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Rossi-Tamisier M.,Center Hospitalo University Timone | Gerolami R.,Center Hospitalo University Conception | Colson P.,Center Hospitalo University Timone | Colson P.,Aix - Marseille University
Journal of Clinical Virology | Year: 2013

Background: Hepatitis E virus (HEV) is an emerging clinical threat in Europe among kidney and liver-transplant recipients. The incidence and prevalence of HEV infection in this special population are poorly known. False-negative results have been observed for anti-HEV IgG detection in severely immunocompromized persons. Moreover, large discrepancies have been reported between rates of anti-HEV IgG detection in blood donors and hepatitis E cases. Objectives: To compare anti-HEV IgG and IgM prevalence using two different commercial microplate enzyme-immuno assays (MEIAs) (Adaltis and Wantai) in 64 kidney-/liver-transplant recipients. Study design: Serum samples tested in our routine clinical practice over the 12/2009-12/2011 period with Adaltis MEIAs were retrospectively tested using Wantai MEIAs. IgG-positive sera were further tested by an immunoblot while those found IgM-positive were further tested with an immunochromatography rapid test and for the presence of HEV RNA. Results: Positive results on anti-HEV IgG testing were obtained for seven (10.9%) compared to 20 (31.3%) serum samples with Adaltis and Wantai assays, respectively (p= 0.005). Then, 6/7 (86%) of the serum samples positive with Adaltis and 16/20 (80%) of those positive with Wantai were positive with the immunoblot. One patient with chronic HEV infection was IgG-negative with both MEIAs. Regarding anti-HEV IgM, Adaltis and Wantai assays were concordant for 97% of the serum samples, prevalence being 8% with both MEIAs. Conclusions: The accuracy of currently available commercial or in-house anti-HEV IgG MEIAs should be tested comparatively on a panel of serum samples collected from solid organ-transplant recipients, including some who experienced PCR-documented HEV infection. © 2012 Elsevier B.V.


Gerolami R.,Center Hospitalo University Conception | Gerolami R.,Jean Moulin University Lyon 3 | Borentain P.,Center Hospitalo University Conception | Borentain P.,Jean Moulin University Lyon 3 | And 5 more authors.
Journal of Clinical Virology | Year: 2011

Background: Acute hepatitis E is associated with a higher rate of mortality as compared to hepatitis A or B infections in some series. To date no treatment has been recommended for acute hepatitis E. However, ribavirin has been recently reported to be highly effective to treat solid-organ-transplant recipients chronically infected with hepatitis E virus (HEV). Objective and study design: We report here on the use of ribavirin to treat severe acute HEV infection in a non-immunocompromized patient. This 61-year-old-man presented with acute hepatitis with HEV genotype 3. Seven days after admission, prothrombin index was 38%, bilirubinaemia was 550 μmol/L and alanine aminotransferases level was still increasing, reaching 4565. IU/L. No hepatic encephalopathy was noted. Ribavirin (1200. mg/day) was introduced. Results: Liver biological tests showed rapid improvement concurrently with a decrease in HEV RNA levels in serum samples. Therapy was interrupted after 21 days. At that time, ALT had normalized, bilirubinemia was 138 μmol/L, and HEV RNA was almost undetectable in the serum. Conclusion: Ribavirin therapy could be an effective treatment of severe acute hepatitis E. © 2011 Elsevier B.V.


Colson P.,Center Hospitalo University Timone | Colson P.,Aix - Marseille University | Borentain P.,Center Hospitalo University Conception | Queyriaux B.,Institute of Veille Sanitaire | And 9 more authors.
Journal of Infectious Diseases | Year: 2010

Background: The source and route of autochthonous hepatitis E virus (HEV) infections are not clearly established in industrialized countries despite evidence that it is a zoonosis in pigs. We investigated the role of figatellu, a traditional pig liver sausage widely eaten in France and commonly consumed raw, as a source of HEV infection. Methods: A case-control study was conducted of 3 patients who presented autochthonous hepatitis E and 15 members of their 3 different families. Anti-HEV immunoglobulin G and immunoglobulin M antibody testing was performed with commercial assays. HEV RNA was detected in serum samples of patients and in pig liver sausages by means of real-time polymerase chain reaction and sequenced by means of in-house sequencing assays. Genetic links between HEV sequences were analyzed. Results: Acute or recent HEV infection, defined by detection of anti-HEV immunoglobulin M antibodies and/ or HEV RNA, was observed in 7 of 13 individuals who ate raw figatellu and 0 of 5 individuals who did not eat raw figatellu ( ). Moreover, HEV RNA of genotype Pp.041 3 was recovered from 7 of 12 figatelli purchased in supermarkets, and statistically significant genetic links were found between these sequences and those recovered from patients who ate raw figatellu. Conclusion: Our findings strongly support the hypothesis of HEV infection through ingestion of raw figatellu. © 2010 by the Infectious Diseases Society of America. All rights reserved.


