57 Scopus citations


Gammaherpesviruses are important pathogens whose lifelong survival in the host depends critically on their capacity to establish and reactivate from latency, processes regulated by both viral genes and the host immune response. Previous work has demonstrated that gamma interferon (IFN-γ) is a key regulator of chronic infection with murine gammaherpesvirus 68 (γHV68), a virus that establishes latent infection in B lymphocytes, macrophages, and dendritic cells. In mice deficient in IFN-γ or the IFN-γ receptor, γHV68 gene expression is altered during chronic infection, and peritoneal cells explanted from these mice reactivate more efficiently ex vivo than cells derived from wild-type mice. Furthermore, treatment with IFN-γ inhibits reactivation of γHV68 from latently infected wild-type peritoneal cells, and depletion of IFN-γ from wild-type mice increases the efficiency of reactivation of explanted peritoneal cells. These profound effects of IFN-γ on chronic γHV68 latency and reactivation raise the question of which cells respond to IFN-γ to control chronic γHV68 infection. Here, we show that IFN-γ inhibited reactivation of peritoneal cells and spleen cells harvested from mice lacking B lymphocytes, but not wild-type spleen cells, suggesting that IFN-γ may inhibit reactivation in a cell type-specific manner. To directly test this hypothesis, we expressed the diphtheria toxin receptor specifically on either B lymphocytes or macrophages and used diphtheria toxin treatment to deplete these specific cells in vivo and in vitro after establishing latency. We demonstrate that macrophages, but not B cells, are responsive to IFN-γ-mediated suppression of γHV68 reactivation. These data indicate that the regulation of gammaherpesvirus latency by IFN-γ is cell type specific and raise the possibility that cell type-specific immune deficiency may alter latency in distinct and important ways.

Original languageEnglish
Pages (from-to)6134-6140
Number of pages7
JournalJournal of virology
Issue number11
StatePublished - Jun 2007


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