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Y Becker

Publications and source records attributed to Y Becker.

At least 73 records · Page 4Linked to original sources
PubMed1991

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↗
PubMed1990

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↗
PubMed1990

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↗
PubMed1990

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↗
PubMed1990

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↗
PubMed1990

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↗
PubMed1990

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↗
PubMed1990

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↗
PubMed1990

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↗
PubMed1990

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↗
PubMed1990

Rationale for anti-AIDS chemotherapy directed at HIV-1 infected dendritic cells in seropositive individuals prior to the appearance of ARC and AIDS.

An approach to anti-AIDS chemotherapy is presented from the point of view of treating seropositive individuals by eliminating the infected dendritic cells that are the in vivo target of HIV-1. Special attention is given to the treatment of Langerhans (dendritic) cells in the skin and epithelia that are infected in vivo by HIV and are involved in the development of the symptoms leading to AIDS and ARC. Since HIV is released through the cervical and vaginal epithelia in seropositive women, it is suggested that combined local treatment of vaginal epithelium with steroids that inactivate dendritic cells and azidothymidine (AZT) that inhibits HIV-1 replication might prevent virus dissemination. Abrogation of HIV-1 transmission will help to prevent its spread throughout the heterosexual population. Thus a new rationale for anti-AIDS treatment is presented, namely selective elimination of HIV-1 infected dendritic cells in the skin and epithelia of infected individuals before the appearance of ARC or AIDS. Subsequent restoration of dendritic cells in HIV-1-infected persons (and in AIDS patients) by means of orally administered retinoids in combination with an antiviral drug might be a useful approach to prevent or delay AIDS.

AIDS-Related Complex↗
PubMed1990

Effect of aging on epidermal dendritic cell populations in C57BL/6J mice.

The density and function of epidermal dendritic cell populations were investigated in aged C57BL/6J mice. The densities of both Langerhans cells (LC) and Thy-1+ dendritic epidermal cells were found to decrease with age. Epidermal cell suspensions from aged mice showed impaired immunologic function as assessed in vitro by the skin-lymphocyte reaction assay and by measuring the ability of epidermal cell suspensions to stimulate the proliferation of sensitized T cells in the presence of the sensitizing antigen. However, the capacity of LC to transport antigen from the skin to the draining lymph nodes was found in vivo to be comparable to that of young mice. Results of transplantation of bone marrow cells from young and old donors into irradiated recipients indicate that the decreased Langerhans cell density found in old mice may result from a deficiency in Langerhans cell bone marrow progenitors.

Aging↗
PubMed1989

Ataxia-telangiectasia fibroblasts have less fibronectin mRNA than control cells but have the same levels of integrin and beta-actin mRNA.

The expression of fibronectin, integrin and beta-actin genes in skin fibroblasts from patients with the genetic disorder ataxia-telangiectasia (A-T) was studied. These three genes were selected because their protein products contribute to the shape and function of the fibroblast. Expression of mRNA by these genes was compared with that in fibroblasts from normal individuals and from patients with the genetic disorder, hereditary hemorrhagic telangiectasia (HHT). A-T fibroblasts were found to produce less fibronectin mRNA than normal and HHT fibroblasts. A-T fibroblasts senesce around passage level 15 while normal and HHT fibroblasts can be propagated for many more passages in vitro. However, the expression of the integrin gene in A-T fibroblasts was similar to that in normal fibroblasts, while the beta-actin gene was expressed at a higher level. The increased beta-actin mRNA levels were similar in fibroblasts of patients with the two genetic disorders, A-T and HHT, but higher than in normal fibroblasts. HHT fibroblasts differed markedly from A-T fibroblasts in having a high level of fibronectin and integrin mRNA expression. The results indicate that regulation of the fibronectin gene in A-T fibroblasts differs from that of the integrin and beta-actin genes, and that the decline in fibronectin mRNA may be linked to the shortened in vitro life-span of these cells.

Actins↗
PubMed1989

Langerhans cell density and activity in mouse skin and lymph nodes affect herpes simplex type 1 (HSV-1) pathogenicity.

