pactamycin and Herpes-Simplex

Human fibroblast FS-4 cells when infected with herpes simplex virus type 1 (HSV-1) become susceptible to lysis by purified populations of T3- human natural killer (NK) lymphocytes. Blocking of HSV-1 protein synthesis or N-linked glycosylation with pactamycin or tunicamycin, respectively, prevented HSV-1-infected cells from being lysed, suggesting that HSV-1 glycoprotein synthesis is required for recognition by NK cells. However, pactamycin- and tunicamycin-treated cells expressed on their membranes a detectable amount (20 to 40% of the untreated control) of HSV-1 glycoproteins gB, gC and gD, left by the virus during its internalization. Phosphonoformic acid (PFA) blocked HSV-1 DNA replication and inhibited the synthesis and surface expression of newly made gC, gD and gB by 90, 80 and 60% respectively. Despite this reduction, PFA treatment had no effect on NK susceptibility. The target structure recognized seems to be different from those expressed on tumour target cells since there was no competition for the lysis of HSV-1-infected FS-4 by K-562 or HeLa tumour target cells. However, a monoclonal antibody specific for the human transferrin receptor which inhibited NK recognition of tumour cells also blocked NK cytotoxicity of HSV-1-infected cells. In summary our results indicate that although viral glycoprotein synthesis is required, gB, gC and/or gD alone are not the targets for NK recognition of HSV-1-infected cells. In addition, they suggest the involvement of the host cell transferrin receptor in the NK killing process.

Topics: Antigens, Viral; Cytotoxicity, Immunologic; Herpes Simplex; Humans; Immunity, Cellular; Immunity, Innate; In Vitro Techniques; Killer Cells, Natural; Molecular Weight; Pactamycin; Precipitin Tests; Receptors, Transferrin; Simplexvirus; Tunicamycin; Viral Envelope Proteins

Topics: Animals; Antigens, Viral; Canavanine; Cricetinae; Cytotoxicity, Immunologic; Herpes Simplex; Mice; Mice, Inbred BALB C; Mice, Inbred C3H; Pactamycin; Simplexvirus; Species Specificity; T-Lymphocytes