Substitution of warthog NF-κB motifs into RELA of domestic pigs is not sufficient to confer resilience to African swine fever virus
Substitution of warthog NF-κB motifs into RELA of domestic pigs is not sufficient to confer resilience to African swine fever virus
复制标题
将疣猪 NF-κB 基序替换为家猪的 RELA 不足以赋予对非洲猪瘟病毒的抵抗力
作者：
S. McCleary;R. Strong;Ronan R. McCarthy;Ronan R. McCarthy;J. Edwards;J. Edwards;Emma L. Howes;L. Stevens;P. Sánchez;A. Núñez;S. Watson;A. Mileham;S. Lillico;Christine Tait;C. Proudfoot;M. Ballantyne;C. Whitelaw;F. Steinbach;H. Crooke
非洲猪瘟病毒（ASFV）在家猪中引起致命的出血性疾病，威胁着地球仪的养猪生产。与家猪不同，作为病毒野生宿主的疣猪不会屈服于感染的致命影响。在野猪和家猪RELA蛋白的序列之间存在三个氨基酸差异; RELA蛋白是NF-κB转录因子的亚基，在调节对感染的免疫应答中起关键作用。通过基因编辑已经产生了具有来自疣猪RELA直向同源物的所有3或2个氨基酸的家猪。为了评估这些变异是否赋予对ASF的适应性，我们建立了中等毒力ASFV的鼻内攻击模型。在具有2个氨基酸取代的家猪中未观察到临床、病毒学或病理学参数的差异。在疣猪RELA中发现的所有3种氨基酸的家猪对ASF没有弹性，但在一些动物中观察到临床体征的发生延迟以及血液样品和鼻分泌物中的病毒DNA较少。将这些和其他野猪遗传性状纳入家猪中可能是帮助对抗ASFV破坏性影响的一种方法。
African swine fever virus (ASFV) causes a lethal, haemorrhagic disease in domestic swine that threatens pig production across the globe. Unlike domestic pigs, warthogs, which are wildlife hosts of the virus, do not succumb to the lethal effects of infection. There are three amino acid differences between the sequence of the warthog and domestic pig RELA protein; a subunit of the NF-κB transcription factor that plays a key role in regulating the immune response to infections. Domestic pigs with all 3 or 2 of the amino acids from the warthog RELA orthologue have been generated by gene editing. To assess if these variations confer resilience to ASF we established an intranasal challenge model with a moderately virulent ASFV. No difference in clinical, virological or pathological parameters were observed in domestic pigs with the 2 amino acid substitution. Domestic pigs with all 3 amino acids found in warthog RELA were not resilient to ASF but a delay in onset of clinical signs and less viral DNA in blood samples and nasal secretions was observed in some animals. Inclusion of these and additional warthog genetic traits into domestic pigs may be one way to assist in combating the devastating impact of ASFV.
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作者：
Frantz;Laurent Af Frantz;J. Schraiber;O. Madsen;H. Megens;M. Bosse;Yogesh Paudel;G. Semiadi
通讯作者：
Frantz;Laurent Af Frantz;J. Schraiber;O. Madsen;H. Megens;M. Bosse;Yogesh Paudel;G. Semiadi