Factors impacting the expression of membrane-bound proteins in lymphocytes from HIV-positive subjects.
BACKGROUND
The cellular transport proteins ABCB1, ABCC1 and ABCG2 have been implicated in the efflux of some antiretroviral drugs, thus decreasing their intracellular concentrations. Decreased drug accumulation in lymphocytes may allow viral replication and the subsequent emergence of viral resistance leading to treatment failure. Expression of HIV co-receptors on the surface of lymphocytes may influence viral tropism and therefore viral pathogenicity and disease progression. Here, we describe the relationship between expression of transport proteins and chemokine receptors in lymphocytes isolated from HIV-infected individuals and also investigate their relationship with demographic, therapeutic and virological factors.


METHODS
Peripheral blood mononuclear cells (PBMC) isolated from HIV-positive individuals were co-stained for expression of CD4 and ABCB1, ABCC1, ABCG2, CXCR4 and CCR5. The influence of gender, ethnicity, treatment status, viral load and CD4 count was assessed on expression of each protein as well as correlations between expression of the proteins by univariate and multivariate analyses.


RESULTS
Expression of ABCB1 was independently associated with gender (n = 98) and expression of ABCG2 and CXCR4. Gender also correlated with expression of ABCC1 and CXCR4 in univariate analysis with lower expression being detected in females compared with males.


CONCLUSIONS
Here we confirm that the previously reported correlation between ABCB1 and CXCR4 observed in PBMC isolated from healthy volunteers is also found in HIV-positive individuals. The influence of gender on the expression of drug efflux proteins could be a determinant of intracellular drug concentrations in vivo.
Chandler
Becky
B
Department of Pharmacology and Therapeutics, University of Liverpool, Liverpool L69 3GF, UK. rjchand@liv.ac.uk
Detsika
Maria
M
Khoo
Saye H
SH
Williams
Jill
J
Back
David J
DJ
Owen
Andrew
A
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D000328:Adult; D000704:Analysis of Variance; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D005260:Female; D006679:HIV Seropositivity / Q000378:metabolism*; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism*; D008297:Male; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism; D019713:Receptors, CCR5 / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000378:metabolism; D012727:Sex Characteristics; D019562:Viral Load; D014763:Viral Matrix Proteins / Q000378:metabolism*
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009363:Neoplasm Proteins; D019713:Receptors, CCR5; D019718:Receptors, CXCR4; D014763:Viral Matrix Proteins; C513055:ABCB1 protein, human; C116614:ABCG2 protein, human; C421109:multidrug resistance-associated protein 1