LADELL K, BERGER C, BONANOMI A, SCHMITZ N, NIGGLI FK, NADAL D; Interscience Conference on Antimicrobial Agents and Chemotherapy (43rd: 2003: Chicago, Ill.).
Abstr Intersci Conf Antimicrob Agents Chemother Intersci Conf Antimicrob Agents Chemother. 2003 Sep 14-17; 43: abstract no. V-1291.
Univ. Children's Hospital of Zurich, Zurich, Switzerland.
BACKGROUND: Immunosuppressed individuals are at increased risk for Epstein-Barr virus (EBV)-induced lymphoproliferate disease (LPD) against which treatment is unsatisfactory. Different quantitative dynamics of viral gene expression following primary cell infection may predispose towards LPD. METHODS: Expression of viral latent (EBNA1, EBNA2, LMP1, LMP2) and replicative (bzlf1, gp85) genes was quantified in duplicates in human cord (EBV-naive) and peripheral blood (EBV-experienced) +/- cyclosporin A (CSA) before and following EBV infection (B95.8 strain) by real-time polymerase-chain reaction in relation to the housekeeping gene hydroxymethylbilane synthase. Samples were taken at 0, 2, 24, 48, 72, 144 and 168 hours (h) of infection. RESULTS: In infected cord blood lymphocytes (CBL; 7 donors) EBNA2 was the first gene to be expressed at 2h, followed by gp85 at 72h and EBNA1 at 120h. Super-infected peripheral blood lymphocytes (PBL; 3 donors) only showed a transient expression of EBNA1 (2-120h) and gp85 (24-72h). Treatment with CSA resulted in constant expression of EBNA1 after 2h, gp85 after 24h, followed by LMP1 and LMP2 expression after 48h, when expression of all of these genes remained stable until 168h. Bzlf1 was first expressed at 168h. Expression of latent genes was at least 2 to 3-fold higher than of replicative genes and in PBL 2-fold higher than in CBL. CONCLUSIONS: The different patterns observed of EBV gene expression explain the distinct susceptibility of EBV-naive CBL versus EBV-experienced PBL to replicative infection and the activity of EBV during immunosuppression (CSA). Quantification of EBV gene expression could serve to assess the immediate effects of novel antiviral treatments on EBV-associated LPD.
Publication Types:
Keywords:
- Communicable Diseases
- Epstein-Barr Virus Infections
- Gene Expression
- Gene Expression Regulation, Viral
- Genes, Viral
- Herpesvirus 4, Human
- Humans
- Polymerase Chain Reaction
- Viral Proteins
- genetics
Other ID:
UI: 102265237
From Meeting Abstracts