Coleman Stewart, Choi K Yeon, McGregor Alistair
Department of Microbial Pathogenesis & Immunology, Texas A&M University, Health Science Center, College of Medicine, College Station, TX, United States.
Department of Microbial Pathogenesis & Immunology, Texas A&M University, Health Science Center, College of Medicine, College Station, TX, United States.
Virology. 2017 Sep;509:205-221. doi: 10.1016/j.virol.2017.06.008. Epub 2017 Jun 23.
Guinea pig cytomegalovirus (GPCMV) encodes a homolog pentameric complex (PC) for specific cell tropism and congenital infection. In human cytomegalovirus, the PC is an important antibody neutralizing target and GPCMV studies will aid in the development of intervention strategies. Deletion mutants of the C-terminal domains of unique PC proteins (UL128, UL130 and UL131 homologs) were unable to form a PC in separate transient expression assays. Minor modifications to the UL128 homolog (GP129) C-terminal domain enabled PC formation but viruses encoding these mutants had altered tropism to renal and placental trophoblast cells. Mutation of the presumptive CC chemokine motif encoded by GP129 was investigated by alanine substitution of the CC motif (codons 26-27) and cysteines (codons 47 and 62). GP129 chemokine mutants formed PC but GP129 chemokine mutant viruses had reduced epitropism. A GP129 chemokine mutant virus pathogenicity study demonstrated reduced viral load to target organs but highly extended viremia.
豚鼠巨细胞病毒（GPCMV）编码一种同源五聚体复合物（PC），用于特定的细胞嗜性和先天性感染。在人巨细胞病毒中，PC是重要的抗体中和靶点，对GPCMV的研究将有助于开发干预策略。在单独的瞬时表达试验中，独特PC蛋白（UL128、UL130和UL131同源物）C末端结构域的缺失突变体无法形成PC。对UL128同源物（GP129）C末端结构域进行的微小修饰可使PC形成，但编码这些突变体的病毒对肾和胎盘滋养层细胞的嗜性发生了改变。通过对CC基序（密码子26-27）和半胱氨酸（密码子47和62）进行丙氨酸取代，研究了由GP129编码的假定CC趋化因子基序的突变。GP129趋化因子突变体形成了PC，但GP129趋化因子突变病毒的表位嗜性降低。一项GP129趋化因子突变病毒致病性研究表明，其在靶器官中的病毒载量降低，但病毒血症期延长。
