Differential effects of P-glycoprotein and multidrug resistance protein-1 on productive human immunodeficiency virus infection

R. Renae Speck, James Hildreth, James Hildreth, Charles Flexner

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

P-glycoprotein (P-gp) and multidrug-resistance protein-1 (MRP-1) are adenosine triphosphate-binding cassette proteins that may decrease intracellular concentrations of anti-human immunodeficiency virus (HIV) drugs. After HIV-1IIIB infection, HIV-1 protein and infectious virus production were decreased by at least 70-fold in CEM cells overexpressing P-gp but were increased by at least 50-fold in CEM cells overexpressing MRP-1, compared with control CEM cells. After transfection with the HIV-1IIIB genome, cells overexpressing P-gp and MRP-1 expressed similar amounts of HIV protein. Selective inhibitors of MRP-1 and P-gp partially reversed the effect of these transporters in a concentration-dependent manner. P-gp preferentially associated with glycolipid-enriched membrane (GEM) domains, which may be an important site for cellular binding and egress of HIV. In contrast, MRP-1 was not preferentially found in GEM domains. These results suggest that the inhibition of HIV productive infection by P-gp and augmentation by MRP-1 occur predominantly at a preintegration step but act through different mechanisms.

Original languageEnglish (US)
Pages (from-to)332-340
Number of pages9
JournalJournal of Infectious Diseases
Volume186
Issue number3
DOIs
StatePublished - Aug 1 2002
Externally publishedYes

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P-Glycoprotein
Virus Diseases
HIV
Human Immunodeficiency Virus Proteins
Glycolipids
Membranes
Transfection
HIV-1
Carrier Proteins
Adenosine Triphosphate
Binding Sites
Genome
Viruses

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health
  • Immunology

Cite this

Differential effects of P-glycoprotein and multidrug resistance protein-1 on productive human immunodeficiency virus infection. / Speck, R. Renae; Hildreth, James; Hildreth, James; Flexner, Charles.

In: Journal of Infectious Diseases, Vol. 186, No. 3, 01.08.2002, p. 332-340.

Research output: Contribution to journalArticle

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