Rôle des anticorps neutralisants autologues dans la guérison spontanée lors d'une infection par le virus de l'hépatite C

Environ 30% des patients infectés par le virus de l hépatite C guérissent spontanément. Le but de ce travailétait (i) d examiner l évolution des protéines d enveloppe en cas de guérison spontanée (ii) de comparerl infectivité des variants présents aux stades précoces (iii) d explorer la capacité neutralisante des anticorps(Ac) vis-à-vis des variants majoritaires et minoritaires. Nous avons sélectionné 2 patients avec une hépatiteaigue C suivie d une guérison très rapide. Pour explorer la capacité d entrée de ces variants et leur aptitude àêtre neutralisés, nous avons produit des pseudo-particules rétrovirales portant les enveloppes de différentsvariants. Pour le 1er patient, une réponse neutralisante autologue était détectable précocement, avec unmaximum entre le 2ème et le 3èmemois suivant la cytolyse. Elle était encore détectable au 30ème mois. Pourle 2ème patient, des Ac vis-à-vis du variant majoritaire étaient détectés dans le sérum prélevé 4 jours après lacytolyse et dans les sérums plus tardifs. Le titre des Ac était maximum au 5ème mois. La réponse neutralisanteest d apparition précoce et persiste même après l élimination virale. Ces observations nous questionnent parrapport au rôle éventuel joué par ces Ac dans les cas de recontamination.Only 30% of Hepatitis C virus infected individuals recover spontaneously. We investigated the mechanismsleading to early HCV clearance. The purpose of this work was: (i) to explore the diversity and the early geneticevolution of the HCV envelope glycoproteins, and the infectivity spectrum of isolated variants and (ii) toanalyze the ability of the autologous neutralizing response to control these variants. We selected two patientswho developed an acute HCV infection. To explore the impact of mutations on infectivity and neutralization,retroviral pseudoparticules were produced with representative E1 and E2 sequences. For the first case, themaximum neutralizing activity was observed in the serum collected between 2 and 3 months post ALT peak,the activity was still detectable after 30 months. For the second case, autologous neutralizing activity wasdetected in every serum collected between 4 days and 13 months after. A gradual increase of neutralizationactivity was observed over time with a maximum 5 to 6 months. We have shown that the neutralizing responsewas detectable at early stages of primoinfection and was sustained beyond the time at which the virus wascleared. These observations raise interesting questions about the role of such antibodies in case of re-exposure.TOURS-Bibl.électronique (372610011) / SudocSudocFranceF

Long-Term Hepatitis B Virus (HBV) Response to Lamivudine-Containing Highly Active Antiretroviral Therapy in HIV-HBV Co-Infected Patients in Thailand

Background: Approximately 4 million of people are co-infected with HIV and Hepatitis B virus (HBV). In resource-limited settings, the majority of HIV-infected patients initiate first-line highly active antiretroviral therapy containing lamivudine (3TC-containing-HAART) and long-term virological response of HBV to lamivudine-containing HAART in co-infected patients is not well known. Methodology/Principal Finding: HIV-HBV co-infected patients enrolled in the PHPT cohort (ClinicalTrials.gov NCT00433030) and initiating a 3TC-containing-HAART regimen were included. HBV-DNA, HIV-RNA, CD4+ T-cell counts and alanine transaminase were measured at baseline, 3 months, 12 months and then every 6 months up to 5 years. Kaplan-Meier analysis was used to estimate the cumulative rates of patients who achieved and maintained HBV-DNA suppression. Of 30 co-infected patients, 19 were positive for HBe antigen (HBeAg). At initiation of 3TC-containing-HAART, median HBV DNA and HIV RNA levels were 7.35 $log_{10}$ IU/mL and 4.47 $log_{10}$ copies/mL, respectively. At 12 months, 67% of patients achieved HBV DNA suppression: 100% of HBeAg-negative patients and 47% of HBeAg-positive. Seventy-three percent of patients had HIV RNA below 50 copies/mL. The cumulative rates of maintained HBV-DNA suppression among the 23 patients who achieved HBV-DNA suppression were 91%, 87%, and 80% at 1, 2, and 4 years respectively. Of 17 patients who maintained HBV-DNA suppression while still on 3TC, 4 (24%) lost HBsAg and 7 of 8 (88%) HBeAg-positive patients lost HBeAg at their last visit (median duration, 59 months). HBV breakthrough was observed only in HBeAg-positive patients and 6 of 7 patients presenting HBV breakthrough had the rtM204I/V mutations associated with 3TC resistance along with rtL180M and/or rtV173L. Conclusions: All HBeAg-negative patients and 63% of HBeAg-positive HIV-HBV co-infected patients achieved long-term HBV DNA suppression while on 3TC-containing-HAART. This study provides information useful for the management of co-infected patients in resource-limited countries where the vast majority of co-infected patients are currently receiving 3TC

