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P Sonigo

Publications and source records attributed to P Sonigo.

At least 19 recordsLinked to original sources
PubMed1996

Prenatal MRI diagnosis of fetal cerebral tuberous sclerosis.

Tuberous sclerosis (TS) is an autosomal dominant phakomatosis. A high percentage of spontaneous mutations leads to the diagnosis of new cases in normal families. This diagnosis is suspected at antenatal ultrasound on the discovery of multiple cardiac tumors. Antenatal cerebral ultrasound shows a normal appearance in affected fetuses. Eight fetuses with multiple cardiac tumors were studied with antenatal MRI with, in five cases, an abnormal appearance showing hyperintense subependymal and cortical nodules on T1-weighted images. Among the three remaining patients MRI was non-contributive in one due to movement artefact, one had abnormal postnatal MRI consistent with TS and one had a normal postnatal and clinical examination. We conclude that MRI is a valuable tool in making the diagnosis of TS in fetuses with multiple cardiac tumors.

Female↗
PubMed1996

Neutralization sensitivity and accessibility of continuous B cell epitopes of the feline immunodeficiency virus envelope.

Antibodies elicited during natural infection of domestic cats by the feline immunodeficiency virus (FIV) recognize continuous epitopes in nine domains of the virus envelope glycoproteins. Whereas antibodies directed against the V3 envelope region can neutralize laboratory-adapted virus, neutralization of FIV has been shown to depend upon cellular substrate, and virus adaptation to laboratory cell lines may alter sensitivity to neutralizing antibodies. We therefore undertook a systematic analysis of the continuous B cell epitopes of the envelope of a primary FIV isolate, Wo. The capacity of feline antisera elicited against nine envelope domains to neutralize primary and laboratory-adapted virus was evaluated in feline peripheral blood mononuclear cells (PBMC). The laboratory-adapted strain Petaluma was used to compare neutralization in PBMC and Crandell feline kidney cells (CrFK). Antibodies specific for the V3 region neutralized both primary and laboratory-adapted virus whether residual infectivity was measured in CrFK or in feline PBMC. However, a large discrepancy in the efficiency of neutralization was observed in these ex vivo models of infection, perhaps reflecting diversity in the interaction between virus and different cellular targets. We also examined the accessibility of epitopes on the functional oligomeric envelope complex of FIV. Most of the epitopes were poorly exposed on native envelope glycoproteins at the surface of live infected cells. The most accessible domain was the only domain sensitive to neutralizing antibodies. These results suggest that inaccessibility on oligomeric envelope glycoproteins may frequently underlie the insensitivity of diverse lentivirus B cell epitopes to neutralization.

Amino Acid Sequence↗
PubMed1995

Erratic G-->A hypermutation within a complete caprine arthritis-encephalitis virus (CAEV) provirus.

The complete nucleotide sequence of an integrated provirus of caprine arthritis-encephalitis virus (CAEV) has been determined. The provirus was defective due to extensive G-->A hypermutation. Rather than being a smooth phenomenon distributed throughout the genome it was highly erratic with hypermutated and normal regions being juxtaposed, probably reflecting local fluctuations in the intracellular dCTP pool during reverse transcription of the CAEV genome. The pattern of sequence variation within the surface glycoproteins differs subtly from that of the primate lentiviruses.

Adenine↗
PubMed1995

Differences in feline immunodeficiency virus host cell range correlate with envelope fusogenic properties.

