Deletion of a CD2-like gene, 8-DR, from African swine fever virus affects viral infection in domestic swine
Deletion of a CD2-like gene, 8-DR, from African swine fever virus affects viral infection in domestic swine
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DOI：
10.1128/jvi.72.4.2881-2889.1998
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发表时间：
1998-04-01
影响因子：
5.4
通讯作者：
Rock, DL
中科院分区：
文献类型：
--
作者：
Borca, MV;Carrillo, C;Rock, DL
非洲猪瘟病毒（ASFV）基因与t淋巴细胞表面抗原CD2相似，已在非洲致病性分离物马拉维il-20/1（开放阅读框[ORF] 8-DR）和细胞培养适应的欧洲病毒BA71V （ORF EP402R）中发现，该基因已被证明是导致ASFV感染细胞的血液吸附现象的原因。ASFV基因产物的结构和功能与CD2相似，CD2是一种参与细胞-细胞粘附和t细胞介导的免疫反应的细胞蛋白，这表明该基因可能在猪宿主的组织趋向性和/或免疫逃避中起作用。在本研究中，我们从马拉维的il-20/1分离物中构建了ASFV 8-DR基因缺失突变体（Delta 8-DR）及其逆转物（8-DR）来检测基因在体内的功能。体外，rig-DR, 8-DR。R和亲本病毒在原代猪巨噬细胞培养中表现出难以区分的生长特征。体内8-DR对家猪的病毒毒力无明显影响；突变型δ 8-DR的发病、病程和死亡率与反转型δ 8-DR相似。R和亲代病毒然而，在感染Delta 8-DR的猪中观察到病毒感染发生了改变。观察到在引流淋巴结中Delta 8-DR的扩散和/或复制延迟，感染的普遍化延迟，淋巴组织和骨髓中的病毒滴度降低100至1000倍。感染Delta - 8- dr的动物的病毒血症发作明显延迟（2至5天），感染后5天平均病毒血症滴度降低约10,000倍，随后降低30至100倍；此外，与8-DR不同。感染r病毒的动物，病毒血症不再主要与红细胞相关，而是均匀分布于红细胞、白细胞和血浆部分。感染8-DR后，猪外周血单核细胞的丝裂原依赖性淋巴细胞增殖减少了90% ~ 95%。但在δ 8-DR感染后保持不变，表明8-DR具有体外免疫抑制活性。总之，这些结果表明8-DR在猪宿主中的免疫抑制作用促进了病毒感染的早期事件。这可能对ASFV感染其高度适应的自然宿主疣猪最为重要。
An African swine fever virus (ASFV) gene with similarity to the T-lymphocyte surface antigen CD2 has been found in the pathogenic African isolate Malawi Lil-20/1 (open reading frame [ORF] 8-DR) and a cell culture-adapted European virus, BA71V (ORF EP402R) and has been shown to be responsible for the hemadsorption phenomenon observed for ASFV-infected cells. The structural and functional similarities of the ASFV gene product to CD2, a cellular protein involved in cell-cell adhesion and T-cell-mediated immune responses, suggested a possible role for this gene in tissue tropism and/or immune evasion in the swine host, In this study, we constructed an ASFV 8-DR gene deletion mutant (Delta 8-DR) and its revertant (8-DR.R) from the Malawi Lil-20/1 isolate to examine gene function in vivo. In vitro, rig-DR, 8-DR.R, and the parental virus exhibited indistinguishable growth characteristics on primary porcine macrophage cell cultures. In vivo, 8-DR had no obvious effect on viral virulence in domestic pigs; disease onset, disease course, and mortality were similar for the mutant Delta 8-DR its revertant 8-DR.R and the parental virus. Altered viral infection was, however, observed for pigs infected with Delta 8-DR. A delay in spread to and/or replication of Delta 8-DR in the draining lymph node, a delay in generalization of infection, and a 100- to 1,000-fold reduction in virus titers in lymphoid tissue and bone marrow were observed. Onset of viremia for Delta 8-DR-infected animals was significantly delayed (by 2 to 5 days), and mean viremia titers were reduced approximately 10,000-fold at 5 days postinfection and 30- to 100-fold at later times; moreover, unlike in 8-DR.R-infected animals, the viremia was no longer predominantly erythrocyte associated but rather was equally distributed among erythrocyte, leukocyte, and plasma fractions. Mitogen-dependent lymphocyte proliferation of swine peripheral blood mononuclear cells in vitro aas reduced by 90 to 95% following infection with 8-DR.R but remained unaltered following infection with Delta 8-DR, suggesting that 8-DR has immunosuppressive activity in vitro. Together, these results suggest an immunosuppressive role far 8-DR in the swine host which facilitates early events in viral infection. This may be of most significance for ASFV infection of its highly adapted natural host, the warthog.