Feduchi E, Alonso M A, Carrasco L
Centro de Biología Molecular, Universidad Autónoma de Madrid, Spain.
J Virol. 1989 Mar;63(3):1354-9. doi: 10.1128/JVI.63.3.1354-1359.1989.
The replication of herpes simplex virus type 1 (HSV-1) is not inhibited in either HeLa or HEp-2 cells treated with human alpha interferon (HuIFN-alpha), particularly when high multiplicities of infection are used. However, HuIFN-gamma partially inhibits HSV-1 translation in HEp-2 cells infected at low multiplicities. Under these conditions, the transcription of genes alpha 22, TK, and gamma 0 is greatly diminished. The combined addition of human tumor necrosis factor (TNF) and HuIFN-gamma to HEp-2 cells exerts a synergistic inhibition of HSV-1 translation. Cells treated with both cytokines continue synthesizing cellular proteins, even 20 h after HSV-1 infection. As little as 10 U of IFN-gamma per ml blocked HSV-1 DNA replication, provided that TNF was also present in the medium. Analyses of HSV-1 gene transcription suggest that the action of both TNF and IFN-gamma blocked a step that comes at or prior to early HSV-1 gene expression. This early step in HSV-1 replication inhibited by TNF and IFN-gamma occurs after virus attachment and entry into cells, since the internalization of radioactive HSV-1 virion particles was not blocked by the presence of the two cytokines. Therefore, we conclude that the synergistic action of TNF plus IFN-gamma affects a step in HSV-1 replication that comes after virus entry but before or at the transcription of immediate-early genes.
用人类α干扰素（HuIFN-α）处理过的HeLa细胞或HEp-2细胞中，单纯疱疹病毒1型（HSV-1）的复制并未受到抑制，尤其是在使用高感染复数时。然而，HuIFN-γ可部分抑制低感染复数感染的HEp-2细胞中HSV-1的翻译。在这些条件下，α22、TK和γ0基因的转录大幅减少。将人类肿瘤坏死因子（TNF）和HuIFN-γ联合添加到HEp-2细胞中，对HSV-1翻译产生协同抑制作用。用这两种细胞因子处理的细胞即使在HSV-1感染20小时后仍继续合成细胞蛋白。只要培养基中也存在TNF，每毫升低至10单位的IFN-γ就能阻断HSV-1 DNA复制。对HSV-1基因转录的分析表明，TNF和IFN-γ的作用均阻断了HSV-1早期基因表达之前或之时的一个步骤。TNF和IFN-γ抑制的HSV-1复制的这一早期步骤发生在病毒附着并进入细胞之后，因为放射性HSV-1病毒粒子的内化并未被这两种细胞因子的存在所阻断。因此，我们得出结论，TNF加IFN-γ的协同作用影响了HSV-1复制中病毒进入后但在即刻早期基因转录之前或之时的一个步骤。
