Role of Divalent Cations in HIV-1 Replication and Pathogenicity

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.

Inhibitory effect and mechanism of gelatin stabilized ferrous sulfide nanoparticles on porcine reproductive and respiratory syndrome virus

“…Our results indicated that Gel-FeS NPs could not only directly inactivate PRRSV in vitro, but also effectively inhibit PRRSV proliferation in the stages of adsorption and invasion, blocking the virus outside cells or from entering host cells, thus playing an important role in infection inhibition. As a highly biocompatible material, gelatin has been used in the research of drug delivery, wound adjuvant, vaccine adjuvant, and so on [ 49 – 52 ]. The targeting and antiviral effects of the gelatin-modified nanoparticles prepared here can be further improved by coating antiviral drugs or modified functional molecules on their surface in the future studies.…”

Understanding the relationship between viral infections and trace elements from a metallomics perspective: implications for COVID-19

“… 78 When the transferrin binding capacity is exceeded, iron can also be chelated with less affinity for a series of molecules in the plasma, including albumin, citrate, and amino acids. 15 , 77 Some studies have suggested iron chelators (deferoxamine, deferiprone and deferasirox) as an alternative to mitigate viral infections, such as SARS-CoV-2, through multiple mechanisms, including: (i) inhibition of viral replication; (ii) decrease of Fe availability; (iii) upregulation of B cells; (iv) prevention of pulmonary fibrosis and pulmonary decline by reducing the accumulation of pulmonary Fe; (v) improvement of the neutralizing antiviral antibody. 78 Some studies indicate Fe chelators as a potential adjuvant therapy to prevent viral replication, and great care must be taken because iron deficiency can affect other systems, such as the central nervous, gastrointestinal and muscular systems, causing several other diseases, such as anemia and cancer.…”

“… 83 In older people, Cu deficiency is more frequent, being a result of malnutrition, malabsorption, or excessive zinc intake, and can be acquired or inherited. 83 Therefore, Cu supplementation can help fight viral infection, 15 , 77 , 79 , 80 , 82 especially in older people where marginal or severe deficiency of Cu is a strong possibility. 81 , 83 However, at the moment, there is not enough data or knowledge concerning the effect of therapeutic supplementation of Cu regarding the susceptibility and outcome of COVID-19.…”

“…Metal ions participate in the maturation of the genome (RNA or DNA), activation, and catalytic mechanisms, in reverse transcription, initial integration processes, and the protection of newly synthesized DNA. 15 In addition, the host's immune system depends on the presence of these micronutrients to maintain the integrity of its functions. 16 In this sense, the metallome of a biological system is an important object of study for understanding the effect of metals on viral infections.…”

HIV‐1 Tat endocytosis and retention in endolysosomes affects HIV‐1 Tat‐induced LTR transactivation in astrocytes

“…Several strategies exist to combat HIV-1 latency to prevent disease progression and the development of HIV-associated complications; these strategies include gene editing to disrupt the HIV genome, "shock and kill" to reactivate latent HIV-1, and blocking viral reactivation to maintain HIV-1 in a state of prolonged silencing. 22,23 Because HIV-1 trans-activator of transcription (Tat) protein is essential for viral transcription, [24][25][26][27] plays a role in HIV-1 latency, and is involved in the development of HIV-associated systemic and neurological complications, it may represent an attractive therapeutic target for the eradication of HIV-1 and combating HIV-associated complications. [28][29][30] Plus, current anti-HIV strategies do not block the secretion of HIV-1 Tat in PLWH.…”