Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle WA 98109, USA.
Virology. 2012 May 25;427(1):25-33. doi: 10.1016/j.virol.2012.02.001. Epub 2012 Feb 25.
Neutralization properties of human immunodeficiency virus (HIV-1) are often defined using pseudoviruses grown in transformed cells, which are not biologically relevant HIV-1 producer cells. Little information exists on how these viruses compare to viruses produced in primary lymphocytes, particularly for globally relevant HIV-1 strains. Therefore, replication-competent chimeras encoding envelope variants from the dominant HIV-1 subtypes (A, C, and D) obtained early after infection were generated and the neutralization properties explored. Pseudoviruses generated in 293T cells were the most sensitive to antibody neutralization. Replicating viruses generated in primary lymphocytes were most resistant to neutralization by plasma antibodies and most monoclonal antibodies (b12, 4E10, 2F5, VRC01). These differences were not associated with differences in envelope content. Surprisingly, the virus source did not impact neutralization sensitivity of most viruses to PG9. These findings suggest that producer cell type has a major effect on neutralization sensitivity, but in an antibody dependent manner.
人类免疫缺陷病毒 (HIV-1) 的中和特性通常使用转化细胞中生长的假病毒来定义,而这些转化细胞与生物学上相关的 HIV-1 产生细胞不相符。对于全球相关的 HIV-1 株,关于这些病毒与在原代淋巴细胞中产生的病毒如何比较的信息很少。因此,生成了编码感染早期获得的主要 HIV-1 亚型 (A、C 和 D) 包膜变异体的复制型嵌合病毒,并对其中和特性进行了探索。在 293T 细胞中生成的假病毒对抗体中和最敏感。在原代淋巴细胞中产生的复制病毒对血浆抗体和大多数单克隆抗体 (b12、4E10、2F5、VRC01) 的中和最具抵抗力。这些差异与包膜含量的差异无关。令人惊讶的是,病毒来源并不影响大多数病毒对 PG9 的中和敏感性。这些发现表明,产生细胞类型对中和敏感性有重大影响,但这种影响依赖于抗体。