Transcriptome analysis of monocyte-HIV interactions.
BACKGROUND
During HIV infection and/or antiretroviral therapy (ART), monocytes and macrophages exhibit a wide range of dysfunctions which contribute significantly to HIV pathogenesis and therapy-associated complications. Nevertheless, the molecular components which contribute to these dysfunctions remain elusive. We therefore applied a parallel approach of genome-wide microarray analysis and focused gene expression profiling on monocytes from patients in different stages of HIV infection and/or ART to further characterise these dysfunctions.


RESULTS
Processes involved in apoptosis, cell cycle, lipid metabolism, proteasome function, protein trafficking and transcriptional regulation were identified as areas of monocyte dysfunction during HIV infection. Individual genes potentially contributing to these monocyte dysfunctions included several novel factors. One of these is the adipocytokine NAMPT/visfatin, which we show to be capable of inhibiting HIV at an early step in its life cycle. Roughly half of all genes identified were restored to control levels under ART, while the others represented a persistent dysregulation. Additionally, several candidate biomarkers (in particular CCL1 and CYP2C19) for the development of the abacavir hypersensitivity reaction were suggested.


CONCLUSIONS
Previously described areas of monocyte dysfunction during HIV infection were confirmed, and novel themes were identified. Furthermore, individual genes associated with these dysfunctions and with ART-associated disorders were pinpointed. These genes form a useful basis for further functional studies concerning the contribution of monocytes/macrophages to HIV pathogenesis. One such gene, NAMPT/visfatin, represents a possible novel restriction factor for HIV.
Van den Bergh
Rafael
R
Department of Molecular and Cellular Interactions, VIB, Brussels, Belgium. rvdbergh@vub.ac.be
Florence
Eric
E
Vlieghe
Erika
E
Boonefaes
Tom
T
Grooten
Johan
J
Houthuys
Erica
E
Tran
Huyen Thi Thanh
HT
Gali
Youssef
Y
De Baetselier
Patrick
P
Vanham
Guido
G
Raes
Geert
G
D019380:Anti-HIV Agents / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active; D020869:Gene Expression Profiling; D015658:HIV Infections / Q000188:drug therapy / Q000473:pathology* / Q000821:virology*; D015497:HIV-1 / Q000472:pathogenicity*; D054884:Host-Pathogen Interactions; D006801:Humans; D009000:Monocytes / Q000821:virology*; D020411:Oligonucleotide Array Sequence Analysis
D019380:Anti-HIV Agents