G Champier

Publications (2)6.21 Total impact

• Article: Insight into the structure of the pUL89 C-terminal domain of the human cytomegalovirus terminase complex.

  A Couvreux, S Hantz, R Marquant, G Champier, S Alain, N Morellet, S Bouaziz
  [show abstract] [hide abstract]
  ABSTRACT: In a previous study, we identified 12 conserved domains within pUL89, the small terminase subunit of the human cytomegalovirus. A latter study showed that the fragment pUL89(580-600) plays an important role in the formation of the terminase complex by interacting with the large terminase subunit pUL56. In this study, analysis was performed to solve the structure of pUL89(568-635) in 50% H2O/50% acetonitrile (v/v). We showed that pUL89(568-635) consists of four alpha helices, but we did not identify any tertiary structure. The fragment 580-600 formed an amphipathic alpha helix, which had a hydrophobic side highly conserved among herpesviral homologs of pUL89; this was not observed for its hydrophilic side. The modeling of pUL89(457-612) using the recognition fold method allowed us to position pUL89(580-600) within this domain. The theoretical structure highlighted three important features. First, we identified a metal-binding pocket containing residues Asp(463), Glu(534), and Glu(588), which are highly conserved among pUL89 homologs. Second, the model predicted a positively charged surface able to interact with the DNA duplex during the nicking event. Third, a hydrophobic patch on the top of the catalytic site suggested that this may constitute part of the pUL89 site recognized by pUL56 potentially involved in DNA binding.
  Proteins Structure Function and Bioinformatics 05/2010; 78(6):1520-30. · 3.39 Impact Factor
• Article: Detection of ganciclovir resistance after valacyclovir-prophylaxis in renal transplant recipients with active cytomegalovirus infection.

  S Alain, S Hantz, C Scieux, A Karras, M C Mazeron, J C Szelag, B M Imbert, A M Fillet, S Gouarin, C Mengelle, A De Wilde, N Cogne, G Champier, S Rogez, C Legendre, F Denis
  [show abstract] [hide abstract]
  ABSTRACT: Whether valaciclovir (VCV) prophylaxis could be responsible for ganciclovir (GCV)-resistance of Human cytomegalovirus (HCMV) in transplantation has never been documented. A multicentric retrospective pilot study was undertaken to detect GCV-resistance through mutations within the UL97 gene in renal transplant recipients who experienced active HCMV infection and received valacyclovir prophylaxis. Twenty-three patients who experienced HCMV antigenaemia or DNAemia during or at the end of prophylaxis were included. UL97 genotyping was carried out on peripheral blood samples, using a nested in-house PCR, which amplified the full-length UL97 gene. One patient has a resistance-related mutation (M460I); the major risk factor for emergence of resistance in this patient was the presence of early and persistent antigenaemia. GCV-resistance during VCV-prophylaxis was rare after renal transplantation. However, special attention must be paid to patients developing early active HCMV infection under prophylaxis.
  Journal of Medical Virology 09/2004; 73(4):566-73. · 2.82 Impact Factor