Human interleukin-6 facilitates hepatitis B virus infection in vitro and in vivo

Eithan Galun*, Orit Nahor, Ahmed Eid, Oded Jurim, Stefan Rose-John, Hubert E. Blum, Ofer Nussbaum, Ehud Ilan, Nili Daudi, Daniel Shouval, Yair Reisner, Shlomo Dagan

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

Abstract

Background and aim. Research on hepatitis B virus (HBV) infection in vivo has been limited due to the absence of a suitable animal model. We have developed a human-mouse radiation chimera in which normal mice, preconditioned by lethal total body irradiation and radioprotected with SCID mouse bone marrow cells, are permissive for engraftment of human hematopoietic cells and solid tissues. This resulting human-mouse model, which comprises three genetically disparate sources of tissue, is therefore termed Trimera. This study was aimed at assessing the effect of human IL-6 on HBV infection in vivo in Trimera mice. Methods. Trimera mice were transplanted with human liver tissue fragments or with HepG2-derived cell lines, which had been previously infected ex vivo with HBV in the presence or absence of human interleukin-6 (hIL-6) and in the presence of anti-IL-6- neutralizing antibodies. Results. HBV sequences appeared in the sera of animals in which the liver tissue was incubated with both HBV and hIL-6 prior to transplantation. A similar result was obtained when a human hepatoblastoma cell line (HepG2), expressing the hIL-6 receptor, was infected ex vivo with HBV in the presence of hIL-6 prior to their injection into spleens of Trimera mice. However, when liver fragments were infected ex vivo and simultaneously treated with neutralizing antibodies against hIL-6 or were incubated with HBV prior to transplantation without hIL-6, the rate of mice positive for HBV DNA in their sera was lower. Human mononuclear cells are also permissive for HBV infection in vitro: in the presence of hIL-6 the infection of these cells is enhanced; and this infection is suppressed by the chimetic protein named Hyper-IL-6, generated by the fusion of hIL-6 to the soluble hIL-6 receptor (sIL-6Rα, gp80). Conclusion. hIL-6 facilitates HBV infection in vitro and in vivo. (C) 2000 Academic Press.

Original languageAmerican English
Pages (from-to)299-309
Number of pages11
JournalVirology
Volume270
Issue number2
DOIs
StatePublished - 10 May 2000
Externally publishedYes

Keywords

  • Chimeric mice
  • Viral infection
  • Viral receptor

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