Leroy Michaël P-P, Baise Etienne A, Pire Grégory A, Desmecht Daniel J-M
Department of Pathology, Faculty of Veterinary Medicine, University of Liège, B-4000 Liège, Belgium.
Am J Vet Res. 2007 Sep;68(9):988-94. doi: 10.2460/ajvr.68.9.988.
To determine the contribution of MX dynamin, oligoadenylate synthetase (OAS), and double-stranded RNA-dependent protein kinase R (PKR) to the antiviral effects of type 1 interferons (IFNs) against bovine parainfluenza-3 virus (PI-3V) infection of Vero cells.
Vero cell cultures.
PI-3V yield was first compared between control and transfected type 1 IFNs-incompetent Vero cells expressing recombinant OAS or MX proteins. Afterwards, phosphorylation of eukaryotic initiation factor 2 alpha (eIF2alpha) was used to scale the degree of PKR activation upon infection of Vero cells by PI-3V.
Overexpression of OAS did not result in significantly decreased viral replication. Phosphorylated eIF2alpha forms, the hallmark of PKR activation, were not increased in IFNalpha-primed infected Vero cells. Although human MXA contributed to partial blockade of replication of bovine PI-3V, the antiviral effect was not as strong as that of IFNalpha.
The powerful anti-Paramyxovirus activity of type 1 IFNs is mediated by noncanonic pathways.
确定MX发动蛋白、寡腺苷酸合成酶(OAS)和双链RNA依赖性蛋白激酶R(PKR)在1型干扰素(IFN)对牛副流感3型病毒(PI-3V)感染Vero细胞的抗病毒作用中的贡献。
Vero细胞培养物。
首先比较对照Vero细胞与转染表达重组OAS或MX蛋白的无1型IFN能力的Vero细胞之间的PI-3V产量。之后,利用真核起始因子2α(eIF2α)的磷酸化来衡量PI-3V感染Vero细胞后PKR的激活程度。
OAS的过表达并未导致病毒复制显著减少。PKR激活的标志——磷酸化eIF2α形式,在IFNα预处理的感染Vero细胞中并未增加。虽然人MXA有助于部分阻断牛PI-3V的复制,但抗病毒效果不如IFNα强。
1型IFN强大的抗副粘病毒活性由非经典途径介导。