Trafficking to the Plasma Membrane of the Seven-Transmembrane Protein Encoded by Human Herpesvirus 6 U51 Gene Involves a Cell-Specific Function Present in T Lymphocytes

The sequence of human herpesvirus 6 (HHV-6) U51 open reading frame predicts a protein of 301 amino acid residues with seven transmembrane domains. To identify and characterize U51, we derived antipeptide polyclonal antibodies and developed a transient expression assay. We ascertained that U51 was synthesized in cord blood mononuclear cells infected with either variant A- or variant B-HHV-6 and was transported to the surface of productively infected cells. When synthesized in transient expression systems, U51 intracellular trafficking was regulated in a cell-type-dependent fashion. In human monolayer HEK-293 and 143tk− cells, U51 accumulated predominantly in the endoplasmic reticulum and failed to be transported to the cell surface. In contrast, in T-lymphocytic cell lines J-Jhan, Molt-3, and Jurkat, U51 was successfully transported to the plasma membrane. We infer that transport of U51 to the cell surface requires a cell-specific function present in activated T lymphocytes and T-cell lines.

人类疱疹病毒6型（human herpesvirus 6, HHV-6）U51开放阅读框（open reading frame）的序列可编码一条由301个氨基酸残基组成、拥有七个跨膜结构域（transmembrane domains）的蛋白质。为鉴定U51并解析其功能特性，我们制备了抗肽多克隆抗体（antipeptide polyclonal antibodies），并建立了瞬时表达检测方法（transient expression assay）。我们确证，在感染A型或B型HHV-6的脐带血单个核细胞（cord blood mononuclear cells）中，均可合成U51，且该蛋白可被转运至产毒性感染细胞的细胞膜表面。当在瞬时表达系统（transient expression systems）中表达U51时，其细胞内转运过程呈现细胞类型依赖性调控模式。在人类贴壁细胞HEK-293与143tk−中，U51主要蓄积于内质网（endoplasmic reticulum），且无法被转运至细胞膜表面。与之相反，在T淋巴细胞系（T-lymphocytic cell lines）J-Jhan、Molt-3及Jurkat中，U51可被成功转运至质膜（plasma membrane）。据此我们推断，U51向细胞膜表面的转运，需要激活T淋巴细胞及T细胞系中存在的细胞特异性功能。