Cytokines released by human peripheral blood mononuclear cells inhibit the production of early and late cytomegalovirus proteins.
Cytomegalovirus-infected human fibroblasts are susceptible to lysis by natural killer cells and cytotoxic T cells. The purpose of this study was to determine whether non-lytic mechanisms might also contribute to the control of cytomegalovirus infection. The appearance of cytomegalovirus proteins in infected fibroblasts was determined by flow cytometry. Infected fibroblasts incubated with peripheral blood mononuclear cells for 3 days expressed less early and late proteins than fibroblasts incubated without peripheral blood mononuclear cells. Supernatants generated by the cocultivation of peripheral blood mononuclear cells with cytomegalovirus-infected fibroblasts inhibited the production of cytomegalovirus early and late proteins. The soluble factors in supernatants which contributed to the inhibitory effect were identified as interferons alpha, beta and gamma, and tumor necrosis factors alpha and beta. The ability of supernatants to inhibit the production of cytomegalovirus early protein was mimicked by combinations of corresponding recombinant cytokines. The inhibition of cytomegalovirus protein production by cytokines produced by peripheral blood mononuclear cells may contribute to early containment of cytomegalovirus infection.
Torigoe
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Division of Allergy, Immunology, and Infectious Diseases, Joseph Stokes Jr. Research Institute, Children's Hospital of Philadelphia, Pennsylvania 19104, USA.
Campbell
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Starr
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D000956:Antigens, Viral / Q000096:biosynthesis; D000998:Antiviral Agents; D018956:CD5 Antigens / Q000276:immunology; D002478:Cells, Cultured; D018920:Coculture Techniques; D016207:Cytokines / Q000502:physiology*; D003587:Cytomegalovirus / Q000254:growth & development / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology / Q000821:virology; D006680:HLA Antigens / Q000276:immunology; D006801:Humans; D017874:Immediate-Early Proteins / Q000096:biosynthesis; D007372:Interferons / Q000502:physiology; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000276:immunology*; D018950:Lipopolysaccharide Receptors / Q000276:immunology; D008233:Lymphotoxin-alpha / Q000502:physiology; D011994:Recombinant Proteins / Q000494:pharmacology; D012995:Solubility; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology; D014759:Viral Envelope Proteins / Q000096:biosynthesis; D010948:Viral Plaque Assay; D014764:Viral Proteins / Q000096:biosynthesis*
D000956:Antigens, Viral; D000998:Antiviral Agents; D018956:CD5 Antigens; D016207:Cytokines; D006680:HLA Antigens; D017874:Immediate-Early Proteins; D018950:Lipopolysaccharide Receptors; D008233:Lymphotoxin-alpha; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D014759:Viral Envelope Proteins; D014764:Viral Proteins; C077407:glycoprotein L, Human herpesvirus 1; C044582:immediate-early proteins, cytomegalovirus; D007372:Interferons