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Biomedical subjects

C Sureau

Publications and source records attributed to C Sureau.

At least 19 recordsLinked to original sources
PubMed2006

The role of the HBV envelope proteins in the HDV replication cycle.

The hepatitis delta virus (HDV) is a subviral agent that utilizes the envelope proteins of the hepatitis B virus (HBV) for propagation. When introduced into permissive cells, the HDV RNA genome replicates and associates with multiple copies of the HDV-encoded proteins to assemble a ribonucleoprotein (RNP) complex. The mechanism necessary to export the RNP from the cell is provided by the HBV envelope proteins, which have the capacity to assemble lipoprotein vesicles that bud into the lumen of a pre-Golgi compartment before being secreted. In addition to allowing the release of the HDV RNP, the HBV envelope proteins also provide a means for its targeting to an uninfected cell, thereby ensuring the spread of HDV. This chapter covers the molecular aspects of the HBV envelope protein functions in the HDV replication cycle, in particular the activity of the small envelope protein in RNP export and the function of the large envelope protein at viral entry.

Helper Viruses↗
PubMed2004

Taskforce 8: ethics of medically assisted fertility treatment for HIV positive men and women.

In this 8th statement of the ESHRE Taskforce on Ethics and Law, the focus is on the ethical issues raised by (assisted) reproduction for HIV positive men and women. Due to treatment improvements, their life expectancy has increased substantially. This, in combination with the reduction of perinatal transmission to the child, makes the creation of a family more acceptable. Recommendations are made concerning methods of avoiding HIV transmission in the couple and to their offspring. It is concluded that, if certain precautions are taken, medical assistance to reproduction of HIV positive people is ethically acceptable. For the time being, only cases of serodiscordant couples should be considered.

Anti-Retroviral Agents↗
PubMed2003

Taskforce 5: preimplantation genetic diagnosis.

The European Society of Human Reproduction and Embryology (ESHRE) Ethics Task Force sets out a recommended multidisciplinary approach to the application of preimplantation genetic diagnosis (PGD). The statement includes consideration of fundamental ethical principles, specific problems in cases of high genetic risk, and PGD for aneuploidy screening, HLA typing and sex selection for non-medical reasons.

Aneuploidy↗
PubMed2001

[The right to be aborted].

This lecture deals with the difficult problem of so called "wrongful life". Two Court decisions have been issued recently in France and lead to a very ambiguous situation since they differ dramatically. In the "Perruche affair" where a diagnosis of rubella was not done, the parents prevented to get an interruption of pregnancy, and the child severely affected, the Court (Cour de Cassation, i.e. Supreme Court in charge of civil affairs) decided to compensate the child for "not having be aborted". In the "Quarez affair" where a diagnosis of Down syndrome was not done, the parents prevented to get an interruption of pregnancy, the Court (Conseil d'Etat, i.e. Supreme Court in charge of "administrative" affairs, affairs opposing individuals to state administration since the hospital in cause was belonging to the public sector) decided not to compensate directly the affected child. The consequences of these opposite decisions are analysed according to medical, legal, ethical and economic considerations.

Abortion, Induced↗
PubMed2000

[Informed consent and principle of precaution].

The so called principle of precaution can be applied to the medical activity according to two opposite conceptions : in a traditional way, the practitioner is acting following the line he/she presumes to be in the best interests of the patient, despite the psychological burden of this attitude. The information given to the patient is modulated accordingly. Such attitude is nowadays considered as excessively paternalistic. Following the recent Court decisions the information must now become absolutely complete, including the very serious, albeit exceptional, consequences of the treatments, in order to allow the patient to make in every circumstance an informed choice. Such an attitude leads to a very efficient protection of the practitioner. However, the consequences may be detrimental for the individual patients, as well as for the whole society.

Attitude of Health Personnel↗
PubMed1999

Mutations in the carboxyl-terminal domain of the small hepatitis B virus envelope protein impair the assembly of hepatitis delta virus particles.

The carboxyl-terminal domain of the small (S) envelope protein of hepatitis B virus was subjected to mutagenesis to identify sequences important for the envelopment of the nucleocapsid during morphogenesis of hepatitis delta virus (HDV) virions. The mutations consisted of carboxyl-terminal truncations of 4 to 64 amino acid residues and small combined deletions and insertions spanning the entire hydrophobic domain between residues 163 and 224. Truncation of as few as 14 residues partially inhibited glycosylation and secretion of S and prevented assembly or stability of HDV virions. Short internal combined deletions and insertions were tolerated for secretion of subviral particles with the exceptions of those affecting residues 164 to 173 and 219 to 223. However, mutants competent for subviral particle secretion had a reduced capacity for HDV assembly compared to that of the wild type. One exception was a mutant carrying a deletion of residues 214 to 218, which exhibited a twofold increase in HDV assembly (or stability), whereas deletions of residues 179 to 183, 194 to 198, and 199 to 203 were the most inhibitory. Substitutions of single amino acids between residues 194 and 198 demonstrated that HDV assembly deficiency could be assigned to the replacement of the tryptophan residue at position 196. We concluded that assembly of stable HDV particles requires a specific function of the carboxyl terminus of S which is mediated at least in part by Trp-196.

