摘要
人内源性逆转录病毒(human endogenous retroviruses,HERV)是几百万年前整合至人类基因组并遗传至今的外源性逆转录病毒的残余物。因突变、缺失等导致大多数HERV没有完整的开放读码框,但仍有部分家族成员可编码完整的病毒蛋白,如分离自多发性硬化症患者的γ逆转录病毒相似元件家族成员HERV-W的包膜蛋白基因(HERV-W env,又称ERVWE1)编码的ENV蛋白(又称Syncytin-1),在人胎盘发育过程中起细胞融合以及免疫调节作用。在生理条件下,HERV-W受到表观遗传调控而其转录活性被抑制;但亦可被环境、遗传等因素激活,如自身免疫性疾病、精神疾病及癌症等。研究发现HERV-W可能在疾病的发生、发展中起重要的“桥梁”与“触发”作用,靶向Syncytin-1的单克隆抗体GNbAC1已用于多发性硬化症的临床研究,并且在1型糖尿病中也有良好的应用前景。对HERV-W的深入研究可为某些疾病的诊断和治疗提供重要的途径。
Human endogenous retroviruses(HERVs)are residues of exogenous retroviruses which have integrated into the human genome millions of years ago,accounting for about 8%-12%of the whole genome.Most HERVs don’t have an intact open reading frame due to mutations,deletions,etc.However,some HERVs can encode viral proteins,for example,Human endogenous retrovirus W(HERV-W),a member of the gamma retrovirus-like family isolated from patients with multiple sclerosis.Syncytin-1,encoded by HERV-W,plays a role in cell fusion and immunoregulation during human placental development.Under physiological conditions,the transcriptional activity of HERV-W is inhibited by epigenetic regulation,for example,hypermethylation,which can be activated by environmental factors such as drugs,radiations and viral infections as well as genetic factors.Several studies found abnormal expression of HERV-W in patients with some cancers,mental illnesses,and autoimmune diseases.Therefore HERV-W may play an important role as“bridge”and“trigger”in the development of diseases.Currently the monoclonal antibody GNbAC1 targeting Syncytin-1 has been used in clinical research of multiple sclerosis,which also has a good application prospect for type 1 diabetes.Further research on HERV-W might provide a valuable way for diagnosis and treatment of certain diseases.
作者
李旭航
朱帆
LI Xuhang;ZHU Fan(State Key Laboratory of Virology,School of Basic Medical Sciences,Wuhan University,Wuhan 430071,China)
出处
《微生物与感染》
2019年第5期259-266,共8页
Journal of Microbes and Infections
基金
国家自然科学基金(81772196、31470264、 81271820、30870789、30300117)
武汉大学医学腾飞计划(基础医学)(TFJC 2018002)
