Replication of epstein-barr virus primary infection in human tonsil tissue explants

Kensei Gotoh, Yoshinori Ito, Seiji Maruo, Kenzo Takada, Terukazu Mizuno, Masaaki Teranishi, Seiichi Nakata, Tsutomu Nakashima, Seiko Iwata, Fumi Goshima, Shigeo Nakamura, Hiroshi Kimura

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)

Abstract

Epstein-Barr virus (EBV) may cause a variety of virus-associated diseases, but no antiviral agents have yet been developed against this virus. Animal models are thus indispensable for the pathological analysis of EBV-related infections and the elucidation of therapeutic methods. To establish a model system for the study of EBV infection, we tested the ability of B95-8 virus and recombinant EBV expressing enhanced green fluorescent protein (EGFP) to replicate in human lymphoid tissue. Human tonsil tissues that had been surgically removed during routine tonsillectomy were sectioned into small blocks and placed on top of collagen sponge gels in culture medium at the air-interface, then a cell-free viral suspension was directly applied to the top of each tissue block. Increasing levels of EBV DNA in culture medium were observed after 12-15 days through 24 days post-infection in tissue models infected with B95-8 and EGFP-EBV. Expression levels of eight EBV-associated genes in cells collected from culture medium were increased during culture. EBV-encoded small RNA-positive cells were detected in the interfollicular areas in paraffin-embedded sections. Flow cytometric analyses revealed that most EGFP + cells were CD3 - CD56 - CD19 + HLA-DR +, and represented both naïve (immunoglobulin D +) and memory (CD27 +) B cells. Moreover, EBV replication in this model was suppressed by acyclovir treatment in a dose-dependent manner. These data suggest that this model has potential for use in the pathological analysis of local tissues at the time of primary infection, as well as for screening novel antiviral agents.

Original languageEnglish
Article numbere25490
JournalPloS one
Volume6
Issue number10
DOIs
Publication statusPublished - 05-10-2011
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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