[Human diseases caused by parvovirus B 19].
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Erythema Infectiosum↗
Biomedical subjects
Y Becker
Publications and source records attributed to Y Becker.
Computer analysis of human immunodeficiency virus-1 envelope glycoprotein: functional topogenic domains as signals for transfer and cleavage.
Analysis of human immunodeficiency virus-1 (HIV-1) gp160 amino acid sequences by computer programs that provide information on the possible conformation, hydrophilicity, and surface probability was used to identify possible functional domains. Amino acid domains that serve as signals for transfer of the polypeptide chain through the cell membrane were identified. Stop-transfer amino acid domains present in gp160 made possible the identification of the membrane anchorage hydrophobic amino acid sequence. The characterization of amino acid domains that serve as signals for proteolytic cleavage suggest that gp41 might be cleaved in a number of positions in the polypeptide chain, releasing parts of the carboxy-terminus amino acid sequence from that part of gp41 anchored in the cell membrane. The computer analysis deals with the mode of insertion of gp160 into the cell membrane by the cellular signal recognition protein system and subsequent processing of the gp160 to gp120 and gp41 (and subpeptides). The model for the positioning of these peptides is used to predict the organization of the processed envelope proteins in the viral envelope. The possible function of domains in gp120 and gp41 during the interaction with host cells during virus infection is discussed.
Amino Acid Sequence↗
Computer predictions of antigenic domains in herpes simplex virus types 1 and 2 glycoprotein D as compared with experimentally proven domains.
The primary amino-acid sequence of the glycoprotein D (gD) of herpes simplex virus types 1 and 2 (HSV-1, HSV-2) was analyzed by computer programs that provided values for hydrophilicity, surface probability, flexibility, and antigenicity, as well as the secondary structure conformation. Putative antigenic domains with a high hydrophilicity, surface probability, and antigenicity index were determined and compared with the reported antigenic domains in HSV-1 and HSV-2 gD protein based on experimental data. The major experimentally proven antigenic domains were detected by the computer analyses. Additional putative antigenic domains with potential for the synthesis of antigenic viral peptides were determined.
Amino Acid Sequence↗
Identification of viral proteins encoded by two DNA fragments of herpesvirus of turkeys (HVT).
Herpesvirus of turkeys (HVT) vaccine is used worldwide to immunize chickens against Marek's disease (MD). Polyclonal antiserum directed against one virus cross-reacts with proteins of the other, while only 5% homology at the DNA level was demonstrated between the two viruses. A partial library of HVT DNA fragments ranging from 1.5 to 13.5 kbp in size was constructed in pBR 322. Under stringent conditions of hybridization (low salt concentration, 10% dextran sulfate at 68 degrees C), two of the cloned HVT DNA fragments (13.5 and 11.0 kbp) hybridized to three MDV DNA fragments: BamHI-C, D, and G. The 13.5 kbp fragment detected two transcripts of 1.8 and 3.0 kb in RNA extracted from HVT-infected chicken embryo fibroblasts, while the 11.0 kbp fragment detected three transcripts of 1.6, 2.0, and 3.0 kb in the extracted RNA. Using hybrid selection, specific RNA was isolated by hybridization with the two cloned HVT DNA fragments and then was translated in vitro using rabbit reticulocyte lysate, and the resulting proteins were analyzed by NaDodSO4-PAGE. The RNA selected by the two HVT DNA fragments coded for a 30 kD protein and for several smaller proteins 10-20 kD in size, while the RNA selected by the 11.0 kb HVT DNA fragment was translated into a 40 kD protein. Immunoprecipitation of these in vitro synthesized proteins with hyperimmune anti-HVT chicken serum showed that they were of viral origin.
Animals↗
Epstein-Barr virus BHRF1 gene but not the cellular protooncogene bcl-2 is expressed in ataxia-telangiectasia lymphoblastoid lines.
The expression of both the Epstein-Barr virus (EBV) ORF BHRF1 and the cellular protooncogene bcl-2 was studied in EBV-transformed lymphoblastoid B cells from patients with the human genetic disorder ataxia-telangiectasia (A-T). Using the Northern blot technique, it was found that the pattern of transcription of the BHRF1 gene in A-T lymphoblastoids resembled that in EBV-transformed normal lymphoblastoid lines and Burkitt lymphoma (BL) lymphocytes. However, the 1.5-kb mature BHRF1 mRNA species present in normal lymphoblastoid cells and in BL cells was not found in the A-T lymphoblastoid cell lines. Treatment of the A-T lymphoblastoid lines with phorbol ester caused changes in the pattern of the synthesis and quantity of BHRF1-related RNA transcripts. The bcl-2 protooncogene probe did not detect bcl-2-related mRNA in the A-T lymphoblastoid lines.
