An African swine fever virus virulence-associated gene NL-S with similarity to the herpes simplex virus ICP34.5 gene
An African swine fever virus virulence-associated gene NL-S with similarity to the herpes simplex virus ICP34.5 gene
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DOI：
10.1128/jvi.70.12.8865-8871.1996
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发表时间：
1996-12-01
影响因子：
5.4
通讯作者：
Rock, DL
中科院分区：
文献类型：
--
作者：
Zsak, L;Lu, Z;Rock, DL
我们先前描述了非洲猪瘟病毒（ASFV）开放阅读框，23-NL，在非洲分离株马拉维Lil 2011中，其产物在羧基末端结构域与小鼠髓样分化初级应答基因MyD 116和单纯疱疹病毒神经毒性相关基因ICP 34.5（M. D. Sussman，Z. Lu，G.库蒂什角L. Afonso，P. Roberts，and D. L.洛克，J·维罗尔。66：5586-5589，1992）。23-NL与这些基因的相似性表明，该基因可能在ASFV毒力和/或宿主范围的某些方面起作用。其他致病性病毒分离株的序列分析表明，该基因在不同的ASFV分离株中高度保守，并且该基因产物以长形式（如23-NL中的184个氨基酸）或短形式（在其他检查的ASFV分离株中为70至72个氨基酸）存在。该基因的短形式NL-S编码23-NL、MyD 116和ICP34.5共有的56个氨基酸的完全高度保守的亲水性羧基末端结构域。从致病性ASFV分离株E70和E70猴细胞培养适应病毒MS 44中构建了重组NL-S基因缺失突变体及其回复突变体，以研究基因功能。虽然NL-S的缺失不影响病毒在原代猪巨噬细胞或Vero细胞培养物中的体外生长，但无效突变体E70/43表现出明显的猪毒力降低，与死亡率为100%的回复突变体或亲本E70相反，所有E70/43感染的动物在感染后均存活。除了短暂发热反应外，E70/43感染的动物在临床上保持正常，并且平均和最大病毒血症滴度均降低1，000倍。所有恢复期E70/43感染的动物在感染后30天用亲本E70攻击时均存活。这些数据表明，高度保守的NL-S基因的ASFV，而在猪巨噬细胞在体外的生长是不必要的，是一个重要的病毒毒力因子，并可能作为一个主机范围的基因。
We described previously an African swine fever virus (ASFV) open reading frame, 23-NL, in the African isolate Malawi Lil 2011 whose product shared significant similarity in a carboxyl-terminal domain with those of a mouse myeloid differentiation primary response gene, MyD116, and the herpes simplex virus neurovirulence-associated gene, ICP34.5 (M. D. Sussman, Z. Lu, G. Kutish, C. L. Afonso, P. Roberts, and D. L. Rock, J. Virol. 66:5586-5589, 1992). The similarity of 23-NL to these genes suggested that this gene may function in some aspect of ASFV virulence and/or host range. Sequence analysis of additional pathogenic viral isolates demonstrates that this gene is highly conserved among diverse ASFV isolates and that the gene product exists in either a long (184 amino acids as in 23-NL) or a short form (70 to 72 amino acids in other examined ASFV isolates). The short form of the gene, NL-S, encodes the complete highly conserved, hydrophilic, carboxyl-terminal domain of 56 amino acids common to 23-NL, MyD116, and ICP34.5. Recombinant NL-S gene deletion mutants and their revertants were constructed from the pathogenic ASFV isolate E70 and an E70 monkey cell culture-adapted virus, MS44, to study gene function, Although deletion of NL-S did not affect viral growth in primary swine macrophages or Vero cell cultures in vitro, the null mutant, E70/43, exhibited a marked reduction in pig virulence, In contrast to revertant or parental E70 where mortality was 100%, all E70/43-infected animals survived infection, With the exception of a transient fever response, E70/43-infected animals remained clinically normal and exhibited a 1,000-fold reduction in both mean and maximum viremia titers. All convalescent E70/43-infected animals survived infection when challenged with parental E70 at 30 days postinfection. These data indicate that the highly conserved NL-S gene of ASFV, while nonessential for growth in swine macrophages in vitro, is a significant viral virulence factor and may function as a host range gene.