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猫免疫缺陷病毒对人外周血单个核细胞的有效感染:对载体开发的启示

Productive infection of human peripheral blood mononuclear cells by feline immunodeficiency virus: implications for vector development.

作者信息

Johnston J, Power C

机构信息

Department of Clinical Neurosciences and Department of Microbiology and Infectious Diseases, University of Calgary, Calgary, Alberta, Canada T2N 4N1.

出版信息

J Virol. 1999 Mar;73(3):2491-8. doi: 10.1128/JVI.73.3.2491-2498.1999.

DOI:10.1128/JVI.73.3.2491-2498.1999
PMID:9971834
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC104496/
Abstract

Feline immunodeficiency virus (FIV) is a lentivirus causing immune suppression and neurological disease in cats. Like primate lentiviruses, FIV utilizes the chemokine receptor CXCR4 for infection. In addition, FIV gene expression has been demonstrated in immortalized human cell lines. To investigate the extent and mechanism by which FIV infected primary and immortalized human cell lines, we compared the infectivity of two FIV strains, V1CSF and Petaluma, after cell-free infection. FIV genome was detected in infected human peripheral blood mononuclear cells (PBMC) and macrophages at 21 and 14 days postinfection, respectively. Flow cytometry analysis of FIV-infected human PBMC indicated that antibodies to FIV p24 recognized 12% of the cells. Antibodies binding the CCR3 chemokine receptor maximally inhibited infection of human PBMC by both FIV strains compared to antibodies to CXCR4 or CCR5. Reverse transcriptase levels increased in FIV-infected human PBMC, with detection of viral titers of 10(1.3) to 10(2.1) 50% tissue culture infective doses/10(6) cells depending on the FIV strain examined. Cell death in human PBMC infected with either FIV strain was significantly elevated relative to uninfected control cultures. These findings indicate that FIV can productively infect primary human cell lines and that viral strain specificity should be considered in the development of an FIV vector for gene therapy.

摘要

猫免疫缺陷病毒(FIV)是一种慢病毒,可导致猫出现免疫抑制和神经疾病。与灵长类慢病毒一样,FIV利用趋化因子受体CXCR4进行感染。此外,已在永生化人细胞系中证实了FIV基因表达。为了研究FIV感染原代和永生化人细胞系的程度及机制,我们比较了无细胞感染后两种FIV毒株V1CSF和Petaluma的感染性。分别在感染后21天和14天在感染的人外周血单核细胞(PBMC)和巨噬细胞中检测到FIV基因组。对FIV感染的人PBMC进行的流式细胞术分析表明,抗FIV p24抗体识别出12%的细胞。与抗CXCR4或CCR5抗体相比,结合CCR3趋化因子受体的抗体最大程度地抑制了两种FIV毒株对人PBMC的感染。FIV感染的人PBMC中逆转录酶水平升高,根据所检测的FIV毒株,病毒滴度为10(1.3)至10(2.1)50%组织培养感染剂量/10(6)个细胞。与未感染的对照培养物相比,感染任何一种FIV毒株的人PBMC中的细胞死亡均显著升高。这些发现表明FIV可有效感染原代人细胞系,并且在开发用于基因治疗的FIV载体时应考虑病毒株特异性。

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