Kajon A E, Spindler K R
Department of Genetics, University of Georgia, Athens, Georgia 30602, USA.
Virology. 2000 Aug 15;274(1):213-9. doi: 10.1006/viro.2000.0459.
The effects of mouse interferon (IFN)-alpha/beta and recombinant IFN-gamma on mouse adenovirus type 1 (MAV-1) replication were investigated in single-cycle infectious virus yield reduction assays on mouse L929 cells. Viral yields at 3 days postinfection indicated that wt MAV-1 and pmE314, an early region 3 null mutant, were relatively insensitive to both IFN-alpha/beta and IFN-gamma, whereas early region 1A (E1A) mutants pmE109 (null), dlE105 (conserved region 1 deletion, CR1 Delta), dlE102 (CR2 Delta), and dlE106 (CR3 Delta) were sensitive. MAV-1 E1A that was inducibly expressed in mouse fibroblast 37.1 cells rescued vesicular stomatitis virus from the antiviral effect of IFN-alpha/beta but not from the antiviral effect of IFN-gamma. Interferon-inducible gene expression was reduced in 37.1 cells as compared to the parental 3T6 cell line. Steady-state levels of IFN-inducible gene mRNAs were also reduced in 3T6 cells infected with the wild-type virus and pmE314 but not in cells infected with pmE109. These results suggest that the MAV-1 E1A gene product is capable of interfering with the signaling pathways of both types of IFN, although modulation of IFN-alpha/beta antiviral activity was more pronounced.
在对小鼠L929细胞进行的单周期感染性病毒产量降低试验中,研究了小鼠干扰素(IFN)-α/β和重组IFN-γ对1型小鼠腺病毒(MAV-1)复制的影响。感染后3天的病毒产量表明,野生型MAV-1和早期区域3缺失突变体pmE314对IFN-α/β和IFN-γ均相对不敏感,而早期区域1A(E1A)突变体pmE109(缺失)、dlE105(保守区域1缺失,CR1Δ)、dlE102(CR2Δ)和dlE106(CR3Δ)则敏感。在小鼠成纤维细胞37.1细胞中可诱导表达的MAV-1 E1A从IFN-α/β的抗病毒作用中拯救了水疱性口炎病毒,但未从IFN-γ的抗病毒作用中拯救。与亲代3T6细胞系相比,37.1细胞中的干扰素诱导基因表达降低。在感染野生型病毒和pmE314的3T6细胞中,干扰素诱导基因mRNA的稳态水平也降低,但在感染pmE109的细胞中未降低。这些结果表明,MAV-1 E1A基因产物能够干扰两种类型干扰素的信号通路,尽管对IFN-α/β抗病毒活性的调节更为明显。