Kenney Scott P, Wentworth Jacquelyn L, Heffron Connie L, Meng Xiang-Jin
Department of Biomedical Sciences and Pathobiology, College of Veterinary Medicine, Virginia Polytechnic Institute and State University (Virginia Tech), Blacksburg, VA, USA.
Virginia Tech Carilion School of Medicine, Roanoke, VA, USA.
Virology. 2015 Dec;486:198-208. doi: 10.1016/j.virol.2015.09.012. Epub 2015 Oct 27.
The ORF3 protein of hepatitis E virus (HEV) contains a "PSAP" amino acid late domain motif, which allows for interaction with the endosomal sorting complexes required for transport (ESCRT) pathway aiding virion release. Late domain motifs are interchangeable with other viral late domain motifs in several enveloped viruses, however, it remains unknown whether HEV shares this functional interchangeability and what implications this might have on viral replication. In this study, by substituting heterologous late domain motifs (PPPY, YPDL, and PSAA) for the HEV ORF3 late domain (PSAP), we demonstrated that deviation from the PSAP motif reduces virus release as measured by viral RNA in culture media. Virus release could not be restored by insertion of a heterologous late domain motif or by supplying wild-type ORF3 in trans, suggesting that the HEV PSAP motif is required for viral exit which cannot be bypassed by the use of alternative heterologous late domains.
戊型肝炎病毒（HEV）的ORF3蛋白包含一个“PSAP”氨基酸晚期结构域基序，该基序允许与运输所需的内体分选复合物（ESCRT）途径相互作用，有助于病毒粒子释放。晚期结构域基序在几种包膜病毒中可与其他病毒晚期结构域基序互换，然而，HEV是否具有这种功能互换性以及这对病毒复制可能有何影响仍不清楚。在本研究中，通过用异源晚期结构域基序（PPPY、YPDL和PSAA）替代HEV ORF3晚期结构域（PSAP），我们证明，与PSAP基序的偏差会降低病毒释放，这通过培养基中的病毒RNA来衡量。插入异源晚期结构域基序或通过反式提供野生型ORF3均无法恢复病毒释放，这表明HEV PSAP基序是病毒出芽所必需的，使用替代异源晚期结构域无法绕过这一需求。
