Waarts Barry-Lee, Smit Jolanda M, Aneke Onwuchekwa J C, McInerney Gerald M, Liljeström Peter, Bittman Robert, Wilschut Jan
Department of Medical Microbiology, Molecular Virology Section, University Medical Center Groningen, Ant. Deusinglaan 1, 9713 AV Groningen, The Netherlands.
J Virol. 2005 Jun;79(12):7942-8. doi: 10.1128/JVI.79.12.7942-7948.2005.
Previously, it has been shown that the exposure of Semliki Forest virus (SFV) to a mildly acidic environment induces a rapid and complete loss of the ability of the virus to bind and fuse to target membranes added subsequently. In the present study, incubation of SFV at low pH followed by a specific reneutralization step resulted in a partial reversion of this loss of viral fusion capacity, as assessed in a liposomal model system. Also, the ability of the viral E1 fusion protein to undergo liposome-stimulated trimerization was restored. Furthermore, acid-treated and neutralized SFV largely retained infectivity. Exposure of SFV to low pH induced dissociation of the E1/E2 heterodimer, which was not reversed upon neutralization. It is concluded that the SFV E1 fusion protein, after acid-induced dissociation from E2, rapidly adopts an intermediate, nontrimeric conformation in which it is no longer able to interact with target membrane lipids. Neutralization restores the ability of E1 to interact with membranes. This interaction, however, remains strictly dependent on low pH.
此前已有研究表明，将塞姆利基森林病毒（SFV）暴露于轻度酸性环境中会导致该病毒迅速且完全丧失与随后添加的靶膜结合及融合的能力。在本研究中，在脂质体模型系统中评估发现，将SFV在低pH下孵育，随后进行特定的重新中和步骤，可使这种病毒融合能力的丧失部分逆转。此外，病毒E1融合蛋白经历脂质体刺激三聚化的能力也得以恢复。而且，经酸处理并中和后的SFV基本保留了感染性。将SFV暴露于低pH会诱导E1/E2异二聚体解离，中和后这种解离并未逆转。得出的结论是，SFV E1融合蛋白在酸诱导与E2解离后，会迅速采用一种中间的、非三聚体构象，在此构象中它不再能够与靶膜脂质相互作用。中和作用恢复了E1与膜相互作用的能力。然而，这种相互作用仍严格依赖于低pH。
