Yuille M A, Hugunin M, John P, Peer L, Sacks L V, Poiesz B J, Tomar R H, Silverstone A E
Department of Microbiology and Immunology, State University of New York Health Science Center, Syracuse 13210.
J Acquir Immune Defic Syndr (1988). 1988;1(2):131-7.
In order to improve understanding of how HIV-1 infection down-modulates cell surface membrane expression of CD4, we have measured several parameters of CD4 expression in the human tumor T-cell lines CEM and MOLT-4 at different times after infection. Three independent HIV-1 isolates were used including one that encodes a truncated nef protein and another that appeared to be noncytolytic against CEM. The level of CD4 mRNA, the rate of biosynthesis of CD4 protein, and the percentage of CD4-positive cells were measured. With each viral isolate it was found that infection led to a specific and almost complete inhibition of CD4 protein biosynthesis. This substantially exceeded, at every time point after infection, a concomitant reduction in CD4 mRNA. Hence an inhibition of translation probably accounts for much of the decline in the rate of CD4 biosynthesis. This implicates a novel selective translational inhibition of host gene expression by HIV-1 as a factor in the disappearance of surface membrane CD4 from infected cultures.
为了更好地理解HIV-1感染如何下调CD4的细胞表面膜表达，我们在感染后的不同时间测量了人肿瘤T细胞系CEM和MOLT-4中CD4表达的几个参数。使用了三种独立的HIV-1分离株，其中一种编码截短的nef蛋白，另一种似乎对CEM无细胞毒性。测量了CD4 mRNA水平、CD4蛋白的生物合成速率以及CD4阳性细胞的百分比。对于每种病毒分离株，发现感染导致CD4蛋白生物合成受到特异性且几乎完全的抑制。在感染后的每个时间点，这种抑制都大大超过了CD4 mRNA相应的减少。因此，翻译抑制可能是CD4生物合成速率下降的主要原因。这表明HIV-1对宿主基因表达的一种新型选择性翻译抑制是感染培养物中表面膜CD4消失的一个因素。
