Publications by authors named "Coralie Pallier"

35 Publications

Comparison of the Abbott Alinity m and m2000 assays for the quantification of HIV-1, HCV and HBV in clinical samples.

J Clin Virol 2020 05 11;126:104331. Epub 2020 Mar 11.

Virologie, AP-HP, Hôpital Paul Brousse, Villejuif, 94804, France; INSERM U1193, Villejuif, 94804, France; Univ Paris-Sud Villejuif, 94804, France. Electronic address:

Background: Viral load (VL) determination is an essential parameter of the management of patients infected with HIV, HBV or HCV. Many available molecular systems run on a "batch" mode while "random access" systems provide more flexibility.

Objectives: We compared the performance of HIV-1, HCV and HBV quantification assays on the recently developed Abbott Alinity m system to the m2000 RealTime assays.

Study Design: Plasma specimens sent for viral load determination were prospectively tested on m2000 and Alinity m systems, according to manufacturers' instructions. Additional low and high tittered samples were used to assess reproducibility.

Results: Assays concordance was evaluated from 180 samples for HIV-1, 122 for HBV, and 92 for HCV. A good correlation and a linear relation over the quantification range was observed for the three markers (r > 0.974). The Alinity m assays yielded higher results with a mean quantification bias of 0.22 log cp/ml for 75 HIV-1, 0.3 log IU/ml for 79 HBV, and 0.2 log for 35 HCV samples, though results were equivalent within an allowable difference of 0.3-0.4 log. Qualitative discordance was observed for 43/180 HIV results, 10/122 HBV and 7/92 HCV and involved undetectable or low-level VL.

Conclusion: The Alinity m assays have performance equivalent to m2000. Upon implementation, physicians should be aware of the relative overquantification compared to previous Abbott assays, particularly around clinical decision thresholds. With reduced turnarounds and hands-on times compared to the m2000 system, the Alinity m platform may improve significantly the laboratory workflow efficiency for the benefit of physicians and patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jcv.2020.104331DOI Listing
May 2020

Surveillance of HIV-1 primary infections in France from 2014 to 2016: toward stable resistance, but higher diversity, clustering and virulence?

J Antimicrob Chemother 2020 01;75(1):183-193

Centre National de Référence VIH, Paris, France.

Objectives: Patients with primary HIV-1 infection (PHI) are a particular population, giving important insight about ongoing evolution of transmitted drug resistance-associated mutation (TDRAM) prevalence, HIV diversity and clustering patterns. We describe these evolutions of PHI patients diagnosed in France from 2014 to 2016.

Methods: A total of 1121 PHI patients were included. TDRAMs were characterized using the 2009 Stanford list and the French ANRS algorithm. Viral subtypes and recent transmission clusters (RTCs) were also determined.

Results: Patients were mainly MSM (70%) living in the Paris area (42%). TDRAMs were identified among 10.8% of patients and rose to 18.6% when including etravirine and rilpivirine TDRAMs. Prevalences of PI-, NRTI-, first-generation NNRTI-, second-generation NNRTI- and integrase inhibitor-associated TDRAMs were 2.9%, 5.0%, 4.0%, 9.4% and 5.4%, respectively. In a multivariable analysis, age >40 years and non-R5 tropic viruses were associated with a >2-fold increased risk of TDRAMs. Regarding HIV diversity, subtype B and CRF02_AG (where CRF stands for circulating recombinant form) were the two main lineages (56% and 20%, respectively). CRF02_AG was associated with higher viral load than subtype B (5.83 versus 5.40 log10 copies/mL, P=0.004). We identified 138 RTCs ranging from 2 to 14 patients and including overall 41% from the global population. Patients in RTCs were younger, more frequently born in France and more frequently MSM.

Conclusions: Since 2007, the proportion of TDRAMs has been stable among French PHI patients. Non-B lineages are increasing and may be associated with more virulent CRF02_AG strains. The presence of large RTCs highlights the need for real-time cluster identification to trigger specific prevention action to achieve better control of the epidemic.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/jac/dkz404DOI Listing
January 2020

New HIV-1 circulating recombinant form 94: from phylogenetic detection of a large transmission cluster to prevention in the age of geosocial-networking apps in France, 2013 to 2017.

Euro Surveill 2019 Sep;24(39)

Members are listed in the acknowledgements.

BackgroundEnding the HIV pandemic must involve new tools to rapidly identify and control local outbreaks and prevent the emergence of recombinant strains with epidemiological advantages.AimThis observational study aimed to investigate in France a cluster of HIV-1 cases related to a new circulating recombinant form (CRF). The confirmation this CRF's novelty as well as measures to control its spread are presented.MethodsPhylogenetic analyses of HIV sequences routinely generated for drug resistance genotyping before 2018 in French laboratories were employed to detect the transmission chain. The CRF involved was characterised by almost full-length viral sequencing for six cases. Cases' clinical data were reviewed. Where possible, epidemiological information was collected with a questionnaire.ResultsThe transmission cluster comprised 49 cases, mostly diagnosed in 2016-2017 (n = 37). All were infected with a new CRF, CRF94_cpx. The molecular proximity of this CRF to X4 strains and the high median viraemia, exceeding 5.0 log copies/mL, at diagnosis, even in chronic infection, raise concerns of enhanced virulence. Overall, 41 cases were diagnosed in the Ile-de-France region and 45 were men who have sex with men. Among 24 cases with available information, 20 reported finding partners through a geosocial networking app. Prevention activities in the area and population affected were undertaken.ConclusionWe advocate the systematic use of routinely generated HIV molecular data by a dedicated reactive network, to improve and accelerate targeted prevention interventions. Geosocial networking apps can play a role in the spread of outbreaks, but could also deliver local targeted preventive alerts.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2807/1560-7917.ES.2019.24.39.1800658DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6774227PMC
September 2019

Prevalence of hepatitis E virus and reassessment of HIV and other hepatitis virus seroprevalences among French prison inmates.

PLoS One 2019 26;14(6):e0218482. Epub 2019 Jun 26.

Virologie, Hôpital Paul Brousse, AP-HP, Villejuif, France.

