Infection with an H2 recombinant herpes simplex virus vector results in expression of MHC class I antigens on the surfaces of human neuroblastoma cells in vitro and mouse sensory neurons in vivo

The majority of neurons in herpes simplex virus (HSV)-infected murine senso ry ganglia are transiently induced to express MHC-I antigens at the cell su rface, whereas only a minority are themselves productively infected. The ai m of the current work was to determine whether MHC-I antigens can be expres sed on the surfaces of infected neurons in addition to their uninfected nei ghbours. To address this aim a recombinant HSV type 1 strain, S-130, was us ed to deliver a mouse H2K(d) gene, under control of the HCMV IE-1 promoter/ enhancer, into human neuroblastoma cells in vitro and mouse primary sensory neurons in vivo. S-130 expressed H2K(d) antigens on the surfaces of IMR-32 cells, a human neuroblastoma cell line that expresses very low levels of M HC-I constitutively. In K562 cells, which do not express MHC-I constitutive ly, H2K(d) and beta(2)-microglobulin (beta(2)m) were shown to be co-express ed at the cell surface following S-130 infection. This observation was take n as evidence that class I heavy chain (alpha C) molecules encoded by the e xpression cassette in the HSV genome were transported to the cell surface a s stable complexes with beta(2)m Significantly, after introduction of S-130 into Rank skin, H2K(d) antigens were detected on the surfaces of primary s ensory neurons in ganglia innervating the inoculation site, Our data show t hat HSV-infected murine primary sensory neurons and human neuroblastoma cel ls are capable of expressing cell-surface MHC-I molecules encoded by a tran sgene, From this, we infer that up-regulation of alpha C expression is, in principle, sufficient to overcome potential impediments to neuronal cell su rface expression of MHC-I complexes.