Low pH is required for avian sarcoma and leukosis virus Env-dependent viral penetration into the cytosol and not for viral uncoating
Low pH is required for avian sarcoma and leukosis virus Env-dependent viral penetration into the cytosol and not for viral uncoating
复制标题
DOI：
10.1128/jvi.78.19.10433-10441.2004
复制
发表时间：
2004-10-01
影响因子：
5.4
通讯作者：
Young, JAT
中科院分区：
文献类型：
--
作者：
Barnard, RJO;Narayan, S;Young, JAT
禽流感肉瘤和白血病病毒（ASLV）的一种新的进入机制已经被提出，通过与特定细胞表面受体的相互作用激活或启动病毒包膜糖蛋白（Env），使其对酸性细胞内细胞器中随后的低ph依赖性融合触发敏感。然而，ASLV融合似乎在中性pH下进入脂质混合阶段，导致低pH可能需要病毒进入后期，如脱膜（L. J. Earp， S. E. Delos， R. C. Netter， P. Bates和J. M. White）。[j] .中国生物医学工程学报，2009(7):387 - 398。为了解决这种可能性，以人类免疫缺陷病毒1型（HIV-1）（一种已知的不依赖ph的病毒）为核心，并与ASLV Env蛋白亚群a或B合成了杂交病毒颗粒。通过对HIV-1 DNA合成的抑制判断，这些假型病毒粒子对细胞的感染被溶酶体抑制剂阻断。此外，通过使用含有vpr - β -内酰胺酶融合蛋白（Vpr-BlaM）的HIV-1核来监测病毒对细胞质的渗透，我们证明了携带ASLV Env而不是HIV-1 Env的病毒粒子以低ph依赖的方式进入细胞质。这种效应与ASLV Env细胞质尾部的存在无关。这些研究为该模型提供了强有力的支持，表明低pH值是ASLV env依赖性病毒渗透到细胞质中所必需的，而不是病毒脱壳所必需的。
A novel entry mechanism has been proposed for the avian sarcoma and leukosis virus (ASLV), whereby interaction with specific cell surface receptors activates or primes the viral envelope glycoprotein (Env), rendering it sensitive to subsequent low-pH-dependent fusion triggering in acidic intracellular organelles. However, ASLV fusion seems to proceed to a lipid mixing stage at neutral pH, leading to the suggestion that low pH might instead be required for a later stage of viral entry such as uncoating (L. J. Earp, S. E. Delos, R. C. Netter, P. Bates, and J. M. White. J. Virol. 77:3058-3066, 2003). To address this possibility, hybrid virus particles were generated with the core of human immunodeficiency virus type 1 (HIV-1), a known pH-independent virus, and with subgroups A or B ASLV Env proteins. Infection of cells by these pseudotyped virions was blocked by lysosomotropic agents, as judged by inhibition of HIV-1 DNA synthesis. Furthermore, by using HIV-1 cores that contain a Vpr-beta-lactamase fusion protein (Vpr-BlaM) to monitor viral penetration into the cytosol, we demonstrated that virions bearing ASLV Env, but not HIV-1 Env, enter the cytosol in a low-pH-dependent manner. This effect was independent of the presence of the cytoplasmic tail of ASLV Env. These studies provide strong support for the model, indicating that low pH is required for ASLV Env-dependent viral penetration into the cytosol and not for viral uncoating.