Background: Prison inmates are considered a high-risk population for blood-borne and enterically transmitted infections before and during their imprisonment. Hepatitis E virus (HEV) prevalence is unknown among French inmates, whereas a reassessment of human immunodeficiency virus (HIV), hepatitis A virus (HAV), hepatitis B virus (HBV) and hepatitis C virus (HCV) prevalences is required to describe the epidemiologic evolution in this high-risk population.

Methods: A prospective survey was conducted from June to December 2017 in Fresnes prison, a penitentiary center with 2,581 inmates. In addition to HIV, HAV, HBV and HCV testing, which is offered to all patients at admission, we systematically offered HEV screening. Retrospective serological data for HIV, HBV and HCV, collected annually from 2014 to 2017, were also used to assess evolution.

Results: In 2017, 1,093 inmates were screened for HEV, HIV, HAV, HBV and HCV. Prevalences in this population were 8.2%, 1.3%, 62.7%, 1.9% and 2.9%, respectively. HEV seroprevalence increased with age (p<0.0001) and was higher among Eastern Europe born inmates (p<0.0001). Between 2014 and 2017, HIV seroprevalence remained steady, while a decrease in HBV and HCV seroprevalence was observed.

Conclusions: Compared to the reported prevalence in French blood donors, HEV seroprevalence was remarkably low in French inmates. HIV, HAV, HBV and HCV prevalences among prisoners were higher than reported in the general population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0218482PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6594613PMC
February 2020

Dolutegravir Cerebrospinal Fluid Diffusion in HIV-1-Infected Patients with Central Nervous System Impairment.

Open Forum Infect Dis 2019 Jun 3;6(6):ofz174. Epub 2019 Jun 3.

Department of Internal Medicine, Assistance Publique-Hôpitaux de Paris, Hôpitaux Universitaires Paris-Sud, Hôpital Bicêtre, Le Kremlin-Bicêtre, France.

This study aimed to determine dolutegravir cerebrospinal fluid (CSF) diffusion in 13 patients with HIV-related cerebral impairment enrolled in a real-life observational study. Dolutegravir median (range) CSF concentration [9.6 (3.6-22.8) ng/mL] reached CSF therapeutic concentrations whatever the blood-brain barrier status and diffused in correlation with the albumin quotient ( = .0186).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/ofid/ofz174DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6546201PMC
June 2019

Resistance to integrase inhibitors: a national study in HIV-1-infected treatment-naive and -experienced patients.

J Antimicrob Chemother 2019 05;74(5):1368-1375

Sorbonne Université, INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique (IPLESP), AP-HP, Hôpital Pitié-Salpêtrière, Service de Virologie, Paris, France.

Objectives: To describe integrase strand transfer inhibitor (INSTI) resistance profiles and factors associated with resistance in antiretroviral-naive and -experienced patients failing an INSTI-based regimen in clinical practice.

Methods: Data were collected from patients failing an INSTI-containing regimen in a multicentre French study between 2014 and 2017. Failure was defined as two consecutive plasma viral loads (VL) >50 copies/mL. Reverse transcriptase, protease and integrase coding regions were sequenced at baseline and failure. INSTI resistance-associated mutations (RAMs) included in the Agence Nationale de Recherches sur le SIDA genotypic algorithm were investigated.

Results: Among the 674 patients, 359 were failing on raltegravir, 154 on elvitegravir and 161 on dolutegravir therapy. Overall, 90% were experienced patients and 389 (58%) patients showed no INSTI RAMs at failure. The strongest factors associated with emergence of at least one INSTI mutation were high VL at failure (OR = 1.2 per 1 log10 copies/mL increase) and low genotypic sensitivity score (GSS) (OR = 0.08 for GSS ≥3 versus GSS = 0-0.5). Patients failing dolutegravir also had significantly fewer INSTI RAMs at failure than patients failing raltegravir (OR = 0.57, P = 0.02) or elvitegravir (OR = 0.45, P = 0.005). Among the 68 patients failing a first-line regimen, 11/41 (27%) patients on raltegravir, 7/18 (39%) on elvitegravir and 0/9 on dolutegravir had viruses with emergent INSTI RAMs at failure.

Conclusions: These results confirmed the robustness of dolutegravir regarding resistance selection in integrase in the case of virological failure in routine clinical care.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/jac/dkz021DOI Listing
May 2019

Stable prevalence of transmitted drug resistance mutations and increased circulation of non-B subtypes in antiretroviral-naive chronically HIV-infected patients in 2015/2016 in France.

J Antimicrob Chemother 2019 05;74(5):1417-1424

Hopital Bichat Claude Bernard, Virology, Paris, France.

Objectives: We estimated the prevalence of transmitted-drug-resistance-associated mutations (TDRAMs) in antiretroviral-naive chronically HIV-1-infected patients.

Patients And Methods: TDRAMs were sought in samples from 660 diagnosed HIV-1-infected individuals in 2015/2016 in 33 HIV clinical centres. Weighted analyses, considering the number of patients followed in each centre, were used to derive representative estimates of the percentage of individuals with TDRAMs. Results were compared with those of the 2010/2011 survey (n = 661) using the same methodology.

Results: At inclusion, median CD4 cell counts and plasma HIV-1 RNA were 394 and 350/mm3 (P = 0.056) and 4.6 and 4.6 log10 copies/mL (P = 0.360) in the 2010/2011 survey and the 2015/2016 survey, respectively. The frequency of non-B subtypes increased from 42.9% in 2010/2011 to 54.8% in 2015/2016 (P < 0.001), including 23.4% and 30.6% of CRF02_AG (P = 0.004). The prevalence of virus with protease or reverse-transcriptase TDRAMs was 9.0% (95% CI = 6.8-11.2) in 2010/2011 and 10.8% (95% CI = 8.4-13.2) in 2015/2016 (P = 0.269). No significant increase was observed in integrase inhibitor TDRAMs (6.7% versus 9.2%, P = 0.146). Multivariable analysis showed that men infected with the B subtype were the group with the highest risk of being infected with a resistant virus compared with others (adjusted OR = 2.2, 95% CI = 1.3-3.9).

