PMID- 17940612 OWN - NLM STAT- MEDLINE DCOM- 20080715 LR - 20211027 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 2 IP - 10 DP - 2007 Oct 17 TI - Murine gammaherpesvirus-68 inhibits antigen presentation by dendritic cells. PG - e1048 LID - e1048 AB - 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. FAU - Smith, Christopher M AU - Smith CM AD - Division of Virology, Department of Pathology, University of Cambridge, Cambridge, United Kingdom. FAU - Gill, Michael B AU - Gill MB FAU - May, Janet S AU - May JS FAU - Stevenson, Philip G AU - Stevenson PG LA - eng GR - G0400427/MRC_/Medical Research Council/United Kingdom GR - C19612/A6189/CRUK_/Cancer Research UK/United Kingdom GR - G9800903/MRC_/Medical Research Council/United Kingdom GR - GR076956MA/WT_/Wellcome Trust/United Kingdom GR - WT_/Wellcome Trust/United Kingdom PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20071017 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Epitopes) RN - 0 (Histocompatibility Antigens Class I) SB - IM MH - Animals MH - *Antigen Presentation MH - CD8-Positive T-Lymphocytes/metabolism MH - Cricetinae MH - Dendritic Cells/*virology MH - Epitopes/chemistry MH - Gammaherpesvirinae/*metabolism MH - *Gene Expression Regulation MH - Histocompatibility Antigens Class I MH - Lymphocyte Activation MH - Lymphoid Tissue/metabolism MH - Mice MH - Mice, Inbred BALB C MH - Mice, Inbred C57BL MH - NIH 3T3 Cells PMC - PMC2002512 COIS- Competing Interests: The authors have declared that no competing interests exist. EDAT- 2007/10/18 09:00 MHDA- 2008/07/17 09:00 PMCR- 2007/10/17 CRDT- 2007/10/18 09:00 PHST- 2007/08/20 00:00 [received] PHST- 2007/10/01 00:00 [accepted] PHST- 2007/10/18 09:00 [pubmed] PHST- 2008/07/17 09:00 [medline] PHST- 2007/10/18 09:00 [entrez] PHST- 2007/10/17 00:00 [pmc-release] AID - 07-PONE-RA-02026R1 [pii] AID - 10.1371/journal.pone.0001048 [doi] PST - epublish SO - PLoS One. 2007 Oct 17;2(10):e1048. doi: 10.1371/journal.pone.0001048.