Differential expression and interaction of host factors augment HIV-1 gene expression in neonatal mononuclear cells.
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-kappaB, E2F, HAT-1, TFIIE, Cdk9, Cyclin T1), signal transducers (STAT3, STAT5A) and cytokines (IL-1beta, 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-kappaB, 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.
Department of Immunobiology, College of Medicine, University of Arizona, Tucson, AZ 85724, USA.
Vasudha
V
Sundaravaradan
Roshni
R
Mehta
David T
DT
Harris
Jerome A
JA
Zack
Nafees
N
Ahmad
D000328:Adult; D001483:Base Sequence; D015342:DNA Probes / Q000235:genetics; D005260:Female; D005312:Fetal Blood / Q000166:cytology / Q000378:metabolism / Q000821:virology; D015870:Gene Expression; D020869:Gene Expression Profiling; D015658:HIV Infections / Q000235:genetics / Q000635:transmission; D016325:HIV Long Terminal Repeat; D015497:HIV-1 / Q000235:genetics* / Q000472:pathogenicity / Q000502:physiology; D054884:Host-Pathogen Interactions / Q000235:genetics* / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D007231:Infant, Newborn; D018445:Infectious Disease Transmission, Vertical; D015850:Interleukin-6 / Q000235:genetics; D007963:Leukocytes, Mononuclear / Q000378:metabolism* / Q000821:virology*; D011247:Pregnancy; D034622:RNA Interference; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics; D014779:Virus Replication; D000093242:Interleukin-6 Inhibitors
D015342:DNA Probes; D015850:Interleukin-6; D050796:STAT3 Transcription Factor; D014157:Transcription Factors; D000093242:Interleukin-6 Inhibitors; C508600:IL6 protein, human; C494086:STAT3 protein, human