Abstract
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.
Highlights
Persistent viruses commonly infect dendritic cells (DCs); epidemic viruses seem to do so more rarely
Murine gammaherpesvirus-68 (MHV-68) established a predominantly latent infection in immature, bone marrow-derived DCs, much as it does in peritoneal macrophages [38]
Infected DCs showed a K3-dependent inhibition of MHC class I-restricted antigen presentation, a K3-independent down-regulation of CD86 expression, and a highly abnormal response to activation signals
Summary
Persistent viruses commonly infect dendritic cells (DCs); epidemic viruses seem to do so more rarely. The pivotal role DCs play in initiating anti-viral immunity means that virus-infected DCs potentially elicit a rapid and potent immune attack [1,2]. Why persistent viruses should infect them is not clear. The chance to exploit DC functions presumably offers a selective advantage that outweighs the risk of greater immunogenicity. A key factor in the cost/benefit balance of DC infection is MHC class I-restricted antigen presentation. Viral evasion proteins are likely to be important in infected DCs both to promote DC survival and to off-set the increased opportunities for immune priming
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