Department of Molecular and Cell Biology, Division of Immunology and Pathogenesis, University of California, Berkeley, 142 Life Sciences Addition, Berkeley, CA 94720, USA.
J Virol. 2010 Feb;84(3):1265-75. doi: 10.1128/JVI.01775-09. Epub 2009 Nov 18.
Modulation of T-cell receptor expression and signaling is essential to the survival of many viruses. The U24 protein expressed by human herpesvirus 6A, a ubiquitous human pathogen, has been previously shown to downregulate the T-cell receptor. Here, we show that U24 also mediates cell surface downregulation of a canonical early endosomal recycling receptor, the transferrin receptor, indicating that this viral protein acts by blocking early endosomal recycling. We present evidence that U24 is a C-tail-anchored protein that is dependent for its function on TRC40/Asna-1, a component of a posttranslational membrane insertion pathway. Finally, we find that U24 proteins from other roseoloviruses have a similar genetic organization and a conserved function that is dependent on a proline-rich motif. Inhibition of a basic cellular process by U24 has interesting implications not only for the pathogenicity of roseoloviruses but also for our understanding of the biology of endosomal transport.
T 细胞受体表达和信号转导的调节对于许多病毒的存活至关重要。人类疱疹病毒 6A（HHV-6A）表达的 U24 蛋白先前已被证明可下调 T 细胞受体。在这里，我们表明 U24 还介导了经典早期内体再循环受体转铁蛋白受体的细胞表面下调，表明这种病毒蛋白通过阻断早期内体再循环起作用。我们提供的证据表明，U24 是一种 C 尾锚定蛋白，其功能依赖于 TRC40/Asna-1，这是一种翻译后膜插入途径的组成部分。最后，我们发现其他罗斯罗病毒的 U24 蛋白具有相似的遗传组织和保守功能，依赖于富含脯氨酸的基序。U24 对基本细胞过程的抑制不仅对罗斯罗病毒的致病性具有重要意义，而且对我们对内体运输生物学的理解也具有重要意义。
