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Christine Iris Alston, Hsin Chien, Moon Kwon Han, Jessica E Fleming, Richard D Dix; Stimulation of Suppressor of Cytokine Signaling (SOCS)1 and SOCS3 Expression by Murine Cytomegalovirus (MCMV) Does Not Necessarily Require Productive Virus Replication. Invest. Ophthalmol. Vis. Sci. 2014;55(13):2822.
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SOCS family proteins govern the regulation of immune responses to pathogen invasion by a negative feedback regulatory mechanism to dampen cytokine expression and thereby favor pathogenesis and disease development. SOCS1 is an inhibitor of antiviral interferon (IFN-α/β) signaling, whereas SOCS3 regulates signaling by the proinflammatory interleukin-6 (IL-6) cytokine family. We have shown previously that SOCS1 and SOCS3 mRNAs and proteins are robustly upregulated within MCMV-infected eyes of mice susceptible to retinitis during retrovirus-induced immunodeficiency (MAIDS). To determine with greater precision the mechanisms by which MCMV upregulates SOCS1 and SOCS3 expression during MAIDS-related MCMV retinitis, we performed in vitro experiments to determine if SOCS1 and/or SOCS3 expression requires productive (lytic) virus replication.
Monolayers of IC-21 mouse macrophages or murine embryonic fibroblast (MEF) cells were inoculated with either infectious MCMV (moi = 3), noninfectious UV-inactivated MCMV, or maintenance medium (control), harvested at 10 min to 48 hr postinfection (pi), and compared by quantitative real-time RT-PCR assay for SOCS1 and SOCS3 mRNA production.
MCMV infection of both IC-21 and MEF monolayers resulted in significant upregulation of SOCS1 and SOCS3 mRNA production that peaked between 2 to 6 hr pi. In comparison, inoculation of both cell lines with UV-inactivated MCMV also resulted in upregulation of SOCS1 and SOCS3 mRNA production albeit at lower levels than that observed during MCMV infection.
Although UV-inactivated MCMV stimulated SOCS1 and SOCS3 mRNA production, productive (lytic) MCMV replication resulted in more robust stimulation of SOCS1 and SOCS3 mRNA production. That UV-inactivated MCMV stimulated SOCS1 and SOCS3 mRNA production albeit at moderate levels when compared with infectious MCMV nonetheless suggests a role for parental virus tegument protein(s) in SOCS1 and SOCS3 stimulation.
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