Langerhans cells are epidermal antigen-presenting cells that function by taking up antigens in the skin, migrating to the lymph nodes, where they are designated interdigitating cells, and triggering the immune response. The role of interdigitating cells (IDC) was investigated in a murine model of herpes simplex virus-1 infection in the skin. The number of IDC in the lymph nodes began to increase on the first day following infection and reached a peak three days p.i. Low titers of infectious virus were recovered from the fraction of lymph node cells that consisted of 60-80% IDC at one day p.i. Lymph node cells that were obtained from mice immunized with HSV-1 proliferated in vitro in response to viral antigens but did not respond to mock antigens. When mice were immunized with HSV-1 inoculated into skin that had been depleted of Langerhans cells, this in vitro proliferative response was abolished. Thus, the present results suggest that Langerhans cells function in the immune defense of the skin against HSV-1 infection by transporting the virus to the peripheral lymph nodes where an immune response is initiated. Injection of the immunomodulator OK-432 into the footpad skin caused a local increase in the number of Langerhans cells in the epidermis and led to an increased migration of dendritic cells to the lymph nodes. Under these conditions, a decrease in HSV-1 pathogenicity was noted. These observations indicate that the pathogenicity of herpes simplex virus type 1 in the skin is affected by Langerhans cell density and activity in the epidermis and the lymph nodes.

Adenosine Triphosphatases↗
PubMed1989

Langerhans cells in vaccinia virus infection in mouse skin.

Langerhans cells function as potent antigen-presenting cells in the epidermis. They were shown to play an essential role in the mechanisms of defense of the skin against viral infections. In the present study, the response of Langerhans cells to infection of the skin with vaccinia virus was investigated. Decrease in Langerhans cell density in the skin was accompanied by an increase in the pathogenicity of the WR and Noguchi but not of the Lister strain of vaccinia virus. Langerhans cell density was shown to increase rapidly at the site of inoculation with the two pathogenic strains of vaccinia virus.

Animals↗
PubMed1989

Characterization of RNA transcripts from herpes simplex virus-1 DNA fragment BamHI-B.

Herpes simplex virus type 1 (HSV-1) DNA fragment BamHI-B (0.738-0.809 map units) was recently reported to be associated with the phenotype of intraperitoneal pathogenicity and to encode a latency-associated RNA transcript. Part of this fragment resides within the internal repeat sequence of the long (L) region of the viral genome. In this study, RNA transcripts from BamHI-B were characterized. In addition to immediate-early mRNAs IE-1 and IE-2, eight novel RNA species were found. Three transcripts were mapped in the repeat regions of this fragment and five transcripts in the unique L region of BamHI-B. In addition, transcription activity from these regions was compared in several HSV-1 strains. These included the intraperitoneal virulent F and KOS strains, the avirulent strain HFEM, as well as the HFEM/F intratypic virulent recombinant R-MIC1. Several differences were noted and their possible relevance to virulence is discussed.

Animals↗
PubMed1989

Cytofluorometric analysis of thymic interdigitating cells from C57BL/6 mice prior and after leukemogenic X-irradiation.

The thymus is populated by various Ia+ cell populations, including epithelial cells, macrophages and dendritic cells. Thymic cell suspensions were stained with an anti-Ia antibody and shown by cytofluorometry to contain a small number of strongly Ia+ cells characterized by a large diameter. The cell population was separated with the aid of the fluorescence-activated cell sorter (FACS) and characterized. They were shown to express high levels of membranal Ia antigens; they demonstrated ATPase activity and displayed the ultrastructural features characteristic of the previously described thymic interdigitating cells. C57BL/6 mice were submitted to various regimens of X-irradiation. Whereas exposure to a single dose of X-irradiation was followed by an increase in the percentage of strongly Ia+ cells, exposure to a leukemogenic regimen of fractionated X-irradiation led to a decrease in the percentage and absolute numbers of these cells in the thymus. Of the C57BL/6 mice that were irradiated with fractionated X-irradiation, 77% developed leukemia. Intravenous injection of syngeneic bone marrow one day following the last irradiation or protection of the femur during irradiation prevented both the appearance of leukemia and the disappearance of interdigitating cells. Therefore an inverse correlation between the presence of thymic dendritic cells and the incidence of leukemia in C57BL/6 mice could be demonstrated. These findings are discussed in relation to the putative role of dendritic cells in the thymus.

Animals↗