Feline immunodeficiency virus (FIV) establishes persistent infections in cats inducing an acquired immunodeficiency syndrome. Differences in cell tropism have been observed among isolates of FIV (T. R. Phillips et al., J. Virol. 64, 4605-4613, 1990). The progeny of the infectious molecular clone of FIV p34TF10 was able to productively infect a feline fibroblast cell line, Crandell feline kidney cell, (CrFK), while the progeny of the molecular clone pPPR was not. However, pPPR, after transfection of CrFK cells, did produce virions which were able to productively infect feline lymphocytes. To analyze the mechanisms responsible for such differences in tropism and particularly the role of the envelope glycoproteins (Env), Env expression vectors were constructed by deletion of gag and pol genes from 34TF10 and PPR proviral clones. Env expression and function were studied by using a syncytium-formation assay and a quantitative ELISA. After transfection of CrFK, both 34TF10 and PPR Env precursors were correctly processed and Env surface glycoprotein, gp100, was released in culture supernatants. However, the Env of 34TF10 caused a dramatic syncytial effect in CrFK cells, while PPR Env did not induce any syncytium formation. The Env of 34TF10 placed under the control of the long terminal repeat of PPR maintained its ability to induce CrFK fusion. These results suggest that the inability of FIV PPR to infect CrFK fibroblasts is related to a restriction of virus entry mediated by the viral envelope.

Animals↗
PubMed1995

Heterologous HIV-2 challenge of rhesus monkeys immunized with recombinant vaccinia viruses and purified recombinant HIV-2 proteins.

In an attempt to analyse the role of anti-envelope immunity in the protection of rhesus monkeys against an HIV-2 intravenous challenge, rhesus macaques were immunized twice with recombinant HIV-2 ROD vaccinia viruses (10(8) p.f.u. each) at days 0 and 30, followed by booster injections of purified HIV-2 proteins at months 8, 9, 15 and 27. One group of five macaques was immunized with the Gag, Pol, Vif and Nef antigens, whereas a second group received the same antigens with the addition of HIV-2 Env protein. Eight months after the last boost, the animals were challenged by intravenous injection of 100 AID50 of a monkey PBMC-grown stock of HIV-2 SBL. None of the animals was protected in spite of high humoral immune responses on day of challenge as determined by ELISA and Western Blot assays.

AIDS Vaccines↗
PubMed1995

Comparison of serological tests for the diagnosis of feline immunodeficiency virus infection of cats.

A new enzyme-linked-immunosorbent assay (ELISA) for the detection of antibodies to feline immunodeficiency virus was compared with previously described ELISAs. Serum samples from 184 infected or uninfected cats were tested using a whole virus lysate kit and ELISAs based on recognition of one of two synthetic peptides (P237 and P253) localized in the transmembrane domain of the viral envelope. The whole virus lysate commercial kit led to the detection of 6% false positive and 4.3% false negative sera. The ELISA based on peptide P253 gave no false positive result and failed to detect only one serum that was subsequently shown to be positive by radio-immunoprecipitation assay. A sandwich-ELISA test using Galanthus nivalis agglutinin, a lectin that specifically binds terminal mannose groups of the envelope proteins was used as a confirmatory test for equivocal results with peptide ELISA and gave similar results. This study indicates that recognition of P253 could serve as a sensitive and specific test for the diagnosis of seropositivity to feline immunodeficiency virus, and moreover that the Galanthus nivalis ELISA could be useful in equivocal cases as a confirmatory test.

Amino Acid Sequence↗
PubMed1995

Highly attenuated SIVmac142 is immunogenic but does not protect against SIVmac251 challenge.

We report here the use of the highly attenuated SIVmac142 clone, unable to establish permanent infection of rhesus macaques, in a vaccine trial. Four rhesus macaques were immunized over a long time period with HUT-78 cells infected with wild-type SIVmac142 or, in order to reinforce the safety use of the vaccine, a deleted mutant with similar in vitro infectivity. The first two injections were done with living cells and the remaining boosts with cells emulsified in muramyl dipeptide adjuvant. Three control macaques were injected with uninfected HUT-78 cells. Over 3 years, we have been unable except once to detect viral infections by three methods. However, antibodies directed against the viral Gag proteins and envelope glycoproteins were detected by immunoblots and/or in vitro neutralization assays. All macaques were challenged intravenously with a low dose (10 animal infectious doses) of a highly pathogenic biological clone of SIVmac251 grown on macaque PBMCs. All seven animals became persistently viremic following challenge. The cell-associated viral loads of the vaccinated monkeys were not reduced relative to those of unvaccinated controls during the first weeks postchallenge even if vaccinated monkeys did not present a transient CD4 decrease. Thus, our data reinforced the notion that the efficacy of live attenuated SIV requires the establishment of persistent infection.

