Human cytomegalovirus induces upregulation of arginase II: Possible implications for vasculopathies

Koon Chu Yaiw, Abdul Aleem Mohammad, Chato Taher, Vanessa Wilhelmi, Belghis Davoudi, Klas Strååt, Alice Assinger, Olga Ovchinnikova, Eugene Shlyakhto, Afsar Rahbar, Oksana Koutonguk, Piotr Religa, Lynn Butler, Zahidul Khan, Daniel Streblow, John Pernow, Cecilia Söderberg-Nauclér

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

Both human cytomegalovirus (HCMV) and arginase II (ARG II) have been implicated in the pathogenesis of cardiovascular diseases. The effects of HCMV on ARG II are unknown. The aim of this study was to investigate the effects of HCMV on ARG II expression in endothelial and vascular smooth muscle cells (SMC) both in vitro and ex vivo. Endothelial and SMC were infected with either HCMV or UV-irradiated HCMV. Expression of ARG II, endothelial or inducible nitric oxide synthase (eNOS and iNOS, respectively) and viral immediate early (IE) was quantified using quantitative PCR. Ganciclovir and short interfering RNA were used to determine the viral gene mediating the effects on ARG II. Detection of viral antigens and ARG II expression was performed by immunofluorescence or immunohistochemistry. HCMV infection increased both ARG II mRNA and protein levels in the examined cells; this effect was mediated by the HCMV IE2-p86 protein. The upregulation of ARG II was accompanied by a downregulation of eNOS but an induction of iNOS in HCMV-infected endothelial cells. Both eNOS and iNOS expressions were induced in HCMV-infected SMC. ARG II was abundantly expressed in endothelial cells, foam cells and SMC and was importantly significantly upregulated in HCMV-immunoreactive human carotid atherosclerotic plaques. HCMV IE2-p86 mediates ARG II upregulation in vitro and ARG II is co-expressed with HCMV antigens in human carotid atherosclerotic plaques. We speculate that HCMV may contribute to endothelial dysfunction via ARG II induction and reduced eNOS production.

Original languageEnglish (US)
Article number401
JournalBasic Research in Cardiology
Volume109
Issue number2
DOIs
StatePublished - Mar 2014

Keywords

  • Arginase
  • Cytomegalovirus
  • Immediate early gene
  • Nitric oxide synthase

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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    Yaiw, K. C., Mohammad, A. A., Taher, C., Wilhelmi, V., Davoudi, B., Strååt, K., Assinger, A., Ovchinnikova, O., Shlyakhto, E., Rahbar, A., Koutonguk, O., Religa, P., Butler, L., Khan, Z., Streblow, D., Pernow, J., & Söderberg-Nauclér, C. (2014). Human cytomegalovirus induces upregulation of arginase II: Possible implications for vasculopathies. Basic Research in Cardiology, 109(2), [401]. https://doi.org/10.1007/s00395-014-0401-5