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Richard D. Dix, Christine I. Alston, Emily L. Blalock, Hsin Chien; Suppressor of Cytokine Signaling (SOCS)1 and SOCS3 Response to Human Cytomegalovirus (HCMV) Infection is Cell-type Dependent. Invest. Ophthalmol. Vis. Sci. 2012;53(14):2784.
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Suppressor of Cytokine Signaling (SOCS) proteins act as negative regulators when induced by cytokine signaling. Whereas SOCS1 inhibits signaling induced by interferons, SOCS3 inhibits signaling by IL-6. Yu and coworkers recently showed that SOCS1 contributes to progression of uveitis (IOVS 52:6978). Our laboratory also observed that (i) SOCS1 and SOCS3 mRNAs and proteins are upregulated in murine CMV (MCMV)-infected eyes during development of retinitis in mice with retrovirus-induced immunosuppression, and (ii) SOCS1 and SOCS3 mRNA levels initially rise but then significantly fall in splenic cells during the course of acute, systemic MCMV infection of healthy mice. These observations prompted us to examine SOCS1 and SOCS3 expression during HCMV infection by first determining the fate of these negative regulators of cytokines during the course of virus replication in different cell types.
Freshly isolated human peripheral blood mononuclear cells (PBMC), a cell line of human retinal pigment epithelial cells (ARPE-19), and a cell line of immortalized T-lymphocytes (Jurkat) were inoculated with HCMV (Towne) (moi = 5) or mock-infected. At 10 min, 30 min, 1 hr, 2 hr, 4 hr, 6 hr, 24 hr, and/or 48 hr later, all cells were harvested and subjected to real time RT-PCR assay for quantification of SOCS1 and SOCS3 mRNA levels.
The three cell types investigated showed distinct patterns of SOCS1 and SOCS3 mRNA expression during the course of HCMV replication. Whereas SOCS1 mRNA, but not SOCS3 mRNA, was significantly upregulated in PBMC relatively early (1 hr) after HCMV infection, both SOCS1 and SOCS3 mRNAs were significantly upregulated in Jurkat cells relatively early (1 hr) after HCMV infection. In contrast, both SOCS1 and SOCS3 mRNAs were significantly upregulated in ARPE-19 cells, but relatively late (24 hr) after HCMV infection.
SOCS1 and SOCS3 response to HCMV infection is cell-type dependent. This finding is clinically relevant since HCMV infects PBMC during primary clinical infection and RPE during AIDS-related HCMV retinitis. Ongoing studies are investigating expression of SOCS1 and SOCS3 in different cell types in response to infection with different HCMV strains and UV-inactivated virus, the latter to determine tegument protein involvement.
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