Molecular mechanisms of variation in influenza viruses

Webster, Robert G.; Laver, W.G.; Air, Gillian M.; Schild, G. C.

doi:10.1038/296115a0

Cited by 464 publications

(268 citation statements)

References 75 publications

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“…This high degree of conservation of cysteine is comparable to that found between the haemagglutinins of different influenza A virus subtypes (Webster et al, 1982) and is also characteristic for the otherwise highly polymorphic class I major histocompatibility complex antigens (Shiroishi et al, 1984) suggesting their critical role for determining the protein structure and consequently for the expression of biological functions.…”

Section: -7504 O 1987 Sgmmentioning

confidence: 55%

Characterization of a Disulphide Bridge-stabilized Antigenic Domain of Tick-borne Encephalitis Virus Structural Glycoprotein

Winkler

Heinz

Künz

1987

Journal of General Virology

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SUMMARYProteolytic digestion of purified whole tick-borne encephalitis virus or its isolated envelope glycoprotein (E) in the form of rosettes yields an Mr 9000 fragment that is resistant to further digestion and carries polyclonal and monoclonal antibody-defined antigenic determinants. In a denaturation/renaturation experiment it was demonstrated that the antigenic reactivity of this domain, which was lost upon reduction and carboxymethylation, could be regained if the reducing agent was dialysed out before carboxymethylation. By the use of [35S]cysteine-labelled E protein and amino acid analysis it was confirmed that the reacquisition of antigenic reactivity in the renaturation experiment was associated with the reformation of disulphide bridges, which apparently confer structural stability to this part of the molecule. By the experiments performed we have identified an independently folding antigenically active domain of the E protein that is stabilized by disulphide bridges and has a strong tendency for renaturation.

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Section: -7504 O 1987 Sgmmentioning

confidence: 55%

Characterization of a Disulphide Bridge-stabilized Antigenic Domain of Tick-borne Encephalitis Virus Structural Glycoprotein

Winkler

Heinz

Künz

1987

Journal of General Virology

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“…For example, three recognized subtypes of type A -H1Nl, H2N2, and H3N2 -have been isolated from man; and there are several recognized strains (comparatively minor variants) within each subtype. The appearance of several strains is due to the capacity of influenza viruses to change their antigenic structure (see Webster, et al, 1982), which effectively allows them to circumvent individuals' immune responses. Unfortunately, the development of vaccines and vaccination programs, which have been successful for diseases such as smallpox, measles and poliomyelitis, is greatly complicated by an ever-changing virus.…”

Section: Introductionmentioning

confidence: 99%

Epidemiological models with age structure, proportionate mixing, and cross-immunity

et al. 1989

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Infection by one strain of influenza type A provides some protection (cross-immunity) against infection by a related strain. It is important to determine how this influences the observed co-circulation of comparatively minor variants of the H1N1 and H3N2 subtypes. To this end, we formulate discrete and continuous time models with two viral strains, cross-immunity, age structure, and infectious disease dynamics. Simulation and analysis of models with cross-immunity indicate that sustained oscillations cannot be maintained by age-specific infection activity level rates when the mortality rate is constant; but are possible if mortalities are age-specific, even if activity levels are independent of age. Sustained oscillations do not seem possible for a single-strain model, even in the presence of age-specific mortalities; and thus it is suggested that the interplay between cross-immunity and age-specific mortalities may underlie observed oscillations.

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“…These antibodies efficiently mediate high levels of protection against homologous infection (3). However, constant drift occurs in the antigenic regions of the immunodominant HA (4)(5)(6) and, also, the NA (6, 7) of influenza viruses and can render the protection induced by previous vaccination incomplete. For this reason, vaccines need to be continually updated to contain virus strains that are predicted to antigenically resemble those viruses that will be circulating in the human population during the oncoming influenza season.…”

mentioning

confidence: 99%

The Source of the PB1 Gene in Influenza Vaccine Reassortants Selectively Alters the Hemagglutinin Content of the Resulting Seed Virus

Cobbin

Verity

Gilbertson

et al. 2013

J Virol

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The yields of egg-grown influenza vaccines are maximized by the production of a seed strain using a reassortment of the seasonal influenza virus isolate with a highly egg-adapted strain. The seed virus is selected based on high yields of viral hemagglutinin (HA) and expression of the surface antigens from the seasonal isolate. The remaining proteins are usually derived from the highgrowth parent. However, a retrospective analysis of vaccine seeds revealed that the seasonal PB1 gene was selected in more than 50% of reassortment events. Using the model seasonal H3N2 virus A/Udorn/307/72 (Udorn) virus and the high-growth A/Puerto Rico/8/34 (PR8) virus, we assessed the influence of the source of the PB1 gene on virus growth and vaccine yield. Classical reassortment of these two strains led to the selection of viruses that predominantly had the Udorn PB1 gene. The presence of Udorn PB1 in the seed virus, however, did not result in higher yields of virus or HA compared to the yields in the corresponding seed virus with PR8 PB1. The 8-fold-fewer virions produced with the seed virus containing the Udorn PB1 were somewhat compensated for by a 4-fold increase in HA per virion. A higher HA/nucleoprotein (NP) ratio was found in past vaccine preparations when the seasonal PB1 was present, also indicative of a higher HA density in these vaccine viruses. As the HA viral RNA (vRNA) and mRNA levels in infected cells were similar, we propose that PB1 selectively alters the translation of viral mRNA. This study helps to explain the variability of vaccine seeds with respect to HA yield.

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Molecular mechanisms of variation in influenza viruses

Cited by 464 publications

References 75 publications

Characterization of a Disulphide Bridge-stabilized Antigenic Domain of Tick-borne Encephalitis Virus Structural Glycoprotein

Characterization of a Disulphide Bridge-stabilized Antigenic Domain of Tick-borne Encephalitis Virus Structural Glycoprotein

Epidemiological models with age structure, proportionate mixing, and cross-immunity

The Source of the PB1 Gene in Influenza Vaccine Reassortants Selectively Alters the Hemagglutinin Content of the Resulting Seed Virus

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