Differential regulation of cytotoxicity pathway discriminating between HIV, HCV mono- and co-infection identified by transcriptome profiling of PBMCs

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• 作者：Jing Qin Wu ; Monica Miranda Saksena ; Vincent Soriano ; Eugenia Vispo…
• 关键词：HIV ; HCV ; HIV/HCV co ; infection ; Transcriptome ; Cytotoxicity pathway
• 刊名：Virology Journal
• 出版年：2015
• 出版时间：December 2015
• 年：2015
• 卷：12
• 期：1
• 全文大小：3,767 KB
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• 作者单位：Jing Qin Wu (1)
  Monica Miranda Saksena (2)
  Vincent Soriano (3)
  Eugenia Vispo (3)
  Nitin K Saksena (4)
  
  1. School of Biomedical Sciences and Pharmacy, Faculty of Health, The University of Newcastle, University Drive, Callaghan, Newcastle, NSW, 2308, Australia
  2. Herpes Virus Pathogenesis Lab, Center for Virus Research, Westmead Millennium Institute, University of Sydney, Westmead, Sydney, NSW, 2145, Australia
  3. Department of Infectious Diseases, Hospital Carlos III, Sinesio Delgado 10, 28029, Madrid, Spain
  4. Retroviral Genetics Division, Center for Virus Research, Westmead Millennium Institute & Westmead Hospital, University of Sydney, Westmead, Sydney, NSW, 2145, Australia
  
• 刊物主题：Virology;
• 出版者：BioMed Central
• ISSN：1743-422X

文摘

Background Despite the easy accessibility and diagnostic utility of PBMCs and their potential to show distinct expression patterns associated with the accelerated disease progression in HIV/HCV co-infection, there has not been a systematic study focusing on the global dysregulations of the biological pathways in PBMCs from HIV, HCV mono- and co-infected individuals. This study aimed at identifying the transcriptome distinctions of PBMCs between these patient groups. Methods Genome-wide transcriptomes of PBMCs from 10 HIV/HCV co-infected patients, 7 HIV+ patients, 5 HCV+ patients, and 5 HIV/HCV sero-negative healthy controls were analyzed using Illumina microarray. Pairwise comparisons were performed to identify differentially expressed genes (DEGs), followed by gene set enrichment analysis (GSEA) to detect the global dysregulations of the biological pathways between HIV, HCV mono- and co-infection. Results Forty-one, 262, and 44 DEGs with fold change--.5 and FDR (false discovery rate) Conclusions Our study is the first to identify the differential regulation of cytotoxicity pathway discriminating between HIV, HCV mono- and co-infection, which may reflect the distinct patterns of virus-host cell interactions underlying disease progression. Further inspection of cytotoxicity pathway has pinned down to the expression of the KIR genes to be associated with specific patterns of particular virus-host interactions. Between HIV and HCV, the altered cell cycle and WNT signaling pathways may suggest the different impact of HIV and HCV on cell proliferation and differentiation.