Hafsatou Ndama Traoré1, Debra Meyer. 1. Biochemistry Division, Department of Chemistry and Biochemistry, Rand Afrikaans University, P.O. Box 524, Auckland-Park 2006, Johannesburg, South Africa.
Abstract
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. OBJECTIVES: 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). RESULTS AND CONCLUSION: 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.
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. OBJECTIVES: 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). RESULTS AND CONCLUSION: 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.
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