Colson P.,French National Center for Scientific Research | Colson P.,Center Hospitalo University Timone | Gimenez G.,French National Center for Scientific Research | Boyer M.,French National Center for Scientific Research | And 3 more authors.
PLoS ONE | Year: 2011

Background: A recent work has provided strong arguments in favor of a fourth domain of Life composed of nucleo-cytoplasmic large DNA viruses (NCLDVs). This hypothesis was supported by phylogenetic and phyletic analyses based on a common set of proteins conserved in Eukarya, Archaea, Bacteria, and viruses, and implicated in the functions of information storage and processing. Recently, the genome of a new NCLDV, Cafeteria roenbergensis virus (CroV), was released. The present work aimed to determine if CroV supports the fourth domain of Life hypothesis. Methods: A consensus phylogenetic tree of NCLDVs including CroV was generated from a concatenated alignment of four universal proteins of NCLDVs. Some features of the gene complement of CroV and its distribution along the genome were further analyzed. Phylogenetic and phyletic analyses were performed using the previously identified common set of informational genes present in Eukarya, Archaea, Bacteria, and NCLDVs, including CroV. Findings: Phylogenetic reconstructions indicated that CroV is clearly related to the Mimiviridae family. The comparison between the gene repertoires of CroV and Mimivirus showed similarities regarding the gene contents and genome organization. In addition, the phyletic clustering based on the comparison of informational gene repertoire between Eukarya, Archaea, Bacteria, and NCLDVs unambiguously classified CroV with other NCLDVs and clearly included it in a fourth domain of Life. Taken together, these data suggest that Mimiviridae, including CroV, may have inherited a common gene content probably acquired from a common Mimiviridae ancestor. Conclusions: This further analysis of the gene repertoire of CroV consolidated the fourth domain of Life hypothesis and contributed to outline a functional pan-genome for giant viruses infecting phagocytic protistan grazers. © 2011 Colson et al.


Kaba M.,Aix - Marseille University | Kaba M.,Center Hospitalo University Timone | Moal V.,Aix - Marseille University | Gerolami R.,Center Hospitalo University Conception | And 2 more authors.
Intervirology | Year: 2013

Mammalian hepatitis E virus (HEV), the etiological agent of hepatitis E in humans, is a recently discovered infectious agent. It was identified for the first time in 1983 using electron microscopy on a faecal specimen of a person infected with non-A, non-B enterically-transmitted hepatitis. Based on retrospective and prospective studies, HEV was long described as one of the leading causes of acute viral hepatitis in tropical and subtropical countries, whereas in developed countries hepatitis E was considered an imported disease from HEV hyperendemic countries. Data from studies conducted during the past decade have greatly shifted our knowledge on the epidemiology and clinical spectrum of HEV. Recently, it has been shown that contrary to previous beliefs, hepatitis E is also an endemic disease in several developed countries, particularly in Japan and in Europe, as evidenced by reports of high anti-HEV immunoglobulin G prevalence in healthy individuals and an increasing number of non-travel-related acute hepatitis E cases. Moreover, a porcine reservoir and growing evidence of zoonotic transmission have been reported in these countries. This review summarizes the current knowledge on the epidemiology and prevention of transmission of mammalian HEV. Copyright © 2013 S. Karger AG, Basel.


Doudier B.,Service de Medecine Interne | Verrot D.,Service de Medecine Interne | Serratrice C.,Service de Medecine Interne | Poucel C.,Service de Medecine Interne | And 3 more authors.
Journal of Clinical Microbiology | Year: 2015

We describe a case of fatal fulminant hepatitis E concomitant to malignant B cell lymphoma in a 73-year-old French woman. Infection was with an autochthonous hepatitis E virus of genotype 3f. Frequent consumption of uncooked pig liver sausage (figatellu) was the only risk factor found. Copyright © 2015, American Society for Microbiology. All Rights Reserved.


