Archives of Virology

, Volume 157, Issue 1, pp 63–74 | Cite as

Activating transcription factor 4 (ATF4) is upregulated by human herpesvirus 8 infection, increases virus replication and promotes proangiogenic properties

  • Elisabetta Caselli
  • Sabrina Benedetti
  • Jessica Grigolato
  • Arnaldo Caruso
  • Dario Di Luca
Original Article


Human herpesvirus 8 (HHV-8) triggers proangiogenic behaviour in endothelial cells by inducing monocyte chemoattractant protein 1 (MCP-1) through activation of Nuclear Factor κB (NF-κB). However, NF-κB inhibition still results in partial MCP-1 induction and consequent angiogenesis, suggesting the involvement of another transcriptional pathway. We analysed activating transcription factor 4 (ATF4), since it is central in the cellular response to stress and is involved in angiogenesis. The results show that HHV-8 upregulates ATF4 expression, which in turn promotes HHV-8 infection, and induces MCP-1 production and proangiogenic properties in endothelial cells. By contrast, ATF4 silencing decreases virus replication and inhibits virus-induced MCP-1 production and induction of tube-like structures. Therefore, ATF4 plays a role in HHV-8 replication and associated virus-induced angiogenesis. The elucidation of molecular pathways involved in this process will result in a better understanding of the virus-induced angiogenic process and might help in designing novel therapies to reduce tumour growth.


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Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Elisabetta Caselli
    • 1
  • Sabrina Benedetti
    • 1
  • Jessica Grigolato
    • 1
  • Arnaldo Caruso
    • 2
  • Dario Di Luca
    • 1
  1. 1.Section of Microbiology, Department of Experimental and Diagnostic MedicineUniversity of FerraraFerraraItaly
  2. 2.Section of MicrobiologyUniversity of BresciaBresciaItaly

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