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Christine Alston, Hsin Chien, Moon Han, Richard Dix; Suppressor of cytokine signaling (SOCS)1 and SOCS3 expression is upregulated following intraocular, but not systemic, murine cytomegalovirus (MCMV) infection of mice with retrovirus-induced immunosuppression (MAIDS). Invest. Ophthalmol. Vis. Sci. 2013;54(15):128.
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SOCS family proteins govern the regulation of immune responses to pathogen invasion by a negative feedback regulatory mechanism to prevent cytokine over-expression. SOCS1 is an inhibitor of interferon (IFN) signaling, whereas SOCS3 regulates the divergent actions of IL-6 and IL-10. We have shown previously that SOCS1 and SOCS3 mRNA and protein are robustly upregulated in MCMV-infected eyes with retinitis during MAIDS. We therefore sought to determine the patterns of SOCS1 and SOCS3 expression as well as SOCS-regulated cytokines during systemic MCMV infection of mice with MAIDS that fail to develop retinitis.
Groups of C57BL/6 mice with MAIDS or healthy mice were inoculated systemically with MCMV or mock infected (control). At 2, 4, 7, and 10 days postinfection, eyes and spleens were collected from all groups and quantified for SOCS1 and SOCS3 mRNA expression as well as mRNAs for IFNs and IL-6 by real-time RT-PCR assay.
Systemic MCMV infection of MAIDS mice resulted in no statistically significant upregulation of SOCS1, SOCS3, Type I IFNs, or IL-6 mRNAs in whole eyes or whole splenic cells when compared with controls. In comparison, Type II IFN mRNA expression was upregulated significantly in whole eyes, but not in whole splenic cells, of MAIDS mice following systemic MCMV infection.
Whereas direct intraocular MCMV infection and development of retinitis during MAIDS resulted in robust upregulation of SOCS1 and SOCS3 mRNA and protein within the ocular compartment, systemic MCMV infection without retinitis during MAIDS did not lead to significant upregulation of SOCS1, SOCS3, Type I IFNs, or IL-6 mRNAs within the ocular compartment or spleen, although there was a surprising upregulation of Type II IFN in the ocular compartment without retinitis. We conclude that upregulation of SOCS1 and SOCS3 expression takes place within the ocular compartment only during MCMV retinitis development in mice with MAIDS. The precise role in SOCS1 and SOCS3 in the pathogenesis of MAIDS-related MCMV retinitis requires further investigation.
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