Amino Acid Sequence↗
PubMed1998

Effect of mutations in the small envelope protein of hepatitis B virus on assembly and secretion of hepatitis delta virus.

The gene coding for the small (S) envelope protein of hepatitis B virus was mutated to identify sequences important for the envelopment of the nucleocapsid during morphogenesis of hepatitis delta virus (HDV) virions. This study was focused on a domain of the S protein that is exposed in the cytoplasm during synthesis and thereby represented a good candidate for interaction with the viral nucleocapsid during virion assembly. The mutations consisted of deletion/insertions spanning the entire cytosolic domain of S between amino acid residues 24 and 80. Although the expression of mutants clustered between residues 59 and 80 could not be obtained, we demonstrated that a large part of the cytosolic loop, from residues 29-47 and 49-59, does not contain motifs essential for production of hepatitis B virus subviral particles or HDV virions. However, deletion of residues 24-28 led to the synthesis of S protein mutant, which was competent for secretion of subviral particles but deficient for production of HDV. We concluded that the sequence between Arg-24 and Ile-28 located at the carboxyl boundary of the transmembrane signal I for S contains residue or residues important for HDV particle assembly.

Amino Acid Sequence↗
PubMed1998

Ultrastructural analysis of hepatitis B virus in HepG2-transfected cells with special emphasis on subviral filament morphogenesis.

The intracellular accumulation of empty hepatitis B virus (HBV) particles of filamentous shape leads to a direct cytopathic effect in so-called ground-glass hepatocytes. The aim of this study was to investigate how these filaments can be structurally formed at the cellular level. By electron microscopy, we reexamined the HBV-producer HepG2T-14 cells, which have been described as producing a substantial amount of empty HBV filaments compared with the other forms of HBV particles. Examination of ultrathin sections of HepG2T14 cells revealed the presence of HBV virions and filaments at the periphery of extremely large intracellular cisternae, probably related to a pre-Golgi compartment. Very long filaments appeared to be formed by a tubular budding of a long portion of the cisterna membrane. This phenomenon may be identical to that observed in the hepatocytes of HBV chronic carriers, in which the inability of the infected cell to export long HBV filamentous particles through the cellular secretion pathway seems to be at the origin of a direct cytopathic effect.

Actin Cytoskeleton↗
PubMed1998

Structural characterization of viral neutralizing monoclonal antibodies to hepatitis B surface antigen.

In this study we describe the viral neutralizing activity of murine monoclonal antibodies (MAb) specific for hepatitis B surface antigen (HBsAg). This viral neutralizing activity was assessed in vitro by employing Hepatitis Delta Virus (HDV) and human hepatocytes as target cells. To further characterize these viral neutralizing antibodies we generated a panel of anti-idiotypic (anti-Id) reagents and serologically characterized these antibodies for epitope specificity, Id specificity, and Id heterogeneity. Direct binding and competitive inhibition solid phase enzyme immunoassay have demonstrated that two murine MAb specific for HBsAg (anti-HBs), designated A1.2 and A3.1, recognize similar or overlapping epitopes on HBsAg, while monoclonal anti-HBs, designated A2.1 recognizes a unique HBsAg epitope. Further, Id analysis using monoclonal and polyclonal anti-Id reagents have identified both a private and a cross-reactive Id, respectively, on the anti-HBs, A1.2 preparation. The source of the idiotypic cross-reactivity between A1.2 and A3.1 has been identified, using Western blot analysis, to conformational determinants expressed by the heavy (H) and light (L) chains of these monoclonal anti-HBs. Lastly, the intrastrain antibody repertoire induced following HBsAg immunization was found to be relatively restricted in heterogeneity by clonotype analysis using isoelectric focusing and affinity immunoblot analysis. Interspecies variability in the anti-HBs response was observed based on epitope recognition using purified anti-HBs from a variety of species.

Animals↗
PubMed1998

In vitro infection of adult normal human hepatocytes in primary culture by hepatitis C virus.

In vitro infection of adult normal human hepatocytes in primary culture has been performed for investigating the replication cycle of hepatitis C virus (HCV) in differentiated cells. Hepatocytes were prepared from liver tissue resected from donors who tested negative for HCV, and inoculation was performed 3 days after plating with 33 HCV serum samples of different virus load and genotype. The presence of intracellular HCV RNA, detected by a strand-specific rTth RT-PCR assay, was used as evidence of infection. A kinetics analysis of HCV replication revealed that intracellular negative-strand RNA appeared at day 1 post-infection with a maximum level at days 3 and 5, followed by a decrease until day 14. At day 5, we estimated that the copy level of viral RNA was amplified at least 15-fold in infected cells. The level of intracellular HCV RNA in response to different serum samples was reproducible from one hepatocyte culture to another, suggesting that there is no inter-individual variability in the susceptibility of hepatocytes to HCV infection. These findings indicate that adult human hepatocytes in primary culture retain their susceptibility to in vitro HCV infection and support HCV RNA replication. This model should represent a valuable tool for the study of initial steps of the HCV replication cycle and for the evaluation of antiviral molecules.

Adult↗