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Biomedical subjects

F Morinet

Publications and source records attributed to F Morinet.

At least 19 recordsLinked to original sources
PubMed2004

Surveillance network for herpes simplex virus resistance to antiviral drugs: 3-year follow-up.

Herpes simplex virus (HSV) infections are very common in the general population and among immunocompromised patients. Acyclovir (ACV) is an effective treatment which is widely used. We deemed it essential to conduct a wide and coordinated survey of the emergence of ACV-resistant HSV strains. We have formed a network of 15 virology laboratories which have isolated and identified, between May 1999 and April 2002, HSV type 1 (HSV-1) and HSV-2 strains among hospitalized subjects. The sensitivity of each isolate to ACV was evaluated by a colorimetric test (C. Danve, F. Morfin, D. Thouvenot, and M. Aymard, J. Virol. Methods 105:207-217, 2002). During this study, 3900 isolated strains among 3357 patients were collected; 55% of the patients were immunocompetent. Only six immunocompetent patients excreted ACV-resistant HSV strains (0.32%), including one female patient not treated with ACV who was infected primary by an ACV-resistant strain. Among the 54 immunocompromised patients from whom ACV-resistant HSV strains were isolated (3.5%), the bone marrow transplantation patients showed the highest prevalence of resistance (10.9%), whereas among patients infected by human immunodeficiency virus, the prevalence was 4.2%. In 38% of the cases, the patients who excreted the ACV-resistant strains were treated with foscarnet (PFA), and 61% of them developed resistance to PFA. The collection of a large number of isolates enabled an evaluation of the prevalence of resistance of HSV strains to antiviral drugs to be made. This prevalence has remained stable over the last 10 years, as much among immunocompetent patients as among immunocompromised patients.

Acyclovir↗
PubMed2002

Spontaneous resolution of hemophagocytic syndrome associated with acute parvovirus B19 infection and concomitant Epstein-Barr virus reactivation in an otherwise healthy adult.

Reported here is the case of a patient who spontaneously recovered from hemophagocytic syndrome associated with acute B19 infection and concomitant Epstein-Barr virus reactivation. The previously healthy 37-year-old-man was hospitalized after 10 days of high fever, arthralgia and arthritis and was determined to have hemophagocytic syndrome. Immunoglobulin (Ig) M antibodies to Epstein-Barr virus (EBV) capsid antigen, early antigen and parvovirus B19 (B19) were found. B19 DNA and low-level EBV DNA were detected in bone marrow, serum and peripheral blood mononuclear cells. The patient recovered spontaneously without any treatment. Two months later anti-B19 IgG antibodies were detected, while at 9-month follow-up, anti-B19 IgM antibodies were no longer detectable and B19 DNA had disappeared from serum. To the best of our knowledge, this is the first report of spontaneous resolution of hemophagocytic syndrome associated with acute B19 infection and concomitant EBV reactivation in an otherwise healthy adult.

Acute Disease↗
PubMed2002

Parvovirus B19 and erythroid cells.

Parvovirus B19 is a human erythrovirus, i.e. which induces the death of erythroid progenitors. In such cells, until now only ubiquitous transcription factors have been described to regulate promoter driven gene expression. Their possible interactions with erythroid specific transcription factors merit further investigations. Effectively, the high level of replication of B19 in erythroid cells is not well understood. In addition to apoptosis, necrosis or inhibition of cell growth, the death of B19 infected erythroid progenitors has been never clearly reported as the result of immunological attack: this mecanism will merit further investigations. The interactions with other cell types in vitro remain at present not well defined but many obstacles have been mentioned which counteract B19 expression.

Cell Death↗
PubMed2002

High frequency of a 30-bp deletion of Epstein-Barr virus latent membrane protein 1 gene in primary HIV non-Hodgkin's brain lymphomas.

A characteristic 30-base pair (bp) deletion (del) in the 3' end of the Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1) gene, coding for the C-terminal NF-kappa B activation domain, has been identified in various lymphoproliferative disorders and nasopharyngeal carcinomas. In the single report to date of human immunodeficiency virus primary brain lymphomas (HIV-PBLs), del-LMP1 was noted in seven cases out of nine. The present study was designed to identify this deletion in a series of 31 diffuse large B-cell HIV-PBLs, with the aim of determining its possible oncogenic action. The presence of EBV was confirmed by EBER mRNA in situ hybridization. After genomic extraction from frozen tissue, two 20-base oligonucleotide primers flanking the site of the 30-bp deletion were used. DNA sequencing of the polymerase chain reaction (PCR) products confirmed an identical segment spanning 30-bp and 69-bp, frequently associated with mutational hotspots in 19 cases (61%). A role for del-LMP1 in the oncogenic potential of EBV in systemic proliferations is a matter of debate. Its high incidence suggests that the oncogenic mechanism of LMP1 in the brain might differ significantly from that in systemic lymphoid proliferations, and might be enhanced by HIV infection.

