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Abstract
Divalent cations are essential for life and are fundamentally important coordinators of cellular metabolism, cell growth, host-pathogen interactions, and cell death. Specifically, for human immunodeficiency virus type-1 (HIV-1), divalent cations are required for interactions between viral and host factors that govern HIV-1 replication and pathogenicity. Homeostatic regulation of divalent cations’ levels and actions appear to change as HIV-1 infection progresses and as changes occur between HIV-1 and the host. In people living with HIV-1, dietary supplementation with divalent cations may increase HIV-1 replication, whereas cation chelation may suppress HIV-1 replication and decrease disease progression. Here, we review literature on the roles of zinc (Zn2+), iron (Fe2+), manganese (Mn2+), magnesium (Mg2+), selenium (Se2+), and copper (Cu2+) in HIV-1 replication and pathogenicity, as well as evidence that divalent cation levels and actions may be targeted therapeutically in people living with HIV-1.
Highlights
Divalent cations help regulate vital cellular functions and accumulation of divalent cations has been implicated in healthy aging as well as the pathogenesis of various neurodegenerative diseases and cancer [1,2,3,4]
human immunodeficiency virus type-1 (HIV-1) Tat is a virotoxin that is actively secreted from infected cells [53,54,55] and it continues to be implicated in the pathogenesis of HIV-1-associated neurocognitive disorders (HAND) [56,57,58,59]
HIV-1 transcription starts with RNA polymerase II (RNA II) binding to the long terminal repeat (LTR) promoter along with other transcription factors [78,79,80]
Summary
Divalent cations help regulate vital cellular functions and accumulation of divalent cations has been implicated in healthy aging as well as the pathogenesis of various neurodegenerative diseases and cancer [1,2,3,4] Underlying such physiological regulatory events and pathological conditions are divalent cation-dependent metalloproteins and metalloenzymes [5,6,7,8,9]. As above, homeostatic regulation of divalent cation levels is important, because they can affect microbial infection [34,35] This is certainly true for human immunodeficiency virus type-1 (HIV-1), because levels of divalent cations change during HIV-1 infection. It is important to focus additional attention on the involvement of divalent cations in HIV-1 replication and infection
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