Immediate-early gene expression is sufficient for induction of natural killer cell-mediated lysis of herpes simplex virus type 1-infected fibroblasts

Abstract

Herpes simplex virus type 1 (HSV-1)-infected human fibroblast (HSV-FS) targets are susceptible to lysis by natural killer (NK) cells, whereas uninfected FS are resistant to lysis. Studies were undertaken to determine the mechanism of this preferential susceptibility. HSV-FS were not intrinsically less stable than FS, as determined by a 5"Cr release assay under hypotonic shock in the presence of rat granule cytolysin and by sensitivity to anti-human leukocyte antigen class I antibody plus complement. Single-cell assays in agarose demonstrated that although similar numbers of large granular lymphocytes bound to the HSV-FS and FS targets, the conjugates with HSV-FS were lysed at a much higher frequency than those with FS. These results suggested that both targets are bound by the NK cells but only the HSV-FS were able to trigger lysis. The requirement for active virus expression was demonstrated by failure of emetine-treated HSV-FS targets or targets infected with UV-inactivated HSV to be lysed by NK effectors. To evaluate the role of viral glycoproteins in conferring susceptibility to lysis, Fab were prepared from HSV-l-seropositive sera; these Fab were unable to block lysis of the HSV-FS. Furthermore, incubation in phosphonoacetic acid failed to reduce NK(HSV-FS) activity despite * Corresponding author.

Both plasmacytoid dendritic cells and monocytes stimulate natural killer cells early during human herpes simplex virus type 1 infections

“…In turn, monocytes may produce TNF-a to enhance NK cell killing of HSV-infected cells in inflamed tissue. 54 MICA, which was up-regulated on Toll-like receptor-stimulated monocytes, 55 was not induced by HSV-1, consistent with a study in which MICA in infected cells was down-regulated by late HSV-1 gene products. 56 Immediate early gene expression was found to be sufficient for NK cell-mediated lysis of HSV-infected fibroblasts.…”

“…56 Immediate early gene expression was found to be sufficient for NK cell-mediated lysis of HSV-infected fibroblasts. 54 Follow-up studies found that the HSV-1 immediate early protein ICP0 induced lysis of HSV-infected cells via the natural cytotoxicity receptors. 57 Yet, the induced molecules on target cells were not identified.…”

Combined cytotoxic activity of an infectious, but non‐replicative herpes simplex virus type 1 and plasmacytoid dendritic cells against tumour cells

“…The infectious, but replication‐incompetent HSV‐1 d 106S still expresses the immediate early proteins ICP0 and ICP6 . Expression of ICP0 by infected cells was sufficient for recognition of NK cells by natural cytotoxicity receptors . After UV irradiation, viral DNA is cross‐linked and the virus no longer expresses immediate early proteins.…”

Human Herpes Viruses Latent Infection in the Nervous System

“…Aborted viral replication, at stages prior to host cell destruction, is sufficient to obtain an effective immune response against HSV-I. Moreover, limited HSV-1 replication is superior to exposure of the immune system to purified viral proteins (Chan et al 1989, McDermott et al 1989, Fitzgerald-Bocarsly et al 1991. Indeed, immediate early gene expression is sufficient to induce a natural killer cell-mediated immunity (Fitzgerald-Bocarsly et al 1991), while ultraviolet light or heat inactivation of virus reduces the ability to form HSV-specific cytotoxic T lymphocytes (Lawman et al 1980).…”

“…Moreover, limited HSV-1 replication is superior to exposure of the immune system to purified viral proteins (Chan et al 1989, McDermott et al 1989, Fitzgerald-Bocarsly et al 1991. Indeed, immediate early gene expression is sufficient to induce a natural killer cell-mediated immunity (Fitzgerald-Bocarsly et al 1991), while ultraviolet light or heat inactivation of virus reduces the ability to form HSV-specific cytotoxic T lymphocytes (Lawman et al 1980). Likewise, infection of experimental animals with viral mutants that have an aborted replication cycle protects them from the development of encephalitis and keratitis (Nguyen et al 1992, Morrison & Knipe 1994.…”