Roles of the auxiliary genes and AP-1 binding site in the long terminal repeat of feline immunodeficiency virus in the early stage of infection in cats
Roles of the auxiliary genes and AP-1 binding site in the long terminal repeat of feline immunodeficiency virus in the early stage of infection in cats
复制标题
DOI：
10.1128/jvi.70.12.8518-8526.1996
复制
发表时间：
1996-12-01
影响因子：
5.4
通讯作者：
Mikami, T
中科院分区：
文献类型：
--
作者：
Inoshima, Y;Kohmoto, M;Mikami, T
为了检测猫免疫缺陷病毒（FIV）长末端重复中辅助基因和AP-I结合位点的作用，将vif基因（Delta vif）、ORF-A基因（Delta QRF-A）和AP-1结合位点（Delta AP-1）缺陷的三种突变病毒以及作为阳性对照的野生型病毒分别接种到三只无特定病原体的猫中。通过测量外周血单核细胞 (PHSMC) 中原病毒 DNA 拷贝数、CD4/CD8 比率和对 FIV 的抗体反应 16 周，然后检查尸检时的组织学变化来评估这些猫。尽管直到接种后16周，所有12只猫的PBMC中都不同程度地检测到了病毒DNA，但在观察期间，从感染Delta vif病毒的猫的PBMC中没有回收到病毒。然而，一只感染 Delta vif 病毒的猫诱导了非常弱的抗体反应。相比之下，尽管两组感染Delta ORF-A和Delta AP-1病毒的猫均成功恢复了病毒，但该组的抗体反应和CD4/CD8比值的下降均比感染野生型病毒的猫温和，而且观察期间两组PBMC中前病毒DNA拷贝数均未能达到感染野生型病毒的猫的水平。从这些结果中，我们得出结论，这些突变病毒仍然对猫具有感染性，但未能有效进行病毒复制，并表明这些辅助基因和增强子元件对于完整的病毒复制动力学以及可能在体内感染早期阶段的完全致病性是重要或必需的。
To examine the roles of auxiliary genes and the AP-I binding site in the long terminal repeat of feline immunodeficiency virus (FIV) in vise, three mutant viruses, which are defective in the vif gene (Delta vif), ORF-A gene (Delta QRF-A), and AP-1 binding site (Delta AP-1), and wild-type virus as a positive control were separately inoculated into three specific-pathogen-free cats. These cats were assessed by measuring the number of proviral DNA copies in peripheral blood mononuclear cells (PHSMCs), the CD4/CD8 ratio and antibody responses to FIV for 16 weeks and then examining histological changes at necropsy. Although viral DNAs were detected in PBMCs from all 12 cats to various degrees until 16 weeks postinoculation, no virus was recovered from PBMCs of cats infected with Delta vif virus during the observation period. However, a very weak antibody response was induced in one cat infected with the Delta vif virus. In contrast, despite the successful recovery of virus from both groups of cats infected with Delta ORF-A and Delta AP-1 virus, antibody responses and decrease in the CD4/CD8 ratio in the groups were milder than those in cats infected with wild-type virus, Furthermore, the numbers of proviral DNA copies in PBMCs from the two groups were not able to reach the level in cats infected with wild-type virus during the observation period. From these results, we conclude that these mutant viruses are still infectious for cats but failed in efficient viral replication and suggest that these auxiliary genes and enhancer element are important or essential to full viral replication kinetics and presumably to full pathogenicity during the early stage of infection in vivo.