Chinsangaram Jarasvech, Moraes Mauro P, Koster Marla, Grubman Marvin J
Plum Island Animal Disease Center, USDA, ARS, NAA, Greenport, New York 11944, USA.
J Virol. 2003 Jan;77(2):1621-5. doi: 10.1128/jvi.77.2.1621-1625.2003.
We have previously shown that replication of foot-and-mouth disease virus (FMDV) is highly sensitive to alpha/beta interferon (IFN-alpha/beta). In the present study, we constructed recombinant, replication-defective human adenovirus type 5 vectors containing either porcine IFN-alpha or IFN-beta (Ad5-pIFNalpha or Ad5-pIFNbeta). We demonstrated that cells infected with these viruses express high levels of biologically active IFN. Swine inoculated with 10(9) PFU of a control Ad5 virus lacking the IFN gene and challenged 24 h later with FMDV developed typical signs of foot-and-mouth disease (FMD), including fever, vesicular lesions, and viremia. In contrast, swine inoculated with 10(9) PFU of Ad5-pIFNalpha were completely protected when challenged 24 h later with FMDV. These animals showed no clinical signs of FMD and no viremia and did not develop antibodies against viral nonstructural proteins, suggesting that complete protection from infection was achieved.
我们之前已经表明,口蹄疫病毒(FMDV)的复制对α/β干扰素(IFN-α/β)高度敏感。在本研究中,我们构建了含有猪IFN-α或IFN-β的重组、复制缺陷型人5型腺病毒载体(Ad5-pIFNα或Ad5-pIFNβ)。我们证明,感染这些病毒的细胞表达高水平的生物活性IFN。接种10⁹ PFU缺乏IFN基因的对照Ad5病毒并在24小时后用FMDV攻击的猪出现了口蹄疫(FMD)的典型症状,包括发热、水疱性病变和病毒血症。相比之下,接种10⁹ PFU Ad5-pIFNα的猪在24小时后用FMDV攻击时得到了完全保护。这些动物没有表现出FMD的临床症状,没有病毒血症,也没有产生针对病毒非结构蛋白的抗体,这表明实现了对感染的完全保护。