Human cytomegalovirus blocks interferon_gamma stimulate upregulation of MHC class I expression and the class I antigen processing machinery

Abstracts

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CMV Immune Response- Posters G3-43 Cytomegalovirus infections in non-immunosuppressed critically ill surgical patients: An occult epidemic CHARLES COOK The Ohio State University Medical Center, Columbus, OH, USA Background: The incidence and significance of herpes family viral infections in non-immunosuppressed critically ill surgical patients is unknown. Methods: Non-immunosuppressed chronic (> 5 days) general surgical intensive care unit (ICU) patients were prospectively studied with weekly cultures for cytomegalovirus (CMV) and herpes simplex virus (HSV) between 7/96 and 9/97. Results: The overall incidence of occult herpes family virus in 104 study patients was 19%. Fifteen percent (7/48) had CMV positive (CMV+) sputum cultures, six percent (6/104) had CMV viremia, and twenty three percent (11/48) had HSV positive (HSV+) sputum cultures. CMV+ patients had significantly longer hospital admissions (p=0.003), ICU admissions (p=0.001), and periods of ventilator dependence (p=0.001) than CMV negative patients (CMV-), despite having comparable severity of illness. CMV+ patients also had significantly higher numbers of blood transfusions (p=0.002), incidence of hepatic dysfunction (p=0.04), and all were IgG positive at the beginning of the study. In contrast, HSV+ patients had lengths of hospital admissions, lengths of ICU admissions, and periods of ventilator dependence comparable to patients without viral infections (p>0.05). Although mortality in CMV+ patients seemed higher than in CMV- patients, this difference was not significant (p=0.15). Conclusions: At least one in five non-immunosuppressed critically ill general surgical patients have occult herpes virus infections, which may arise from latency. The clinical significance of these infections is currently unknown, although CMV+ patients have significantly higher morbidity rates than CMV- patients. An antiviral treatment trial for critically ill patients with herpes virus infections may help confirm pathogenicity.

G3-44 Human cytomegalovirus blocks interferon_gamma stimulate upregulation of MHC class I expression and the class I antigen processing machinery DANIEL MILLER Ohio State University, Columbus, OH, USA Interferon-g (IFN-g) is a potent inducer of antigen presentation through its upregulation of major histocompatibility complex (MHC) class I and class II genes and the accessory gene products necessary for antigen processing. We have previously reported that human cytomegalovirus (HCMV) inhibits IFN-g stimulated M H C class II expression in infected fibroblasts and endothelial cells secondary to a block in the IFN-g signal transduction pathway (Jak/Stat pathway). Herein, we tested the hypothesis that HCMV blocks the ability of IFN-g to upregulate multiple components of the M H C class I antigen processing machinery, including the expression of HLA-B7, b2-microglobulin, the transporter associated with antigen processing proteins (TAP] and TAP2), and IFN-g inducible components of the proteasome complex (LMP2 and LMP7). IFN-g upregulated the expression of HLA-B7, b2-microglobulin, TAP1, TAP2, LMP2, and LMP7 mRNA in noninfected fibroblasts and endothelial cells; however, IFN-g treatment did not upregulate the expression of any of these class I antigen processing genes in HCMV infected fibroblasts or endothelial cells. Supernatant transfer assays demonstrated that this effect was not dependent upon soluble factors in the supernatants of HCMV infected cultures. These observations suggest a novel mode of H C M V interference with the M H C class I pathway: HCMV inhibition of IFN-g stimulated upregulation of the class I antigen processing machinery.

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