April 2014
Volume 55, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2014
Pyroptosis and AIDS-related human cytomegalovirus (HCMV) retinitis: Caspase-1-dependent or caspase-1-independent interleukin-1β expression in response to HCMV infection is cell-type dependent
Author Affiliations & Notes
  • Richard D Dix
    Department of Biology, Georgia State University, Atlanta, GA
    Department of Ophthalmology, Emory University School of Medicine, Atlanta, GA
  • Christine Iris Alston
    Department of Biology, Georgia State University, Atlanta, GA
  • Hsin Chien
    Department of Biology, Georgia State University, Atlanta, GA
  • Footnotes
    Commercial Relationships Richard Dix, None; Christine Alston, None; Hsin Chien, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science April 2014, Vol.55, 2818. doi:
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      Richard D Dix, Christine Iris Alston, Hsin Chien; Pyroptosis and AIDS-related human cytomegalovirus (HCMV) retinitis: Caspase-1-dependent or caspase-1-independent interleukin-1β expression in response to HCMV infection is cell-type dependent. Invest. Ophthalmol. Vis. Sci. 2014;55(13):2818.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: Pyroptosis, a cell death pathway different from apoptosis and necroptosis, is triggered by active caspase-1. Secretion of interleukin-1β (IL-1β) and IL-18 coincides with pyroptosis-associated cell death. We showed previously that caspase-1, IL-1β, and IL-18 mRNAs are upregulated within murine cytomegalovirus (MCMV)-infected eyes of mice with retrovirus-induced immunosuppression (MAIDS), a finding that suggests a role for pyroptosis in AIDS-related HCMV retinitis pathogenesis. This observation prompted us to investigate the expression of these pyroptosis-related molecules in various cell types during productive (lytic) HCMV infection.

Methods: Cultures of freshly isolated human peripheral blood mononuclear cells (PBMCs) as well as monolayers of human retinal pigment epithelial cells (ARPE-19 cells), immortalized human T-lymphocytes (Jurkat cells), and human lung fibroblasts (MRC-5 cells) were inoculated with HCMV (Towne) (moi = 5) or maintenance medium (control), harvested at 10 min to 48 hr postinfection (pi), and compared by quantitative real time RT-PCR assay for caspase-1, IL-1β, and IL-18 mRNA levels.

Results: When compared with mock-infected cells, HCMV-infected ARPE-19 cells and HCMV-infected PMBCs showed upregulation of caspase-1, IL-1β, and IL-18 mRNAs at some time during HCMV infection from 10 min to 48 hr pi, although their temporal patterns of synthesis were cell-type specific. In contrast, HCMV-infected Jurkat cells showed upregulation of IL-1β mRNA at 10 min to 24 hr pi, but caspase-1 and IL-18 mRNAs were not upregulated at any time up to 48 hr pi. Similarly, HCMV-infected MRC-5 cells showed upregulation of IL-1β and IL-18 mRNAs at 24 to 48 hr pi, but caspase-1 mRNA was not upregulated at any time up to 48 hr pi.

Conclusions: Although IL-1β mRNA was upregulated in all cell types at some time following HCMV infection, concurrent expression of caspase-1 and IL-18 mRNAs was observed only in HCMV-infected ARPE-19 cells and HCMV-infected PBMCs suggesting HCMV-induced pyroptosis. Jurkat cells and MRC-5 cells infected with HCMV failed to show induction of all pyroptosis-related molecules. We conclude that caspase-1-dependent and caspase-1-independent IL-1β mRNA expression (and possibly pyroptosis) during productive (lytic) HCMV infection is cell-type specific.

Keywords: 492 cytomegalovirus • 415 AIDS/HIV • 702 retinitis  
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