Human cytomegalovirus infection induces transcription and secretion of transforming growth factor beta 1

J Virol. 1994 Sep;68(9):5730-7. doi: 10.1128/JVI.68.9.5730-5737.1994.


Human cytomegalovirus (CMV) infection can elicit a transitory, but profound, immunodepression in immunocompetent individuals. Cytopathogenic destruction of CMV-infected leukocytes alone does not seem sufficient to explain this phenomenon, which suggests that immune system mediators (cytokines) may play a role in amplifying local modifications wrought by CMV infection. We reported previously that transforming growth factor beta 1 (TGF-beta 1) stimulates CMV replication (J. Alcami, C. V. Paya, J. L. Virelizier, and S. Michelson, J. Gen. Virol. 74:269-274, 1993). Since TGF-beta 1 can have profound negative effects on cell growth and immune responses, we investigated the induction of TGF-beta 1 following CMV infection of permissive fibroblasts. TGF-beta 1 promoter was activated by immediate-early (IE) proteins in the absence of infection and transactivated at 5 and 9 h after infection. TGF-beta 1 mRNA increased during the early phase of infection, suggesting that this phenomenon is due to enhanced transcription of the TGF-beta 1 gene. A comparative study of the influence of CMV infection and IE protein expression on TGF-beta 1 promoter function in permissive cells pointed to a possible cooperative role between IE proteins and protein(s) expressed during the early phase of viral infection. Induction of TGF-beta 1 by CMV infection could modify infected cells individually, surrounding tissues, and systemic immune reactions to the advantage of virus replication by both upregulating CMV replication and downregulating host immune responses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cytomegalovirus Infections / physiopathology*
  • Gene Expression Regulation, Viral
  • Humans
  • Immediate-Early Proteins / physiology
  • Interleukin-2 / pharmacology
  • Interleukin-6 / genetics
  • Promoter Regions, Genetic
  • RNA, Messenger / genetics
  • Transcription, Genetic
  • Transcriptional Activation
  • Transforming Growth Factor beta / genetics*
  • Tumor Necrosis Factor-alpha / genetics
  • Viral Proteins / physiology


  • Immediate-Early Proteins
  • Interleukin-2
  • Interleukin-6
  • RNA, Messenger
  • Transforming Growth Factor beta
  • Tumor Necrosis Factor-alpha
  • Viral Proteins