The effect of iron overload on in vitro HIV-1 infection.
BACKGROUND
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.


OBJECTIVE
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).


CONCLUSIONS
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.
Traoré
Hafsatou Ndama
HN
Biochemistry Division, Department of Chemistry and Biochemistry, Rand Afrikaans University, P.O. Box 524, Auckland-Park 2006, Johannesburg, South Africa.
Meyer
Debra
D
D002470:Cell Survival; D015658:HIV Infections / Q000150:complications / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D007376:Interleukin-2 / Q000494:pharmacology; D007501:Iron / Q000494:pharmacology*; D007502:Iron Chelating Agents / Q000494:pharmacology; D014779:Virus Replication / Q000187:drug effects*
D007376:Interleukin-2; D007502:Iron Chelating Agents; D007501:Iron