Hornig Julia, 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 Apr;504:122-140. doi: 10.1016/j.virol.2017.01.023. Epub 2017 Feb 10.
Guinea pig cytomegalovirus (GPCMV) immediate early proteins, IE1 and IE2, demonstrated structural and functional homologies with human cytomegalovirus (HCMV). GPCMV IE1 and IE2 co-localized in the nucleus with each other, the viral polymerase and guinea pig ND10 components (gpPML, gpDaxx, gpSp100, gpATRX). IE1 showed direct interaction with ND10 components by immunoprecipitation unlike IE2. Additionally, IE1 protein disrupted ND10 bodies. IE1 mutagenesis mapped the nuclear localization signal to the C-terminus and identified the core domain for gpPML interaction. Individual knockout of GPCMV GP122 or GP123 (IE2 and IE1 unique exons respectively) was lethal to the virus. However, an IE1 mutant (codons 234-474 deleted), was viable with attenuated viral growth kinetics and increased susceptibility to type I interferon (IFN-I). In HCMV, the IE proteins are important T cell target antigens. Consequently, characterization of the homologs in GPCMV provides a basis for their evaluation in candidate vaccines against congenital infection.
豚鼠巨细胞病毒（GPCMV）的即刻早期蛋白IE1和IE2与人巨细胞病毒（HCMV）在结构和功能上具有同源性。GPCMV的IE1和IE2在细胞核中彼此共定位，还与病毒聚合酶以及豚鼠ND10成分（gpPML、gpDaxx、gpSp100、gpATRX）共定位。与IE2不同，通过免疫沉淀法发现IE1与ND10成分存在直接相互作用。此外，IE1蛋白会破坏ND10小体。IE1诱变将核定位信号定位到C末端，并确定了与gpPML相互作用的核心结构域。单独敲除GPCMV的GP122或GP123（分别为IE2和IE1的独特外显子）对病毒是致死性的。然而，一种IE1突变体（缺失234 - 474位密码子）是可存活的，但其病毒生长动力学减弱，且对I型干扰素（IFN - I）的敏感性增加。在HCMV中，IE蛋白是重要的T细胞靶抗原。因此，对GPCMV中同源物的表征为在针对先天性感染的候选疫苗中评估它们提供了依据。
