Münch Jan, Janardhan Ajit, Stolte Nicole, Stahl-Hennig Christiane, Ten Haaft Peter, Heeney Jonathan L, Swigut Tomek, Kirchhoff Frank, Skowronski Jacek
Abteilung Virologie, Universitätsklinikum, 89081 Ulm, Germany.
J Virol. 2002 Dec;76(23):12360-4. doi: 10.1128/jvi.76.23.12360-12364.2002.
We investigated the function of severely truncated simian immunodeficiency virus (SIV) Nef proteins (tNef) in vitro and in vivo. These variants emerged in rhesus monkeys infected with SIVmac239 containing a 152-bp deletion in the nef-unique region and have been suggested to enhance SIV virulence (E. T. Sawai, M. S. Hamza, M. Ye, K. E. Shaw, and P. A. Luciw, J. Virol. 74:2038-2045, 2000). We found that the tNef proteins were unable to down-regulate the cell surface expression of major histocompatibility complex class I proteins, CD4, and CD28 and neither stimulated SIV replication nor enhanced virion infectivity. The tNef proteins did efficiently down-regulate T-cell receptor (TCR):CD3 cell surface expression. Nevertheless, the SIVmac239 tnef variants were strongly attenuated in six infected juvenile rhesus macaques. Thus, while the ability of SIV Nef to down-modulate TCR:CD3 cell surface expression apparently confers a selective advantage in vivo, it is insufficient for efficient viral replication in infected macaques. Additional mutations elsewhere in SIVmac239 tnef genomes are required for a virulent phenotype.
我们在体外和体内研究了严重截短的猿猴免疫缺陷病毒（SIV）Nef蛋白（tNef）的功能。这些变体出现在感染了SIVmac239的恒河猴中，该病毒在nef独特区域有一个152碱基对的缺失，并且有人认为这些变体增强了SIV的毒力（E.T. 泽井、M.S. 哈姆扎、M. 叶、K.E. 肖和P.A. 卢西夫，《病毒学杂志》74:2038 - 2045，2000年）。我们发现tNef蛋白无法下调主要组织相容性复合体I类蛋白、CD4和CD28的细胞表面表达，既不刺激SIV复制，也不增强病毒体感染性。tNef蛋白确实有效地下调了T细胞受体（TCR）:CD3的细胞表面表达。然而，SIVmac239 tnef变体在六只受感染的幼年恒河猴中严重减毒。因此，虽然SIV Nef下调TCR:CD3细胞表面表达的能力显然在体内赋予了一种选择优势，但这对于在受感染的猕猴中进行有效的病毒复制是不够的。SIVmac239 tnef基因组其他位置的额外突变是产生毒力表型所必需的。
