Transcriptome analysis of primary monocytes from HIV-positive patients with differential responses to antiretroviral therapy

Virology Journal

Nitin K Saksena¹  Monica Miranda Saksena²  Tara Ruth Sassé¹  Jing Qin Wu³ 

[1] Retroviral Genetics Division, Center for Virus Research, Westmead Millennium Institute & Westmead Hospital, University of Sydney, Westmead, Sydney, NSW, 2145, Australia;Herpes Virus Pathogenesis Lab, Center for Virus Research, Westmead Millennium Institute, University of Sydney, Westmead, Sydney, NSW, 2145, Australia;School of Biomedical Sciences and Pharmacy, Faculty of Health, The University of Newcastle, University Drive, Callaghan, Newcastle, NSW, 2308, Australia

关键词: Antigen presentation;    Virological failure;    HAART;    Transcriptome;    Monocyte;    HIV;   

Others  :  819922
DOI  :  10.1186/1743-422X-10-361

 received in 2013-10-25, accepted in 2013-12-18,  发布年份 2013

【 摘 要 】

Background

Despite the significant contributions of monocytes to HIV persistence, the HIV-monocyte interaction remains elusive. For patients on antiretroviral therapy, previous studies observed a virological suppression rate of >70% and suggested complete viral suppression as the primary goal. Although some studies have reported genetic dysregulations associated with HIV disease progression, research on ex vivo-derived monocytic transcriptomes from HIV+ patients with differential responses to therapy is limited. This study investigated the monocytic transcriptome distinctions between patients with sustained virus suppression and those with virological failure during highly active antiretroviral therapy (HAART).

Methods

Genome-wide transcriptomes of primary monocytes from five HIV+ patients on HAART who sustainably controlled HIV to below detection level (BDL), five HIV+ patients on HAART who consecutively experienced viremia, and four healthy HIV sero-negative controls were analyzed using Illumina microarray. Pairwise comparisons were performed to identify differentially expressed genes followed by quantitative PCR validation. Gene set enrichment analysis was used to check the consistency of our dataset with previous studies, as well as to detect the global dysregulations of the biological pathways in monocytes between viremic patients and BDLs.

Results

Pairwise comparisons including viremic patients versus controls, BDL versus controls, and viremic patients versus BDLs identified 473, 76, and 59 differentially expressed genes (fold change > 2 and FDR < 0.05), respectively. The reliability of our dataset was confirmed by gene set enrichment analysis showing that 6 out of 10 published gene lists were significantly enriched (FDR < 0.01) in at least one of the three pairwise comparisons. In the comparison of viremic patients versus BDLs, gene set enrichment analysis revealed that the pathways characterizing the primary functions of monocytes including antigen processing and presentation, FcγR mediated phagocytosis, and chemokine signaling were significantly up-regulated in viremic patients.

Conclusions

This study revealed the first transcriptome distinctions in monocytes between viremic patients and BDLs on HAART. Our results reflected the outcome balanced between the subversion of the monocyte transcriptome by HIV and the compensatory effect adapted by host cells. The up-regulation of antigen presentation pathway in viremic patients particularly highlighted the role of the interface between innate and adaptive immunity in HIV disease progression.

【 授权许可】

   
2013 Wu et al.; licensee BioMed Central Ltd.

【 图 表 】

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