HUMAN CYTOMEGALOVIRUS-INFECTION INDUCES TRANSCRIPTION AND SECRETION OF TRANSFORMING GROWTH-FACTOR-BETA-1

Human cytomegalovirus (CMV) infection can elicit a transitory, but pro found, immunodepression in immunocompetent individuals. Cytopathogenic destruction of CMV-infected leukocytes alone does not seem sufficient to explain this phenomenon, which suggests that immune system mediato rs (cytokines) may play a role in amplifying local modifications wroug ht by CMV infection. We reported previously that transforming growth f actor 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, 1 993). Since TGF-beta 1 can have profound negative effects on cell grow th and immune responses, we investigated the induction of TGF-beta 1 f ollowing CMV infection of permissive fibroblasts. TGP-beta 1 promoter was activated by immediate-early (IE) proteins in the absence of infec tion and transactivated at 5 and 9 h after infection. TGF-beta 1 mRNA increased during the early phase of infection, suggesting that this ph enomenon is due to enhanced transcription of the TGF-beta 1 gene. A co mparative study of the influence of CMV infection and IE protein expre ssion on TGF-beta 1 promoter function in permissive cells pointed to a possible cooperative role between IE proteins and protein(s) expresse d during tile early phase of viral infection. Induction of TGF-beta 1 by CMV infection could modify. infected cells individually, surroundin g tissues, and systemic immune reactions to the advantage of virus rep lication by both upregulating CMV replication and downregulating host immune responses.