Ataxia Telangiectasia↗
In vitro transcription and translation of proteins encoded by the BamHI-B genomic fragment of herpes simplex virus-1.
The BamHI-B DNA fragment of herpes simplex virus type-1 (HSV-1) is associated with intraperitoneal pathogenicity. Among the recently mapped RNA transcripts from this fragment (15), one was reported to be associated with latency. To relate the RNA transcripts to virus pathogenicity, the in vitro-transcribed RNAs from BamHI-B fragments of three HSV-1 strains--F (pathogenic), R19, and HFEM (apathogenic), were studied by in vitro translation. When the BamHI-HpaI (0.738-0.755 map units) DNA fragment from HSV-1 strain F was transcribed rightward and translated, three proteins of 70, 63, and 51 kD were detected. The 63 kD protein resembles in size and orientation the protein encoded by the ICP-27 (IE-2) gene (0.740-0.749 mu). The 51 kD polypeptide is assumed to be a prematurely terminated form of this protein. No proteins were obtained from RNA transcribed in the opposite direction. The SalI-NcoI (0.746-0.761 mu) fragment of the three HSV-1 strains yielded two proteins of 25 and approximately 15 kD when transcribed rightward and a 35 kD polypeptide from RNA transcribed in the opposite direction. As a result of the genomic deletion in HFEM, it was possible to obtain the 35 kD protein from the SalI-SalI DNA fragment (0.746-0.761 mu) as well. In vitro transcription and translation of the PstI-SalI (0.778-0.790 mu) DNA fragment (the right-hand side of HpaI-P) did not result in protein synthesis. The possibility that the UL56 gene is connected with the intraperitoneal pathogenicity of HSV-1 is discussed.
Animals↗
Monospecific antibodies to Marek's disease virus antigen B dimer (200 kDa) and monomer (130 and 60 kDa) glycoproteins neutralize virus infectivity and detect the antigen B proteins in infected cell membranes.
Monospecific antibodies were prepared by nitrocellulose blot immunoaffinity to 3 polypeptide components of the host-membrane associated B antigen of Marek's disease herpesvirus (MDV) and to its soluble A antigen. The B antigen comprised a 200 kDa dimer which is 2-mercaptoethanol (2-ME) labile, a monomer of 130 kDa and a 60 kDa protein, both of which are 2-ME resistant. Cross-immunoblotting studies showed that the anti-dimer antibody recognized the dimer protein as well as the 130 and 60 kDa components. In contrast, the anti-130 kDa antibody gave the strongest signal on blots of reducing gels indicating that the monomer is largely formed by in vitro reduction with 2-ME. All four antibodies recognized membrane antigens on chicken embryo fibroblasts infected with MDV vaccine viruses representative of the three serotypes and in addition, neutralized the homologous MDV isolate. The anti-dimer antibody was greatest, the anti-monomer antibody was the weakest and the anti-60 kDa antibody intermediate in neutralizing efficacy to all four viruses. We conclude from these studies that the B antigen presents at least two classes of neutralizing epitopes: one is discontinuous and of broad specificity on the intact dimer molecule and the other, on the 130 and 60 kDa proteins, is continuous and of lower avidity.
Animals↗
Interleukin-1 alpha gene-transcription in murine keratinocytes is inhibited by HSV-1 infection.
The effect of in vitro infection with herpes simplex virus 1 (HSV-1) on the Interleukin-1 (IL-1) activity of murine keratinocytes was investigated. IL-1 alpha mRNA synthesis was measured by the Northern blot technique, and the IL-1 protein production was measured in terms of the ability of dialysed supernatants from cultures of uninfected and HSV-1 infected keratinocytes to enhance mitogen-induced murine thymocyte proliferation. IL-1 alpha mRNA-synthesis in uninfected keratinocytes was detected 24 h and 48 h after isolation of the keratinocytes. IL-1 protein secretion by these keratinocytes was measureable at 18 h and reached a peak of 73 h, whereas intracellular and membrane-bound IL-1 protein production reached a maximum after 25 h. Keratinocytes, which had been cultured in vitro for 18 h, were infected with HSV-1 for 2 h and further cultured for an additional 4 h or 22 h before IL-1 measurements. A marked reduction of IL-1 alpha gene-expression was noted 6 hours after HSV-1-infection of keratinocytes, and nearly total shut-off was detected after infection for 24 h. Reduced gene-expression was paralleled by a reduction in the IL-1 protein secretion from the HSV-1 infected keratinocytes.
