Potential cellular signatures of viral infections in human hematopoietic cells.
Expression profiling of cellular genes was performed using a 10,000 cDNA human gene array in order to identify expression changes following chronic infection of human hematopoietic cells with Kaposi's Sarcoma-associated Virus (KSHV) also known as Human Herpesvirus 8 (HHV8) and Human T cell leukemia virus-1 (HTLV-1). We performed cell-free in vitro infection of primary bone marrow derived CD34+ cells using semi-purified HHV8 and a mature IL-2 dependent T cell line, KIT 225, using highly concentrated viral stocks prepared from an infectious molecular clone of HTLV-1. Thirty days post infection, mRNA was isolated from infected cultures and uninfected controls and submitted for microarray analysis. More than 400 genes were differentially expressed more than two-fold following HHV8 infection of primary bone marrow derived CD34+ cells. Of these 400, interferon regulatory factor 4 (IRF4), cyclin B2, TBP-associated factor, eukaryotic elongation factor and pim 2 were up-regulated more than 3.5 fold. In contrast, less than 100 genes were differentially expressed more than two-fold following chronic infection of a mature T cell line with HTLV-1. Of these, only cdc7 was up-regulated more than 3.5 fold. These data may provide insight into cellular signatures of infection useful for diagnosis of infection as well as potential targets for therapeutic intervention.
Mikovits
J
J
Laboratory of Antiviral Drug Mechanisms, SAIC Frederick, NCI-FCRDC, PO Box B, Bldg. 439, Frederick, MD 21702-1201, USA. Mikovits@ncifcrf.gov
Ruscetti
F
F
Zhu
W
W
Bagni
R
R
Dorjsuren
D
D
Shoemaker
R
R
D002460:Cell Line; D005786:Gene Expression Regulation; D015490:HTLV-I Infections / Q000235:genetics*; D006412:Hematopoietic Stem Cells / Q000821:virology*; D006566:Herpesviridae Infections / Q000235:genetics*; D019288:Herpesvirus 8, Human; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis