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Christine I. Alston, Hsin Chien, Emily L. Blalock, Richard D. Dix; Characteristics of Suppressor of Cytokine Signaling (SOCS)1 and SOCS3 Expression in Response to Murine Cytomegalovirus (MCMV) Infection During Health and Retrovirus-Induced Immunosuppression (MAIDS). Invest. Ophthalmol. Vis. Sci. 2012;53(14):6227.
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© ARVO (1962-2015); The Authors (2016-present)
Suppressor of Cytokine Signaling (SOCS) proteins are induced upon cytokine signaling and act as negative feedback regulators by interfering with the JAK/STAT pathway. Whereas SOCS1 inhibits signaling induced by Type 1 and Type 2 interferon (IFN), SOCS3 inhibits signaling by IL-6 family cytokines. Previous work by us determined that SOCS1 and SOCS3 mRNA and protein levels were significantly upregulated in MCMV-infected eyes of mice with MAIDS during progression of retinitis suggesting a pathogenic role for these cytokine regulators during MAIDS-related MCMV retinitis. Studies were therefore performed to characterize SOCS1 and SOCS3 expression during systemic MCMV infection of healthy mice versus MAIDS mice with focus on splenic cells.
Groups of healthy C57BL/6 mice or C57BL/6 mice with MAIDS were injected intraperitonally with MCMV or mock-injected. At 1 - 10 days after injection, splenic cells were collected from all mice and subjected to real time RT-PCR assay for quantification of SOCS1, SOCS3, MCMV IE1, MCMV gH, IFN-β, IFN-γ, and/or IL-6 mRNA levels.
When compared with splenic cells from mock-infected healthy mice, splenic cells from MCMV-infected healthy mice showed detectable SOCS1 and SOCS3 mRNA levels that peaked significantly at day 2 postinfection (pi), but declined thereafter, and by days 7 and 10 pi were at levels less than those found in mock-infected mice. Splenic cells collected from MAIDS animals with systemic MCMV infection showed a similar pattern of SOCS1 and SOCS3 mRNA synthesis including a significant decrease in mRNA levels late in the course of infection. Splenic cells collected from healthy mice at 2 days pi also showed a significant increase in levels of IFN-γ and IL-6 mRNAs, but not IFN-β mRNA. MCMV infection of splenic cells as assessed by detection of MCMV-specific IE1 and gH mRNAs was observed at days 1 - 4 pi, but was undetectable at days 7 and 10 pi.
SOCS1 and SOCS3 may play a role in the pathogenesis of systemic MCMV infection during health and MAIDS by affecting IFN-γ and IL-6 production, respectively. Our findings serve to set baseline data for future studies on the mechanism(s) by which SOCS1 and SOCS3 impact onset and progression of MAIDS-related MCMV retinitis.
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