Marchetti Barbara, Ashrafi G Hossein, Tsirimonaki Emmanouella, O'Brien Philippa M, Campo M Saveria
Institute of Comparative Medicine, Glasgow University Veterinary School, Garscube Estate, Glasgow G61 1QH, UK.
Oncogene. 2002 Nov 7;21(51):7808-16. doi: 10.1038/sj.onc.1205885.
During papillomavirus infection, the E5 protein localizes in the cell Golgi apparatus and other endomembrane compartments. Cells transformed by E5 do not express major histocompatibility class I complex (MHC I) on the cell surface, while cells transformed by the other transforming proteins E6 and E7 do. In addition, the total amount of both MHC I protein and mRNA is reduced in E5-transformed cells. Here we show that expression of bovine papillomavirus E5 causes the retention of MHC I in the Golgi apparatus, thus preventing its transport to the cell surface. We ascribe this effect to a failure of acidification of the Golgi apparatus, as similar effects are observed in control cells treated with the ionophore monensin. Treatment of E5-transformed cells with either beta- or gamma-interferon increases the synthesis of MHC I, showing that inhibition of MHC I expression by E5 is not irreversible. However, even after interferon treatment, MHC I, although increased in quantity, is not transported to the cell surface. E5 therefore affects MHC I at several levels, but prevention of MHC I transport to the cell surface appears to be the dominant effect. Lack of surface MHC I would have profound consequences for presentation of viral peptides to the immune system.
在乳头瘤病毒感染期间，E5蛋白定位于细胞高尔基体和其他内膜区室。被E5转化的细胞在细胞表面不表达主要组织相容性复合体I类（MHC I），而被其他转化蛋白E6和E7转化的细胞则表达。此外，在E5转化的细胞中，MHC I蛋白和mRNA的总量均减少。在此我们表明，牛乳头瘤病毒E5的表达导致MHC I滞留在高尔基体中，从而阻止其转运至细胞表面。我们将这种效应归因于高尔基体酸化失败，因为在用离子载体莫能菌素处理的对照细胞中观察到了类似的效应。用β-干扰素或γ-干扰素处理E5转化的细胞会增加MHC I的合成，表明E5对MHC I表达的抑制不是不可逆的。然而，即使在干扰素处理后，MHC I虽然数量增加，但仍未转运至细胞表面。因此，E5在多个水平上影响MHC I，但阻止MHC I转运至细胞表面似乎是主要效应。缺乏表面MHC I将对向免疫系统呈递病毒肽产生深远影响。
