Namita Kumari

Center for Sickle Cell Disease, Howard University, Washington,U.S.A

Title: Heme Inhibits HIV-1 Through the Induction of Heme Oxygenase 1, Ferroportin, IKBα and p21


Namita Kumari is a researcher at Center for Sickle Cell Disease Howard University which is located in USA


Hemin inhibits HIV-1 infection in cultured macrophages and T-cells and also in HIV-1 infected humanized mice by inducing heme oxygenase -1 (HO-1) via a protein kinase C-dependent pathway (reviewed in [1]). HO-1 expression in LPS-treated human macrophages protects them against HIV-1 infection in part through production of MIP1α, MIP1β and LD78β chemokines that decrease CCR5 expression. Iron depletion by iron chelators or through the expression of ferroportin, an iron export protein, inhibited HIV-1 [2, 3]. Here, we show that in heme-treated THP1 cells, mRNA expression of ferroportin, p21, hypoxia-induced factor (HIF)-1α and IKBα, an NF-κB inhibitor was increased and CDK2 expression decreased. HIV-1 replication was also suppressed in THP-1 cells treated with hemin but subsequent treatment with hepcidin restored HIV-1 replication, suggesting that ferroportin played a key role in the HIV-1 inhibition. Stable ferroportin knock-down in THP-1 cells led to the inability of hemin to inhibit HIV-1, further supporting the idea that that ferroportin plays a key role in this process. In addition, hemin treatment reduced the expression of p65 subunit of NF-kB and induced expression of IKBα. Cells treated with hemin were arrested in G1 phase of cell cycle suggesting that expression of p21 and decreased in CDK2 expression affected the cells cycle. Stable HIF-1α knockdown in THP-1 cells increased HIV replication indicating that HIF-1 might also restrict HIV-1 replication. Taken together, our study shows that induction of HIF-1 and iron export pathways might protect hemin-treated THP-1 cells from HIV-1 infection. Additional molecular mechanisms of heme-mediated HIV-1 inhibition might also include NF-kB inhibition by IKBα, reduction of CDK2 epxression and induction of p21 leading to the inhibition of HIV-1 transcription.

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