Curcumin inhibits HIV-1 by promoting Tat protein degradation.
HIV-1 Tat is an intrinsically unfolded protein playing a pivotal role in viral replication by associating with TAR region of viral LTR. Unfolded proteins are degraded by 20S proteasome in an ubiquitin independent manner. Curcumin is known to activate 20S proteasome and promotes the degradation of intrinsically unfolded p53 tumor suppressor protein. Since HIV-1 Tat protein is largerly unfolded, we hypothesized that Tat may also be targeted through this pathway. Curcumin treated Tat transfected HEK-293T cells showed a dose and time dependent degradation of Tat protein. Contrary to this HIV-1 Gag which is a properly folded protein, remained unaffected with curcumin. Semi-quantitative RT-PCR analysis showed that curcumin treatment did not affect Tat gene transcription. Curcumin increased the rate of Tat protein degradation as shown by cycloheximide (CHX) chase assay. Degradation of the Tat protein is accomplished through proteasomal pathway as proteasomal inhibitor MG132 blocked Tat degradation. Curcumin also decreased Tat mediated LTR promoter transactivation and inhibited virus production from HIV-1 infected cells. Taken together our study reveals a novel observation that curcumin causes potent degradation of Tat which may be one of the major mechanisms behind its anti HIV activity.
Laboratory of Virology, National Institute of Immunology, New Delhi, India.
Amjad
A
Ali
Laboratory of Virology, National Institute of Immunology, New Delhi, India.
Akhil C
AC
Banerjea
D003474:Curcumin / Q000008:administration & dosage*; D015967:Gene Expression Regulation, Viral / Q000187:drug effects; D015658:HIV Infections / Q000188:drug therapy* / Q000473:pathology / Q000821:virology; D015497:HIV-1 / Q000187:drug effects* / Q000472:pathogenicity; D006801:Humans; D059748:Proteolysis / Q000187:drug effects; D014162:Transfection; D014779:Virus Replication / Q000187:drug effects; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000737:chemistry / Q000235:genetics*
D054322:tat Gene Products, Human Immunodeficiency Virus; D003474:Curcumin