Abstract
At present, there are no antiretroviral drugs that inhibit incorporation of the envelope glycoprotein into newly-synthesized virus particles. The botanical glycoside, oleandrin, derived from extracts of Nerium oleander, has previously been shown to reduce the levels of the gp120 envelope glycoprotein on human immunodeficiency virus type-1 (HIV-1) particles and inhibit HIV-1 infectivity in vitro. We therefore tested whether oleandrin or an extract from N. oleander could also inhibit the infectivity of the human T-cell leukemia virus type-1 (HTLV-1): A related enveloped retrovirus and emerging tropical infectious agent. The treatment of HTLV-1+ lymphoma T-cells with either oleandrin or a N. oleander extract did not significantly inhibit viral replication or the release of p19Gag-containing particles into the culture supernatants. However, the collected virus particles from treated cells exhibited reduced infectivity on primary human peripheral blood mononuclear cells (huPBMCs). Unlike HIV-1, extracellular HTLV-1 particles are poorly infectious and viral transmission typically occurs via direct intercellular interactions across a virological synapse. We therefore investigated whether oleandrin or a N. oleander extract could inhibit virus transmission from a GFP-expressing HTLV-1+ lymphoma T-cell-line to huPBMCs in co-culture assays. These results demonstrated that both oleandrin and the crude phytoextract inhibited the formation of virological synapses and the transmission of HTLV-1 in vitro. Importantly, these findings suggest oleandrin may have broad antiviral activity against enveloped viruses by reducing the incorporation of the envelope glycoprotein into mature particles, a stage of the infection cycle not targeted by modern HAART.
Highlights
The botanical glycoside, oleandrin, and an extract of Nerium oleander have been shown to prevent the incorporation of the gp120 envelope glycoprotein of human immunodeficiency virus type-1 (HIV-1) into mature virus particles and inhibit viral infectivity in vitro [1]
It is an intriguing notion that the ability of oleandrin to cross the BBB and inhibit human T-cell leukemia virus type-1 (HTLV-1) infectivity and the expression of viral antigens could have potential therapeutic implications for the treatment of HTLV-1-associated neuroinflammatory diseases, including HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) [25,26]
Oleandrin is a lipid-soluble, botanical cardiac glycoside comprised of: (1) the steroid aglycone, oleandrigenin, and (2) a sugar moiety (e.g., D-diginosyl) and its chemical structure is shown in Figure 1a [1,4,78]
Summary
The botanical glycoside, oleandrin, and an extract of Nerium oleander have been shown to prevent the incorporation of the gp120 envelope glycoprotein of HIV-1 into mature virus particles and inhibit viral infectivity in vitro [1]. These findings prompted us to investigate whether oleandrin could inhibit another related retrovirus, the HTLV-1. Oleandrin has been shown to accumulate in the central nervous system (CNS) and penetrate the blood-brain-barrier (BBB) following injection [23]; and Garofalo et al [3] have further demonstrated that oleandrin inhibited tumor growth and disease progression in a murine xenograft model of malignant glioma. It is an intriguing notion that the ability of oleandrin to cross the BBB and inhibit HTLV-1 infectivity and the expression of viral antigens could have potential therapeutic implications for the treatment of HTLV-1-associated neuroinflammatory diseases, including HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) [25,26]
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