Conclusions: In France in 2015/2016, the overall prevalence of TDRAMs was 10.8% and stable compared with 9.0% in the 2010/2011 survey. Non-B subtypes dramatically increased after 2010. Men infected with B subtype were the group with the highest risk of being infected with a resistant virus, highlighting the need to re-emphasize safe sex messages.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/jac/dkz011DOI Listing
May 2019

False hepatitis B and C viral serologies in patients with multiple sclerosis receiving high-dose biotin.

Mult Scler 2020 02 11;26(2):257-258. Epub 2018 Dec 11.

Department of Neurology, Hôpital Pitié-Salpêtrière, AP-HP, Paris, France.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/1352458518818294DOI Listing
February 2020

Phenotypic analysis of HIV-1 E157Q integrase polymorphism and impact on virological outcome in patients initiating an integrase inhibitor-based regimen.

J Antimicrob Chemother 2018 04;73(4):1039-1044

IAME, UMR 1137, INSERM, Université Paris Diderot, Sorbonne Paris Cité, AP-HP, Laboratoire de Virologie, Hôpital Bichat, AP-HP, Paris, France.

Objectives: To assess the phenotypic susceptibility of the E157Q polymorphism in HIV-1 integrase (IN) and the virological outcome of patients infected with E157Q-mutated virus initiating an IN inhibitor (INI)-based regimen.

Methods: This was a multicentre study assessing IN sequences from INI-naive patients among 17 French HIV clinical centres. E157Q site-directed mutants in pNL4.3 and pCRF02_AG contexts were assessed in a recombinant phenotypic assay.

Results: Prevalence of the E157Q polymorphism was 2.7% among 8528 IN sequences from INI-naive patients and its distribution was 1.7%, 5.6% and 2.2% in B, CRF02_AG and various non-B subtypes, respectively. Thirty-nine INI-naive patients with E157Q-mutated virus initiated an INI-based regimen. Among them, 15 had a viral load (VL) <50 copies/mL at initiation and virological suppression was maintained during the first year of follow-up in all but two exhibiting a viral blip. Twenty-four patients had a VL > 50 copies/mL at the time of INI-based regimen initiation. Among them eight were receiving a first-line regimen and the only two patients who did not reach VL < 50 copies/mL at week 24 were receiving elvitegravir. The 16 remaining patients were ART experienced in virological failure with drug-resistant viruses displaying several virological outcomes independently of the genotypic susceptibility score. Phenotypic analyses showed a fold change in EC50 of 0.6, 0.9 and 1.9 for raltegravir, dolutegravir and elvitegravir, respectively, in a subtype B context, and 1.1, 1.9 and 2.4 for raltegravir, dolutegravir and elvitegravir, respectively, in a CRF02_AG context.

Conclusions: Assessment of virological response in 39 patients initiating an INI-based regimen with E157Q-mutated virus, in combination with phenotypic analysis, suggests that particular attention should be paid to antiretroviral-naive patients and dolutegravir should be preferentially used in these patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/jac/dkx511DOI Listing
April 2018

Impact of Human Immunodeficiency Virus Type 1 Minority Variants on the Virus Response to a Rilpivirine-Based First-line Regimen.

Clin Infect Dis 2018 05;66(10):1588-1594

Institut national de la santé et de la recherche médicale (INSERM).

Background: Minority resistant variants of human immunodeficiency virus type 1 (HIV-1) could influence the virological response to treatment based on nonnucleoside reverse transcriptase inhibitors (NNRTIs). Data on minority rilpivirine-resistant variants are scarce. This study used next-generation sequencing (NGS) to identify patients harboring minority resistant variants to nucleos(t)ide reverse transcriptase inhibitors and NNRTIs and to assess their influence on the virological response (VR).

Methods: All the subjects, 541 HIV-1-infected patients started a first-line regimen containing rilpivirine. VR was defined as a HIV-1 RNA load <50 copies/mL at month 6 with continued suppression at month 12. NGS was performed at baseline (retrospectively) on the 454 GS-FLX platform (Roche).

Results: NGS revealed resistance-associated mutations accounting for 1% to <5% of variants in 17.2% of samples, for 5%-20% in 5.7% of samples, and for >20% in 29% of samples. We identified 43 (8.8%) and 36 (7.4%) patients who harbored rilpivirine-resistant variants with a 1% sensitivity threshold according to the French National Agency for Research on AIDS and Viral Hepatitis and Stanford algorithms, respectively. The VR was 96.9% at month 12. Detection of minority rilpivirine resistant variants was not associated with virological failure (VF). Multivariate analysis indicated that VF at month 12 was associated with a CD4 count <250 cells/µL at baseline, a slower decrease in viral load at month 3, and rilpivirine resistance at baseline using the Stanford algorithm with a 20% threshold.

Conclusions: Minority resistant variants had no impact on the VR of treatment-naive patients to a rilpivirine-based regimen.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/cid/cix1070DOI Listing
May 2018

Antiretroviral-treated HIV-1 patients can harbour resistant viruses in CSF despite an undetectable viral load in plasma.

J Antimicrob Chemother 2017 08;72(8):2351-2354

Sorbonne Universités, UPMC Univ. Paris 06-UMR_S 1136 Pierre Louis Institute of Epidemiology and Public Health, F-75005 Paris, France.

Background: HIV therapy reduces the CSF HIV RNA viral load (VL) and prevents disorders related to HIV encephalitis. However, these brain disorders may persist in some cases. A large population of antiretroviral-treated patients who had a VL > 1.7 log 10 copies/mL in CSF with detectable or undetectable VL in plasma associated with cognitive impairment was studied, in order to characterize discriminatory factors of these two patient populations.

Methods: Blood and CSF samples were collected at the time of neurological disorders for 227 patients in 22 centres in France and 1 centre in Switzerland. Genotypic HIV resistance tests were performed on CSF. The genotypic susceptibility score was calculated according to the last Agence Nationale de Recherche sur le Sida et les hépatites virales Action Coordonnée 11 (ANRS AC11) genotype interpretation algorithm.

