Specific structural alteration of the influenza haemagglutinin by amantadine.

Sugrue, Richard J.; Bahadur, Gulam; Zambon, M; Hall-Smith, M.; Douglas, A. R.; Hay, Alan J.

doi:10.1002/j.1460-2075.1990.tb07555.x

Cited by 209 publications

(195 citation statements)

References 34 publications

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“…Consequently, a conversion of HA into its low-pH form can take place, resulting in failure of virus assembly. The M2 channel, as a cation channel, can provide the means for the regulation of pH of the trans-Golgi vesicles in order to prevent the conversion of HA into the low-pH form (Sugrue et al, 1990;Ruigrok et al, 1991;Steinhauer et al, 1991;.…”

Section: Uncoating Of Influenza a Virusmentioning

confidence: 99%

Entry and uncoating of enveloped viruses

Lanzrein

Schlegel

Kempf

1994

Biochemical Journal

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Section: Uncoating Of Influenza a Virusmentioning

confidence: 99%

Entry and uncoating of enveloped viruses

Lanzrein

Schlegel

Kempf

1994

Biochemical Journal

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“…Below a ratio of two, no escape mutants were detected. Preliminary sequencing of the HA gene of an escape mutant selected by antiserum WR45 Bj6 revealed an inferred single amino acid substitution at amino acid 161 in antigenic site B (data not shown), as was found in escape mutants to Mab HC10 [23], and confirmed the immunological data that this antiserum was indeed selecting conventional neutralizing antibody escape mutants in site B. When antisera were used at a titre of 10 000 HIU\ml, no virus multiplication was detected, showing that both wt and potential escape mutants were neutralized.…”

Section: Properties Of Antisera That Select Escape Mutantsmentioning

confidence: 79%

“…Briefly, double escape mutants were prepared as above from wt FPV\R by sequential selection with 2 of 3 FPV\R neutralizing Mabs (HC2, HC10 and HC61). These are directed to epitopes which are assumed to correspond with antigenic sites A, B or D respectively of the H3 haemagglutinin [23,24]. In our short-hand nomenclature these are referred to by the site which has not been mutated as a result of Mab selection : e.g. '…”

Section: Assay Of Ha-epitope Specificities Present In Antiseramentioning

confidence: 99%

Selection of neutralizing antibody escape mutants with type A influenza virus HA-specific polyclonal antisera: possible significance for antigenic drift

1997

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Ten antisera were produced in rabbits by two or three intravenous injections of inactivated whole influenza type A virions. All contained haemagglutination-inhibition (HI) antibody directed predominantly to an epitope in antigenic site B and, in addition, various amounts of antibodies to an epitope in site A and in site D. The ability of untreated antisera to select neutralization escape mutants was investigated by incubating virus possessing the homologous haemagglutinin with antiserum adjusted to contain anti-B epitope HI titres of 100, 1000 and 10000 HIU/ml. Virus-antiserum mixtures were inoculated into embryonated hen's eggs, and progeny virus examined without further selection. Forty percent of the antisera at a titre of 1000 HIU/ml selected neutralizing antibody escape mutants as defined by their lack of reactivity to Mab HC10 (site B), and unchanged reactivity to other Mabs to site A and site D epitopes. All escape mutant-selecting antisera had a ratio of anti-site B (HC10)-epitope antibody[ratio ]other antibodies of [ges ]2·0[ratio ]1. The antiserum with the highest ratio (7·4[ratio ]1) selected escape mutants in all eggs tested in four different experiments. No antiserum used at a titre of 10000 HIU/ml allowed multiplication of any virus. All antisera used at a titre of 100 HIU/ml permitted virus growth, but this was wild-type (wt) virus. We conclude that a predominant epitope-specific antibody response, a titre of [ges ]1000 HIU/ml, and a low absolute titre of other antibodies ([les ]500 HIU/ml) are three requirements for the selection of escape mutants. None of the antisera in this study could have selected escape mutants without an appropriate dilution factor, so the occurrence of an escape mutant-selecting antiserum in nature is likely to be a rare event.

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“…Although the H7 HA has not been mapped in detail, it has three antigenic sites which correspond exactly with sites A, B and D of the H3 HA, and seven independent, non-overlapping epitopes [defined by MAbs HC2, HC3, HC10, HC58 and HC61 (Sugrue et al, 1990) and I-2 and I-7 (unpublished data)]. Thus there is no shortage of potentially immunogenic epitopes, but our rabbits were, for unknown reasons, unable to respond significantly to more than two of these.…”

Section: Discussionmentioning

confidence: 99%

“…Mouse MAbs HC2 (site A, amino acid 144), HC10 (site B, amino acid 161) and HC61 (site D, amino acid 210) (Sugrue et al, 1990) were provided by A. R. Douglas and J. J. Skehel (National Institute for Medical Research, London, UK). All are IgG2a.…”

Section: Methodsmentioning

confidence: 99%

All rabbits immunized with type A influenza virions have a serum haemagglutination-inhibition antibody response biased to a single epitope in antigenic site B

Lambkin

Dimmock

1995

Journal of General Virology

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Nine rabbits were immunized with type A influenza virions and the epitope specificities of the secondary serum haemagglutination-inhibition (HI) antibody response were analysed with a panel of neutralizing monoclonal (MAb) antibody double escape mutants. Each of the latter was made by sequential selection using a MAb directed to an epitope of a discrete antigenic site, site A, site B or site D, of the haemagglutinin (HA). Thus the epitope reactivity of the escape mutants was represented as A+B-D -, A-B+D and A-B-D +. The HI antibody response of all antisera was biased to the site B epitope. In 9/12 antisera, obtained from seven rabbits immunized with whole virions, the site B epitope was predominant, representing 65-82% of the total HI antibody. The restriction of HI antibody was unaffected by strain of rabbit, route of inoculation (intravenous or subcutaneous), use of Freund's adjuvant, and up to four immunizing injections. In 3/7 rabbits immunized with whole virus, there was a HI antibody response to the HC2 (site A) or HC10 (site D) epitope, but not both, of equal magnitude to the site B epitope. The HI antibody response in one of the rabbits (#40) became more biased to the site B epitope between the third and fourth immunizing doses. Two further rabbits were immunized with virions which had been partially digested with bromelain and then purified from free HA. Both of these made equal HI antibody responses to the site B epitope and the site D epitope, possibly because their remaining HA spikes were better exposed. Overall, these data demonstrate an unexpected degree of restriction in the production of biologically relevant antibody, such that some rabbits (e.g. #45) mount an HI antibody response which is essentially epitope-specific. Implications for epitope specificity of HI antibody stimulated by human influenza vaccines, and also for the generation of antigenic drift variants are discussed. The reason for the non-responsiveness of the immune system to the many other HI epitopes of the HA is not known.

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Specific structural alteration of the influenza haemagglutinin by amantadine.

Cited by 209 publications

References 34 publications

Entry and uncoating of enveloped viruses

Entry and uncoating of enveloped viruses

Selection of neutralizing antibody escape mutants with type A influenza virus HA-specific polyclonal antisera: possible significance for antigenic drift

All rabbits immunized with type A influenza virions have a serum haemagglutination-inhibition antibody response biased to a single epitope in antigenic site B

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