Animals↗
Elimination of UL56 gene by insertion of LacZ cassette between nucleotide position 116030 to 121753 of the herpes simplex virus type 1 genome abrogates intraperitoneal pathogenicity in tree shrews and mice.
In order to investigate whether or not the UL56 gene is involved in those processes determining the viral pathogenicity and latency, a recombinant virus HSV-1-M-LacZ was constructed in which the DNA sequences between nucleotide position (np) 116030 and 121753 were replaced by the E. coli beta-galactosidase (LacZ) gene. This deletion spans from the carboxyterminus of UL55 (np 116030) to the second exon of IE110 (np 121753) eliminating UL56 and the variable region of the BamHI DNA fragment B which were implicated in intraperitoneal pathogenicity and latency. The host range and growth kinetics of the recombinant virus HSV-1 M-LacZ were comparable to the parental strain HSV-1 F. As expected it was found that HSV-1-M-LacZ lost its virulent phenotype and was not able to develop acute infection in animals. The state of the UL56 gene was investigated by determining the cDNA sequence of the UL56 gene transcript of HSV-1 F using PCR products obtained after amplification of the cDNA with oligonucleotide primers corresponding to the translational start and stop codons of this gene. This analysis revealed that the DNA sequence of the UL56 gene of HSV-1 F differed from those DNA sequences determined for the genomic DNA of HSV-1 strain 17. Between nucleotide position 116343 and 116344 two nucleotides -AG- are inserted which prolong the ORF of the UL56 gene to 233 amino acids with a predicted molecular weight of 30 kDa.
Adrenal Glands↗
Computer analysis of antigenic domains and RGD-like sequences (RGWG) in the E glycoprotein of flaviviruses: an approach to vaccine development.
Antigenic domains and RGD-like sequences in the E glycoprotein of the flaviviruses Japanese encephalitis virus, yellow fever virus, West Nile virus, dengue type 4 virus, and tick-borne encephalitis virus were analyzed by computer programs that provide information on the physical properties of the polypeptides. The use of computer programs for the development of vaccines based on the synthesis of antigenic peptides is discussed. Synthetic viral peptides are proposed to be used for topical application so as to interfere with the virus-cell interaction. Viral peptides with antigenic epitopes to protect against dengue virus infection without enhancing pathogenesis may also be developed on the basis of the computer analysis.
Amino Acid Sequence↗
The effect of peptides containing the arginine-glycine-aspartic acid sequence on the adsorption of foot-and-mouth disease virus to tissue culture cells.
Sequencing of the VP1 of a large number of subtypes of foot-and-mouth disease virus (FMDV) has revealed the presence of a conserved arginine-glycine-aspartic acid (RGD) sequence located in a highly exposed region. This sequence has been shown to be essential for the interaction of certain extracellular matrix and adhesion proteins with a superfamily of cell-surface receptors called integrins. We have examined the effects of synthetic peptides containing the RGD sequence on the binding of eight different subtypes of FMDV to tissue culture cells. The results showed that such peptides inhibited viral adsorption by 50-80%. The inhibition was dose dependent but not as great as that achieved by using a saturating amount of virus as an inhibitor. Substitution of other amino acids for any of the three main residues lowered the inhibitory properties of the peptides. These results suggest that the RGD sequence in FMDV VP1 appears to be important for the interaction of virus with cellular receptor sites.
Adsorption↗
Effect of genetically determined immunodeficiency on epidermal dendritic cell populations in C57BL/6J mice.
Mice homozygous for three different recessive mutations known to cause pleiotropic defects in the immune system and in the skin were used to evaluate the relationship between the classical immune system and dendritic epidermal cell populations. Numbers of Langerhans cells (LCs) and Thy-1+ dendritic cells (Thy-1+DEC) were determined using indirect immunofluorescence microscopy of epidermal whole mounts taken from viable motheaten (mev), nude (nu), and rhino (rhhr) mice. All mutants were maintained on the C57BL/6J strain background and were compared with their respective littermate normal controls. Viable motheaten mice had normal numbers of LCs at 1 month of age. However, by 8 weeks of age, LC density had decreased threefold. Nude and rhino mice had normal numbers of LCs at all ages tested. There was no significant effect of the viable motheaten mutation on numbers of Thy-1+DEC. Although nude mice showed normal numbers of Thy-1+ DEC at 1 month of age, these athymic mice had a threefold decrease in numbers of such cells by 6 months. In contrast to the reduced numbers of Thy-1+DEC seen in nude mice, rhino mice showed a four- to fivefold increase in the numbers of these epidermal cells at all ages tested. These findings suggest new mouse models for investigating the development, regulation, and biological properties of epidermal dendritic cell populations.
