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Biomedical subjects

E D Kilbourne

Publications and source records attributed to E D Kilbourne.

At least 91 records · Page 5Linked to original sources
PubMed1970

Developmental sequence and intracellular sites of synthesis of three structural protein antigens of influenza A2 virus.

Specific antisera for hemagglutinin (HA) and neuraminidase antigens of influenza A(2) virus (A(2)E) were produced through the segregation of the two proteins in reciprocal viral recombinants of A(2)E and A(0)e viruses. Gamma globulin fractions of these specific antisera and of antiserum specific for the nucleoprotein (NP) antigen of A(0)e virus were conjugated with fluorescein isothiocyanate and employed to follow the synthesis of the three structural proteins in clone 1-5C-4 human aneuploid cells, with parallel measurement of serological and biological activity of the antigens by other techniques. In this system, NP antigen appeared first (at 3 hr) in the cell nucleus, whereas HA and neuraminidase appeared coincidentally, at 4 hr after infection, in the cytoplasm. The initial detectability of biological or complement-fixing activity of the proteins coincided with their demonstrability as stainable antigens. Late in infection, all three antigens were detected at the cell surface. Antibody specific for HA partially blocked the intracellular staining of neuraminidase and inhibited the enzymatic activity of both extracted and intact extracellular virus. These observations suggest the close intracytoplasmic proximity of the two envelope antigens and perhaps their initial association in a larger protein.

Animals↗
PubMed1969

Independent variation in nature of hemagglutinin and neuraminidase antigens of influenza virus: distinctiveness of hemagglutinin antigen of Hong Kong-68 virus.

Antigenic variations of the two virus-coded surface proteins of influenza virus-hemagglutinin and neuraminidase-were examined in seven strains of influenza A(2) virus (including the Hong Kong/68 strain) isolated from 1957 to 1968. Changes in the two antigens were found to occur independently in nature, resulting in new viruses which differ from older strains more with respect to one antigen than the other. The Hong Kong/68 strain is markedly different from previous A(2) strains in its hemagglutinin antigen but possesses neuraminidase indistinguishable antigenically from that of recent strains. Immunization experiments in mice provided evidence that only the neuraminidase component of an earlier A(2) strain provided protection against Hong Kong virus challenge. Segregation of hemagglutinin and neuraminidase antigens through recombination of each of the seven strains of influenza A(2) virus with A(0)/NWS virus made it possible to investigate antigenic variation of the two dissociated surface proteins independently in a common plaque assay system. Comparison of these hybrid viruses with the parent A(2) strains provided evidence that all the cross-reactivity of the Hong Kong strain with previous A(2) viruses is explicable on the basis of its similar neuraminidase component. It is proposed that the taxonomy of influenza A viruses must take into account differences in neuraminidase as well as hemagglutinin antigens.

Animals↗
PubMed1969

The antigenic relationship of the neuraminidase of Hong Kong virus to that of other human strains of influenza A virus.

Segregation of the haemagglutinin and neuraminidase antigens of 6 representative influenza A2 viruses and the Hong Kong virus by genetic recombination permitted a precise analysis of the antigenic constitution of each virus. Although cross-reactivity of the Hong Kong influenza virus and all 6 influenza A2 strains was demonstrated, the cross-reactivity was shown to be entirely dependent upon and mediated through the viral neuraminidase and not the haemagglutinin. The neuraminidase of the Hong Kong virus is slightly reactive with the neuraminidase of older A2 strains but is apparently identical to the enzyme of the recent (1967-68) variants.

Antigens↗
PubMed1969

Future influenza vaccines and the use of genetic recombinants.

Genetic recombination of influenza viruses provides the possibility of immediate reassortment and combination of genes and gene products in a single step. Thus, genetic variants with desirable attributes for vaccine production can be produced by deliberate genetic manipulation of viruses rather than by the empirical "hit or miss" methods of the past. Recombination of a high-yield laboratory strain (A0/PR/8) with a low-yield Hong Kong virus (Aichi strain) produced a high-yield recombinant virus (X-31) of Hong Kong antigenicity suitable for vaccine production. It is proposed that a prefabricated "library" of recombinants might anticipate the mutations which may arise in the future and also that live virus vaccines of greater stability may be produced by recombination of new and old viruses.

Influenza Vaccines↗
PubMed1968

Antiviral activity of antiserum specific for an influenza virus neuraminidase.

Antiserum specific for influenza A(2) neuraminidase was produced by immunization of rabbits with the purified enzyme which had been isolated by electrophoresis from the proteins of a detergent-disrupted A(0)A(2) influenza virus recombinant [X-7 (F1)]. This recombinant contained hemagglutinin of the A(0) subtype and A(2) neuraminidase. Antiserum to the isolated A(2) neuraminidase did not react in any of four serological tests with A(0) or A(2) subtype viruses that lacked the A(2) enzyme. In contrast, the antiserum inhibited the neuraminidase activity only of wild-type and recombinant viruses containing the A(2) enzyme, regardless of the nature of their hemagglutinin proteins. The antiserum caused hemagglutination-inhibition of some, but not all, viruses bearing the A(2) enzyme, and it reduced the plaque size or plaque number of all viruses tested that contained A(2) neuraminidase. In the chick embryo and in cell culture, low dilutions of antiserum reduced the yield of virus. True neutralization of virus in the chick embryo did not occur. We conclude that an antiserum specific for A(2) neuraminidase influenced the yield and release of virus from influenza virus-infected cells.

Animals↗
PubMed1968

Protective effects of specific immunity to viral neuraminidase on influenza virus infection of mice.

Antibody specific for viral neuraminidase can be demonstrated in mice following (i) pulmonary infection with influenza virus, (ii) immunization with ultraviolet-in-activated influenza virus, (iii) immunization with isolated neuraminidase of influenza A(2) virus, and (iv) passive immunization with sera of rabbits immunized with isolated A(2) neuraminidase. Neuraminidase antibody produced by any of these methods exerts a profound inhibiting effect on virus replication in the lungs of mice challenged with strains of virus having homologous neuraminidase protein, even in the absence of hemagglutinating inhibiting antibody to the challenge virus, and results in markedly decreased pulmonary virus titers and diminished lung lesions. These observations suggest that antineuraminidase immunity may play a significant role in the protection against influenza virus challenge observed in mice after infection or artificial immunization.

Aerosols↗
PubMed1966

The influence of cortisone on experimental viral infection. 8. Suppression by cortisone of interferon formation in mice injected with Newcastle disease virus.

The administration, of 5.0 mg of cortisone 6 to 24 hr prior to the intravenous injection of mice with NDV was associated with a marked reduction in the interferon response as measured in serum and spleen. Reduced concentrations of interferon following cortisone pretreatment were demonstrable from 6 to 16 hr following injection of virus.

Animals↗
PubMed1966

An antiviral substance from Penicillium funiculosum. V. Induction of interferon by helenine.

Helenine, a substance obtained from broth cultures of Penicillium funiculosum and known to exert a protective effect in vivo in experimental animals against several unrelated viruses, has been shown to elicit the formation in cell cultures and in intact mice of an inhibitor of viral plaque formation. Because the biological and chemical characteristics of the viral inhibitor induced by helenine are similar to those of interferon, it is suggested that the antiviral effect of helenine may be mediated through the formation of interferon.

Animals↗