Th2 cytokine modulates herpesvirus reactivation in a cell type-specific manner

Guoxun Wang, Christina Zarek, Tyron Chang, Lili Tao, Alexandria Lowe, Tiffany A. Reese

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


Gammaherpesviruses such as Epstein-Barr virus (EBV), Kaposi's sarcomaassociated virus (KSHV), and murine gammaherpesvirus 68 (MHV68) establish latent infection in B cells, macrophages, and nonlymphoid cells and can induce both lymphoid and nonlymphoid cancers. Research on these viruses has relied heavily on immortalized B cell and endothelial cell lines. Therefore, we know very little about the cell type-specific regulation of virus infection. We have previously shown that treatment of MHV68-infected macrophages with the cytokine interleukin-4 (IL-4) or challenge of MHV68-infected mice with an IL-4-inducing parasite leads to virus reactivation. However, we do not know if all latent reservoirs of the virus, including B cells, reactivate the virus in response to IL-4. Here, we used an in vivo approach to address the question of whether all latently infected cell types reactivate MHV68 in response to a particular stimulus. We found that IL-4 receptor expression on macrophages was required for IL-4 to induce virus reactivation but that it was dispensable on B cells. We further demonstrated that the transcription factor STAT6, which is downstream of the IL-4 receptor and binds the virus gene 50 N4/N5 promoter in macrophages, did not bind to the virus gene 50 N4/N5 promoter in B cells. These data suggest that stimuli that promote herpesvirus reactivation may affect latent virus only in particular cell types but not in others.

Original languageEnglish (US)
Article numbere01946
JournalJournal of virology
Issue number8
StatePublished - Apr 2021


  • Cytokines
  • Gammaherpesvirus
  • MHV68
  • Reactivation

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology


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