Murine Gammaherpesvirus 68 Efficiently Infects Myeloid Cells Resulting In An Atypical, Restricted Form Of Infection

The gammaherpesviruses establish a lifelong infection, with the cellular outcome of infection intimately regulated by cell type. Though myeloid cells are an early infection target, infection results in widely divergent outcomes without a clear explanation. Here we use murine gammaherpesvirus 68 to demonstrate that macrophages are readily infectable, resulting in three divergent infection outcomes dictated by viral and host factors. Infection in vivo and in a cell culture model results in a high frequency of viable cells characterized by restricted viral transcription and unexpected transcription of the ORF75 locus, with rare cells initiating but failing to complete lytic replication. In contrast, infection with a high viral dose triggers abortive infection and cell death. Restricted infection can be fully converted to productive lytic replication by pre-treatment with the host cytokine IL-4. These studies demonstrate stepwise regulation of virus infection and identify virus and host factors that dictate divergent outcomes in a single cell type. HighlightsO_LIMHV68 efficiently infects macrophages C_LIO_LIInfection results in three divergent outcomes regulated by discrete inputs C_LIO_LIMacrophages limit lytic replication at two distinct stages C_LIO_LIMacrophages are capable of lytic replication, promoted by the host cytokine IL-4 and viral genes. C_LI O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=192 SRC="FIGDIR/small/545948v3_ufig1.gif" ALT="Figure 1"> View larger version (48K): org.highwire.dtl.DTLVardef@3d0dadorg.highwire.dtl.DTLVardef@4cda00org.highwire.dtl.DTLVardef@17c72adorg.highwire.dtl.DTLVardef@14cd436_HPS_FORMAT_FIGEXP M_FIG C_FIG