title: A flavonoid, luteolin, cripples HIV-1 by abrogation of tat function.
abstract: Despite the effectiveness of combination antiretroviral treatment (cART) against HIV-1, evidence indicates that residual infection persists in different cell types. Intensification of cART does not decrease the residual viral load or immune activation. cART restricts the synthesis of infectious virus but does not curtail HIV-1 transcription and translation from either the integrated or unintegrated viral genomes in infected cells. All treated patients with full viral suppression actually have low-level viremia. More than 60% of treated individuals also develop minor HIV-1 -associated neurocognitive deficits (HAND) due to residual virus and immune activation. Thus, new therapeutic agents are needed to curtail HIV-1 transcription and residual virus. In this study, luteolin, a dietary supplement, profoundly reduced HIV-1 infection in reporter cells and primary lymphocytes. HIV-1inhibition by luteolin was independent of viral entry, as shown by the fact that wild-type and VSV-pseudotyped HIV-1 infections were similarly inhibited. Luteolin was unable to inhibit viral reverse transcription. Luteolin had antiviral activity in a latent HIV-1 reactivation model and effectively ablated both clade-B- and -C -Tat-driven LTR transactivation in reporter assays but had no effect on Tat expression and its sub-cellular localization. We conclude that luteolin confers anti-HIV-1 activity at the Tat functional level. Given its biosafety profile and ability to cross the blood-brain barrier, luteolin may serve as a base flavonoid to develop potent anti-HIV-1 derivatives to complement cART.
authors.affiliation: Department of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, Columbia, South Carolina, United States of America.
authors.forename: Rajeev
authors.initials: R
authors.lastname: Mehla
authors.forename: Shalmali
authors.initials: S
authors.lastname: Bivalkar-Mehla
authors.forename: Ashok
authors.initials: A
authors.lastname: Chauhan
mesh_terms: D004279:DNA, Viral / Q000378:metabolism; D015967:Gene Expression Regulation, Viral / Q000187:drug effects; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D019169:Jurkat Cells; D047311:Luteolin / Q000737:chemistry / Q000494:pharmacology*; D008214:Lymphocytes / Q000187:drug effects / Q000821:virology; D008954:Models, Biological; D048348:Reverse Transcription / Q000187:drug effects; D015533:Transcriptional Activation / Q000187:drug effects; D014775:Virus Activation / Q000187:drug effects; D016662:Virus Integration / Q000187:drug effects; D053586:Virus Internalization / Q000187:drug effects; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000378:metabolism*
chemical_list: D004279:DNA, Viral; D054322:tat Gene Products, Human Immunodeficiency Virus; D047311:Luteolin