Neutralization Of Animal Viruses Research Articles

Neutralization of animal viruses.

1 Introduction.- 2 Immunoglobulin G Neutralization by Inhibition of Attachment of Virus to the Cell.- 3 Immunoglobulin G Neutralization Which Does Not Inhibit Attachment of Virus to the Cell.- 4 Immunoglobulin G Neutralization by Aggregation of Virions . ..- 5 Immunoglobulin G Neutralization Mechanisms which Operate After Attachment of the Virus-Antibody Complex to a Cell Receptor Unit.- 5.1 Inhibition of Fusion at the Plasma Membrane.- 5.2 Inhibition of Endocytosis.- 5.3 Inhibition of Fusion of Viral and Cellular Membranes.- 5.4 Inhibition of Non-fusion Uncoating.- 5.5 Inhibition of Events which Occur After Primary Uncoating.- 6 Neutralization which Occurs by Virus Binding Antibody After It Has Attached to a Cell.- 7 Role of the Cell in Neutralization.- 8 Antibody-Dependent Enhancement of Infectivity by Neutralizing Antibody: Fc and Complement Receptors.- 9 Neutralization by Polymeric Immunoglobulin A.- 10 Neutralization by Immunoglobulin M.- 11 The Relevance of Immunoglobulin Isotype to Neutralization.- 12 Viral Carbohydrates, Proteins and Neutralization.- 12.1 Carbohydrates and Neutralization.- 12.2 Proteinsand Neutralization.- 13 Properties of Protein and Peptide Antigens Which Elicit Neutralizing Antibody.- 14 Neutralization In Vivo.- 15 Complement and Neutralization.- 16 Neutralization by Inhibition of Release of Progeny Virus from the Infected Cell.- 17 Changes in Virus Proteins and Virion Structure on Binding Antibody, Including Synergistic Neutralization.- 18 Reversibility of Neutralization.- 19 Neutralization by Fragments of Antibody.- 20 Quantitative Aspects of Neutralization.- 21 Unconventional Neutralization.- 21.1 Genetic Engineering of Antibodies and Viruses.- 21.2 Anti-idiotype Antibodies and Neutralization.- 22 The Evolutionary Significance of Neutralization Sites.- 22.1 Why Do Viruses Have Neutralization Sites?.- 22.2 Strategies which Avoid or Minimize Expression of, or Response, to Neutralization Sites.- 22.2.1 Relating to the Virus Particle.- 22.2.2 Relating to the Immune System.- 23 Neutralization of Poliovirus and Rhinovirus: A Summary.- 23.1 Introduction.- 23.2 Attachment.- 23.3 Internalization.- 23.4 Post-internalization.- 23.5 Aggregation.- 23.6 Conformational Changes on Binding Antibody.- 24 Neutralization of Type a Influenza Virus by Immunoglobulins M, A and G: A Summary.- 24.1 Introduction.- 24.2 IgM Neutralization.- 24.3 IgA Neutralization.- 24.4 IgG Neutralization.- 24.5 Discussion.- 25 Neutralization of HIV-1: A Summary.- 26 Conclusions.- References.

The Neutralization of Animal Viruses

Summary The quantal assay system of influenza virus multiplying in surviving bits of the allantois is shown to be suited to the quantitative study of neutralization. Complications, such as bias due to the continued presence of serum or to shielding of infectible cells from the action of antibody, are not evident in standard tests. It is demonstrated that a) the final equilibrium is the same whether approached from the side of virus or antibody excess; b) changes in test volume lead to predictable shifts of equilibrium; c) the effect of noninfective virus particles is compatible only with random reversible combination of antibody molecules with antigenic sites. On this evidence a model of neutralization based on the law of mass action is accepted as working hypothesis. The assay is not sensitive to minor inhomogeneity of the reagents, and thus not suited to the study of heterogenity either of the virus or of the antibody population.

The Neutralization of Animal Viruses

Summary The equilibrium between three strains of influenza virus and their homologous antibodies is determined by two independent methods, with an accuracy of better than ±10%. Counts of virus particles, of hemagglutinating and infective units are presented for the same preparations, and two techniques are developed for estimating the number of antibody molecules within sera (accuracy about ±30%). From these data the number of antigenic sites per virus particle is calculated, and shown to be of the order of 2000 for each of the viruses tested. The equilibrium constants of the antigen antibody reaction fell within the range of 9 by 1010 and 5 by 1011 (in centimeter-gram-second (CGS) units), and were significantly different for each pair of reactants. These estimates carry over-all errors between ±25 and ±50%. The parameters of virus-antibody interaction are also estimated by two special in vivo techniques. The number of antigenic sites per virus particle is the same as obtained by in vitro measurements, but the equilibrium constants are consistently lower. This both indicates some heterogeneity within the antibody population and points to the preferential involvement of the more firmly binding antibody molecules in the process of neutralization.

The Neutralization of Animal Viruses

Summary The experimental data of Dulbecco, Vogt and Strickland are used to discriminate between two hypotheses on the mechanism by which the infectivity of viruses is neutralized. The orthodox hypothesis of dissociation, as developed by Fazekas de St.Groth, Watson and Reid (2) and the nondissociation hypothesis of Dulbecco et al. (1) are found to account equally well for the trivial features of the neutralization process. At the quantitative level however, the nondissociation hypothesis becomes incompatible with the experimental evidence on several counts; what it postulates as constants are seen to vary systematically; and its basic assumptions prove to be either inadequate or unnecessary. The dissociation hypothesis is not contradicted at any point by the same evidence. Finally, it is shown that the discriminatory tests listed in support of the nondissociation hypothesis by Dulbecco et al. are, for the most part, inconclusive as their results are confounded with the systematic errors of the assay technique; the remainder directly contradicts their hypothesis. The dissociation hypothesis fits this further set of data too.

The Neutralization of Animal Viruses

Summary The statistical-kinetic theory of reactions is applied to the system of virus and its specific antibody. The mathematical model defines, without any additional assumptions whatever, the rate at which virus-antibody unions are formed and broken, as well as the equilibrium state of the system. Equations covering the effects of dilution, of altering the concentration of any component, and of competition set up between similar reagents are derived and solved explicitly. Based on this model, the biological action of antibodies is considered in the form of several equally likely alternatives. Choice of the appropriate mechanism of neutralization must rest on experiment. The methods available for the study of the neutralization of infectivity are shown to carry various systematic errors. The nature and magnitude of these is discussed, and means are proposed by which they can be either avoided or accounted for quantitatively.