Work T M, Dagenais J, Balazs G H, Schettle N, Ackermann M
U.S. Geological Survey, National Wildlife Health Center, Honolulu Field Station, Honolulu, HI, USA
U.S. Geological Survey, National Wildlife Health Center, Honolulu Field Station, Honolulu, HI, USA.
Vet Pathol. 2015 Nov;52(6):1195-201. doi: 10.1177/0300985814560236. Epub 2014 Dec 1.
Cancers in humans and animals can be caused by viruses, but virus-induced tumors are considered to be poor sites for replication of intact virions (lytic replication). Fibropapillomatosis (FP) is a neoplastic disease associated with a herpesvirus, chelonid herpesvirus 5 (ChHV5), that affects green turtles globally. ChHV5 probably replicates in epidermal cells of tumors, because epidermal intranuclear inclusions (EIIs) contain herpesvirus-like particles. However, although EIIs are a sign of herpesvirus replication, they have not yet been firmly linked to ChHV5. Moreover, the dynamics of viral shedding in turtles are unknown, and there are no serological reagents to confirm actual presence of the specific ChHV5 virus in tissues. The investigators analyzed 381 FP tumors for the presence of EIIs and found that overall, about 35% of green turtles had lytic replication in skin tumors with 7% of tumors showing lytic replication. A few (11%) turtles accounted for more than 30% cases having lytic viral replication, and lytic replication was more likely in smaller tumors. To confirm that turtles were actively replicating ChHV5, a prerequisite for shedding, the investigators used antiserum raised against F-VP26, a predicted capsid protein of ChHV5 that localizes to the host cell nucleus during viral replication. This antiserum revealed F-VP26 in EIIs of tumors, thus confirming the presence of replicating ChHV5. In this light, it is proposed that unlike other virus-induced neoplastic diseases, FP is a disease that may depend on superspreaders, a few highly infectious individuals growing numerous small tumors permissive to viral production, for transmission of ChHV5.
人类和动物的癌症可能由病毒引起,但病毒诱导的肿瘤被认为不是完整病毒粒子复制(裂解复制)的理想场所。纤维乳头瘤病(FP)是一种与疱疹病毒——绿海龟疱疹病毒5(ChHV5)相关的肿瘤性疾病,全球范围内的绿海龟都会受到影响。ChHV5可能在肿瘤的表皮细胞中复制,因为表皮核内包涵体(EIIs)含有疱疹病毒样颗粒。然而,尽管EIIs是疱疹病毒复制的标志,但它们尚未与ChHV5建立确凿的联系。此外,海龟体内病毒脱落的动态情况尚不清楚,而且也没有血清学试剂来确认组织中是否实际存在特定的ChHV5病毒。研究人员分析了381个FP肿瘤中EIIs的存在情况,发现总体而言,约35%的绿海龟皮肤肿瘤中有裂解复制,其中7%的肿瘤表现出裂解复制。少数(11%)海龟的裂解病毒复制病例占比超过30%,而且较小的肿瘤更有可能出现裂解复制。为了确认海龟是否在积极复制ChHV5(这是病毒脱落的一个先决条件),研究人员使用了针对F-VP26产生的抗血清,F-VP26是ChHV5的一种预测衣壳蛋白,在病毒复制过程中定位于宿主细胞核。这种抗血清在肿瘤的EIIs中检测到了F-VP26,从而证实了复制型ChHV5的存在。有鉴于此,有人提出,与其他病毒诱导的肿瘤性疾病不同,FP可能是一种依赖超级传播者的疾病,即少数具有高度传染性的个体长出许多允许病毒产生的小肿瘤,从而实现ChHV5的传播。