Hepatitis E Virus: An emerging enigmatic and underestimated pathogen

Hepatitis E virus (HEV) is an RNA virus causing hepatitis E disease. The virus is of one serotype but has diverse genotypes infecting both humans and animals. Based on evidence from seroprevalence studies, about 2 billion people are estimated to have been infected with HEV globally. HEV, therefore, poses a significant public health and economic challenge worldwide. HEV was discovered in the 1980s and was traced back to the 1955 – 1956 outbreak of hepatitis that occurred in India. Subsequently, several HEV epidemics involving thousands of individuals have occurred nearly annually in different countries in Asia and Africa. Initially, the virus was thought to be only enterically transmitted, and endemic in developing countries. Due to the environmental hygiene and sanitation challenges in those parts of the world. However, recent studies have suggested otherwise with the report of autochthonous cases in industrialised countries with no history of travel to the so-called endemic countries. Thus, suggesting that HEV has a global distribution with endemicity in both developing and industrialised nations. Studies have also revealed that HEV has multiple risk factors, and modes of transmission as well as zoonotic potentials. Additionally, recent findings have shown that HEV leads to severe disease, particularly among pregnant women. In contrast to the previous narration of a strictly mild and self-limiting infection. Studies have likewise demonstrated chronic HEV infection among immunocompromised persons. Consequent to these recent discoveries, this pathogen is considered a re – emerging virus, particularly in the developed nations. However, despite the growing public health challenges of this pathogen, the burden is still underestimated. The underestimation is often attributed to poor awareness among clinicians and a lack of routine checks for the disease in the hospitals. Thus, leading to misdiagnosis and underdiagnosis. Hence, this review provides a concise overview of epidemiology, diagnosis, and prevention of hepatitis E.     

粘膜免疫戊型肝炎试验性疫苗的研究

采用原核表达的戊型肝炎病毒结构区基因(HEV ORF2)编码蛋白,与新型人用疫苗佐剂类MF59配制成试验性疫苗,通过粘膜免疫途径免疫实验小鼠,研究其产生粘膜免疫和体液免疫的效果。结果表明,通过滴鼻和灌胃两种粘膜免疫途径免疫BALB／c小鼠,均能诱导小鼠产生针对HEV ORF2试验性疫苗的血清IgG和IgA,血清IgG的抗体滴度为1：800～1：1600,血清IgA抗体滴度为1：100～1：200。对免疫小鼠血清中IgG的动态观察表明,血清抗体可持续存在至少6个月以上。比较类MF159佐剂和传统铝盐佐剂经注射免疫所诱导产生的血清IgG抗体滴度,发现类MF59佐剂可有效增强HEV0RF2重组蛋白的免疫原性4倍左右。类MF159佐剂可诱导粘膜免疫反应,在肠道粘膜部位产生SIgA,滴度为1：100。这些结果为新型戊型肝炎病毒基因工程重组疫苗的研制提供了一条新的思路。     

我国HEV废旧镍氢电池包中稀贵金属资源化利用环境效益分析

废旧动力电池包中含有丰富的镍、钴、稀土等稀贵金属,其资源化利用是实现混合动力汽车(Hybrid Electrical Vehicle,简称HEV)全生命周期绿色化管理的重要内容之一。随着HEV的不断发展,动力电池包在未来几年将逐渐进入批量报废阶段,其资源化利用的环境效益成为值得关注的问题。鉴于此,以丰田混合动力汽车镍氢电池包为研究对象,利用GREET模型和LIME值法测算出,相比于原生矿开采,单位废旧镍氢电池包中稀贵金属资源化利用所产生的环境效益为1083元;根据报废周期,对我国市场上现存的HEV镍氢电池包的未来报废情况进行预测。结果表明,这些电池包将从2018年开始迎来报废,在2021年达到报废高峰,至2024年基本完成报废;预计其稀贵金属资源化利用的环境效益,可累计达9421万元。提出了加强废旧动力电池回收体系和资源化利用体系建设的政策建议。     

An Integrin α4β7?IgG Heterodimeric Chimera Binds to MAdCAM-1 on High Endothelial Venules in Gut-Associated Lymphoid Tissue