Results: Among the 227 studied patients with VL > 1.7 log 10 copies/mL in CSF, 195 had VL detectable in plasma [median (IQR) HIV RNA was 3.7 (2.7-4.7) log 10 copies/mL] and 32 had discordant VL in plasma (VL < 1.7 log 10 copies/mL). The CSF VL was lower (median 2.8 versus 4.0 log 10 copies/mL; P  <   0.001) and the CD4 cell count was higher (median 476 versus 214 cells/mm 3 ; P  <   0.001) in the group of patients with VL < 1.7 log 10 copies/mL in plasma compared with patients with plasma VL > 1.7 log 10 copies/mL. Resistance to antiretrovirals was observed in CSF for the two groups of patients.

Conclusions: Fourteen percent of this population of patients with cognitive impairment and detectable VL in CSF had well controlled VL in plasma. Thus, it is important to explore CSF HIV (VL and genotype) even if the HIV VL is controlled in plasma because HIV resistance may be observed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/jac/dkx128DOI Listing
August 2017

Coexistence of circulating HBsAg and anti-HBs antibodies in chronic hepatitis B carriers is not a simple analytical artifact and does not influence HBsAg quantification.

J Clin Virol 2015 Jan 18;62:32-7. Epub 2014 Nov 18.

AP-HP, Pitié-Salpêtrière Hospital, Virology Department, Paris, France; Inserm U1135, F-75013 Paris, France. Electronic address:

Background: Presence at the same time of HBsAg and anti-HBs antibodies (HBsAg/Ab) is an entity sometimes encountered in chronic hepatitis B (CHB) carriers.

Objectives: This study was designed to characterize such serological profiles and to assess the reliability of serological marker quantification by three commercially available assays in this setting.

Study Design: Among 2578 CHB identified patients, 129 (5%) had an HBsAg/Ab profile as determined by Abbott Architect. After exclusion of co-infections (HIV, HCV, HDV), HBV reactivation or HBIg treatment, 101 samples from 62 patients were tested for HBsAg and anti-HBs quantification using Architect, DiaSorin Liaison-XL and Roche Modular-Cobas. Influence of genotype and HBsAg variants was studied in 31 samples with HBV replication.

Results: HBsAg detection was confirmed with the 3 techniques for 98% (n = 99) of the samples while the HBsAg/Ab profile was concordant between all techniques for 65% of them. The overall correlation between the 3 HBsAg quantification techniques was good (R(2): 0.94-0.97). The median HBsAg concentration was comparable for the 99 samples whatever the used technique but a bias of -0.11 and 0.02 log IU/mL were noticed for DiaSorin and Roche compared to Abbott, respectively. Anti-HBs quantifications were poorly correlated between techniques with major discrepancies observed. Genotype and substitutions within the "a" determinant showed an impact on HBsAg quantification.

Conclusions: The double HBsAg/Ab profile is not an analytical artifact and is confirmed on all commercially available techniques. While such profile does not influence HBsAg quantification, differences of HBsAg quantification were noticed according to HBV genotype or HBsAg variant.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jcv.2014.11.015DOI Listing
January 2015

Antiretroviral-naive and -treated HIV-1 patients can harbour more resistant viruses in CSF than in plasma.

J Antimicrob Chemother 2015 Feb 25;70(2):566-72. Epub 2014 Oct 25.

Sorbonne Universités, UPMC Université de Paris, 06-UMR_S 1136 Pierre Louis Institute of Epidemiology and Public Health, F-75005 Paris, France INSERM-UMR_S 1136 Pierre Louis Institute of Epidemiology and Public Health, F-75013 Paris, France AP-HP, Groupe hospitalier Pitié Salpêtrière, Laboratoire de Virologie, F-75013 Paris, France.

Objectives: The neurological disorders in HIV-1-infected patients remain prevalent. The HIV-1 resistance in plasma and CSF was compared in patients with neurological disorders in a multicentre study.

Methods: Blood and CSF samples were collected at time of neurological disorders for 244 patients. The viral loads were >50 copies/mL in both compartments and bulk genotypic tests were realized.

Results: On 244 patients, 89 and 155 were antiretroviral (ARV) naive and ARV treated, respectively. In ARV-naive patients, detection of mutations in CSF and not in plasma were reported for the reverse transcriptase (RT) gene in 2/89 patients (2.2%) and for the protease gene in 1/89 patients (1.1%). In ARV-treated patients, 19/152 (12.5%) patients had HIV-1 mutations only in the CSF for the RT gene and 30/151 (19.8%) for the protease gene. Two mutations appeared statistically more prevalent in the CSF than in plasma: M41L (P=0.0455) and T215Y (P=0.0455).

Conclusions: In most cases, resistance mutations were present and similar in both studied compartments. However, in 3.4% of ARV-naive and 8.8% of ARV-treated patients, the virus was more resistant in CSF than in plasma. These results support the need for genotypic resistance testing when lumbar puncture is performed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/jac/dku419DOI Listing
February 2015

Inhibition of RNA binding to hepatitis C virus RNA-dependent RNA polymerase: a new mechanism for antiviral intervention.

Nucleic Acids Res 2014 Aug 22;42(14):9399-409. Epub 2014 Jul 22.

Inserm U955, Hôpital Henri Mondor, 51 avenue du Maréchal de Lattre de Tassigny, 94010 Créteil, France National Reference Center for Viral Hepatitis B, C, and Delta, Department of Virology, Hôpital Henri Mondor, Université Paris-Est, 51 avenue du Maréchal de Lattre de Tassigny, 94010 Créteil, France

The hepatitis C virus (HCV) RNA-dependent RNA polymerase (RdRp) is a key target for antiviral intervention. The goal of this study was to identify the binding site and unravel the molecular mechanism by which natural flavonoids efficiently inhibit HCV RdRp. Screening identified the flavonol quercetagetin as the most potent inhibitor of HCV RdRp activity. Quercetagetin was found to inhibit RdRp through inhibition of RNA binding to the viral polymerase, a yet unknown antiviral mechanism. X-ray crystallographic structure analysis of the RdRp-quercetagetin complex identified quercetagetin's binding site at the entrance of the RNA template tunnel, confirming its original mode of action. This antiviral mechanism was associated with a high barrier to resistance in both site-directed mutagenesis and long-term selection experiments. In conclusion, we identified a new mechanism for non-nucleoside inhibition of HCV RdRp through inhibition of RNA binding to the enzyme, a mechanism associated with broad genotypic activity and a high barrier to resistance. Our results open the way to new antiviral approaches for HCV and other viruses that use an RdRp based on RNA binding inhibition, that could prove to be useful in human, animal or plant viral infections.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/nar/gku632DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4132742PMC
August 2014

National sentinel surveillance of transmitted drug resistance in antiretroviral-naive chronically HIV-infected patients in France over a decade: 2001-2011.

