Human herpes simplex virus (HSV)-specific CD8+ CTL clones recognize HSV-2-infected fibroblasts after treatment with IFN-γ or when virion host shutoff functions are disabled

Michael A. Tigges, Song Leng, David Johnson, Rae Lyn Burke

Research output: Contribution to journalArticle

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Abstract

Herpes simplex virus (HSV)-specific CD8+ CTL cloned from individuals infected with HSV-2 efficiently lyse HSV-infected EBV-transformed B lymphoblastoid cells; however, these same CTL fail to lyse infected dermal fibrobfasts. By 3 h after infection (early), class I MHC expression is reduced to less than 20% of that in uninfected fibroblasts, and expression is further reduced to less than 1% of the level in uninfected cells between 6 and 18 h after infection (late). We used an HSV-2 mutant that lacked the virion host shutoff (vhs) function to demonstrate that vhs plays a role in the loss of class I expression. While fibroblasts infected with this mutant are lysed by CTL that recognize virion proteins presented early as a consequence of introduction into the cytoplasm by the infecting virus, they are resistant to lysis by CTL that recognize viral proteins that must be synthesized de novo to be presented as class I Ags. Fibroblasts infected with a mutant that lacks the transporter-associated protein inhibitor ICP47 and is partially vhs defective are sensitive to CTL lysis. Pretreatment of fibroblasts with IFN-γ prior to HSV infection sustained the level of class I expression for longer periods after infection, and these fibroblasts, infected with wild-type HSV-2, were partially sensitive to lysis by HSV-specific CTL. Taken together, these results suggest that the combined effects of the HSV-2 vhs and ICP47 gene products are to block Ag presentation by class I MHC. However, this effect can be transiently counteracted by IFN-γ providing an early role for CD8+ CTL in the cellular immune response to HSV-2.

Original languageEnglish (US)
Pages (from-to)3901-3910
Number of pages10
JournalJournal of Immunology
Volume156
Issue number10
StatePublished - May 15 1996

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Human Herpesvirus 2
Simplexvirus
Virion
Clone Cells
Fibroblasts
Infection
Viral Proteins
Virus Diseases
Human Herpesvirus 4
Cellular Immunity
Cytoplasm
Proteins
Viruses
Skin
Genes

ASJC Scopus subject areas

  • Immunology

Cite this

Human herpes simplex virus (HSV)-specific CD8+ CTL clones recognize HSV-2-infected fibroblasts after treatment with IFN-γ or when virion host shutoff functions are disabled. / Tigges, Michael A.; Leng, Song; Johnson, David; Burke, Rae Lyn.

In: Journal of Immunology, Vol. 156, No. 10, 15.05.1996, p. 3901-3910.

Research output: Contribution to journalArticle

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abstract = "Herpes simplex virus (HSV)-specific CD8+ CTL cloned from individuals infected with HSV-2 efficiently lyse HSV-infected EBV-transformed B lymphoblastoid cells; however, these same CTL fail to lyse infected dermal fibrobfasts. By 3 h after infection (early), class I MHC expression is reduced to less than 20{\%} of that in uninfected fibroblasts, and expression is further reduced to less than 1{\%} of the level in uninfected cells between 6 and 18 h after infection (late). We used an HSV-2 mutant that lacked the virion host shutoff (vhs) function to demonstrate that vhs plays a role in the loss of class I expression. While fibroblasts infected with this mutant are lysed by CTL that recognize virion proteins presented early as a consequence of introduction into the cytoplasm by the infecting virus, they are resistant to lysis by CTL that recognize viral proteins that must be synthesized de novo to be presented as class I Ags. Fibroblasts infected with a mutant that lacks the transporter-associated protein inhibitor ICP47 and is partially vhs defective are sensitive to CTL lysis. Pretreatment of fibroblasts with IFN-γ prior to HSV infection sustained the level of class I expression for longer periods after infection, and these fibroblasts, infected with wild-type HSV-2, were partially sensitive to lysis by HSV-specific CTL. Taken together, these results suggest that the combined effects of the HSV-2 vhs and ICP47 gene products are to block Ag presentation by class I MHC. However, this effect can be transiently counteracted by IFN-γ providing an early role for CD8+ CTL in the cellular immune response to HSV-2.",
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