Vasavada R, Eager K B, Barbanti-Brodano G, Caputo A, Ricciardi R P
Proc Natl Acad Sci U S A. 1986 Jul;83(14):5257-61. doi: 10.1073/pnas.83.14.5257.
The adenovirus type 12 (Ad12) early region 1A (E1A) gene is thought to play a major role in repressing class I major histocompatibility complex expression in transformed rodent cells. However, since transformation by adenovirus requires both E1A and E1B genes, it has not been demonstrated whether the Ad12 E1A gene acts alone or synergistically with the E1B gene to accomplish this effect. Moreover, it is not known whether the repression of class I antigen synthesis by Ad12-transforming gene products occurs only in rodent cells. We show that the Ad12 E1A gene, in the absence of the E1B gene, is capable of greatly reducing the levels of class I HLA antigens and mRNAs in primary human cells transformed by the E1A gene of Ad12 and the large tumor antigen (T-antigen) gene of BK virus; control cells transformed by BK virus T-antigen gene alone or the highly related simian virus 40 T-antigen gene showed no apparent alteration in class I HLA expression. Human recombinant interferon gamma was able to restore synthesis of class I HLA antigens in transformed cells that produced Ad12 E1A proteins, indicating that these cells were not deficient for class I genes. These results strongly indicate that the Ad12 E1A proteins modulate class I gene expression by similar mechanisms in both transformed rodent and human cells.
腺病毒12型（Ad12）早期区域1A（E1A）基因被认为在抑制转化的啮齿动物细胞中的I类主要组织相容性复合体表达中起主要作用。然而，由于腺病毒转化需要E1A和E1B基因，所以尚未证明Ad12 E1A基因是单独起作用还是与E1B基因协同作用来实现这种效果。此外，尚不清楚Ad12转化基因产物对I类抗原合成的抑制是否仅发生在啮齿动物细胞中。我们发现，在没有E1B基因的情况下，Ad12 E1A基因能够大幅降低由Ad12的E1A基因和BK病毒的大肿瘤抗原（T抗原）基因转化的原代人细胞中I类HLA抗原和mRNA的水平；单独由BK病毒T抗原基因或高度相关的猿猴病毒40 T抗原基因转化的对照细胞在I类HLA表达上没有明显变化。人重组干扰素γ能够恢复产生Ad12 E1A蛋白的转化细胞中I类HLA抗原的合成，这表明这些细胞的I类基因并不缺乏。这些结果有力地表明，Ad12 E1A蛋白在转化的啮齿动物和人细胞中通过类似机制调节I类基因表达。