J Antimicrob Chemother 2013 Nov 24;68(11):2626-31. Epub 2013 Jun 24.

Laboratoire de Virologie, AP-HP Groupe hospitalier Bichat-Claude Bernard and EA 4409 Université Paris-Diderot, Paris 7, PRES Sorbonne Paris Cité, Paris, France.

Objectives: As recommended by the French ANRS programme for the surveillance of HIV-1 resistance, we estimated the prevalence of transmitted drug resistance-associated mutations (RAMs) in antiretroviral-naive, chronically HIV-1-infected patients.

Methods: RAMs were sought in samples from 661 newly diagnosed HIV-1-infected patients in 2010/11 at 36 HIV clinical care centres. Weighted analyses were used to derive representative estimates of the percentage of patients with RAMs.

Results: At patient inclusion, the prevalence of virus with protease (PR) or reverse transcriptase (RT) RAMs was 9.0% (95% CI 6.8%-11.2%). No integrase RAMs were observed. The prevalences of protease inhibitor, nucleoside RT inhibitor and non-nucleoside RT inhibitor RAMs were 1.8%, 6.2% and 2.4%, respectively. Resistance to one, two and three classes of antiretroviral agent was observed in 7.9%, 0.9% and 0.2% of patients, respectively. The frequency of RAMs was higher in patients infected with B compared with non-B subtype virus (11.9% versus 5.1%, P = 0.003). Baseline characteristics (gender, age, country of transmission, CD4 cell count and viral load) were not associated with the prevalence of transmitted RAMs. However, men having sex with men (MSM) were more frequently infected with resistant virus than were other transmission groups (12.5% versus 5.8%, P = 0.003). Compared with the 2006/07 survey, the overall prevalence of resistance remained stable. However, a significant decrease in the frequency of virus with PR RAMs was observed in 2010/11 compared with the 2006/07 survey (1.8% versus 5.0%, P = 0.003).

Conclusions: In France in 2010/11, the global prevalence of transmitted drug-resistant variants was 9.0%, and the prevalence was stable compared with the 2006/07 survey. MSM and B subtype-infected patients are the groups with a higher prevalence of drug resistance.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/jac/dkt238DOI Listing
November 2013

Epidemiological, virological and clinical characteristics of HBV infection in 223 HIV co-infected patients: a French multi-centre collaborative study.

Virol J 2013 Mar 15;10:87. Epub 2013 Mar 15.

Pitie-Salpetriere, Paris, France.

Background: Chronic hepatitis B (CHB) is a clinical concern in human immunodeficiency virus (HIV)-infected individuals due to substantial prevalence, difficulties to treat, and severe liver disease outcome. A large nationwide cross-sectional multicentre analysis of HIV-HBV co-infected patients was designed to describe and identify parameters associated with virological and clinical outcome of CHB in HIV-infected individuals with detectable HBV viremia.

Methods: A multicenter collaborative cross-sectional study was launched in 19 French University hospitals distributed through the country. From January to December 2007, HBV load, genotype, clinical and epidemiological characteristics of 223 HBV-HIV co-infected patients with an HBV replication over 1000 IU/mL were investigated.

Results: Patients were mostly male (82%, mean age 42 years). Genotype distribution (A 52%; E 23.3%; D 16.1%) was linked to risk factors, geographic origin, and co-infection with other hepatitis viruses. This genotypic pattern highlights divergent contamination event timelines by HIV and HBV viruses. Most patients (74.7%) under antiretroviral treatment were receiving a drug with anti-HBV activity, including 47% receiving TDF. Genotypic lamivudine-resistance detected in 26% of the patients was linked to duration of lamivudine exposure, age, CD4 count and HIV load. Resistance to adefovir (rtA181T/V) was detected in 2.7% of patients. Advanced liver lesions were observed in 54% of cases and were associated with an older age and lower CD4 counts but not with viral load or genotype. Immune escape HBsAg variants were seldom detected.

Conclusions: Despite the detection of advanced liver lesions in most patients, few were not receiving anti-HBV drugs and for those treated with the most potent anti-HBV drugs, persistent replication suggested non-optimal adherence. Heterogeneity in HBV strains reflects epidemiological differences that may impact liver disease progression. These findings are strong arguments to further optimize clinical management and to promote vaccination in HIV-infected patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/1743-422X-10-87DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3602101PMC
March 2013

Discovery of naturally occurring aurones that are potent allosteric inhibitors of hepatitis C virus RNA-dependent RNA polymerase.

J Med Chem 2011 Aug 6;54(15):5395-402. Epub 2011 Jul 6.

Département de Pharmacochimie Moléculaire, Université de Grenoble, CNRS, UMR 5063, Grenoble, France.

We have identified naturally occurring 2-benzylidenebenzofuran-3-ones (aurones) as new templates for non-nucleoside hepatitis C virus (HCV) RNA-dependent RNA polymerase (RdRp) inhibitors. The aurone target site, identified by site-directed mutagenesis, is located in thumb pocket I of HCV RdRp. The RdRp inhibitory activity of 42 aurones was rationally explored in an enzyme assay. Molecular docking studies were used to determine how aurones bind to HCV RdRp and to predict their range of inhibitory activity. Seven aurone derivatives were found to have potent inhibitory effects on HCV RdRp, with IC(50) below 5 μM and excellent selectivity index (inhibition activity versus cellular cytotoxicity). The most active aurone analogue was (Z)-2-((1-butyl-1H-indol-3-yl)methylene)-4,6-dihydroxybenzofuran-3(2H)-one (compound 51), with an IC(50) of 2.2 μM. Their potent RdRp inhibitory activity and their low toxicity make these molecules attractive candidates as direct-acting anti-HCV agents.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/jm200242pDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3579765PMC
August 2011

Induction of B cell-activating factor by viral infection is a general phenomenon, but the types of viruses and mechanisms depend on cell type.

J Innate Immun 2011 3;3(2):200-7. Epub 2010 Nov 3.

