Ephedrine enhances HIV-1 reactivation from latency through elevating tumor necrosis factor receptor II (TNFRII) expression

Jutatip Panaampon; Eriko Kudo; Ryusho Kariya; Seiji Okada

doi:10.1016/j.heliyon.2019.e02490

Ephedrine enhances HIV-1 reactivation from latency through elevating tumor necrosis factor receptor II (TNFRII) expression

Heliyon. 2019 Sep 26;5(9):e02490. doi: 10.1016/j.heliyon.2019.e02490. eCollection 2019 Sep.

Authors

Jutatip Panaampon¹, Eriko Kudo¹, Ryusho Kariya¹, Seiji Okada¹

Affiliation

¹ Division of Hematopoiesis, Graduate School of Medical Sciences, and Joint Research Center for Human Retrovirus Infection, Kumamoto University, 2-2-1 Honjo, Chuo-ku, Kumamoto, 860-0811, Japan.

Abstract

HIV-1 persists during antiretroviral therapy (ART) due to long-lived and proliferating latently-infected host cells, with the outcome being an incomplete cure. The latently-infected cells, or reservoir cells, are transcriptionally absent and invisible to the immune response. Elimination of latency is one strategy in activating virus production, making it visible to immune clearance. We previously showed that Ephedrae herba reactivated HIV-1 from latency. In this study, we used ephedrine, a major component of Ephedra herba, to reactivate HIV-1 from latency. The results showed that ephedrine enhances HIV-1 reactivation in the presence of TNFα. Combination treatment demonstrates a synergistic effect of HIV-1 reactivation compared to TNFα alone. Ephedrine treatment shows a higher TNFRII expression level, which is related to increased HIV-1 reactivation. However, the mechanism of ephedrine in HIV-1 reactivation is still unclear, and may be related to TNFRII receptor expression. Our results indicate that ephedrine enhances HIV-1 reactivation from latency in combination with TNFα treatment. This new reagent could be a promising latency reversal agent (LRA).

Keywords: Cell biology; Ephedrine; HIV-1 reactivation; Hematological system; Infectious disease; Microbiology; Molecular biology; Tumor necrosis factor receptor II.