Detection of a novel Borna disease virus-encoded 10 kDa protein in infected cells and tissues.

Borna disease (BD) is a transmissible, progressive polioencephalomyelitis primarily of horses and sheep. The genomes of two cell-adapted strains of Borna disease virus (BDV), the aetiological agent of BD, have been cloned and sequenced. According to the structural characterization achieved so far, BDV contains a non-segmented negative-sense 8.

Mapping of cross-reacting and serotype-specific epitopes on the VP3 structural protein of the infectious bursal disease virus (IBDV).

The binding sites of a panel of monoclonal antibodies cross-reacting with the structural protein VP3 of the two serotypes of the infectious bursal disease virus (IBDV) could be mapped to four segments of the VP3 gene. Two of these antigenic domains also carry epitopes which are specific for one serotype only. Formation of the common or type-specific epitopes is in agreement with homologous or mismatching amino acid sequences yielding hydrophilic segments on the VP3 polypeptide.

Protection of mice against an influenza virus infection by oral vaccination with viral nucleoprotein incorporated into immunostimulating complexes.

Influenza A virus nucleoprotein (NP) was integrated into immunostimulating complexes (ISCOMs) after attachment of bacterial lipopolysaccharide to the antigen. Oral immunization with these NP-ISCOMs protected mice fully against an otherwise lethal challenge infection with an unrelated influenza virus subtype without the appearance of severe clinical signs or extensive pathological lesions in the lungs. Mice immunized with analogous bovine serum albumine-incorporated ISCOMs all died.

Isolation and immunogenic properties of a monomeric form of the HA1 subunit of the influenza virus haemagglutinin from infected cells.

A monomeric, truncated form of the HA1 subunit of the haemagglutinin of fowl plague virus can be isolated from chorioallantoic membranes of infected eggs. This type of soluble HA1 seems to be generated by the elimination of the amino-terminal 19 amino acids from the native HA1, including the disulphide linkage to the HA2 subunit. The same type of truncated HA1 could be isolated from a filtrate of the allantoic fluid of infected embryonated eggs.

[Concentration of species alien (bovine) IgG in the blood serum of foals after the intake of non-species specific colostrum preparation].

Sixteen vital foals with free access to maternal colostrum received a additional non-species-specific commercial colostrum additive within the first 18 hours of their life. The additive had been prepared from bovine colostrum. At birth no bovine IgG was detectable.

Analysis of virus-specific RNA species and proteins in Freon-113 preparations of the Borna disease virus.

Treatment of homogenates from Borna disease virus (BDV)-infected brain tissue or cell cultures with Freon-113 yielded infectious particles with a buoyant density of 1.16-1.22 g/ml.

The genetic basis for the antigenicity of the VP2 protein of the infectious bursal disease virus.

The genomic region coding for the antigenic structure responsible for the induction of neutralizing antibodies was localized in the central variable region of the VP2 gene by comparing the nucleotide sequence of five escape mutants derived from the standard infectious bursal disease virus strain Cu-1. Exchange of a single amino acid at one of the prominent hydrophilic parts of this region proved to be sufficient for altering the neutralizing properties. The reactivity of neutralizing antibodies with peptides expressed in vitro encompassing both hydrophilic areas suggests that the entire variable region is engaged in the formation of this conformation-dependent antigenic site.

Infectious bursal disease of poultry: antigenic structure of the virus and control.

The present knowledge of genome organisation, structural basis of pathogenicity and antigenicity of infectious bursal disease virus (IBDV) are briefly reviewed. The current situation of IBDV infection in various countries is stated and recommendations for improved vaccination schemes are given.

Virus disease as a consequence of viral pathogenicity and the anti-viral immune response.

The brief description of two virus systems, influenza and infectious bursal disease, shows enigmatically how at least two requirements must be met to render a virus pathogenic: the array of the whole genome rather than the formation of a particular "pathogenicity gene" and the capacity of the host cell to provide the appropriate microenvironment for an optimal posttranslational processing of structural proteins. In the case of influenza viruses this relates particularly to the cleavability of the haemagglutinin. Efficient virus replication in cells of vital importance, however, does not necessarily result in the development of pathological conditions, as in Borna disease, where neural cells are loaded with virus, and the disease is mediated by a T cell immune response.

The structural polypeptide VP3 of infectious bursal disease virus carries group- and serotype-specific epitopes.

Two independent non-overlapping epitopes could be demonstrated on the structural protein VP3 of infectious bursal disease virus by non-neutralizing monoclonal antibodies produced against serotypes I and II. Both serotypes have one epitope in common, whereas the second epitope is distinct for serotype I and serotype II.

The influenza virus-infected host cell, a target for the immune response.

The exposure of some viral antigens at the surface of infected host cells was studied as an essential stimulus for the immune response during influenza virus infections. Only antibodies directed against the HA1 of the haemagglutinin were bound to the cell surface, anti-HA2 antibodies did not gain access to the membrane. Attempts to purify the cell-associated haemagglutinin (formerly called "viromicrosomes" by, R.

Infectious bursal disease--B cell dependent immunodeficiency syndrome in chickens.

Infectious bursal disease of chickens can run an acute lethal course, or death can result from a B cell-dependent immunodefect due to destruction of the bursa of Fabricius following infection with infectious bursal disease virus (IBDV). This member of the Birnaviridae has been characterized, the nucleotide sequence and coding capacity of the two genomic segments of dsRNA has been determined, and the functional significance of the four structural proteins has been largely elucidated. The antigenic structure of the two main structural components permits differentiation of two serotypes; the antigenic domain responsible for the induction of neutralizing antibodies resides, in a conformation-dependent fashion, on one of these proteins.