Service de Rhumatologie, Institut National de la Santé et la Recherche Médicale U 1012, Hôpital Bicêtre, Assistance Publique-Hôpitaux de Paris, Université Paris-Sud 11, Paris, France.

B cell-activating factor of the TNF family (BAFF) plays a key role in promoting B lymphocyte activation and survival. We previously showed in primary Sjögren's syndrome that salivary gland epithelial cells (SGECs), the resident targeted cells of autoimmunity in this disease, can produce BAFF after infection with a double-stranded RNA (dsRNA) virus by a protein kinase RNA (PKR)-dependent mechanism. This study aimed to assess the effect of different viruses on various cell types - SGECs but also dendritic cells (DCs) and monocytes - in the induction of BAFF. BAFF induction was observed after Sendai virus infection of monocytes and SGECs, as well as poly(I:C) stimulation of DCs. However, PKR inhibition by 2-aminopurine failed to reduce BAFF expression in these infected or stimulated cells. Conversely, in Sendai virus-infected monocytes, blocking type 1 interferon (IFN) receptor by anti-IFNAR1 antibody strongly inhibited BAFF expression. These results provide additional data suggesting that both dsRNA virus stimulation of DCs and single-stranded RNA virus infection of SGECs or monocytes can induce BAFF expression, but through a PKR-independent mechanism for these 3 cell types and a type 1 IFN-dependent mechanism in monocytes and SGECs. Thus, BAFF induction by viral infection is a general phenomenon, but the types of viruses and mechanisms of the induction depend on the cell type.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000321194DOI Listing
June 2011

Increasing prevalence of transmitted drug resistance mutations and non-B subtype circulation in antiretroviral-naive chronically HIV-infected patients from 2001 to 2006/2007 in France.

J Antimicrob Chemother 2010 Dec 21;65(12):2620-7. Epub 2010 Oct 21.

Laboratoire de Virologie, AP-HP Groupe hospitalier Bichat-Claude Bernard and EA 4409 Université Paris-Diderot Paris 7, Paris, France.

Objectives: To estimate the prevalence of transmitted drug resistance mutations and non-B subtype circulation in antiretroviral-naive chronically HIV-1-infected patients in France.

Methods: Resistance mutations were sought in samples from 530 newly diagnosed HIV-1-infected patients from October 2006 to March 2007. Protease and reverse transcriptase mutations were identified from the 2007 Stanford Resistance Surveillance list.

Results: Reverse transcriptase and protease resistance mutations were determined in 466 patients with duration of seropositivity <5 years. 42% of patients were infected with non-B subtype strains (CRF02 18.3%). The overall prevalence of viruses with protease or reverse transcriptase mutations was 10.6% (95% confidence interval 6.7-16.3). The prevalence of protease inhibitor, nucleoside reverse transcriptase inhibitor and non-nucleoside reverse transcriptase inhibitor resistance-associated mutations was 4.7%, 5.8% and 2.8%, respectively. Frequency of resistance was not different in patients infected with B (9.5%) and non-B (CRF02 7.8% and other 11.2%) subtypes. Baseline characteristics such as gender, age, transmission group, country of transmission, disease stage, CD4 counts and viral load were not associated with the prevalence of transmitted drug resistance.

Conclusions: In France in 2006/2007, the prevalence of transmitted drug-resistant variants was 10.6%. Prevalence of transmitted drug resistance was comparable in B and non-B subtypes. Prevalence of non-B subtypes is still rising.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/jac/dkq380DOI Listing
December 2010

Evaluation of the genotypic prediction of HIV-1 coreceptor use versus a phenotypic assay and correlation with the virological response to maraviroc: the ANRS GenoTropism study.

Antimicrob Agents Chemother 2010 Aug 7;54(8):3335-40. Epub 2010 Jun 7.

Laboratoire de Virologie, CHU de Bordeaux, Bordeaux Cedex, France.

Genotypic algorithms for prediction of HIV-1 coreceptor usage need to be evaluated in a clinical setting. We aimed at studying (i) the correlation of genotypic prediction of coreceptor use in comparison with a phenotypic assay and (ii) the relationship between genotypic prediction of coreceptor use at baseline and the virological response (VR) to a therapy including maraviroc (MVC). Antiretroviral-experienced patients were included in the MVC Expanded Access Program if they had an R5 screening result with Trofile (Monogram Biosciences). V3 loop sequences were determined at screening, and coreceptor use was predicted using 13 genotypic algorithms or combinations of algorithms. Genotypic predictions were compared to Trofile; dual or mixed (D/M) variants were considered as X4 variants. Both genotypic and phenotypic results were obtained for 189 patients at screening, with 54 isolates scored as X4 or D/M and 135 scored as R5 with Trofile. The highest sensitivity (59.3%) for detection of X4 was obtained with the Geno2pheno algorithm, with a false-positive rate set up at 10% (Geno2pheno10). In the 112 patients receiving MVC, a plasma viral RNA load of <50 copies/ml was obtained in 68% of cases at month 6. In multivariate analysis, the prediction of the X4 genotype at baseline with the Geno2pheno10 algorithm including baseline viral load and CD4 nadir was independently associated with a worse VR at months 1 and 3. The baseline weighted genotypic sensitivity score was associated with VR at month 6. There were strong arguments in favor of using genotypic coreceptor use assays for determining which patients would respond to CCR5 antagonist.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1128/AAC.00148-10DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2916345PMC
August 2010

Silibinin and related compounds are direct inhibitors of hepatitis C virus RNA-dependent RNA polymerase.

Gastroenterology 2010 Mar 4;138(3):1112-22. Epub 2009 Dec 4.

Research Team Pathophysiology and Therapy of Chronic Viral Hepatitis, INSERM U955, Créteil, France.

Background & Aims: Silymarin is a mixture of flavonolignans extracted from the milk thistle. Silymarin contains several molecules, including silibinin A, silibinin B, isosilibinin A, isosilibinin B, silicristin, and silidianin. Intravenous infusion of silibinin induces dose-dependent reduction of hepatitis C virus (HCV) RNA levels. The aim of this study was to test the principal isomers contained in silymarin preparations for their ability to inhibit HCV enzymatic functions and replication in different models.

