Affiliations: Laboratory of Antiviral Drug Mechanisms, Frederick,
MD, USA | Laboratory of Leukocyte Biology, DBS, National Cancer
Institute-Frederick Cancer Research Center, Frederick, MD 21702-1201,
USA | Intramural Research Support Program SAIC Frederick,
Frederick, MD, USA | Screening Technologies Branch, Developmental
Therapeutics Program, DCTD, Frederick, MD, USA
Abstract: 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 Kapsosi'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 {\it 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.
