Human cytomegalovirus infection induces transcription and secretion of transforming growth factor beta 1.
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.
Michelson
S
S
Unité d'Immunologie Virale, Institut Pasteur, Paris, France.
Alcami
J
J
Kim
S J
SJ
Danielpour
D
D
Bachelerie
F
F
Picard
L
L
Bessia
C
C
Paya
C
C
Virelizier
J L
JL
D003586:Cytomegalovirus Infections / Q000503:physiopathology*; D015967:Gene Expression Regulation, Viral; D006801:Humans; D017874:Immediate-Early Proteins / Q000502:physiology; D007376:Interleukin-2 / Q000494:pharmacology; D015850:Interleukin-6 / Q000235:genetics; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D016212:Transforming Growth Factor beta / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D014764:Viral Proteins / Q000502:physiology
D017874:Immediate-Early Proteins; D007376:Interleukin-2; D015850:Interleukin-6; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D014764:Viral Proteins