Methods: The inhibitory activity of silymarin components was tested in HCV RNA-dependent RNA polymerase and NS3/4A protease enzyme assays. Their ability to inhibit replication of an HCV genotype 1b replicon model and the JFH1 infectious HCV model in cell culture was also studied.

Results: Silibinin A, silibinin B, their water-soluble dihydrogen succinate forms and Legalon SIL, a commercially available intravenous preparation of silibinin, inhibited HCV RNA-dependent RNA polymerase function, with inhibitory concentrations 50% of the order of 75-100 microM. Silibinin A and silibinin B also inhibited HCV genotype 1b replicon replication and HCV genotype 2a strain JFH1 replication in cell culture. None of these compounds inhibited HCV protease function.

Conclusions: Silibinin A and silibinin B, as well as Legalon SIL, inhibit HCV replicon and JFH1 replication in cell culture. This effect is at least partly explained by the ability of these compounds to inhibit HCV RNA-dependent RNA polymerase activity. Our results provide a basis for the optimization and subsequent development of members of the Flavonoid family as specific HCV antivirals.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1053/j.gastro.2009.11.053DOI Listing
March 2010

Identification and biochemical characterization of human plasma soluble IL-7R: lower concentrations in HIV-1-infected patients.

J Immunol 2009 Jun;182(12):7389-97

Institut Pasteur, Unité d'Immunogénétique Cellulaire, Paris France.

The IL-7R alpha-chain and the common gamma-chain (gamma(c)) are both components of IL-7R. Human plasma harbors soluble forms of IL-7R (sIL-7Ralpha and sgamma(c)) that are detected and assayed by Western blotting, showing that the levels of sIL-7Ralpha are higher than the levels of sgamma(c) (47.5 ng/ml and 1.5 ng/ml, respectively). Gel electrophoresis and tandem mass spectrometry used to analyze deglycosylated, affinity-purified protein showed that sIL-7Ralpha is generated through differentially spliced mRNA, not by membrane receptor shedding. Plasma sIL-7Ralpha and sgamma(c) are present as heterocomplexes and sgamma(c) was found to be mainly associated with sIL-7Ralpha. The affinities of two IL-7 binding sites (K(d) = 35 +/- 8 pM and K(d) = 3 +/- 1 nM) were similar to that of the membrane receptor, suggesting that the sIL-7Ralpha/sgamma(c) complex retains high affinity for IL-7. sIL-7Ralpha mRNA is constitutively present among peripheral T lymphocytes and is down-modulated in vitro by IL-7. Chronically HIV-1-infected patients (n = 20) showed no significant (p > 0.714) variation in sgamma(c) levels and a significant (p < 0.0014) 2-fold decrease in plasma sIL-7Ralpha levels compared with those in control healthy individuals. Plasma IL-7 and sIL-7Ralpha levels did not show any obvious relationship.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4049/jimmunol.0900190DOI Listing
June 2009

Complex dynamics of hepatitis B virus resistance to adefovir.

Hepatology 2009 Jan;49(1):50-9

French National Reference Center for Viral Hepatitis B, C, and delta, Department of Virology, Hôpital Henri Mondor, Université Paris 12, Créteil, France.

Unlabelled: In patients with hepatitis B e antigen-negative chronic hepatitis B, adefovir dipivoxil administration selects variants bearing reverse transcriptase rtN236T and/or rtA181V/T substitutions in 29% of cases after 5 years. The aim of this study was to characterize the dynamics of adefovir-resistant variant populations during adefovir monotherapy in order to better understand the molecular mechanisms underlying hepatitis B virus resistance to this class of nucleotide analogues. Patients included in a 240-week clinical trial of adefovir monotherapy who developed adefovir resistance-associated substitutions were studied. The dynamics of hepatitis B virus populations were analyzed over time, after generating nearly 4,000 full-length reverse transcriptase sequences, and compared with the replication kinetics of the virus during therapy. Whatever the viral kinetics pattern, adefovir resistance was characterized by exclusive detection of a dominant wild-type, adefovir-sensitive variant population at baseline and late and gradual selection by adefovir of several coexisting resistant viral populations, defined by the presence of amino acid substitutions at position rt236, position rt181, or both. The gain in fitness of one or the other of these resistant populations during adefovir administration was never associated with the selection of additional amino acid substitutions in the reverse transcriptase.

Conclusion: Our results suggest that adefovir administration selects poorly fit preexisting or emerging viral populations with low-level adefovir resistance, which subsequently compete to fill the replication space. Viral kinetics depends on the initial virological response to adefovir. Lamivudine add-on restores some antiviral efficacy, but adefovir-resistant variants remain predominant. Whether these adefovir resistance-associated substitutions may confer cross-resistance to tenofovir in vivo will need to be determined.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/hep.22634DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2956748PMC
January 2009

Resting regulatory CD4 T cells: a site of HIV persistence in patients on long-term effective antiretroviral therapy.

PLoS One 2008 Oct 1;3(10):e3305. Epub 2008 Oct 1.

INSERM U802, Université Paris 11, Le Kremlin Bicêtre, France.

Background: In HIV-infected patients on long-term HAART, virus persistence in resting long-lived CD4 T cells is a major barrier to curing the infection. Cell quiescence, by favouring HIV latency, reduces the risk of recognition and cell destruction by cytotoxic lymphocytes. Several cell-activation-based approaches have been proposed to disrupt cell quiescence and then virus latency, but these approaches have not eradicated the virus. CD4+CD25+ regulatory T cells (Tregs) are a CD4+ T-cell subset with particular activation properties. We investigated the role of these cells in virus persistence in patients on long-term HAART.

Methodology/principal Findings: We found evidence of infection of resting Tregs (HLADR(-)CD69(-)CD25(hi)FoxP3+CD4+ T cells) purified from patients on prolonged HAART. HIV DNA harbouring cells appear more abundant in the Treg subset than in non-Tregs. The half-life of the Treg reservoir was estimated at 20 months. Since Tregs from patients on prolonged HAART showed hyporesponsiveness to cell activation and inhibition of HIV-specific cytotoxic T lymphocyte-related functions upon activation, therapeutics targeting cell quiescence to induce virus expression may not be appropriate for purging the Treg reservoir.