Animals↗
Putative antigenic domains in glycoprotein G of rabies virus: is the RGK sequence involved in virus adsorption to cellular receptors?
Computer analysis of rabies virus glycoprotein G provides a means for identification of functional domains in the viral glycoprotein. The computer analysis suggested 22 putative antigenic domains, of which three are RG-containing amino acid sequences that might be involved in the binding of rabies virions to cellular receptors. Synthetic RG peptides may be able to interfere with rabies virus adsorption to cellular receptors.
Adsorption↗
Computer predictions of antigenic domains in human immunodeficiency virus-1 envelope glycoprotein: comparison with reported experimental data.
Computer analyses of amino acid sequences in the human immunodeficiency virus-1 (HIV-1) envelope glycoprotein revealed that antigenic domains in the viral protein can be predicted on the basis of the physical properties of amino acids in the polypeptide chain. Relatively high values of surface probability, flexibility, and hydrophilicity were used as markers for domains of putative antigenicity. Comparison of the computer-predicted antigenic domains in the HIV-1 envelope with those reported experimentally indicate that computer analyses are able to predict antigenic domains. This study shows the usefulness of computer programs for the prediction of the antigenic domains in the HIV-1 envelope protein.
Amino Acid Sequence↗
Induction of interleukin-1 alpha and beta gene transcription in mouse peritoneal exudate cells after intraperitoneal infection with herpes simplex virus-1.
Macrophages have been shown to play a determining role in the immune defense against herpes simplex virus-1 (HIV-1) intraperitoneal infection in the mouse. In the present study, the effect of HSV-1 infection on interleukin-1 alpha and beta gene transcription in peritoneal exudate cells was investigated. HSV-1 infection was found to induce interleukin-1 alpha and beta gene transcription in these cells. Induction of the interleukin-1 beta gene initiated 6 h postinfection (p.i.) and terminated at 48 h p.i. In contrast, interleukin-1 alpha RNA was detectable at high levels at 6h p.i. but not at 24 h p.i. Inactivation of virus prior to infection prevented HSV-1-induced IL-1 gene induction, indicating that only infectious virus is able to stimulate IL-1 gene transcription. These findings are discussed in relation to the role of macrophages in the immunological mechanisms of defense against HSV-1 infection.
Animals↗
Importance of the HpaI-P sequence for herpes simplex virus-1 replication in the adrenal glands.
The ability of several strains and recombinants of herpes simplex virus 1 (HSV-1) to proliferate in the adrenal glands and to invade the spinal cord was studied. After intraperitoneal infection, pathogenic HSV-1 strains replicated in the adrenal glands, penetrated the spinal cord and migrated to the brain. The nonpathogenic strain HFEM could not replicate in the adrenal glands, but the recombinant virus MLC1 was able to do so after rescue by reinsertion of the HpaI-P sequence into the BamHI fragment of HFEM DNA. However the recombinant MLC1 virus could not penetrate the spinal cord. The effect of HSV-1 infection on the expression of the cellular genes for multidrug resistance (in the adrenal glands) and proenkephalin A (in the spinal cord) was also studied.
Adrenal Glands↗
Mouse footpad Langerhans cells as an indicator for safety of foot and mouth disease virus vaccines.
The effect of various vaccines against foot and mouth disease virus (FMDV) was tested on Langerhans cell density in the footpad epidermis of mice. Injection of monovalent, bivalent and trivalent FMDV vaccines caused a reduction in Langerhans cell density in the murine skin, which was more marked at the center of the footpad, the site of injection, than at the periphery. Testing of the various components of the vaccine showed that saponin caused a marked reduction in Langerhans cells while injection of aluminium hydroxide had a lesser effect and the virus alone had no effect on these cells. Thus Langerhans cell density could serve as an efficient marker to test the safety of vaccines to FMDV since the integrity of Langerhans cells, which are the antigen-presenting cells in the skin epidermis, is needed for an effective immune response to the vaccine.
Adenosine Triphosphatases↗
Concepts and trends in antiviral chemotherapy in the period of AIDS: a review.
The spread of acquired immune deficiency syndrome (AIDS) in man has accentuated the need for an effective drug against the human immunodeficiency virus (HIV). The inability of devising a vaccine to stop the spread of the virus and its ability to damage the immune response in infected individuals has increased the need for effective antiviral agents. The present review analyzes the approaches that have led to the development of effective anti-herpes simplex virus chemotherapy. The emerging concepts in antiviral chemotherapy such as interference with HIV-1 attachment to its cellular receptor CD4 are presented and the current state of research on antiviral agents is evaluated.
Acquired Immunodeficiency Syndrome↗