TY - JOUR
T1 - Comparative transcriptome analysis of PBMC from HIV patients pre- and post-antiretroviral therapy
AU - Zhao, Fang-Jie
AU - Ma, Jinmin
AU - Huang, Lihua
AU - Deng, Yong
AU - Li, Liqiang
AU - Zhou, Yang
AU - Li, Jiandong
AU - Li, Shaxi
AU - Jiang, Hui
AU - Yang, Huanming
AU - Gao, Shan
AU - Wang, Hui
AU - Liu, Yingxia
PY - 2017/6
Y1 - 2017/6
N2 - Infections of the human immunodeficiency virus (HIV) trigger host immune responses, but the virus can destroy the immune system and cause acquired immune deficiency syndrome (AIDS). Highly active antiretroviral therapy (HAART) can suppress viral replication and restore the impaired immune function. To understand HIV interactions with host immune cells during HAART, the transcriptomes of peripheral blood mononuclear cells (PBMC) from HIV patients and HIV negative volunteers before and two weeks after HAART initiation were analyzed using RNA sequencing (RNA-Seq) technology. Differentially expressed genes (DEGs) in response to HAART were firstly identified for each individual, then common features were extracted by comparing DEGs among individuals and finally HIV-related DEGs were obtained by comparing DEGs between the HIV patients and HIV negative volunteers. To demonstrate the power of this approach, minimum numbers of patients (one HIV alone; one HIV + tuberculosis, TB; one HIV + TB with immune reconstitution inflammatory syndrome during HAART) and two HIV negative volunteers were used. More than 15,000 gene transcripts were detected in each individual sample. Fourteen HAART up-regulated and eleven down-regulated DEGs were specifically identified in the HIV patients. Among them, nine up-regulated (CXCL1, S100P, AQP9, BASP1, MMP9, SOD2, LIMK2, IL1R2 and BCL2A1) and nine down-regulated DEGs (CD160, CD244, CX3CR1, IFIT1, IFI27, IFI44, IFI44L, MX1 and SIGLEC1) have already been reported as relevant to HIV infections in the literature, which demonstrates the credibility of the method. The newly identified HIV-related genes (up-regulated: ACSL1, GPR84, GPR97, ADM, LRG1; down-regulated: RASSF1, PATL2) were empirically validated using qRT-PCR. The Gene Set Enrichment Analysis (GSEA) was also used to determine pathways significantly affected by HAART. GSEA further confirmed the HAART relevance of five genes (ADM, AQP9, BASP1, IL1R2 and MMP9). The newly identified HIV-related genes, ADM (which encodes Adrenomedullin), a peptide hormone in circulation control, may contribute to HIV-associated hypertensions, providing new insights into HIV pathology and novel strategies for developing anti-HIV target. More importantly, we demonstrated that comparative transcriptome analysis is a very powerful tool to identify infection related DEGs using a very small number of samples. This approach could be easily applied to improve the understanding of pathogen-host interactions in many infections and anti-infection treatments.
AB - Infections of the human immunodeficiency virus (HIV) trigger host immune responses, but the virus can destroy the immune system and cause acquired immune deficiency syndrome (AIDS). Highly active antiretroviral therapy (HAART) can suppress viral replication and restore the impaired immune function. To understand HIV interactions with host immune cells during HAART, the transcriptomes of peripheral blood mononuclear cells (PBMC) from HIV patients and HIV negative volunteers before and two weeks after HAART initiation were analyzed using RNA sequencing (RNA-Seq) technology. Differentially expressed genes (DEGs) in response to HAART were firstly identified for each individual, then common features were extracted by comparing DEGs among individuals and finally HIV-related DEGs were obtained by comparing DEGs between the HIV patients and HIV negative volunteers. To demonstrate the power of this approach, minimum numbers of patients (one HIV alone; one HIV + tuberculosis, TB; one HIV + TB with immune reconstitution inflammatory syndrome during HAART) and two HIV negative volunteers were used. More than 15,000 gene transcripts were detected in each individual sample. Fourteen HAART up-regulated and eleven down-regulated DEGs were specifically identified in the HIV patients. Among them, nine up-regulated (CXCL1, S100P, AQP9, BASP1, MMP9, SOD2, LIMK2, IL1R2 and BCL2A1) and nine down-regulated DEGs (CD160, CD244, CX3CR1, IFIT1, IFI27, IFI44, IFI44L, MX1 and SIGLEC1) have already been reported as relevant to HIV infections in the literature, which demonstrates the credibility of the method. The newly identified HIV-related genes (up-regulated: ACSL1, GPR84, GPR97, ADM, LRG1; down-regulated: RASSF1, PATL2) were empirically validated using qRT-PCR. The Gene Set Enrichment Analysis (GSEA) was also used to determine pathways significantly affected by HAART. GSEA further confirmed the HAART relevance of five genes (ADM, AQP9, BASP1, IL1R2 and MMP9). The newly identified HIV-related genes, ADM (which encodes Adrenomedullin), a peptide hormone in circulation control, may contribute to HIV-associated hypertensions, providing new insights into HIV pathology and novel strategies for developing anti-HIV target. More importantly, we demonstrated that comparative transcriptome analysis is a very powerful tool to identify infection related DEGs using a very small number of samples. This approach could be easily applied to improve the understanding of pathogen-host interactions in many infections and anti-infection treatments.
KW - HAART
KW - HIV
KW - PBMC
KW - RNA-Seq
KW - Transcriptome
UR - http://www.scopus.com/inward/record.url?scp=85010427046&partnerID=8YFLogxK
U2 - 10.1016/j.mgene.2017.01.004
DO - 10.1016/j.mgene.2017.01.004
M3 - Journal article
AN - SCOPUS:85010427046
SN - 2214-5400
VL - 12
SP - 50
EP - 61
JO - Meta Gene
JF - Meta Gene
ER -