Conclusions: Our results identify Tregs as a particular compartment within the latent reservoir that may require a specific approach for its purging.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0003305PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2551739PMC
October 2008

HIV-1-infected patients from the French National Observatory experiencing virological failure while receiving enfuvirtide.

J Antimicrob Chemother 2008 Sep 13;62(3):451-5. Epub 2008 Jun 13.

AP-HP, Groupe Hospitalier Bichat-Claude Bernard, Laboratoire de Virologie, Paris F-75018, France.

Objectives: We studied gp41 mutations associated with failing enfuvirtide salvage therapy.

Methods: This multicentre study involved patients with HIV-1 plasma viral load (pVL) > 5000 copies/mL after at least 3 months of uninterrupted enfuvirtide therapy and with plasma samples available at inclusion (T0), at initial enfuvirtide failure (T1) and at last follow-up visit during continued failing enfuvirtide therapy (T2). The HR-1 and HR-2 domains of the gp41 gene were sequenced at T0, T1 and T2.

Results: Ninety-nine patients were enrolled. At baseline, the median pVL and CD4 cell count were 5.1 log copies/mL and 72 cells/mm(3), respectively. Based on the ANRS Resistance Group algorithm, the proportion of patients harbouring viruses with enfuvirtide resistance mutations increased significantly between T0 and T1. In the HR-1 domain, the V38A/M, Q40H, N42T, N43D and L45M mutations wereselected (P < 0.02). In the HR-2 domain, no mutations were significantly selected during the follow-up. None of the mutations was associated with a CD4 cell count increment.

Conclusions: Mutations selected during failing enfuvirtide salvage therapy are mainly located in the HR-1 domain of the gp41 gene, between codons 38 and 45. No mutations were associated with an increase in the CD4 cell count.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/jac/dkn225DOI Listing
September 2008

Prolonged valproic acid treatment does not reduce the size of latent HIV reservoir.

AIDS 2008 Jun;22(10):1125-9

INSERM, U802, Bicêtre, France.

Objective: To investigate the impact of prolonged valproic acid treatment on the HIV reservoir in patients on highly active antiretroviral therapy.

Design: In a single-center pilot study, the size of the HIV reservoir of 11 patients receiving valproic acid for seizures for more than 2 years was compared with 13 matched patients. In addition, the outcome of patients receiving valproic acid in the French clinical trials of scheduled treatment interruption was recorded.

Methods: Total and integrated HIV-1 DNA in, respectively, peripheral blood mononuclear cells and CD4 T cells of the patients were quantified by real-time PCR methods. The frequency of CD4 T cells carrying replication-competent virus was estimated by a quantitative limiting-dilution assay in which virus growth was detected by RT-PCR in culture supernatants of activated CD4 T cells. Clinical charts of the patients included in scheduled treatment interruption trials receiving valproic acid were reviewed.

Results: Total and integrated HIV DNA were logarithmically more abundant than cells carrying replication-competent virus, but there was no significant difference in these three parameters between the two groups of matched patients. Three patients receiving valproic acid were included in scheduled treatment interruption trials. The rebound of viral replication was similar to that of the other patients of the trials.

Conclusion: Long-term valproic acid therapy seems to be insufficient to reduce the size of the HIV-1 reservoir.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/QAD.0b013e3282fd6ddcDOI Listing
June 2008

Viruses induce high expression of BAFF by salivary gland epithelial cells through TLR- and type-I IFN-dependent and -independent pathways.

Eur J Immunol 2008 Apr;38(4):1058-64

Rhumatologie, Institut Pour la Santé et la Recherche Médicale INSERM U 802, Hôpital Bicêtre, Assistance Publique-Hôpitaux de Paris, Université Paris-Sud 11, Le Kremlin Bicêtre, France.

B cell activating factor (BAFF) plays a key role in promoting B lymphocyte activation. We investigated whether danger signals induce BAFF secretion by cultured salivary gland epithelial cells (SGEC), which are the target of primary Sjögren's syndrome, a prototypic systemic autoimmune disease. SGEC cultures were established from minor salivary glands obtained from ten patients with pSS or sicca symptoms. BAFF mRNA and protein were measured after stimulation of the different Toll-like receptors (TLR) by agonists or viruses. The expression of TLR2, -3, and -7 was detected in SGEC. Poly (I:C) (a synthetic TLR3 agonist) and reovirus-1 (a dsRNA virus) induced high expression of BAFF mRNA (multiplied by a factor of 246 +/- 39 (SEM) and 347 +/- 66, respectively) and of BAFF protein secretion (58.49 +/- 4.34 pg/mL and 69.73 +/- 5.67). Inhibition of both the endosomal (by chloroquine) and IFN (by anti-IFNAR antibody) pathways partly inhibited BAFF expression. Treatment with both dsRNA virus and poly (I:C) induced high levels of BAFF mRNA and protein expression by SGEC, through pathways dependent on and independent of TLR and dependent on and independent of IFN. BAFF induction by target organs of autoimmune diseases after viral infection may be a link between innate immunity and autoimmunity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/eji.200738013DOI Listing
April 2008

[Fatal liver failure after hepatitis B reactivation following chemotherapy for lymphoma in a patient with only anti-HBc antibody and review of the literature].

Gastroenterol Clin Biol 2007 Nov;31(11):1028-31

Service des maladies du foie et de l'appareil digestif, Hôpital de Bicêtre, Le Kremlin-Bicêtre.

Hepatitis B reactivation after chemotherapy is well known when Ag HBs is positive. Recommendation is to give preventive antiviral treatment before starting chemotherapy. The reactivation when there is only an anti-HBc antibody is rare. We report the case of a woman who developed an hepatitis B reactivation two weeks after the end of a chemotherapy for a high grade non Hodgkin lymphoma. Before chemotherapy, hepatitis B virus serology was positive only for anti-HBc antibody and viral load was negative. She had a fulminant hepatitis with fatal issue although a treatment by lamivudine and adefovir was rapidly started. In the literature, only 13 cases of patients with positive anti body anti-HBc alone who developed an hepatitis B reactivation after chemotherapy have been reported.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/s0399-8320(07)78326-4DOI Listing
November 2007