Lymphocyte homing is regulated by a multistep process mediated by sequential adhesive interactions between circulating lymphocytes and high endothelial venules (HEVs). In gut-associated lymphoid tissue (GALT), the initial interactive step, “tethering and rolling,” is partly mediated by integrin α4β7 expressed on GALT-homing lymphocytes and its ligand MAdCAM-1, which is exclusively expressed on HEVs in GALT. To probe functional MAdCAM-1 in tissue sections, we developed a soluble integrin α4β7 heterodimeric IgG chimera by joining the extracellular region of mouse integrin α4 and β7 subunits to a human IgG Fc domain. Western blot analysis revealed that co-transfection of HEK 293T cells with expression vectors encoding integrin α4•IgG and β7•IgG results in the formation of α4β7•IgG heterodimeric chimeras. This complex preferentially binds to CHO cells expressing MAdCAM-1 and, to a lesser extent, to cells expressing VCAM-1, but not to cells expressing ICAM-1. Moreover, α4β7•IgG specifically binds to HEVs in GALT in situ in a divalent cation–dependent fashion and inhibits lymphocyte binding to HEVs in GALT. These findings indicate that α4β7•IgG can be used as a probe for functional MAdCAM-1 expressed on HEVs in GALT and could potentially serve as an anti-inflammatory drug inhibiting GALT-specific lymphocyte migration.     

免疫胶体金试剂的制备及应用胶体金免疫电镜技术检测戊型肝炎病毒

报道了用胶体金免疫电镜技术检测戊型肝炎病毒（ＨＥＶ）的方法。实验采用１０ｎｍ胶体金标记纯化兔抗鼠ＩｇＧ制备了免疫胶体金探针试剂。用本法从戊型肝炎患者粪便提取物中检出ＨＥＶ呈球形,直径３２±５ｎｍ。此方法具有快速、灵敏、直观等特点,在ＨＥＶ生物学性质研究中,有一定的应用价值。     

The unique ultrastructure of high-endothelial venules in inguinal lymph nodes of the pig

Lymph nodes in pigs are unique in their inverted structure, with the medulla in the periphery and the cortex in central areas. Furthermore, in this species most migrating lymphocytes do not use the classical route via efferent lymphatics to leave the lymph node. High-endothelial venules (HEV) are the entry sites for lymphocytes and in pigs probably also the exit site for recirculating lymphocytes. Therefore, the blood vessels and especially the HEV of the pig superficial inguinal lymph node were investigated as to whether morphological peculiarities could be found in the vascular system, using vascular casting, transmission- and scanning electron microscopy. A thin layer of capillary network surrounded the periphery of the lymph node and HEV branched acutely. The endothelial cells of HEV possessed well developed cytoplasmic organelles, interdigitated with each other, and demonstrated local cell-cell contacts. There were unusual cells bridging the adluminal wall of HEV. These cells were called intravascular bridging cells. They were characterized by an often invaginated nucleus, few pinocytotic vesicles, many microvilli on the surface, wide, flat, cytoplasmic processes like a pseudopod, Weibel-Palade bodies and local cell-cell contacts with endothelial cells. The pseudopod-like processes ramified over the endothelial junctions and covered lymphocytes. Lymphocytes were seen in different phases of migration between endothelial cells and in the intercellular junctions. The previous functional studies on the peculiar route of lymphocyte recirculation in pig lymph nodes are extended by these morphological data, showing a unique structure of HEV in pigs.     

Expression of long-form N-acetylglucosamine-6-O-sulfotransferase 1 in human high endothelial venules

Two members of the N-acetylglucosamine-6-O-sulfotransferase (GlcNAc6ST) family, GlcNAc6ST-1 and GlcNAc6ST-2, function in the biosynthesis of 6-sulfo sialyl Lewis X-capped glycoproteins expressed on high endothelial venules (HEVs) in secondary lymphoid organs. Thus, both enzymes play a critical role in L-selectin-expressing lymphocyte homing. Human GlcNAc6ST-1 is encoded by a 1593-bp open reading frame exhibiting two 5' in-frame methionine codons spaced 141 bp apart. Both resemble the consensus sequence for translation initiation. Thus, it has been hypothesized that both long and short forms of GlcNAc6ST-1 may be present, although endogenous expression of either form has not been confirmed in humans. Here, the authors developed an antibody recognizing amino acid residues between the first two human GlcNAc6ST-1 methionines. This antibody specifically recognizes the long form of the enzyme, a finding validated by Western blot analysis and immunofluorescence cytochemistry of HeLa cells misexpressing long and/or short forms of human GlcNAc6ST-1. Using this antibody, the authors carried out immunofluorescence histochemistry of human lymph node tissue sections and found endogenous expression of the long form of the enzyme in human tissue, predominantly in the trans-Golgi network of endothelial cells that form HEVs.     

戊型肝炎病毒ORF3及其蛋白的研究进展

戊型肝炎病毒(HEV)是发展中国家急性肝炎流行的重要病原体之一,由于缺少有效的细胞培养系统和廉价的小型动物模型,对病毒的生物学特性及发病机理了解较少。近几年在HEV ORF3及其蛋白的分子生物学特性和功能研究方面取得了一些进展,为深入了解HEV的感染和致病机理提供了新的理论依据,对这些研究成果进行了综述。