HIV-1 Tat Protein Enhances Expression and Function of Breast Cancer Resistance Protein

AIDS Res Hum Retroviruses. 2016 Jan;32(1):1-3. doi: 10.1089/aid.2015.0117. Epub 2015 Sep 14.

Abstract

ATP binding cassette (ABC) transporters can transfer a variety of antiviral agents from the cytoplasm to body fluid, which results in a reduced intracellular concentration of the drugs. Proteins of HIV-1, e.g., Tat and gp120, altered some types of ABC transporter expression in brain microvascular endothelial cells and astrocytes. However, the effect of Tat on ABC transporters in T lymphocytes is unclear. In this study the status of breast cancer resistance protein (BCRP) in Tat expressing cell lines was examined with real-time PCR and flow cytometry. It was found that HIV-1 Tat protein upregulated BCRP expression and enhanced efflux mediated by BCRP significantly, which could inhibit antiviral drugs from entering infected cells and interfere with the therapeutic effect of HAART.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily G, Member 2 / agonists*
  • ATP Binding Cassette Transporter, Subfamily G, Member 2 / antagonists & inhibitors
  • ATP Binding Cassette Transporter, Subfamily G, Member 2 / genetics*
  • ATP Binding Cassette Transporter, Subfamily G, Member 2 / metabolism
  • Antibiotics, Antineoplastic / pharmacology
  • Benzimidazoles / metabolism
  • Biological Transport / drug effects
  • Biological Transport / genetics
  • Cell Survival / drug effects
  • Diketopiperazines / pharmacology
  • Doxorubicin / pharmacology
  • Flow Cytometry
  • Gene Expression
  • HIV-1 / chemistry
  • HIV-1 / genetics
  • Heterocyclic Compounds, 4 or More Rings / pharmacology
  • Humans
  • Inhibitory Concentration 50
  • Jurkat Cells
  • Neoplasm Proteins / agonists*
  • Neoplasm Proteins / antagonists & inhibitors
  • Neoplasm Proteins / genetics*
  • Neoplasm Proteins / metabolism
  • Real-Time Polymerase Chain Reaction
  • Transgenes
  • tat Gene Products, Human Immunodeficiency Virus / genetics*
  • tat Gene Products, Human Immunodeficiency Virus / metabolism

Substances

  • 3-(6-isobutyl-9-methoxy-1,4-dioxo-1,2,3,4,6,7,12,12a-octahydropyrazino(1',2'-1,6)pyrido(3,4-b)indol-3-yl)propionic acid tert-butyl ester
  • ABCG2 protein, human
  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • Antibiotics, Antineoplastic
  • Benzimidazoles
  • Diketopiperazines
  • Heterocyclic Compounds, 4 or More Rings
  • Neoplasm Proteins
  • tat Gene Products, Human Immunodeficiency Virus
  • Doxorubicin
  • bisbenzimide ethoxide trihydrochloride