Adult↗
PubMed2000

Resistant herpes simplex virus type 1 infection: an emerging concern after allogeneic stem cell transplantation.

Fourteen cases of severe acyclovir-resistant herpes simplex virus type 1 (HSV-1) infection, 7 of which showed resistance to foscarnet, were diagnosed among 196 allogeneic stem cell transplant recipients within a 29-month period. Recipients of unrelated stem cell transplants were at higher risk. All patients received foscarnet; 8 subsequently received cidofovir. Strains were initially foscarnet-resistant in 3 patients and secondarily so in 4 patients. In vitro resistance to acyclovir or foscarnet was associated with clinical failure of these drugs; however, in vitro susceptibility to foscarnet was associated with complete response in only 5 of 7 patients. No strain from any of the 7 patients was resistant in vitro to cidofovir; however, only 3 of 7 patients achieved complete response. Therefore, acyclovir- and/or foscarnet-resistant HSV-1 infections after allogeneic stem cell transplantation have become a concern; current strategies need to be reassessed and new strategies must be evaluated in this setting.

Acyclovir↗
PubMed1999

Usefulness of the cytomegalovirus (CMV) antigenemia assay for predicting the occurrence of CMV disease and death in patients with AIDS.

A cohort study of 214 human immunodeficiency virus (HIV)-infected patients was performed to assess the usefulness of the cytomegalovirus (CMV) antigenemia assay for predicting the occurrence of CMV disease and death. Multivariate analysis revealed that only positive baseline CMV antigenemia assays (relative risk [RR], 7.2; 95% confidence interval [CI], 3.7-14.2; P = .0001) and CD4 cell counts (RR, 0.98; 95% CI, 0.97-0.99; P = .009) were associated with CMV disease. A positive baseline CMV antigenemia assay was also associated with death by multivariate analysis (RR, 2.2; 95% CI, 1.5-3.4; P = .0003). Increasing levels of CMV antigenemia during follow-up were associated with increased risks of CMV disease and death. A positive CMV antigenemia assay that showed > 10 cells per 2 x 10(5) polymorphonuclear leukocytes during follow-up was 91% sensitive and 84% specific for predicting a diagnosis of CMV disease; the negative predictive value for this positive test was high (97%). Therefore, the CMV antigenemia assay appears to be a simple, rapid, and inexpensive test for predicting the occurrence of CMV disease and death in patients with advanced HIV infection.

AIDS-Related Opportunistic Infections↗
PubMed1999

Possible interactions between the NS-1 protein and tumor necrosis factor alpha pathways in erythroid cell apoptosis induced by human parvovirus B19.

Human erythroid progenitor cells are the main target cells of the human parvovirus B19 (B19), and B19 infection induces a transient erythroid aplastic crisis. Several authors have reported that the nonstructural protein 1 (NS-1) encoded by this virus has a cytotoxic effect, but the underlying mechanism of NS-1-induced primary erythroid cell death is still not clear. In human erythroid progenitor cells, we investigated the molecular mechanisms leading to apoptosis after natural infection of these cells by the B19 virus. The cytotoxicity of NS-1 was concomitantly evaluated in transfected erythroid cells. B19 infection and NS-1 expression induced DNA fragmentation characteristic of apoptosis, and the commitment of erythroid cells to undergo apoptosis was combined with their accumulation in the G(2) phase of the cell cycle. Since B19- and NS-1-induced apoptosis was inhibited by caspase 3, 6, and 8 inhibitors, and substantial caspase 3, 6, and 8 activities were induced by NS-1 expression, there may have been interactions between NS-1 and the apoptotic pathways of the death receptors tumor necrosis factor receptor 1 and Fas. Our results suggest that Fas-FasL interaction was not involved in NS-1- or B19-induced apoptosis in erythroid cells. In contrast, these cells were sensitized to tumor necrosis factor alpha (TNF-alpha)-induced apoptosis. Moreover, the ceramide level was enhanced by B19 infection and NS-1 expression. Therefore, our results suggest that there may be a connection between the respective apoptotic pathways activated by TNF-alpha and NS-1 in human erythroid cells.

