模型中证实：携带乳头瘤病毒的血液可在易感位点引发感染，且可检测到病毒DNA、RNA转录本与蛋白产物。经血液感染诱导产生的兔皮肤肿瘤，其基因表达谱与局部感染诱导的肿瘤一致：SLN、TAC1、MYH8、PGAM2及APOBEC2的表达水平下调，而SDRC7、KRT16、S100A9、IL36G与FABP9的表达水平上调。此外，本研究证实感染小鼠的血液可将病毒传播至未感染个体。最后，本研究证实经血液感染的动物胃部组织中存在乳头瘤病毒感染及病毒诱导的增生病变。上述结果表明，血液传播可能是乳头瘤病毒感染的另一途径，这意味着当前未针对乳头瘤病毒进行筛查的人类血液供应系统，可能成为HPV感染及后续引发与病毒原本无关组织发生恶性肿瘤的潜在传染源。