Grumet R, Sanford J C, Johnston S A
Botany Department, Duke University, Durham, North Carolina 27706.
Virology. 1987 Dec;161(2):561-9. doi: 10.1016/0042-6822(87)90152-8.
The principle of pathogen-derived resistance (the use of pathogen-derived genes to interfere with the pathogenic process and thereby confer disease resistance to the host) has been put forward as a broadly applicable conceptual tool for use in the genetic engineering of resistance to pathogens and parasites. It was previously predicted that four mechanisms of pathogen-derived resistance could be established using the bacteriophage QB and its host, Escherichia coli, as a model system. This paper demonstrates and helps ellucidate the first of these mechanisms by using a viral regulatory protein, the QB coat protein, to block viral replication. The QB coat protein gene was transferred to susceptible E. coli. Expression of this gene had no obvious detrimental effect on the host. Low-level, constitutive expression of the coat protein conditions very high levels of resistance to QB infection. The resulting resistance is not associated with RNA interference or loss of pili as attachment sites, and does not appear to be associated with premature encapsidation. This low-level expression of the QB coat protein also produces an intermediate level of resistance to the closely related phage SP, but fails to protect against the unrelated phage f2. Thus the resistance does not result from a generalized antiviral host response induced by the presence of the coat protein. We conclude that the QB coat protein blocks viral infection, as was predicted, due to its action as a negative regulatory molecule. The use of negative regulatory molecules may provide an effective mechanism for use in the genetic engineering of pathogen-derived resistance.
病原体衍生抗性原理（利用病原体衍生基因干扰致病过程从而赋予宿主抗病性）已被提出，作为一种广泛适用的概念工具用于病原体和寄生虫抗性的基因工程。此前预测，以噬菌体QB及其宿主大肠杆菌作为模型系统，可建立四种病原体衍生抗性机制。本文通过使用病毒调节蛋白——QB外壳蛋白来阻断病毒复制，展示并有助于阐明其中的第一种机制。将QB外壳蛋白基因转移至易感大肠杆菌。该基因的表达对宿主没有明显的有害影响。外壳蛋白的低水平组成型表达赋予了对QB感染的极高抗性。产生的抗性与RNA干扰或作为附着位点的菌毛缺失无关，并且似乎与过早衣壳化无关。QB外壳蛋白的这种低水平表达还对密切相关的噬菌体SP产生中等水平的抗性，但无法抵御不相关的噬菌体f2。因此，这种抗性并非由外壳蛋白的存在诱导的全身性抗病毒宿主反应所致。我们得出结论，正如所预测的那样，QB外壳蛋白因其作为负调节分子的作用而阻断病毒感染。使用负调节分子可能为病原体衍生抗性的基因工程提供一种有效机制。
