The expression and function of HSV ICP47 and its promoter in mice

Abstract

Herpes simplex virus (HSV) protein immediate early-infected cell protein (ICP)47 inhibits the transporter associated with antigen presentation, thereby concealing infected cells from the CD8+ T-cell response in humans. By contrast, in mouse cells, ICP47 was found to be ineffective in vitro, despite some evidence for a role of this protein in vivo, specifically in the nervous system. Recent evidence suggests that the promoter that drives ICP47 might be active in the establishment of latency and during latency, leading to the possibility that a role might be found in protecting neurons that are latently infected with HSV from T-cell attack. Here, we explored this idea by studying a set of recombinant HSVs that were null for ICP47 protein and/or express Cre recombinase from ICP47 promoters, for use in a Cre-marking mouse model. Using these viruses, we found that contrary to previous studies, the activity of ICP47 in mouse cells is efficient enough to detectably reduce antigen presentation, albeit at levels much lower than in human cells. However, in vivo, we found no evidence of ICP47 influencing HSV pathogenesis or latency in a model where the virus does not spread beyond the peripheral nervous system. Finally, we show that the ability of the ICP47 promoter to drive protein expression during HSV latency is dependent on the location that it is placed in a recombinant virus genome and that such expression is undetectable from its native locus. Show more