[Scrapie, still always a puzzling infection].

Scrapie belongs to the spongiform encephalopathies in man and animals. The nature of the infectious agent, an "unconventional virus", has not been elucidated so far. The agent starts to replicate in lymphoid tissue, reaches high titers in the brain and induces the formation of amyloid in this organ.

Heterogeneity of the antigenic site responsible for the induction of neutralizing antibodies in infectious bursal disease virus.

Using neutralizing monoclonal antibodies, three categories of escape mutants were selected from a stock of wild-type infectious bursal disease virus (IBDV). Additional mutants were found, where alterations coexisted in two or three of these epitopes. Although each group of mutants had a distinct reaction pattern with neutralizing monoclonal antibodies, all types of mutants were neutralized by convalescent chicken sera to the same extent.

Characterization and immunological properties of influenza A virus nucleoprotein (NP): cell-associated NP isolated from infected cells or viral NP expressed by vaccinia recombinant virus do not confer protection.

A nucleoprotein (NP) preparation purified from the chorioallantoic membrane of chicken eggs infected with fowl plague virus (A/FPV/Rostock/34, H7N1) yielded, in addition to the commonly known 56K protein, a 42K component that could not be detected in virus particles. After testing with a series of NP-specific monoclonal antibodies it was found that some reacted with both proteins and others were bound only by the 56K protein. Among both types of NP-specific monoclonal antibodies only a limited number were bound to infected murine cells.

Immunogenic properties of ISCOM prepared with influenza virus nucleoprotein.

After covalent attachment of bacterial lipopolysaccharide to the nucleoprotein of influenza A virus, this water-soluble antigen could be incorporated firmly into ISCOM. This potent "immunostimulating complex" induced the production of high antibody titers in mice and could partially protect the animals from a lethal challenge infection. After immunization with ISCOM preparations NP-specific cytotoxic T cell activity could not be demonstrated.

The glycoprotein of influenza C virus is the haemagglutinin, esterase and fusion factor.

Of the biological activities of influenza C virus, haemagglutination, receptor inactivation and fusion, only the latter has been conclusively correlated with its surface glycoprotein (gp). We have purified the gp by octylglucoside treatment of influenza C virions followed by centrifugation into a sucrose gradient. Evidence was obtained that gp also represents the receptor-destroying enzyme of influenza C virus, which has been characterized as a neuraminate 9-O-acetylesterase: (i) it inactivated the receptors for influenza C virus on chicken erythrocytes; (ii) it had acetylesterase activity as indicated by the release of acetate from bovine submandibulary mucin; (iii) monoclonal antibodies directed against gp inhibited the acetylesterase activity of influenza C virus.

Comparative studies on structural and antigenic properties of two serotypes of infectious bursal disease virus.

The electrophoretic mobilities of the two genome segments and the structural polypeptides of the chicken strain Cu-1 (serotype I) and the turkey isolate 23/82 (serotype II) of infectious bursal disease virus were compared. There is a close antigenic relationship between the smaller of the two major structural proteins (32K) of both strains. Neutralizing monoclonal antibodies are induced by the larger protein (40K in Cu-1) which differentiates between the two serotypes.

Properties of RNA polymerase activity associated with infectious bursal disease virus and characterization of its reaction products.

An RNA-dependent RNA polymerase activity of infectious bursal disease virus (IBDV) could be demonstrated without any special treatment of the virus particles. Ca2+ ions had to be removed from the reaction mixture. Mg2+ (4 mM) was essential for the polymerase activity which was optimal at pH 8.

Pathogenic and structural properties of wild type infectious bursal disease virus (IBDV) and virus grown in vitro.

Large plaque (LP) and small plaque (SP) variants of Infectious Bursal Disease Virus (IBDV) which are formed in vitro after serial passages in CE-cells at low or high multiplicities of infection were tested for their pathogenic properties in susceptible chickens. LP virus caused clinical manifestations and destruction of the Bursa of Fabricius (BF) without killing the animals. No signs of a disease appeared after infection with SP virus, and only limited necrotic foci developed in the BF.

Formation, characterization and interfering capacity of a small plaque mutant and of incomplete virus particles of infectious bursal disease virus.

Serial undiluted passages of infectious bursal disease virus in chick embryo cells were accompanied by a von Magnus type fluctuation of infectivity in viral harvests and a gradual decrease of plaque size. From the 9th undiluted passage on, the whole virus population consisted of small plaque-forming virus. The small plaque size remained constant when subsequent infections were carried out at low multiplicities.

Purification and properties of an intranuclear virus-specific antigen from tissue infected with Borna disease virus.

A virus-specific antigen was extracted from brains of rats and from MDCK cells infected with Borna disease (BD) virus and purified to homogeneity by immunoaffinity chromatography and HPLC. The antigen consists of two components which are almost equal in size (38 000 mol. wt.

Recognition of viral antigens by human influenza A virus-specific T lymphocyte clones.

The nature of the viral antigens recognized by influenza A virus-immune cytotoxic T lymphocytes (CTL) is still a matter of debate. We have used four human influenza A virus-specific T lymphocyte clones with antigen-specific cytotoxic and proliferative activity to investigate the requirements for recognition of viral antigens on infected cells. One clone recognized a cross-reactive determinant on the viral hemagglutinin, and two clones were specific for different epitopes on the viral nucleoprotein (NP).