Apoptosis↗
PubMed1998

Squamous cell carcinomas after allogeneic bone marrow transplantation for aplastic anemia: further evidence of a multistep process.

BACKGROUND: Secondary solid tumors are rare events occurring in patients who underwent allogeneic marrow transplantation for aplastic anemia and Fanconi's anemia. Human herpes virus 8 (HHV8), Epstein-Barr virus (EBV), and human papillomaviruses (HPV) sequences have been found in squamous cell carcinoma (SCC) occurring in organ transplant recipients. The tumor suppressor gene p53 has been strongly linked to the occurrence of SCC in the nonimmunocompromised population. PATIENTS AND METHODS: In eight patients with SCC, we searched for HHV8, EBV, varicella zoster virus, adenovirus, and HPV sequences from DNA extracted from selected areas of SCC. We also looked for p53 expression in those specimens as well as the presence of anti-p53 antibodies in the serum of these patients at the onset of SCC. RESULTS: In one patient, we found the presence of both HHV8 and EBV sequences, and in another patient we found HPV16 sequences. All five tumors that could be studied disclosed evidence of p53 accumulation, but none of the eight patients had anti-p53 antibodies in the sera. CONCLUSION: SCC developing in marrow transplant recipients seems to occur via a multistep process. Genetic predisposition may be present, as in patients with Fanconi's anemia. Transplantation-related factors, such as irradiation and chronic graft-versus-host disease, also have a role. In this article, we add two more potent risk factors: p53 alteration(s) and in some cases the presence of oncogenic viruses.

Anemia, Aplastic↗
PubMed1998

Regulation of human B19 parvovirus promoter expression by hGABP (E4TF1) transcription factor.

The genetic expression of human B19 parvovirus is only dependent on one promoter in vivo and in vitro. This is the P6 promoter, which is located on the left side of the genome and is a single-stranded DNA molecule. This led us to investigate the regulation of the P6 promoter and the possible resulting variability of the nucleotide sequence. After analysis of the promoter region of 17 B19 strains, only 1.5% variability was found. More exciting was the finding of mutations that were clustered around the TATA box and defined a highly conserved region (nucleotides 113-210) in the proximal part of the P6 promoter. HeLa and UT7/Epo cell extracts were found to protect this region, which contained a core motif for Ets family proteins, with YY1 and Sp1 binding sites on either side. Gel mobility shift assays performed with nuclear proteins from HeLa and UT7/Epo cells identified DNA-binding proteins specific for these sites. By supershift analysis, we demonstrated the binding of the hGABP (also named E4TF1) protein to the Ets binding site and the fixation of Sp1 and YY1 proteins on their respective motifs. In Drosophila SL2 cells, hGABPalpha and -beta stimulated P6 promoter activity, and hGABPalpha/hGABPbeta and Sp1 exerted synergistic stimulation of this activity, an effect diminished by YY1.

Base Sequence↗
PubMed1998

Characterization of cis-acting and NS1 protein-responsive elements in the p6 promoter of parvovirus B19.

Parvovirus B19 infections are associated with diverse clinical manifestations, ranging from no symptoms to severe symptoms. The virus shows an extreme tropism for replication in erythroid progenitor cells, possibly due to the activity of the only functional promoter (p6) of the B19 virus genome in combination with both cell- and cell cycle-specific factors and the trans-activator protein NS1. As presented here, p6 promoter sequences derived from several B19 virus isolates proved to be highly conserved. Furthermore, mutations did not affect any of the potential binding sites for transcription factors. One variation of the base at position 223 was identified only in B19 virus isolates derived from patients with persistent infection or chronic arthritis. To determine promoter activity and to characterize regulatory elements, sequences spanning the total p6 promoter and subfragments of them were introduced into a eukaryotic expression vector upstream of the luciferase gene (from Photinus pyralis). After transfection into HeLa, CEM, BJAB, and K562 cells, the p6 promoter was found to be highly active. When introduced into the erythroid cell line K562, p6-controlled transcription exceeded that of the simian virus 40 promoter-enhancer used as a control by more than 25-fold. Sequence elements relevant for promoter activity mapped to the regions from nucleotides (nt) 100 to 190 and 233 to 298. Also, the segment from nt 343 to 400 downstream of the TATA box was important for transcriptional activity in HeLa and K562 cells. By transfecting the promoter-luciferase constructs into a HeLa cell line stably carrying the viral NS1 gene under the control of an inducible promoter, transcriptional activity mediated by the p6 promoter rose significantly after induction of NS1 expression. The region from nt 100 to 160 proved to be essential for NS1-mediated transcriptional activation. Furthermore, NS1-mediated transactivation was dependent on the presence of two GC-rich elements arranged in tandem upstream of the TATA box. These data indicate that NS1-mediated p6 transactivation is dependent on a multicomponent complex combining NS1 with ATF, NF-kappaB/c-Rel, and GC-box binding cellular factors.

