Effect of hepatitis C virus core protein on the molecular profiling of human B lymphocytes.
Hepatitis C virus (HCV) core protein features many intriguing properties and plays a pivotal role in cellular immunity, cell growth, apoptosis, cell transformation, and eventually in tumor development. However, the role of B cells, the primary players in the humoral immune response, during HCV infection is largely unknown. To explore the molecular effects of HCV core on human B cells, we conducted gene expression profiling of serial RNA samples from B cells that were infected with adenovirus harboring full-length HCV core protein and beta-galactosidase as a reference using a microarray platform containing 22,149 human oligo probes. The entire experiment was performed in duplicate in B lymphocytes that were isolated from two individual donors and incubated for up to 3 days after infection with adenovirus expressing HCV core protein to identify dynamic gene expression patterns. Differential expression of representative genes was validated by quantitative RT-PCR. We found that HCV core significantly inhibited B-lymphocyte apoptosis. We showed a dramatic downregulation of MHC class II molecules in B cells expressing HCV core, whereas the expression of immunoglobulin genes was not significantly altered. Moreover, genes associated with leukemia and B-lymphoma were consistently upregulated by HCV core. In contrast, downregulation of caspase-1 and caspase-4 was found to be associated with core's ability to prevent B-lymphocyte apoptosis. In summary, we have identified several clusters of genes that are differentially expressed in human B lymphocytes expressing HCV core, suggesting a potential impairment of antigen processing and presentation, which may provide more insights into HCV infection in B lymphocytes.
Wu
Chuan-ging
CG
Division of Hematology, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892-4255, USA. wu@cber.fda.gov
Budhu
Anuradha
A
Chen
Sheng
S
Zhou
Xiaoling
X
Popescu
Nicholas C
NC
Valerie
Kristoffer
K
Wang
Xin Wei
XW
D000256:Adenoviridae / Q000235:genetics; D017209:Apoptosis; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism* / Q000821:virology*; D015153:Blotting, Western; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D016174:Hepacivirus / Q000502:physiology; D006801:Humans; D046228:Microarray Analysis; D005810:Multigene Family; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015203:Reproducibility of Results; D014758:Viral Core Proteins / Q000276:immunology / Q000378:metabolism*; D001616:beta-Galactosidase / Q000378:metabolism
D012333:RNA, Messenger; D014758:Viral Core Proteins; C069130:nucleocapsid protein, Hepatitis C virus; D001616:beta-Galactosidase