title: Cytomegalovirus production by infected astrocytes correlates with transforming growth factor-beta release.
abstract: Cytomegalovirus (CMV) encephalitis is well documented in immunosuppressed persons, but its pathogenesis has received little investigative attention. The examination of brain tissue from 2 patients with acquired immunodeficiency syndrome who had CMV encephalitis showed colocalization of CMV inclusions and transforming growth factor (TGF)-beta in cells that contained astrocyte-specific glial filaments. To investigate the relationship between CMV and TGF-beta in the brain, an ex vivo murine model of CMV-infected astrocytes was established. Cultures of primary murine (strain FVB/N) astrocytes inoculated with murine (Smith strain) CMV expressed, over time, increasing amounts of infectious CMV in parallel with increasing levels of TGF-beta mRNA and peptide. Astrocyte release of CMV declined in the presence of antibody to TGF-beta and increased substantially after the addition of exogenous TGF-beta. These findings suggest that CMV infection of astrocytes induces the production of TGF-beta, which in turn enhances productive CMV expression.
authors.affiliation: Oral Infection and Immunity Branch, National Institute of Dental and Crainofacial Research, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Kossmann
authors.forename: M Cristina
authors.initials: MC
authors.lastname: Morganti-Kossmann
authors.forename: Jan M
authors.initials: JM
authors.lastname: Orenstein
authors.forename: William J
authors.initials: WJ
authors.lastname: Britt
authors.forename: Sharon M
authors.initials: SM
authors.lastname: Wahl
authors.forename: Phillip D
authors.initials: PD
authors.lastname: Smith
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000378:metabolism* / Q000821:virology*; D000818:Animals; D001253:Astrocytes / Q000378:metabolism* / Q000821:virology*; D001921:Brain / Q000378:metabolism* / Q000821:virology*; D002478:Cells, Cultured; D003587:Cytomegalovirus / Q000302:isolation & purification*; D003586:Cytomegalovirus Infections / Q000378:metabolism* / Q000821:virology*; D004195:Disease Models, Animal; D018792:Encephalitis, Viral / Q000378:metabolism* / Q000473:pathology / Q000821:virology*; D015497:HIV-1; D006801:Humans; D008297:Male; D051379:Mice; D012333:RNA, Messenger / Q000032:analysis; D016212:Transforming Growth Factor beta / Q000096:biosynthesis* / Q000235:genetics / Q000494:pharmacology; D014779:Virus Replication / Q000187:drug effects
chemical_list: D012333:RNA, Messenger; D016212:Transforming Growth Factor beta