Viral sequence variation in chronic carriers of hepatitis C virus has a low impact on liver steatosis.: HCV variability and steatosis

International audienceMost clinical studies suggest that the prevalence and severity of liver steatosis are higher in patients infected with hepatitis C virus (HCV) genotype 3 than in patients infected with other genotypes. This may reflect the diversity and specific intrinsic properties of genotype 3 virus proteins. We analyzed the possible association of particular residues of the HCV core and NS5A proteins known to dysregulate lipid metabolism with steatosis severity in the livers of patients chronically infected with HCV. We used transmission electron microscopy to quantify liver steatosis precisely in a group of 27 patients, 12 of whom were infected with a genotype 3 virus, the other 15 being infected with viruses of other genotypes. We determined the area covered by lipid droplets in liver tissues and analyzed the diversity of the core and NS5A regions encoded by the viral variants circulating in these patients. The area covered by lipid droplets did not differ significantly between patients infected with genotype 3 viruses and those infected with other genotypes. The core and NS5A protein sequences of the viral variants circulating in patients with mild or severe steatosis were evenly distributed throughout the phylogenic trees established from all the collected sequences. Thus, individual host factors seem to play a much greater role than viral factors in the development of severe steatosis in patients chronically infected with HCV, including those infected with genotype 3 viruses

Bilan du dépistage et du suivi des infections liées aux papillomavirus dans une cohore de 509 femmes présentant un frottis de type ASCUS ou AGC (2007-2008)

TOURS-BU Sciences Pharmacie (372612104) / SudocSudocFranceF

Diagnostic biologique de l'infection par le virus de l'hépatite E (analyse de 9 cas recensés au CHRU [centre hospitalier régional universitaire] de Tours (2005-2007))

POITIERS-BU Médecine pharmacie (861942103) / SudocSudocFranceF

Recherche des mutations du virus de l'hépatite B aux analogues nucléo(t)idiques chez 88 patients (bilan des indications, principaux profils mutationnels et impact sur les options thérapeutique)

TOURS-BU Sciences Pharmacie (372612104) / SudocSudocFranceF

Caractérisation des mutants du promoteur basal du core, et de la région précore du virus de l'hépatite B (étude de 36 souches isolées chez des patients suivis dans le service de gastroentérologie du CHRU de Tours)

TOURS-BU Sciences Pharmacie (372612104) / SudocSudocFranceF

Factors associated with influenza vaccination failure and severe disease in a French region in 2015

International audienceCurrent influenza vaccination strategy is based on limited analyses of circulating strains and has some drawbacks, as illustrated during the 2014-2015 season with the circulation of A(H3N2) viruses belonging to divergent genetic subgroups. We reasoned that these strains, poorly neutralized in vitro, may have been associated with vaccination failure and more severe diseases. We conducted a study on a continuous series of 249 confirmed influenza infections. Incidence was three fold greater than in the previous three years. Most isolates were A(H3N2) viruses (78%) and clustered in subgroups 3C.2a (57%) and 3C.3b (43%). We identified 23 non-synonymous mutations that had already been identified during previous seasons at low frequencies, except mutation Q197H, present in 26% of 3C.3b isolates. We identified lung disorder, tobacco smoking and A(H1N1)pdm09 infection as risk factor of severe influenza disease. In contrast, young age (< 5 years), A(H3N2) infection and initial admission to an emergency department were associated with a better outcome of influenza infection

Acute respiratory distress syndrome secondary to human metapneumovirus infection in a young healthy adult

International audienc

Antibody Responses after a Third Dose of COVID-19 Vaccine in Kidney Transplant Recipients and Patients Treated for Chronic Lymphocytic Leukemia

International audienceThe impact of a third dose of COVID-19 vaccine on antibody responses is unclear in immunocompromised patients. The objective of this retrospective study was to characterize antibody responses induced by a third dose of mRNA COVID-19 vaccine in 160 kidney transplant recipients and 20 patients treated for chronic lymphocytic leukemia (CLL). Prevalence of anti-spike IgG ≥ 7.1 and ≥ 30 BAU/mL after the third dose were 47% (75/160) and 39% (63/160) in kidney transplant recipients, and 57% (29/51) and 50% (10/20) in patients treated for CLL. Longitudinal follow-up identified a moderate increase in SARS-CoV-2 anti-spike IgG levels after a third dose of vaccine in kidney transplant recipients (0.19 vs. 5.28 BAU/mL, p = 0.03) and in patients treated for CLL (0.63 vs. 10.7 BAU/mL, p = 0.0002). This increase in IgG levels had a limited impact on prevalence of anti-spike IgG ≥ 30 BAU/mL in kidney transplant recipients (17%, 2/12 vs. 33%, 4/12, p = 0.64) and in patients treated for CLL (5%, 1/20 vs. 45%, 9/20, p = 0.008). These results highlight the need for vaccination of the general population and the importance of non-medical preventive measures to protect immunocompromised patients