Expression levels of MDR1, MRP1, MRP4, and MRP5 in peripheral blood mononuclear cells from HIV infected patients failing antiretroviral therapy.
The aim of the study was to evaluate the mRNA expression of four relevant ABC-transporter genes [MDR1 (P-glycoprotein; Pgp), MRP1, MRP4, and MRP5] in HIV-positive individuals failing treatment and analyze the association between the levels of their expression and viral load, CD4 cell count, and therapeutic history. Ninety-eight HIV-positive samples and 20 samples from healthy donors were analyzed, retrospectively. Peripheral blood mononuclear cells (PBMCs) from HIV1-positive individuals were collected at the time of virological failure. Expression of mRNA of Pgp, MRP1, MRP4, and MRP5 in PBMCs was evaluated by real-time PCR. A high inter-individual variability was observed in both HIV-positive individuals and healthy donors but the expression levels of all mRNA analyzed were significantly higher in the HIV-infected group (P < 0.05). A weak but significant inverse correlation was observed between CD4 cell counts and expression levels of MRP4 and MRP5. Comparison of mRNA expression between individuals with different therapeutic histories showed that expression of MRP4 and MRP5 genes in patients who were both protease inhibitor (PI) and non-nucleoside reverse transcriptase inhibitor (NNRTI)-experienced was significantly higher than in patients who were PI experienced but NNRTI-naïve. In conclusion, the mRNA expression of Pgp, MRP1, MRP4, and MRP5 varies among HIV-infected patients and healthy donors but is significantly higher in HIV-positive patients than in donors. The expression of MRP4 and MRP5 seems to correlate with CD4 cell counts. The same protein seems to be overexpressed in patients receiving NNRTIs.
Turriziani
Ombretta
O
Department of Experimental Medicine, Virology Section, Sapienza, University of Rome, Rome, Italy. ombretta.turriziani@uniroma1.it
Gianotti
Nicola
N
Falasca
Francesca
F
Boni
Arianna
A
Vestri
Anna Rita
AR
Zoccoli
Alice
A
Lazzarin
Adriano
A
Antonelli
Guido
G
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis*; D018791:CD4 Lymphocyte Count; D015870:Gene Expression; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects*; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000096:biosynthesis; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019562:Viral Load
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D012333:RNA, Messenger; C513055:ABCB1 protein, human; C073492:ABCC4 protein, human; C120809:ABCC5 protein, human; C421109:multidrug resistance-associated protein 1