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Differential gene expression in HIV-infected individuals following ART

Differential gene expression in HIV-infected individuals following ART
Differential gene expression in HIV-infected individuals following ART
Previous studies of the effect of ART on gene expression in HIV-infected individuals have identified small numbers of modulated genes. Since these studies were underpowered or cross-sectional in design, a paired analysis of peripheral blood mononuclear cells (PBMCs), isolated before and after ART, from a robust number of HIV-infected patients (N = 32) was performed. Gene expression was assayed by microarray and 4157 differentially expressed genes (DEGs) were identified following ART using multivariate permutation tests. Pathways and gene ontology (GO) terms over-represented for DEGs reflected the transition from a period of active virus replication before ART to one of viral suppression (e.g., repression of JAK-STAT signaling) and possible prolonged drug exposure (e.g., oxidative phosphorylation pathway) following ART. CMYC was the DEG whose product made the greatest number of interactions at the protein level in protein interaction networks (PINs), which has implications for the increased incidence of Hodgkin’s lymphoma (HL) in HIV-infected patients. The differential expression of multiple genes was confirmed by RT-qPCR including well-known drug metabolism genes (e.g., ALOX12 and CYP2S1). Targets not confirmed by RT-qPCR (i.e., GSTM2 and RPL5) were significantly confirmed by droplet digital (ddPCR), which may represent a superior method when confirming DEGs with low fold changes. In conclusion, a paired design revealed that the number of genes modulated following ART was an order of magnitude higher than previously recognized.
antiretroviral therapy, droplet digital PCR, gene expression, HIV, microarray, paired analysis
0166-3542
420-428
Massanella, M.
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Singhania, A.
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Beliakova-Bethell, N.
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Pier, R.
eac4303d-f73a-4daf-9a14-cff10adda9a7
Lada, S.
761120a8-eb82-4317-af63-ba82b91e6476
White, C.H.
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Perez-Santiago, J.
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Blanco, J.
e0bb79a1-35dd-46b0-888d-572157c73c28
Richman, D.D.
1d5f38e4-c778-4b0b-b542-9d1160e63041
Little, S.J.
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Woelk, C.H.
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Massanella, M.
eeb62381-5782-4bd5-9b99-fdeac4337bcc
Singhania, A.
9a5f2c6b-fc46-4223-bcae-de70bf14da6b
Beliakova-Bethell, N.
5919f4d5-b2a8-4d9a-a3be-d0a78d8485b1
Pier, R.
eac4303d-f73a-4daf-9a14-cff10adda9a7
Lada, S.
761120a8-eb82-4317-af63-ba82b91e6476
White, C.H.
45233a78-f0c9-4696-8aaf-1b2673f83c91
Perez-Santiago, J.
f949a54e-37d9-4bb2-8998-93cbad4a80f7
Blanco, J.
e0bb79a1-35dd-46b0-888d-572157c73c28
Richman, D.D.
1d5f38e4-c778-4b0b-b542-9d1160e63041
Little, S.J.
97d16cb1-b00a-40f8-9746-2300b5f7174d
Woelk, C.H.
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Massanella, M., Singhania, A., Beliakova-Bethell, N., Pier, R., Lada, S., White, C.H., Perez-Santiago, J., Blanco, J., Richman, D.D., Little, S.J. and Woelk, C.H. (2013) Differential gene expression in HIV-infected individuals following ART. Antiviral Research, 100 (2), 420-428. (doi:10.1016/j.antiviral.2013.07.017).

Record type: Article

Abstract

Previous studies of the effect of ART on gene expression in HIV-infected individuals have identified small numbers of modulated genes. Since these studies were underpowered or cross-sectional in design, a paired analysis of peripheral blood mononuclear cells (PBMCs), isolated before and after ART, from a robust number of HIV-infected patients (N = 32) was performed. Gene expression was assayed by microarray and 4157 differentially expressed genes (DEGs) were identified following ART using multivariate permutation tests. Pathways and gene ontology (GO) terms over-represented for DEGs reflected the transition from a period of active virus replication before ART to one of viral suppression (e.g., repression of JAK-STAT signaling) and possible prolonged drug exposure (e.g., oxidative phosphorylation pathway) following ART. CMYC was the DEG whose product made the greatest number of interactions at the protein level in protein interaction networks (PINs), which has implications for the increased incidence of Hodgkin’s lymphoma (HL) in HIV-infected patients. The differential expression of multiple genes was confirmed by RT-qPCR including well-known drug metabolism genes (e.g., ALOX12 and CYP2S1). Targets not confirmed by RT-qPCR (i.e., GSTM2 and RPL5) were significantly confirmed by droplet digital (ddPCR), which may represent a superior method when confirming DEGs with low fold changes. In conclusion, a paired design revealed that the number of genes modulated following ART was an order of magnitude higher than previously recognized.

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More information

Accepted/In Press date: 25 July 2013
e-pub ahead of print date: 6 August 2013
Published date: 2013
Keywords: antiretroviral therapy, droplet digital PCR, gene expression, HIV, microarray, paired analysis
Organisations: Human Development & Health, Clinical & Experimental Sciences

Identifiers

Local EPrints ID: 379196
URI: http://eprints.soton.ac.uk/id/eprint/379196
ISSN: 0166-3542
PURE UUID: c3c2b993-6243-40e5-8fdd-359fce88f4d3

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Date deposited: 18 Jul 2015 13:59
Last modified: 22 Jul 2022 19:28

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Contributors

Author: M. Massanella
Author: A. Singhania
Author: N. Beliakova-Bethell
Author: R. Pier
Author: S. Lada
Author: C.H. White
Author: J. Perez-Santiago
Author: J. Blanco
Author: D.D. Richman
Author: S.J. Little
Author: C.H. Woelk

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