Hötzel Isidro, Cheevers William P
Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, Washington 99164-7040, USA.
J Virol. 2003 Nov;77(21):11578-87. doi: 10.1128/jvi.77.21.11578-11587.2003.
A sequence similarity between surface envelope glycoprotein (SU) gp135 of the lentiviruses maedi-visna virus and caprine arthritis-encephalitis virus (CAEV) and human immunodeficiency virus type 1 (HIV-1) gp120 has been described. The regions of sequence similarity are in the second and fifth conserved regions of gp120, and the similarity is highest in sequences coinciding with beta-strands 4 to 8 and 25, which are located in the most virion-proximal region of the gp120 inner domain. A subset of this structure, formed by gp120 beta-strands 4, 5, and 25, is conserved in most or all lentiviruses. Because of the orientation of gp120 on the virion, this highly conserved virion-proximal region of the gp120 core may interact with the transmembrane glycoprotein (TM) together with the amino and carboxy termini of full-length gp120. Therefore, interactions between SU and TM of lentiviruses may be structurally related. Here we tested whether the amino acid residues in the putative virion-proximal region of CAEV gp135 comprising putative beta-strands 4, 5, and 25, as well as its amino and carboxy termini, are important for stable interactions with TM. An amino acid change at gp135 position 119 or 521, located in the turn between putative beta-strands 4 and 5 and near beta-strand 25, respectively, specifically disrupted the epitope recognized by monoclonal antibody 29A. Thus, similar to the corresponding gp120 regions, these gp135 residues are located in close proximity to each other in the folded protein, supporting the hypothesis of a structural similarity between the gp120 virion-proximal inner domain and gp135. Amino acid changes in the amino- and carboxy-terminal and putative virion-proximal regions of gp135 increased gp135 shedding from the cell surface, indicating that these gp135 regions are involved in interactions with TM. Our results indicate structural and functional parallels between CAEV gp135 and HIV-1 gp120 that may be more broadly applicable to the SU of other lentiviruses.
慢病毒梅迪 - 维斯纳病毒和山羊关节炎 - 脑炎病毒（CAEV）的表面包膜糖蛋白（SU）gp135与人类免疫缺陷病毒1型（HIV - 1）gp120之间的序列相似性已被描述。序列相似区域位于gp120的第二和第五保守区域，在与β链4至8和25一致的序列中相似性最高，这些β链位于gp120内部结构域最靠近病毒粒子的区域。由gp120的β链4、5和25形成的该结构子集在大多数或所有慢病毒中是保守的。由于gp120在病毒粒子上的取向，gp120核心的这个高度保守的靠近病毒粒子的区域可能与跨膜糖蛋白（TM）以及全长gp120的氨基和羧基末端相互作用。因此，慢病毒的SU和TM之间的相互作用可能在结构上相关。在这里，我们测试了CAEV gp135假定的靠近病毒粒子区域中的氨基酸残基，该区域包括假定的β链4、5和25以及其氨基和羧基末端，对于与TM的稳定相互作用是否重要。分别位于假定的β链4和5之间的转角处以及靠近β链25的gp135第119位或521位的氨基酸变化，特异性地破坏了单克隆抗体29A识别的表位。因此，与相应的gp120区域类似，这些gp135残基在折叠蛋白中彼此靠近，支持了gp120靠近病毒粒子的内部结构域与gp135之间结构相似性的假设。gp135的氨基和羧基末端以及假定的靠近病毒粒子区域中的氨基酸变化增加了gp135从细胞表面的脱落，表明这些gp135区域参与了与TM的相互作用。我们的结果表明CAEV gp135和HIV - 1 gp120之间在结构和功能上的相似性可能更广泛地适用于其他慢病毒的SU。
