Department of Molecular and Cellular Interactions, VIB, Brussels, Belgium.
PLoS One. 2012;7(4):e35074. doi: 10.1371/journal.pone.0035074. Epub 2012 Apr 6.
The immune system exerts a diversifying selection pressure on HIV through cellular, humoral and innate mechanisms. This pressure drives viral evolution throughout infection. A better understanding of the natural immune pressure on the virus during infection is warranted, given the clinical interest in eliciting and sustaining an immune response to HIV which can help to control the infection. We undertook to evaluate the potential of the novel HIV-induced, monocyte-derived factor visfatin to modulate viral infection, as part of the innate immune pressure on viral populations.
We show that visfatin is capable of selectively inhibiting infection by R5 HIV strains in macrophages and resting PBMC in vitro, while at the same time remaining indifferent to or even favouring infection by X4 strains. Furthermore, visfatin exerts a direct effect on the relative fitness of R5 versus X4 infections in a viral competition setup. Direct interaction of visfatin with the CCR5 receptor is proposed as a putative mechanism for this differential effect. Possible in vivo relevance of visfatin induction is illustrated by its association with the dominance of CXCR4-using HIV in the plasma.
As an innate factor produced by monocytes, visfatin is capable of inhibiting infections by R5 but not X4 strains, reflecting a potential selective pressure against R5 viruses.
免疫系统通过细胞、体液和先天机制对 HIV 施加多样化的选择压力。这种压力在整个感染过程中推动病毒进化。鉴于人们对引发和维持对 HIV 的免疫反应以帮助控制感染的临床兴趣，因此有必要更好地了解感染过程中病毒自然受到的免疫压力。我们着手评估新型 HIV 诱导的单核细胞衍生因子内脂素在病毒群体的先天免疫压力中调节病毒感染的潜力。
我们表明，内脂素能够在体外选择性地抑制巨噬细胞和静止 PBMC 中 R5 HIV 株的感染，同时对 X4 株的感染保持漠不关心甚至有利。此外，内脂素在病毒竞争设置中对 R5 与 X4 感染的相对适应性产生直接影响。提出内脂素与 CCR5 受体的直接相互作用作为这种差异作用的潜在机制。内脂素诱导的可能体内相关性通过其与 CXCR4 利用 HIV 在血浆中占优势相关联得到说明。
作为单核细胞产生的先天因子，内脂素能够抑制 R5 但不能抑制 X4 株的感染，反映了对 R5 病毒的潜在选择压力。