Animals↗
PubMed1995

Structural analysis of the principal immunodominant domain of the feline immunodeficiency virus transmembrane glycoprotein.

In the transmembrane envelope glycoprotein (TM) of lentiviruses, including human immunodeficiency virus type 1 (HIV-1) and feline immunodeficiency virus (FIV), two cysteine residues, conserved in most retroviruses, are thought to form a loop containing five to seven amino acids. These elements make up a B-cell epitope recognized by nearly 100% of sera from infected patients or animals, designated the principal immunodominant domain (PID). The PID amino acid sequences are highly conserved between isolates of the same lentivirus but are unrelated, except for the two cysteines, when divergent lentiviruses are compared. The aim of this study was to analyze the relationship between amino acid sequence in the PID and envelope function. We introduced two kinds of mutations in the PID of FIV: mutations which impeded the formation of a loop and mutations which substituted the sequence of FIV with the corresponding sequences from other lentiviruses, HIV-1, visna virus, and equine infectious anemia virus. We analyzed antibody recognition, processing, and fusogenic properties of the modified envelopes, using two methods of Env expression: a cell-free expression system and transfection of a feline fibroblast cell line with gag-pol-deleted FIV proviruses. Most mutations in the PID of FIV severely affected envelope processing and abolished syncytium formation. Only the chimeric envelope containing the HIV-1 PID sequence was correctly processed and maintained the capacity to induce syncytium formation, although less efficiently than the wild-type envelope. We computed three-dimensional structural models of the PID, which were consistent with mutagenesis data and confirmed the similarity of FIV and HIV-1 PID structures, despite their divergence in amino acid sequence. Considering these results, we discussed the respective importance of selection exerted by functional requirements or host antibodies to explain the observed variations of the PIDs in lentiviruses.

Amino Acid Sequence↗
PubMed1995

Influence of transmembrane domains on the fusogenic abilities of human and murine leukemia retrovirus envelopes.

The envelopes of two highly divergent oncoviruses, human T-cell leukemia virus type 1 (HTLV-1) and Friend murine leukemia virus (F-MuLV), have distinct patterns of cellular receptor recognition, fusion, and syncytium formation. To analyze the influence of the transmembrane envelope subunit (TM) on fusogenic properties, we substituted either the entire TM or distinct domains from F-MuLV for the corresponding domains in the HTLV-1 envelope. Parental, chimeric, and truncated envelopes cloned into a eukaryotic expression vector were monitored for fusogenic potential in human, rat, and murine indicator cell lines by using a quantitative assay. This highly sensitive assay allowed us to assess the fusogenic properties and syncytium-forming abilities of the HTLV-1 envelope in murine NIH 3T3 cells. All chimeric envelopes containing extracellular sequences of the F-MuLV TM were blocked in their maturation process. Although deletions of the HTLV-1 cytoplasmic domain, alone and in combination with the membrane-spanning domain, did not prevent envelope cell surface expression, they impaired and suppressed fusogenic properties, respectively. In contrast, envelopes carrying substitutions of membrane-spanning and cytoplasmic domains were highly fusogenic. Our results indicate that these two domains in F-MuLV and HTLV-1 constitute structural entities with similar fusogenic properties. However, in the absence of a cytoplasmic domain, the F-MuLV membrane-spanning domain appeared to confer weaker fusogenic properties than the HTLV-1 membrane-spanning domain.

3T3 Cells↗
PubMed1995

Continuous secretion of human soluble CD4 in mice transplanted with genetically modified cells.

