Tropism, pathology, and transmission of equine parvovirus-hepatitis

Equine parvovirus-hepatitis (EqPV-H) has recently been associated with cases of Theiler's disease, a form of fulminant hepatic necrosis in horses. To assess whether EqPV-H is the cause of Theiler's disease, we first demonstrated hepatotropism by PCR on tissues from acutely infected horses. We then experimentally inoculated horses with EqPV-H and 8 of 10 horses developed hepatitis. One horse showed clinical signs of liver failure. The onset of hepatitis was temporally associated with seroconversion and a decline in viremia. Liver histology and <i>in situ</i> hybridization showed lymphocytic infiltrates and necrotic EqPV-H-infected hepatocytes. We next investigated potential modes of transmission. Iatrogenic transmission via allogeneic stem cell therapy for orthopedic injuries was previously suggested in a case series of Theiler's disease, and was demonstrated here for the first time. Vertical transmission and mechanical vectoring by horse fly bites could not be demonstrated in this study, potentially due to limited sample size. We found EqPV-H shedding in oral and nasal secretions, and in feces. Importantly, we could demonstrate EqPV-H transmission via oral inoculation with viremic serum. Together, our findings provide additional information that EqPV-H is the likely cause of Theiler's disease and that transmission of EqPV-H occurs via both iatrogenic and natural routes.

马细小病毒肝炎（Equine parvovirus-hepatitis, EqPV-H）近期被发现与泰勒氏病（Theiler's disease）存在关联，该疾病是马的一种暴发性肝坏死病症。为评估EqPV-H是否为泰勒氏病的致病病原体，本研究首先通过聚合酶链反应（PCR）对急性感染马匹的组织样本进行检测，证实了该病毒的嗜肝性。随后，研究团队对马匹实施EqPV-H实验接种，10匹受试马中有8匹出现肝炎症状，其中1匹表现出肝功能衰竭的临床体征。肝炎的发病时间与血清转换及病毒血症的消退存在时间相关性。肝脏组织学检查与原位杂交（in situ hybridization）结果显示，组织内存在淋巴细胞浸润，且可见被EqPV-H感染的肝细胞发生坏死。本研究进一步探究了EqPV-H的潜在传播途径。此前有泰勒氏病的病例系列研究提出，针对骨科损伤的同种异体干细胞治疗可引发医源性传播，本研究首次证实了这一途径。本研究未能证实垂直传播以及马蝇叮咬介导的机械媒介传播，该结果可能受限于样本量偏小。研究人员在马匹的口腔、鼻腔分泌物及粪便中检测到EqPV-H的排毒现象。值得注意的是，本研究证实通过经口接种含病毒血症的血清可实现EqPV-H的传播。综上，本研究结果进一步支持EqPV-H极有可能是泰勒氏病的致病原，且该病毒可通过医源性与自然两种途径进行传播。