Sayed Ibrahim M, Seddik Mohamed Ismail, Gaber Marwa A, Saber Saber H, Mandour Sahar A, El-Mokhtar Mohamed A
Department of Medical Microbiology and Immunology, Faculty of Medicine, Assiut University, Assiut 71515, Egypt.
Department of Pathology, School of Medicine, University of California, San Diego, CA 92093, USA.
Vaccines (Basel). 2020 May 21;8(2):239. doi: 10.3390/vaccines8020239.
HEV is the most causative agent of acute viral hepatitis globally. HEV causes acute, chronic, and extrahepatic manifestations. Chronic HEV infection develops in immunocompromised patients such as organ transplant patients, HIV-infected patients, and leukemic patients. The source of chronic HEV infection is not known. Also, the source of extrahepatic manifestations associated with HEV infection is still unclear. Hepatotropic viruses such as HCV and HBV replicate in peripheral blood mononuclear cells (PBMCs) and these cells become a source of chronic reactivation of the infections in allograft organ transplant patients. Herein, we reported that PBMCs and bone marrow-derived macrophages (BMDMs), isolated from healthy donors (n = 3), are susceptible to HEV in vitro. Human monocytes (HMOs), human macrophages (HMACs), and human BMDMs were challenged with HEV-1 and HEV-3 viruses. HEV RNA was measured by qPCR, the marker of the intermediate replicative form (ds-RNA) was assessed by immunofluorescence, and HEV capsid protein was assessed by flow cytometry and ELISA. HEV infection was successfully established in primary HMOs, HMACs, and human BMDMs, but not in the corresponding cells of murine origin. Intermediate replicative form (ds RNA) was detected in HMOs and HMACs challenged with HEV. The HEV load was increased over time, and the HEV capsid protein was detected intracellularly in the HEV-infected cells and accumulated extracellularly over time, confirming that HEV completes the life cycle inside these cells. The HEV particles produced from the infected BMDMs were infectious to naive HMOs in vitro. The HEV viral load was comparable in HEV-1- and HEV-3-infected cells, but HEV-1 induced more inflammatory responses. In conclusion, HMOs, HMACs, and human BMDMs are permissive to HEV infection and these cells could be the source of chronic and recurrent infection, especially in immunocompromised patients. Replication of HEV in human BMDMs could be related to hematological disorders associated with extrahepatic manifestations.
戊型肝炎病毒是全球急性病毒性肝炎最主要的致病原。戊型肝炎病毒可引发急性、慢性及肝外表现。慢性戊型肝炎病毒感染见于免疫功能低下的患者，如器官移植患者、HIV感染患者及白血病患者。慢性戊型肝炎病毒感染的来源尚不清楚。此外，与戊型肝炎病毒感染相关的肝外表现的来源也仍不明确。丙型肝炎病毒和乙型肝炎病毒等嗜肝病毒在外周血单核细胞（PBMC）中复制，在同种异体器官移植患者中，这些细胞成为感染慢性再激活的来源。在此，我们报告从健康供者（n = 3）分离的PBMC和骨髓来源的巨噬细胞（BMDM）在体外对戊型肝炎病毒易感。用人单核细胞（HMO）、人巨噬细胞（HMAC）和人BMDM分别用戊型肝炎病毒1型和3型病毒进行攻击。通过qPCR检测戊型肝炎病毒RNA，通过免疫荧光评估中间复制形式（ds-RNA）的标志物，通过流式细胞术和ELISA评估戊型肝炎病毒衣壳蛋白。在原代HMO、HMAC和人BMDM中成功建立了戊型肝炎病毒感染，但在相应的鼠源细胞中未成功建立。在用戊型肝炎病毒攻击的HMO和HMAC中检测到中间复制形式（ds RNA）。戊型肝炎病毒载量随时间增加，在戊型肝炎病毒感染的细胞内检测到戊型肝炎病毒衣壳蛋白，并随时间在细胞外积累，证实戊型肝炎病毒在这些细胞内完成生命周期。从受感染的BMDM产生的戊型肝炎病毒颗粒在体外对未感染的HMO具有感染性。戊型肝炎病毒1型和3型感染的细胞中戊型肝炎病毒载量相当，但戊型肝炎病毒1型诱导更多的炎症反应。总之，HMO、HMAC和人BMDM对戊型肝炎病毒感染易感，这些细胞可能是慢性和复发性感染的来源，尤其是在免疫功能低下的患者中。戊型肝炎病毒在人BMDM中的复制可能与肝外表现相关的血液系统疾病有关。
