title: Low multiplicity cytomegalovirus infection of human aortic smooth muscle cells increases levels of major histocompatibility complex class I antigens and induces a proinflammatory cytokine milieu in the absence of cytopathology.
abstract: BACKGROUND
  Cytomegalovirus has been implicated in the development of allograft vasculopathy in heart transplant recipients. Given that allograft vasculopathy is a form of chronic rejection, it is conceivable that cytomegalovirus somehow alters the allogeneic response to the vasculature. Prior work has demonstrated that smooth muscle cells (SMCs) are highly permissive for cytomegalovirus and exhibit cytopathologic characteristics and alterations in MHC class I antigens in response to cytomegalovirus at a high multiplicity of infection (MOI).
  
  
  METHODS
  To determine whether cytomegalovirus at low, more clinically relevant MOI, can alter SMCs phenotypically, human aortic SMCs were infected with approximately 1 plaque forming units/3000 cells of cytomegalovirus strain AD169.
  
  
  RESULTS
  One week after infection, human aortic SMCs (compared with human foreskin fibroblasts) demonstrated no cytopathologic characteristics (n = 6), released reduced amounts of intact virion into the culture media (assessed by exposing naive monolayers of human foreskin fibroblasts to media and staining for cytomegalovirus immediate-early antigen, n = 3), yet had at least, if not greater detectable total cytomegalovirus vital DNA levels. Infected HASMCs uniformly increased their expression of MHC class I antigen by 55% +/- 21% above constitutive levels (assessed by flow cytometry (n = 5, p < 0.0001). Cytomegalovirus infection resulted in an increase in interleukin-6 mRNA expression compared to control (297 +/- 63 vs 188 +/- 50, respectively; p = 0.02, n = 6) and reduced the expression of transforming growth factor-beta mRNA (802 +/- 152 vs 1201 +/- 236, respectively; p = 0.05).
  
  
  CONCLUSIONS
  These data suggest that low MOI of cytomegalovirus can infect SMCs without producing cell cytolysis and, in spite of this lack of overt infection, modulate cell surface antigens and cytokine mRNA levels that can influence allogeneic responses.
authors.affiliation: Cardiovascular Research Center, Medical College of Wisconsin, Milwaukee, 53226, USA.
authors.forename: B
authors.initials: B
authors.lastname: Arkonac
authors.forename: K A
authors.initials: KA
authors.lastname: Mauck
authors.forename: S
authors.initials: S
authors.lastname: Chou
authors.forename: J D
authors.initials: JD
authors.lastname: Hosenpud
mesh_terms: D000956:Antigens, Viral / Q000032:analysis / Q000276:immunology; D001018:Aortic Diseases / Q000276:immunology / Q000821:virology*; D002478:Cells, Cultured; D002908:Chronic Disease; D004396:Coloring Agents; D003327:Coronary Disease / Q000821:virology; D003470:Culture Media; D016207:Cytokines / Q000032:analysis* / Q000276:immunology; D003587:Cytomegalovirus / Q000276:immunology* / Q000502:physiology; D003586:Cytomegalovirus Infections / Q000276:immunology*; D003588:Cytopathogenic Effect, Viral; D004279:DNA, Viral / Q000032:analysis; D005347:Fibroblasts / Q000276:immunology / Q000821:virology; D015967:Gene Expression Regulation, Viral; D006084:Graft Rejection / Q000821:virology; D016027:Heart Transplantation / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000032:analysis* / Q000276:immunology; D006801:Humans; D017874:Immediate-Early Proteins / Q000032:analysis / Q000276:immunology; D015850:Interleukin-6 / Q000032:analysis / Q000235:genetics; D009131:Muscle, Smooth, Vascular / Q000276:immunology / Q000821:virology*; D010641:Phenotype; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000032:analysis / Q000235:genetics; D014184:Transplantation, Homologous; D014771:Virion / Q000378:metabolism; D014779:Virus Replication
chemical_list: D000956:Antigens, Viral; D004396:Coloring Agents; D003470:Culture Media; D016207:Cytokines; D004279:DNA, Viral; D015395:Histocompatibility Antigens Class I; D017874:Immediate-Early Proteins; D015850:Interleukin-6; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta