Antiviral activity of bone morphogenetic proteins and activins

Understanding the control of viral infections is of broad importance. Chronic hepatitis C virus (HCV) infection causes decreased expression of the iron hormone hepcidin, which is regulated by hepatic bone morphogenetic protein (BMP)/SMAD signalling. We found that HCV infection and the BMP/SMAD pathway are mutually antagonistic. HCV blunted induction of hepcidin expression by BMP6, probably via tumour necrosis factor (TNF)-mediated downregulation of the BMP co-receptor haemojuvelin. In HCV-infected patients, disruption of the BMP6/hepcidin axis and genetic variation associated with the BMP/SMAD pathway predicted the outcome of infection, suggesting that BMP/SMAD activity influences antiviral immunity. Correspondingly, BMP6 regulated a gene repertoire reminiscent of type I interferon (IFN) signalling, including upregulating interferon regulatory factors (IRFs) and downregulating an inhibitor of IFN signalling, USP18. Moreover, in BMP-stimulated cells, SMAD1 occupied loci across the genome, similar to those bound by IRF1 in IFN-stimulated cells. Functionally, BMP6 enhanced the transcriptional and antiviral response to IFN, but BMP6 and related activin proteins also potently blocked HCV replication independently of IFN. Furthermore, BMP6 and activin A suppressed growth of HBV in cell culture, and activin A inhibited Zika virus replication alone and in combination with IFN. The data establish an unappreciated important role for BMPs and activins in cellular antiviral immunity, which acts independently of, and modulates, IFN

Molecular comparison of echovirus 11 strains circulating in Europe during an epidemic of multisystem hemorrhagic disease of infants indicates that evolution generally occurs by recombination.

International audienceWe compared echovirus 11 (E11) strains implicated in a severe epidemic in Hungary in 1989 with the prototype E11 strain Gregory and with other E11 strains, most of which were isolated over the same period in Europe (Finland, The Netherlands, Romania, Russia) from sporadic cases or from environmental water. Partial sequencing indicated that the Hungarian strains were closely related to each other and to most European strains. They were particularly closely related to one Romanian strain associated with a sporadic case of hemiparesis and several Finnish strains isolated from environmental water. Sequencing of the complete genomes of one Hungarian strain, the Romanian strain, and one Finnish strain revealed differences of only a few nucleotides in the 5' half of the genome, including the 5' nontranslated region (5'-NTR) and the capsid coding region. However, significant differences were observed in the nucleotide sequences of the 3' half of the genome (nonstructural viral protein region and 3'-NTR), indicating that these strains evolved recently and independently by genetic recombination with other unknown E11 or enterovirus strains

Multicenter Evaluation of the Cepheid Xpert^® HBV Viral Load Test

Accurate measurement of the hepatitis B virus (HBV) DNA is important for the management of patients with chronic HBV infection. Here, the performance of the Xpert® HBV Viral Load test (Xpert HBV Viral Load) versus the Roche COBAS® Ampliprep/COBAS® TaqMan® system (CAP/CTM HBV) HBV test v2.0 was evaluated. From September 2017 to December 2017, a total of 876 prospectively collected or archived serum or EDTA plasma specimens from subjects chronically infected with HBV were tested using the Xpert HBV Viral Load and the CAP/CTM HBV v2.0 assays. Of the 876 specimens tested, 560 were within the quantitative range of both assays. The agreement between the two methods was 90.0%. No difference in plasma or serum samples was observed. Deming regression analysis showed a good correlation of the Xpert HBV Viral Load assay with the CAP/CTM HBV v2.0 assay. The Bland–Altman analysis showed a good agreement between the results of the Xpert HBV Viral Load assay and the CAP/CTM HBV assay, with a mean difference (±1.96 standard deviation) of 0.0091 ± 0.3852 Log IU/mL. Comparing the two assays, only nineteen specimens (2.1%) had a difference greater than 1.96 times the standard deviation. The Xpert® HBV Viral Load test is suitable for monitoring patients with HBV infection and is useful in diagnostic settings

Prévalence de l’antigène HBs dans deux populations exposées : les usagers de drogues (ANRS-Coquelicot 2011-2013) et les hommes ayant des relations sexuelles avec des hommes (Prevagay 2009) à Paris, France

International audienceThe French Institute for Public Health Surveillance set up two communities based surveys which provide both Hepatitis B surface antigen (HBsAg). The first one, the ANRS-Coquelicot survey, studied in 2011-2013 drug users (DUs) who attend specialized structures in health care and risk reduction. The second survey, Prevagay, concerned men who have sex with men (MSM) who attended Paris gay venues in 2009. Persons recruited for both surveys were invited to collect a fingerprick whole blood sample on filter paper, and to respond to a behavioral questionnaire. This questionnaire was anonymous and administered by interviewers for DUs, and self-completed for MSM. Blood samples were screened for the presence of HBs Ag using the Monolisa HBs Ag ULTRA (Biorad®) assay. Among the 647 DUs and the 876 MSM investigated in Paris and included in the analysis, 15 DUs and 12 MSM were diagnosed HBs Ag-positive, representing HBs Ag seroprevalence of 2.1% (IC95% [1.0-4.2]) and 1.4%,respectively. In these two specific populations, different in terms of socio-demographic profiles, and both at risk of HBV transmission, due to their drug use practices or their sexual behaviors, HBs Ag seroprevalence was closeto the one observed in the general population.L’Institut de veille sanitaire a mené deux études de séroprévalence de l’antigène HBs (AgHBs) en populations spécifiques. La première, l’enquête ANRS-Coquelicot, a étudié en 2011-2013 les usagers de drogue (UD) fréquentant les structures de prise en charge et de réduction des risques. La seconde, Prevagay, concernait les hommes ayant des rapports sexuels avec des hommes (HSH) fréquentant les lieux de convivialité gay parisiens en 2009. Les personnes recrutées pour ces deux études déposaient sur un papier buvard un échantillon de sang par auto-prélèvement capillaire au bout du doigt, puis répondaient à un questionnaire comportemental. Ce questionnaire était anonyme et passé en face-à face avec des enquêteurs pour les UD, et auto-administré pour les HSH. La recherche de l’AgHBs a été réalisée en laboratoire, à l’aide de la trousse Elisa Monolisa HBsAg ULTRA (Biorad®). Parmi les 647 hommes UD et les 876 HSH enquêtés à Paris et retenus pour l’analyse, 15 UD et 12 HSH étaient porteurs de l’AgHBs, soit des séroprévalences respectives de 2,1% (IC95% [1,0-4,2]) et 1,4%. Ces deux populations spécifiques, différentes en termes de profils sociodémographiques, toutes deux exposées aux risques de transmission du VHB de par leurs pratiques d’usage de drogues ou leurs pratiques sexuelles, avaient des séroprévalences de l’AgHBs proches de celle de la population générale

Prevalence of hepatitis C infection, screening and associated factors among men who have sex with men attending gay venues: a cross-sectional survey (PREVAGAY), France, 2015

Abstract Background Over the last 20 years, Hepatitis C virus (HCV) infection prevalence has dramatically increased among HIV-infected men who have sex with men (MSM) in many countries worldwide. It is suspected that this increase is primarily driven by sexual behaviours linked to blood exposure. Monitoring these behaviours is crucial to understand the drivers of the epidemic. This study assessed the prevalence of chronic HCV infection among MSM attending gay venues and associated chronic HCV risk factors. HCV screening and associated factors were described. Methods The cross-sectional survey PREVAGAY, based on time-location sampling, was conducted in 2015 among MSM attending gay venues in 5 French metropolitan cities. A self-administered questionnaire was completed and capillary whole blood on dried blood spots (DBS) collected. Possible factors associated with chronic HCV prevalence and with HCV screening in the previous year were investigated using Poisson regression. Results Chronic HCV infection prevalence from DBS analysis was 0.7% [IC95%: 0.3–1.5] in the study’s 2645 participants and was 3.0% [1.5–5.8] in HIV-positive MSM. It was significantly higher in those who reported the following: (lifetime) slamming (with or without the sharing of injection equipment); (during the previous year) fisting and chemsex, unprotected anal intercourse with casual partners, using gay websites and/or of mobile-based GPS applications, and having more than 10 sexual partners. Only 41.3% [38.2–44.5] of the participants reported HCV screening during the previous year. Screening was significantly more frequent in MSM under 30 years of age, those who were HIV-positive, those vaccinated against hepatitis B and meningococcus C, and those who reported the following (during the previous year): more than 10 sexual partners, at least one sexually transmitted infection and fisting. Conclusion Chronic HCV infection prevalence in MSM attending gay venues was significantly higher in HIV-positive MSM and in those with risky sexual behaviours. Reflecting current screening recommendations for specific populations, previous HCV screening was more frequent in HIV-positive individuals and those with risky sexual behaviours. Nevertheless, HCV screening coverage needs to be improved in these populations. Comprehensive medical management, which combines screening and linkage to care with prevention strategies, is essential to control HCV among MSM

Grazoprevir/elbasvir for the immediate treatment of recently acquired HCV genotype 1 or 4 infection in MSM

International audienceBackground: In Europe, increases in HCV infection have been observed over the last two decades in MSM, making them a key population for recently acquired HCV. Alternative combinations of direct-acting antiviral agents against early HCV infection need to be assessed.Patients and methods: In this pilot trial, MSM with recently acquired genotype 1 or 4 HCV infection were prospectively included and received 8 weeks of oral grazoprevir 100 mg and elbasvir 50 mg in a fixed-dose combination administered once daily. The primary endpoint was sustained virological response evaluated 12 weeks after the end of treatment (EOT) (SVR12). Secondary endpoints were the virological characterization of failures, the quality of life before, during and after treatment and the rate of reinfection.Results: In a 15 month period, 30 patients were enrolled, all of whom were MSM. Of the 29 patients completing follow-up, 28 (96%, 95% CI = 82%–99%) achieved SVR12. One patient interrupted follow-up (suicide) but had undetectable plasma HCV RNA at EOT. One patient with suboptimal adherence confirmed by plasma drug monitoring relapsed and developed NS3, NS5A and NS5B resistance-associated substitutions (V36M, M28V and S556G). The most common adverse events related to study drug were diarrhoea (n = 4, 13%), insomnia (n = 2, 7%) and fatigue (n = 2, 7%), although no patient discontinued treatment. No HIV RNA breakthrough was reported in the 28 patients with HIV coinfection. At Week 48, reinfection was diagnosed in three patients.Conclusions: Our data support the use of grazoprevir/elbasvir for immediate treatment against HCV in order to reduce HCV transmission in MSM

Self-reported injection practices among people who use drugs in French prisons: Public health implications (ANRS-Coquelicot survey 2011–2013)

International audienceIntroduction and Aims:The Aims:of this study were to describe the prevalences of injection practices and needle/syringe sharing in people who use drugs in French prisons, and to investigate associated factors. Design and Methods: Using the ANRS-Coquelicot survey (2011−2013), a random sample of 1718 people who used drugs in free society was included. Information regarding a history of incarceration, drug-injection practices inside prison and needle/syringe sharing was collected during interviews. Results: In our sample, 65.5% reported a history of injection and 57.4% had been incarcerated at least once. Among those who reported both of these conditions, 14% reported injection practices inside prison, 40.5% of whom had shared needles/syringes. In the multivariable model, the following variables were associated with injection practices inside prison: being a Russian-speaking detainee, having spent more time in prison, and having started to inject before 1996 and especially before 1987. Being Russian speaking was also associated with needle/syringe sharing in prison. Discussion and Conclusions: The prevalences of injection practices and needle/syringe sharing in prisons are alarmingly high. Effective interventions to prevent the transmission of infectious diseases among people who use drugs in the prison setting are essential. The implementation of international recommendations on the principle of equivalence between prisons and the community is still very limited in most countries, and should be complemented with tailored interventions for the most vulnerable prison populations, especially Russian-speaking detainees

Sofosbuvir-Daclatasvir Is Suboptimal in Patients with Genotype 2 Chronic Hepatitis C Infection: Real-life Experience from the HEPATHER ANRS CO22 Cohort

International audienc