Somatic transgenesis can be used to confer endogenous production of proteins with therapeutic properties. One such product, recombinant soluble human CD4 (sCD4), has been shown to be an efficient inhibitor of human immunodeficiency virus 1 (HIV-1) in vitro, but its too short half-life in vivo has impaired long-term clinical trials in AIDS patients. Using a retroviral vector, we introduced the cDNA of sCD4 into primary mouse fibroblasts. The cells were enclosed in a lattice of collagen and synthetic fibers coated with basic fibroblast growth factor, and implanted in the peritoneal cavity of syngeneic mice. Implantation of such sCD4-secreting organoids into cyclosporin A-treated C3H mice elicited a strong antibody response against sCD4. Implantation of sCD4-secreting organoids into immunotolerant mice (transgenic for transmembrane human CD4) resulted in continuous sCD4 production, detected during 60 days in animal sera. The serum levels obtained were significant, but too limited as yet for anti-HIV purposes. Nevertheless, this model may be of interest in various fields, as it provides the first demonstration that one potentially therapeutic protein, despite its half-life of a few hours, could remain present in vivo 2 months after a single somatic transgenesis.

Animals↗
PubMed1994

Prenatal diagnosis of tuberous sclerosis. Use of magnetic resonance imaging and its implications for prognosis.

Tuberous sclerosis (TS) is an autosomal dominant disorder with a high rate of de novo mutation. The real difficulty is to ascertain the diagnosis and to give the neurological prognosis in each case. Prenatal diagnosis of TS is generally based on ultrasonographic signs of multiple cardiac tumours, i.e. rhabdomyomas. Recent progress in magnetic resonance imaging (MRI) enables the diagnosis in a large proportion of cases based on typical brain lesions. It may have a role in the prenatal management of TS, although MRI images seem to underestimate the anatomical findings. Two cases in which TS was diagnosed prenatally are presented with reference to the value of MRI in the prenatal management and comparison with anatomical findings.

Female↗
PubMed1994

Antibody reactivity to the immunodominant epitopes of the caprine arthritis-encephalitis virus gp38 transmembrane protein associates with the development of arthritis.

High titers of antibodies to caprine arthritis-encephalitis virus (CAEV) envelope (Env) glycoproteins are found in infected goats developing a progressive arthritis. In order to identify linear B epitopes of the CAEV Env, which may be involved in the immunopathology of arthritis, we constructed a lambda gt11 Env expression library. By combining library screening with sera from naturally infected Swiss goats with an enzyme immunoassay with overlapping peptides (pepscan), four group-specific epitopes could be precisely defined in the transmembrane envelope proteins: TM1 to TM4, including a conserved structure (TM3) that corresponds to the immunodominant epitope of human immunodeficiency virus type 1 and other lentiviruses. A panel of 190 CAEV naturally infected goat serum samples, obtained from animals with defined clinical status, was tested for reactivity to synthetic peptides corresponding to the TM epitopes in an enzyme-linked immunosorbent assay. Antibody reactivity to two epitopes was highly associated (TM3, P = 0.002, and TM4, P < 0.001) with the presence of clinically detectable arthritis. Such an association is absent for anti-Gag antibody. Antibodies to the immunodominant structures of the TM glycoprotein could thus have an important role in the immunopathogenic process leading to disease.

Amino Acid Sequence↗
PubMed1993

Phenotypic suppression by incorporation of an alien amino acid.

Azaleucine is a naturally occurring amino acid antibiotic that can be incorporated into proteins by mimicking leucine. In spite of its highly toxic character, the contrast between the hydrophobic side-chain of leucine and the basic side-chain of azaleucine suggested a mechanism for rescuing certain mutants. We constructed a thymidine auxotrophic mutant of Escherichia coli by replacing an arginine residue with leucine in the catalytic centre of thymidylate synthase, and indeed showed that activity could be restored by incorporation of azaleucine. This result extends the current scope of phenotypic suppression to mischarging with amino acid analogues. Microbial strains with a clear-cut requirement for an additional amino acid, as reported here, should be instrumental for widening the genetic code experimentally.

Amino Acids↗
PubMed1993

Structure and variations of feline immunodeficiency virus envelope glycoproteins.

