TY - JOUR
T1 - Differential expression and interaction of host factors augment HIV-1 gene expression in neonatal mononuclear cells
AU - Sundaravaradan, Vasudha
AU - Mehta, Roshni
AU - Harris, David T.
AU - Zack, Jerome A.
AU - Ahmad, Nafees
N1 - Funding Information:
This work was supported by a grant to NA by Arizona Biomedical Research Commission ( 7002 ). We thank the Arizona Research Laboratories (ARL) for assistance with Microarray assays, cord and adult blood donors, the phlebotomy group at University Medical Center, Tucson, AZ, the Krieg Lab for help with EMSA standardization and Lonnie Lybarger's lab for assistance with shRNA strategy and standardization.
PY - 2010/4/25
Y1 - 2010/4/25
N2 - We have previously shown a higher level of HIV-1 replication and gene expression in neonatal (cord) blood mononuclear cells (CBMC) compared with adult blood cells (PBMC), which could be due to differential expression of host factors. We performed the gene expression profile of CBMC and PBMC and found that 8013 genes were expressed at higher levels in CBMC than PBMC and 8028 genes in PBMC than CBMC, including 1181 and 1414 genes upregulated after HIV-1 infection in CBMC and PBMC, respectively. Several transcription factors (NF-κB, E2F, HAT-1, TFIIE, Cdk9, Cyclin T1), signal transducers (STAT3, STAT5A) and cytokines (IL-1β, IL-6, IL-10) were upregulated in CBMC than PBMC, which are known to influence HIV-1 replication. In addition, a repressor of HIV-1 transcription, YY1, was down regulated in CBMC than PBMC and several matrix metalloproteinase (MMP-7, -12, -14) were significantly upregulated in HIV-1 infected CBMC than PBMC. Furthermore, we show that CBMC nuclear extracts interacted with a higher extent to HIV-1 LTR cis-acting sequences, including NF-κB, NFAT, AP1 and NF-IL6 compared with PBMC nuclear extracts and retroviral based short hairpin RNA (shRNA) for STAT3 and IL-6 down regulated their own and HIV-1 gene expression, signifying that these factors influenced differential HIV-1 gene expression in CBMC than PBMC.
AB - We have previously shown a higher level of HIV-1 replication and gene expression in neonatal (cord) blood mononuclear cells (CBMC) compared with adult blood cells (PBMC), which could be due to differential expression of host factors. We performed the gene expression profile of CBMC and PBMC and found that 8013 genes were expressed at higher levels in CBMC than PBMC and 8028 genes in PBMC than CBMC, including 1181 and 1414 genes upregulated after HIV-1 infection in CBMC and PBMC, respectively. Several transcription factors (NF-κB, E2F, HAT-1, TFIIE, Cdk9, Cyclin T1), signal transducers (STAT3, STAT5A) and cytokines (IL-1β, IL-6, IL-10) were upregulated in CBMC than PBMC, which are known to influence HIV-1 replication. In addition, a repressor of HIV-1 transcription, YY1, was down regulated in CBMC than PBMC and several matrix metalloproteinase (MMP-7, -12, -14) were significantly upregulated in HIV-1 infected CBMC than PBMC. Furthermore, we show that CBMC nuclear extracts interacted with a higher extent to HIV-1 LTR cis-acting sequences, including NF-κB, NFAT, AP1 and NF-IL6 compared with PBMC nuclear extracts and retroviral based short hairpin RNA (shRNA) for STAT3 and IL-6 down regulated their own and HIV-1 gene expression, signifying that these factors influenced differential HIV-1 gene expression in CBMC than PBMC.
KW - Cord and adult blood mononuclear cells
KW - Cytokines
KW - HIV-1 gene expression
KW - Host factors
KW - Transcriptional factors
KW - shRNA
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U2 - 10.1016/j.virol.2010.01.018
DO - 10.1016/j.virol.2010.01.018
M3 - Article
C2 - 20138641
AN - SCOPUS:77649178596
SN - 0042-6822
VL - 400
SP - 32
EP - 43
JO - Virology
JF - Virology
IS - 1
ER -