Khalil J.Y.B.,Aix - Marseille University | Andreani J.,Aix - Marseille University | La Scola B.,Aix - Marseille University | La Scola B.,Center Hospitalo University Timone
Current Opinion in Microbiology | Year: 2016

Almost fifteen years ago, the discovery of Acanthamoeba polyphaga mimivirus, the first giant virus, changed how we define a virus. It was discovered incidentally in a process of isolating Legionella sp. from environmental samples in the context of pneumonia epidemics using a co-culture system with Acanthamoeba. Since then, much effort and improvement has been put into the original technique. In addition to the known families of Mimiviridae and Marseilleviridae, four new proposed families of giant viruses have been isolated: Pandoravirus, Pithovirus, Faustovirus and Mollivirus. Major improvements were based on enrichment systems, targeted use of antibiotics and high-throughput methods. The most recent development, using flow cytometry for isolation and presumptive identification systems, opens a path to large environmental surveys that may discover new giant virus families in new protozoa supports used for culture support. © 2016 Elsevier Ltd.


Colson P.,Center Hospitalo University Timone | Colson P.,Aix - Marseille University | Gayet S.,Center Hospitalo University Sainte Marguerite | Gerolami R.,Center Hospitalo University Conception
Antiviral Therapy | Year: 2011

HCV displays considerable levels of nucleotide and amino acid diversity. Recently, the relevance of natural polymorphisms in worldwide isolates has been addressed in view of future protease inhibitor (PI)-based treatments; geno-type-and subtype-specific natural polymorphisms within HCV NS3 protease were identified at amino acid sites associated either with resistance to PIs or with compensatory mutations. Here, we describe a case of chronic infection with HCV of genotype 3 subtype h (HCV-3h), formerly only described from three patients originating from Somalia, and we provide the first NS3 protease sequence for such strains. NS3 protease sequences of HCV-3h recovered in the present study harbour specific amino acid residues not encountered in other reference HCV genotypes and sub-types at nine of the 181 NS3 protease positions; none of these amino acids are known to confer resistance to PIs. Of note, 5′ untranslated region sequence-based genotyping classifies them into genotype 1. ©2011 International Medical Press.


Motte A.,Center Hospitalo University Timone | Roquelaure B.,Center Hospitalo University Timone | Galambrun C.,Center Hospitalo University Timone | Bernard F.,Center Hospitalo University Timone | And 3 more authors.
Journal of Clinical Virology | Year: 2012

Hepatitis E virus (HEV) causes an emerging autochthonous disease in developed countries where links with a viral porcine reservoir have been evidenced. Moreover, chronic HEV infection and associated-cirrhosis have been described in severely immunocompromized patients. Nonetheless, only few studies have focused on pediatric HEV infections worldwide and only four autochthonous cases have been reported in children in developed countries. We describe here acute hepatitis E in three immunocompromized children. Case no. 1 was a 9-year-old liver transplant recipient girl in whom H1N1 2009 flu infection was diagnosed concurrently with hepatitis E. Case no. 2 was a 12-year-old boy presenting early medullar relapse of lymphoblastic leukemia of type B and in whom HEV RNA was detected over a 29-week period. Case no. 3 was a 9-year-old boy with a rare primary immunodeficiency due to XIAP deficiency. HEV infections were all autochthonously acquired and involved different viruses classified as subtype f, c, and e of genotype 3, which are those described in autochthonous cases in Europe. These three observations prompt to consider HEV as a causative agent of hepatitis in children in developed countries, and to perform particularly HEV testing in those severely immunocompromized who may develop chronic hepatitis E. © 2011 Elsevier B.V.


Sharma V.,École Centrale Marseille | Colson P.,Aix - Marseille University | Colson P.,Center Hospitalo University Timone | Pontarotti P.,École Centrale Marseille | And 2 more authors.
Current Opinion in Microbiology | Year: 2016

Mimivirus and other giant viruses are visible by light microscopy and bona fide microbes that differ from other viruses and from cells that have a ribosome. They can be defined by: giant virion and genome sizes; their complexity, with the presence of DNA and mRNAs and dozens or hundreds of proteins in virions; the presence of translation-associated components; a mobilome including (pro)virophages (and a defence mechanism, named MIMIVIRE, against them) and transpovirons; their monophyly; the presence of the most archaic protein motifs they share with cellular organisms but not other viruses; a broader host range than other viruses. These features show that giant viruses are specific, autonomous, biological entities that warrant the creation of a new branch of microbes. © 2016 The Authors.

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