Murine gammaherpesvirus-68 inhibits antigen presentation by dendritic cells.
Dendritic cells (DCs) play a central role in initiating adaptive immunity. Murine gammaherpesvirus-68 (MHV-68), like many persistent viruses, infects DCs during normal host colonization. It therefore provides a means to understanding what host and viral genes contribute to this aspect of pathogenesis. The infected DC phenotype is likely to depend on whether viral gene expression is lytic or latent and whether antigen presentation is maintained. For MHV-68, neither parameter has been well defined. Here we show that MHV-68 infects immature but not mature bone marrow-derived DCs. Infection was predominantly latent and these DCs showed no obvious defect in antigen presentation. Lytically infected DCs were very different. These down-regulated CD86 and MHC class I expression and presented a viral epitope poorly to CD8(+) T cells. Antigen presentation improved markedly when the MHV-68 K3 gene was disrupted, indicating that K3 fulfils an important function in infected DCs. MHV-68 infects only a small fraction of the DCs present in lymphoid tissue, so K3 expression is unlikely to compromise significantly global CD8(+) T cell priming. Instead it probably helps to maintain lytic gene expression in DCs once CD8(+) T cell priming has occurred.
Smith
Christopher M
CM
Division of Virology, Department of Pathology, University of Cambridge, Cambridge, United Kingdom.
Gill
Michael B
MB
May
Janet S
JS
Stevenson
Philip G
PG
D000818:Animals; D017951:Antigen Presentation; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D006224:Cricetinae; D003713:Dendritic Cells / Q000821:virology*; D000939:Epitopes / Q000737:chemistry; D018142:Gammaherpesvirinae / Q000378:metabolism*; D005786:Gene Expression Regulation; D015395:Histocompatibility Antigens Class I; D008213:Lymphocyte Activation; D008221:Lymphoid Tissue / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D041681:NIH 3T3 Cells
D000939:Epitopes; D015395:Histocompatibility Antigens Class I