Traoré Hafsatou Ndama, Meyer Debra
Biochemistry Division, Department of Chemistry and Biochemistry, Rand Afrikaans University, P.O. Box 524, Auckland-Park 2006, Johannesburg, South Africa.
J Clin Virol. 2004 Dec;31 Suppl 1:S92-8. doi: 10.1016/j.jcv.2004.09.011.
It has been shown that Fe is required by HIV-infected cells for production of viral particles. Excess iron in the cell is detrimental to the host but beneficial to the pathogen.
Here, we investigated the effect of excess Fe (overload) and chelation of the metal on in vitro HIV infection by assessing host cell responses (viability/death, stress protein expression and cytokine production) as well as virus replication (core protein content and enzyme activity).
Excess iron decreased viability (21%, P<0.01) of HIV-infected cells, increased p24 levels by 8.6% (P=0.32) and elevated reverse transcriptase (RT) activity (81.7%, P<0.01). The stimulation of viral replication was decreased when Fe was first complexed to desferrioxamine (DFO). DFO alone (in the absence of excess Fe), lowered cell viability (35%, P=0.039) and in the presence of virus lowered both p24 levels (66%, P=0.054) and RT activity (43%, P<0.01) and unexpectedly increased cell viability (25%, P=0.01047). Interleukin-2 (IL-2) production of infected cells was completely inhibited by DFO and excess iron while stress protein (Hsp70) levels were lowered in the presence of HIV in combination with excess iron (37%, P<0.01) or DFO (47.2%, P<0.01) when compared to untreated cells. According to flow cytometric data, HIV infection caused a two-fold increase in the numbers of necrotic (P=0.006) and decreased apoptotic cells (28.5%, P=0.15) cells. These findings indicate that Fe overload associated with HIV infection is detrimental to host cell responses against viral infection and that chelation can prevent and/or reverse this effect.
研究表明，HIV感染的细胞需要铁来产生病毒颗粒。细胞内过量的铁对宿主有害，但对病原体有益。
在此，我们通过评估宿主细胞反应（活力/死亡、应激蛋白表达和细胞因子产生）以及病毒复制（核心蛋白含量和酶活性），研究了过量铁（过载）和金属螯合对体外HIV感染的影响。
过量铁降低了HIV感染细胞的活力（21%，P<0.01），使p24水平升高了8.6%（P=0.32），并提高了逆转录酶（RT）活性（81.7%，P<0.01）。当铁首先与去铁胺（DFO）络合时，病毒复制的刺激作用降低。单独使用DFO（在没有过量铁的情况下）会降低细胞活力（35%，P=0.039），在有病毒存在的情况下，会降低p24水平（66%，P=0.054）和RT活性（43%，P<0.01），并且意外地提高了细胞活力（25%，P=0.01047）。DFO和过量铁完全抑制了感染细胞白细胞介素-2（IL-2）的产生，而与未处理的细胞相比，在HIV与过量铁（37%，P<0.01）或DFO（47.2%，P<0.01）共同存在的情况下，应激蛋白（Hsp70）水平降低。根据流式细胞术数据，HIV感染导致坏死细胞数量增加两倍（P=0.006），凋亡细胞数量减少（28.5%，P=0.15）。这些发现表明，与HIV感染相关的铁过载对宿主细胞抵抗病毒感染的反应有害，而螯合作用可以预防和/或逆转这种效应。
