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 sensory ganglia are transiently induced to express MHC-I antigens at the cell surface, whereas only a minority are themselves productively infected. The aim of the current work was to determine whether MHC-I antigens can be expressed on the surfaces of infected neurons in addition to their uninfected neighbours. To address this aim a recombinant HSV type 1 strain, S-130, was used 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 MHC-I constitutively. In K562 cells, which do not express MHC-I constitutively, H2K(d) and beta(2)-microglobulin (beta(2)m) were shown to be co-expressed at the cell surface following S-130 infection. This observation was taken as evidence that class I heavy chain (alphaC) molecules encoded by the expression cassette in the HSV genome were transported to the cell surface as stable complexes with beta(2)m. Significantly, after introduction of S-130 into flank skin, H2K(d) antigens were detected on the surfaces of primary sensory neurons in ganglia innervating the inoculation site. Our data show that HSV-infected murine primary sensory neurons and human neuroblastoma cells are capable of expressing cell-surface MHC-I molecules encoded by a transgene. From this, we infer that up-regulation of alphaC expression is, in principle, sufficient to overcome potential impediments to neuronal cell surface expression of MHC-I complexes.
Abendroth
Allison
A
Infectious Diseases Laboratories, Institute of Medical and Veterinary Science, Frome Road, Adelaide, South Australia 5000, Australia1.
Simmons
Anthony
A
Infectious Diseases Laboratories, Institute of Medical and Veterinary Science, Frome Road, Adelaide, South Australia 5000, Australia1.
Efstathiou
Stacey
S
Infectious Diseases Laboratories, Institute of Medical and Veterinary Science, Frome Road, Adelaide, South Australia 5000, Australia1.
Pereira
Rosemarie A
RA
Infectious Diseases Laboratories, Institute of Medical and Veterinary Science, Frome Road, Adelaide, South Australia 5000, Australia1.
D000818:Animals; D002522:Chlorocebus aethiops; D004274:DNA, Recombinant; D005822:Genetic Vectors; D006183:H-2 Antigens / Q000378:metabolism; D018259:Herpesvirus 1, Human; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis*; D006801:Humans; D020014:K562 Cells; D051379:Mice; D009447:Neuroblastoma / Q000276:immunology* / Q000821:virology; D009475:Neurons, Afferent / Q000276:immunology* / Q000821:virology; D013499:Surface Properties; D014407:Tumor Cells, Cultured; D014709:Vero Cells
D004274:DNA, Recombinant; D006183:H-2 Antigens; C024755:H-2K(K) antigen; D015395:Histocompatibility Antigens Class I