Base Sequence↗
PubMed1997

[Mechanisms of viral diseases and means of natural defense].

This article concentrates on the mechanisms by which viruses cause disease. Although the emphasis is on mechanisms rather than on a description of individual viral infections, selected viruses that best exemplify important or novel virus-host interactions are singled out. Twenty years ago, some viruses have helped understanding cell differentiation, and at present molecular and cellular biology are necessary to explain in depth the mechanisms of viral illnesses. Understanding and control of viral diseases are not mutually exclusive but rather simultaneous processes with multidisciplinary approaches. Like some bacterial toxins, virus may be deleterious without infecting cells. To use the cell machinery efficiently, viruses must be able to escape the immune system.

Humans↗
PubMed1997

Low prevalence of active parvovirus B19 infection in HIV-infected patients.

In a prospective study to determine the prevalence of parvovirus B19 in adult patients positive for the human immunodeficiency virus, a series of 55 consecutively presenting patients was tested for antibodies to parvovirus B19 and parvovirus B19 DNA. Specific IgG antibodies were detected in 96% of cases; specific IgM antibodies were present in 10%. Viral DNA was not detected in any of the sera analysed by polymerase chain reaction. Anemia could not be correlated with the presence of either IgG or IgM antibodies to parvovirus B19. Thus, no evidence of acute or chronic parvovirus B19 infection was found in the 55 patients. These findings suggest that active parvovirus B19 infection is uncommon in HIV-infected patients.

AIDS-Related Opportunistic Infections↗
PubMed1997

Establishment of a cell line expressing human parvovirus B19 non-structural protein from an inducible promoter.

Human parvovirus B19 non-structural (NS) protein is supposed to play a major role in B19 replication and transcription, and therefore in B19 pathogenicity. Constitutive expression of NS protein in stable cell lines has failed so far, presumably because of its cytotoxicity. To avoid this cytotoxic effect, we have cloned the NS gene in an Epstein-Barr virus episomal vector under the control of a steroid inducible promoter (5xGRE) and transfected this construction into HeLa cells. We obtained stable cell lines inducibly expressing high level of NS protein, with 50% of the cells demonstrating specific nucleo-cytoplasmic staining. In Western blot analysis, three B19 NS proteins (72, 68 and 60 kDa) were found but a unique NS transcript was detected by Northern blotting. The NS protein expressed in HeLa cell lines was demonstrated to be functional as it trans-activates the B19 P6 promoter. These cell lines might be major tools for further study and characterization of B19 NS protein.

Blotting, Western↗
PubMed1997

The 3' untranslated region of the B19 parvovirus capsid protein mRNAs inhibits its own mRNA translation in nonpermissive cells.

Although parvoviruses are found throughout the animal kingdom, only the human pathogenic B19 virus has so far been shown to possess a limited host range, with erythroid progenitor cells as the main target cells supporting B19 propagation. The underlying mechanism of such erythroid tropism is still unexplained. Synthesis of the NS1 nonstructural protein occurs in permissive and nonpermissive cells, such as megakaryocytes, whereas synthesis of the VP1 and VP2 capsid proteins seems to be restricted to burst-forming units and CFU of erythroid cells. In nonpermissive cells, the NS1 protein is overexpressed and the NS1 RNAs are the predominant RNA species. However, the VP1 and VP2 proteins are not detectable, although the corresponding mRNAs are synthesized. Since all transcripts have part of the 5' untranslated region (5' UTR) in common but distinct 3' UTRs characterizing the nonstructural- and structural-protein mRNAs, we investigated, in transient transfection assays, the possible involvement of the 3' UTR of the capsid protein mRNAs in VP1 and VP2 protein synthesis in nonpermissive Cos cells. The results showed that (i) the 3' UTR of mRNAs coding for the capsid proteins repressed VP1 and VP2 protein synthesis, (ii) the 3' UTR did not affect nuclear export or mRNA stability, and (iii) mRNAs bearing the 3' UTR of the capsid protein mRNAs did not associate with ribosomes at all. Taken together, these results indicate that in nonpermissive cells, the 3' UTR of the capsid protein mRNAs represses capsid protein synthesis at the translational level by inhibiting ribosome loading.

Animals↗