Roukaerts Inge D M, Grant Chris K, Theuns Sebastiaan, Christiaens Isaura, Acar Delphine D, Van Bockstael Sebastiaan, Desmarets Lowiese M B, Nauwynck Hans J
Ghent University, Faculty of Veterinary Medicine, Department of Virology, Parasitology and Immunology, Laboratory of Virology, Merelbeke, Belgium.
Custom Monoclonals International, West Sacramento, United States.
Virus Res. 2017 Jan 2;227:249-260. doi: 10.1016/j.virusres.2016.11.008. Epub 2016 Nov 9.
Env and Gag are key components of the FIV virion that are targeted to the plasma membrane for virion assembly. They are both important stimulators and targets of anti-FIV immunity. To investigate and compare the expression pattern and antigenic changes of Gag and Env in various research models, infected PBMC (the natural FIV host cells) and GFox, and transfected CrFK were stained over time with various Env and Gag specific MAbs. In FIV infected GFox and PBMC, Env showed changes in epitope availability for antibody binding during processing and trafficking, which was not seen in transfected CrFK. Interestingly, epitopes exposed on intracellular Env and Env present on the plasma membrane of CrFK and GFox seem to be hidden on plasma membrane expressed Env of FIV infected PBMC. A kinetic follow up of Gag and Env expression showed a polarization of both Gag and Env expression to specific sites at the plasma membrane of PBMC, but not in other cell lines. In conclusion, mature trimeric cell surface expressed Env might be antigenically distinct from intracellular monomeric Env in PBMC and might possibly be unrecognizable by feline humoral immunity. In addition, Env expression is restricted to a small area on the plasma membrane and co-localizes with a large moiety of Gag, which may represent a preferred FIV budding site, or initiation of virological synapses with direct cell-to-cell virus transmission.
Env和Gag是猫免疫缺陷病毒(FIV)病毒体的关键组成部分,它们被靶向运输到质膜进行病毒体组装。它们既是抗FIV免疫的重要刺激物,也是其靶点。为了研究和比较Gag和Env在各种研究模型中的表达模式和抗原变化,对感染的外周血单核细胞(PBMC,FIV的天然宿主细胞)、GFox以及转染的CrFK细胞随时间用各种Env和Gag特异性单克隆抗体进行染色。在FIV感染的GFox和PBMC中,Env在加工和运输过程中抗体结合的表位可用性发生了变化,而在转染的CrFK细胞中未观察到这种情况。有趣的是,细胞内Env暴露的表位以及CrFK和GFox质膜上的Env,在FIV感染的PBMC质膜上表达的Env中似乎被隐藏了。对Gag和Env表达的动力学跟踪显示,Gag和Env的表达都向PBMC质膜上的特定位点极化,但在其他细胞系中则没有。总之,成熟的三聚体细胞表面表达的Env在抗原性上可能与PBMC中的细胞内单体Env不同,可能无法被猫的体液免疫识别。此外,Env的表达局限于质膜上的一个小区域,并与大部分Gag共定位,这可能代表了一个优先的FIV出芽位点,或者是直接细胞间病毒传播的病毒学突触的起始点。