Department of Microbiology & Immunology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania, USA.
Department of Microbiology & Immunology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania, USA
J Virol. 2020 Jul 1;94(14). doi: 10.1128/JVI.00474-20.
Little is known about the human cytomegalovirus (HCMV) tegument protein UL88. Large-scale genomic studies have reported disparate results for UL88-null viruses, reporting both no phenotype and a >1-log decrease in virus titers. UL88 has also been reported to interact with UL69 and UL48, but the functional relevance of this interaction is unknown. Here, we report that UL88, which is conserved among different viral strains, is dispensable for production of infectious HCMV virions in multiple HCMV strains and cell types. However, the specific infectivity of HCMV virions suffers in the absence of UL88, as more genomes are required per PFU. This may be a result of altered virion tegument protein composition, as Western blot analysis shows a significant reduction in the tegument levels of pp71, UL47, and UL48 in viruses lacking UL88. While an interaction between UL88 and UL48 has previously been reported, we show that UL88 can interact with UL47; however, UL88 does not appear to be part of a stable complex consisting of UL47 and UL48. These findings identify an important role for UL88 in incorporating the viral proteins UL47 and UL48 into the virion tegument layer. A better understanding of the role and functions of tegument proteins in HCMV, many of which remain uncharacterized, will contribute to our understanding of the biology of HCMV. The virus has a large genome, greater than 230 kb, and functional annotation of these genes is important for identifying novel targets for improving therapeutic intervention. This study identifies a role for a viral tegument protein with unknown function, UL88, in maintaining the proper tegument composition of HCMV virions. Virions produced in the absence of UL88 exhibit decreased fitness and require more genomes per infectious unit.
人类巨细胞病毒 (HCMV) 衣壳蛋白 UL88 的相关信息知之甚少。大规模基因组研究报告称 UL88 缺失病毒的结果存在差异，报告称既无表型，又有病毒滴度下降 >1 个对数级。据报道，UL88 还与 UL69 和 UL48 相互作用，但这种相互作用的功能相关性尚不清楚。在这里，我们报告称，在不同病毒株中保守的 UL88 在多种 HCMV 株和细胞类型中对产生感染性 HCMV 病毒粒子是可有可无的。然而，在没有 UL88 的情况下，HCMV 病毒粒子的特定感染力会受到影响，因为每个 PFU 需要更多的基因组。这可能是由于衣壳蛋白组成发生改变所致，因为 Western blot 分析显示缺乏 UL88 的病毒中 pp71、UL47 和 UL48 的衣壳水平显著降低。虽然之前已经报道了 UL88 与 UL48 之间存在相互作用，但我们表明 UL88 可以与 UL47 相互作用；然而，UL88 似乎不是由 UL47 和 UL48 组成的稳定复合物的一部分。这些发现确定了 UL88 在将病毒蛋白 UL47 和 UL48 掺入病毒衣壳层中的重要作用。更好地了解 HCMV 中衣壳蛋白的作用和功能，其中许多衣壳蛋白的功能仍不清楚，将有助于我们了解 HCMV 的生物学特性。该病毒具有超过 230kb 的大型基因组，这些基因的功能注释对于确定改善治疗干预的新靶标非常重要。本研究确定了一种具有未知功能的病毒衣壳蛋白 UL88 在维持 HCMV 病毒粒子适当衣壳组成中的作用。缺乏 UL88 产生的病毒粒子表现出适应性降低，并且每个感染单位需要更多的基因组。