We report the characterization of the env gene of a feline immunodeficiency virus isolate from France (FIV Wo). FIV Wo gag and env genes were cloned directly from cat peripheral blood mononuclear cells, using polymerase chain reaction. The env molecular clone was shown to be functional and to express antigenically relevant envelope glycoproteins in vitro. Alignment of FIV Wo sequences with available FIV sequences and application of a regionalization algorithm resulted in delineation of variable and conserved domains of FIV Env. These data were used to build a schematic folding model of FIV envelope glycoproteins. The Env molecular clone, variability map, and structural model constitute helpful tools for future studies of FIV envelope aimed at the determination of structure-function relationships or design of diagnostics or vaccine reagents.

Animals↗
PubMed1993

Congenital cystic adenomatoid malformation of the lung: prenatal management and prognosis.

Thirty-two cases of congenital cystic adenomatoid malformation of the lung diagnosed antenatally are reported. Antenatal diagnosis has made it possible to document the progress of the condition in utero and the postnatal prognosis. It has been possible to advise on termination and intrauterine intervention, to counsel the parents, and to plan arrangements for delivery and postnatal care among obstetricians, neonatologists, and pediatric surgeons. According to Stocker's classification there were 12 cases of type I, 15 of type II, and 5 of type III. Five pregnancies were terminated. Antenatal drainage of a cyst was performed in four patients with two survivors. Thirteen babies showed relative regression of the cyst as pregnancy progressed. After delivery the extent of the cystic malformation was assessed by chest x-rays and computed tomography scanning in 25 and angiography in 6. Treatment consisted of observation in 4, embolization in 2, operation as an emergency in 3, and electively around 4 months in 15.

Cystic Adenomatoid Malformation of Lung, Congenita↗
PubMed1993

Prenatal management of congenital cystic adenomatoid malformation of the lung.

In utero evolution and postnatal outcome were studied for 18 cases of congenital adenomatoid malformation (CAM) diagnosed by prenatal ultrasound. Five were macrocystic CAM, 9 were microcystic, and 4 were homogeneously hyperechogenic. Three fetuses presented with hydrops. Pulmonary amniotic shunting was performed in 3 patients. Outcome was the following: 4 were aborted, 1 died neonatally, and 13 survived. Four of these infants required no surgery in the neonatal or postneonatal period. In three of these, the size of the mass had decreased spontaneously in utero. Outcome did not appear to be related to the anatomic type of CAM nor to the presence of moderate polyhydramnios, but was related to the degree of mediastinal compression and to the existence of hydrops. A clearer understanding of the natural evolution of CAM is useful to determine the indications for in utero therapy.

Cystic Adenomatoid Malformation of Lung, Congenita↗
PubMed1993

B epitopes and selection pressures in feline immunodeficiency virus envelope glycoproteins.

In order to map linear B epitopes in feline immunodeficiency virus (FIV) envelope glycoproteins (Env), a random library of FIV Env polypeptides fused to beta-galactosidase and expressed in Escherichia coli was screened by using sera from experimentally FIV-infected cats. We mapped five antibody-binding domains in the surface envelope glycoprotein (SU1 to SU5) and four in the transmembrane envelope glycoprotein (TM1 to TM4). Immunological analysis with 48 serum samples from naturally or experimentally infected cats of diverse origins revealed a broad group reactivity for epitopes SU2, TM2, and TM3, whereas SU3 appeared as strictly type specific. To study selection pressures acting on the identified immunogenic domains, we analyzed structural constraints and distribution of synonymous and nonsynonymous mutations (amino acids unchanged or changed). Two linear B epitopes (SU3 and TM4) appeared to be submitted to positive selection for change, a pattern of evolution predicting their possible involvement in antiviral protection. These experiments provide a pertinent choice of oligopeptides for further analysis of the protective response against FIV envelope glycoproteins, as a model to understand the role of antibody escape in lentiviral persistence and to design feline AIDS vaccines.

Animals↗