Service de Biostatistique, Hospices Civils de Lyon, Lyon, France.
PLoS One. 2013;8(2):e56135. doi: 10.1371/journal.pone.0056135. Epub 2013 Feb 7.
The early events of human immunodeficiency virus infection seem critical for progression toward disease and antiretroviral therapy initiation. We wanted to clarify some still unknown prognostic relationships between inoculum size and changes in various immunological and virological markers. Feline immunodeficiency virus infection could be a helpful model.
Viremia and T-cell markers (number of CD4, CD8, CD8β(low)CD62L(neg) T-cells, CD4/CD8 ratio, and percentage of CD8β(low)CD62L(neg) cells among CD8 T-cells) were measured over 12 weeks in 102 cats infected with different feline immunodeficiency virus strains and doses. Viremia and T-cell markers trajectory groups were determined and the dose-response relationships between inoculum titres and trajectory groups investigated.
Cats given the same inoculum showed different patterns of changes in viremia and T-cell markers. A statistically significant positive dose-response relationship was observed between inoculum titre and i) viremia trajectory-groups (r = 0.80, p<0.01), ii) CD8β(low)CD62L(neg) cell-fraction trajectory-groups (r = 0.56, p<0.01). Significant correlations were also found between viremia and the CD4/CD8 ratio and between seven out of ten T-cell markers.
In cats, the infectious dose determines early kinetics of viremia and initial CD8+ T-cell activation. An expansion of the CD8β(low)CD62L(neg) T-cells might be an early predictor of progression toward disease. The same might be expected in humans but needs confirmation.
人类免疫缺陷病毒感染的早期事件似乎对疾病进展和抗逆转录病毒治疗的启动至关重要。我们想阐明一些仍未知的、与接种量和各种免疫及病毒学标志物变化之间的预后关系。猫免疫缺陷病毒感染可能是一个有用的模型。
在 102 只感染不同猫免疫缺陷病毒株和剂量的猫中,在 12 周内测量了病毒血症和 T 细胞标志物(CD4、CD8、CD8β(low)CD62L(neg)T 细胞数量、CD4/CD8 比值以及 CD8 T 细胞中 CD8β(low)CD62L(neg)细胞的百分比)。确定了病毒血症和 T 细胞标志物轨迹组,并研究了接种量与轨迹组之间的剂量反应关系。
给予相同接种量的猫显示出不同的病毒血症和 T 细胞标志物变化模式。接种量与 i)病毒血症轨迹组(r=0.80,p<0.01)和 ii)CD8β(low)CD62L(neg)细胞分数轨迹组(r=0.56,p<0.01)之间存在显著的正剂量反应关系。病毒血症与 CD4/CD8 比值以及十个 T 细胞标志物中的七个标志物之间也存在显著相关性。
在猫中,感染剂量决定了病毒血症的早期动力学和初始 CD8+T 细胞的激活。CD8β(low)CD62L(neg)T 细胞的扩增可能是疾病进展的早期预测指标。这在人类中可能也是如此,但需要进一步证实。