An immunomodulatory drug called fingerolimod, which is approved for the treatment of multiple sclerosis, blocks human immunodeficiency virus (HIV) infection and transmission in human immune cells, according to a study published August 13 in the open-access journal PLOS Pathogens by Postdoctoral Fellow Rachel Resop and assistant professor Alberto Bosque of George Washington University, and colleagues. These preliminary findings suggest that this compound may be a promising new therapy for HIV treatment and prevention. Credit: NIAID
An immunomodulatory drug called fingerolimod, which is approved for the treatment of multiple sclerosis, blocks human immunodeficiency virus (HIV) infection and transmission in human immune cells, according to a study published today (August 13, 2020) in the Open Access Journal PLOS Pathogens by postdoctoral fellow Rachel Resop and assistant professor Alberto Bosque of George Washington University, and colleagues. Although future studies in animals and humans are necessary, these preliminary findings suggest that this compound may be a promising new therapy for HIV treatment and prevention.
Nearly 40 million people worldwide currently live with HIV. Treatment of infection is lifelong, due to the ability of the virus to establish latency by integrating the genome into that of host cells, resulting in potential viral reactivation at a future time. By establishing latency, HIV escapes destruction through host defense mechanisms and drug treatment. HIV is currently managed by antiretroviral drugs, which do not specifically target latent infection, may have side effects, and are of limited use in preventing the transmission of the virus between individuals. For this reason, the discovery of new strategies to target HIV infection and latency is crucial.
Bosque and colleagues investigated an alternative tactic to fight HIV infection by targeting Sphingosine-1-phosphate (S1P) receptors – a part of the immune system involved in the progression of infection. To do this, she focused on FTY720 (fingolimod) – a well-tolerated drug that blocks the action of S1P receptors and is approved by the U.S. Food and Drug Administration. They found that FTY720 blocks HIV infection in human immune cells called CD4 + T cells by inhibiting multiple steps in the HIV life cycle. For example, FTY720 decreases the density of CD4 – a protein found on the surface of T cells – thereby inhibiting viral binding and fusion. The drug blocked HIV transmission between the cells, thereby reducing detectable latent virus. According to the authors, the role of S1P signaling was in the establishment of HIV infection, and the potential to modulate this pathway to alter the course of infection or prevent the establishment of the latent reservoir in CD4 + T cells, not previously reported. As such, aligning the S1P pathway with FTY720 may be a new strategy to inhibit HIV replication and reduce latent reservoir.
The authors note, “These results indicate that Fingolimod deserves further research as an exciting new therapy for HIV.”
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Reference: “Fingolimod inhibits multiple stages of HIV-1 life cycle” by Resop RS, Fromentin R, Newman D, Rigsby H, Dubrovsky L, Bukrinsky M, et al., August 13, 2020, PLOS Pathogens.
DOI: 10.1371 / journal.ppat.1008679
Funding: Research reported in this publication was supported in part by the NIAID (https: //
