Publications (22) View all
-
Article: Novel DNA polymerase mutations conferring cytomegalovirus resistance: Input of BAC-recombinant phenotyping and 3D model.
[show abstract] [hide abstract]
ABSTRACT: Long-term exposure to antiviral therapy in immunocompromised patients favors emergence of human cytomegalovirus (HCMV) resistance mutations. Two new UL54 DNA polymerase mutations (deletion of codon 524 and N408S substitution) identified in a kidney recipient and a bone marrow recipient respectively were characterized. Marker transfer experiment through recombination into a HCMV AD169 BAC demonstrated del524 and mutation N408S confer GCV and CDV resistance. These results suggest continued mutation of UL54 under selective antiviral pressure. Characterization of each new mutation is thus required to inform genotypic assays and to better understand the functional regions of UL54 for the development of novel antivirals.Antiviral research 02/2013; · 3.61 Impact Factor -
Article: [Gardasil®-induced erythema nodosum].
[show abstract] [hide abstract]
ABSTRACT: Erythema nodosum is a panniculitis occurring more frequently in young women. We report a 16-year-old woman who presented with erythema nodosum that occurred following Gardasil® administration (vaccine against HPV types 6, 11, 16 and 18) and that is proposed to young female. This adverse effect is not a contraindication to the HPV vaccination because its benefit against the oncogene risk of Papillomavirus is documented.La Revue de Médecine Interne 03/2011; 33(3):e17-8. · 0.61 Impact Factor -
Article: Insight into the structure of the pUL89 C-terminal domain of the human cytomegalovirus terminase complex.
[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: Drug-resistant cytomegalovirus in transplant recipients: a French cohort study.
[show abstract] [hide abstract]
ABSTRACT: Cytomegalovirus (CMV) drug resistance is a therapeutic challenge in the transplant setting. No longitudinal cohort studies of CMV resistance in a real-life setting have been published in the valganciclovir era. We report findings for a French multicentre prospective cohort of 346 patients enrolled at initial diagnosis of CMV infection (clinical trial registered at clinicaltrials.gov: NCT01008540). Patients were monitored for detection of CMV infection for ≥2 years. Real-time detection of resistance by UL97 and UL54 gene sequencing and antiviral phenotyping was performed if viral replication persisted for >21 days of appropriate antiviral treatment. Plasma ganciclovir assays were performed when resistance was suspected. Resistance was suspected in 37 (10.7%) patients; 18/37 (5.2% of the cohort) had virological resistance, associated with poorer outcome. Most cases involved single UL97 mutations, but four cases of multidrug resistance were due to UL54 mutations. In solid organ transplant recipients, resistance occurred mainly during primary CMV infection (odds ratio 8.78), but also in two CMV-seropositive kidney recipients. Neither CMV prophylaxis nor antilymphocyte antibody administration was associated with virological resistance. These data show the feasibility of surveying resistance. Virological resistance was frequent in patients failing antiviral therapy. More than 1/5 resistant isolates harboured UL54 mutations alone or combined with UL97 mutations, which conferred a high level of resistance and sometimes were responsible for cross-resistance, leading to therapeutic failure.Journal of Antimicrobial Chemotherapy 10/2010; 65(12):2628-40. · 5.07 Impact Factor -
Article: [HPV detection and typing by INNO-LiPA assay on liquid cytology media Easyfix Labonord after extraction QIAamp DNA Blood Mini Kit Qiagen and Nuclisens easyMAG Biomérieux].
[show abstract] [hide abstract]
ABSTRACT: The objective of this study is to validate the use of test INNO-LIPA HPV Genotyping Extra (Innogenetics) on liquid cytology media EasyFix Labonord by comparing the extraction kit QIAamp DNA Blood Mini Kit (Qiagen) and an automated method, Nuclisens easyMAG (Biomérieux). Thirty-two samples were typed by the technique Hybrid Capture 2 (HC2) Digene (Qiagen). DNA was extracted through manual or automated extraction and quality controlled PCR "HLA". Typing was performed with the INNO-LIPA test. A nested PCR followed by sequencing was used to compare different results. Similar results were found for the two types of extraction, with an increase of sensitivity after automated extraction. Among the nine patients with a negative result with the HC2 test, seven had a negative result in INNO-LIPA and two a positive result (one untypable and one HPV66). On the 23 patients with a positive result with the HC2 test, 17 are consistent results. The six discordant results include one negative, one HPV54, two untypable HPV and two HPV53. The overall concordance between the HC2 and INNO-LIPA tests is 81% with a kappa test of 0.79. Coupled with an automated extraction, the test INNO-LIPA confirmed its high sensitivity for detecting and typing HPV in the EasyFix media Labonord, especially in the presence of multiple genotypes. This typing systematic approach is becoming increasingly relevant in the context of HPV vaccination.Pathologie Biologie 10/2009; 58(2):179-83. · 1.53 Impact Factor
