The influence of toll-like receptor stimulation on expression of EBV lytic genes.
Epstein-Barr virus (EBV) establishes latency in the resting memory B-cell compartment. It has been recently suggested that maintenance of chronic infection is dependent on periodic reactivation. Although the stimuli for EBV reactivation in vivo during natural infections are largely unknown, there is evidence indicating that heterologous infections could trigger herpesviruses reactivation. The purpose of this work was to identify the influence of Toll-like receptors stimulation on EBV replication in EBV latently infected Burkitt lymphoma cells (P3HR-1, Raji and Namalwa). The cells were stimulated with Pam3CSK4 (synthetic triacylated lipoprotein), PolyI:C (synthetic analog of dsRNA), LPS (lipopolysaccharide from E.coli), measles virus (MeV) and PMA (phorbol myristate acetate). Non-stimulated cells (NS) served as control. EBV expression was investigated at mRNA level for three viral lytic genes: BZLF1 (immediate early, ZEBRA), BALF2 (early, EA) and BcLF1 (late, VCA). Additionally, the effect of stimulation on NF-kBp65 and inflammatory cytokines (IL-lb, IL-6, IL-8, IL-10, IL-12p70, and TNF) was investigated. Stimulation of TLRs led to limited changes in EBV expression manifesting as increase of ZEBRA at mRNA level in cells treated with PolyI:C and Pam3CSK4. Stimulation with PolyI:C, Pam3CSK4 and LPS also lead to considerable increase of NF-kBp65, while increased levels of inflammatory cytokines were observed for IL-8, TNF and IL-6 in cells treated with PMA and MeV. In conclusion, the results of our experiments support the suggestion that TLRs stimulation with microbial ligands influences EBV virus replication.
Department of Virology, National Institute of Public Health - National Institute of Hygiene, Warsaw, Poland. jsiennicka@pzh.gov.pl
Joanna
J
Siennicka
Department of Virology, National Institute of Public Health - National Institute of Hygiene, Warsaw, Poland.
Agnieszka
A
Trzcińska
Department of Virology, National Institute of Public Health - National Institute of Hygiene, Warsaw, Poland.
Agnieszka
A
Cześcik
Department of Virology, National Institute of Public Health - National Institute of Hygiene, Warsaw, Poland.
Milena
M
Dunal-Szczepaniak
Department of Virology, National Institute of Public Health - National Institute of Hygiene, Warsaw, Poland.
Barbara
B
Lagosz
D045744:Cell Line, Tumor; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D020031:Epstein-Barr Virus Infections / Q000235:genetics / Q000378:metabolism* / Q000821:virology; D015967:Gene Expression Regulation, Viral; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051193:Toll-Like Receptors / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation; D014764:Viral Proteins / Q000235:genetics* / Q000378:metabolism; D014779:Virus Replication
D016207:Cytokines; D051193:Toll-Like Receptors; D014764:Viral Proteins