Understanding neutralization is particularly relevant to an appreciation of the interaction between a virus and its antibody-synthesizing host since it is likely that viruses and the antibody system have evolved in response to reciprocally imposed selective pressures. Neutralization of viruses which only infect non-antibody-synthesizing hosts, while of considerable interest from of points of view is de facto without any such evolutionary signifi a number cance. In this second category are viruses of plants, invertebrates, vertebrates below fish in the evolutionary scale which do not synthesize antibody and most bacteria. Viruses of organisms parasitic on or commensal with antibody synthesizing vertebrates, such as enteric bacteria, protozoa or metazoan parasites, will be in contac, with antibody at some stage of their existence, and arthropod-borne viruses which have a higher vertebrate as second host are obviously bona fide members of the first category. There is an urgent need to understand the principles by which antibodies inactivate virus infectivity since, at present, we are unable to rationally construct effective vaccines against new agents like the human immuno deficiency viruses or to improve existing vaccines. The intention of this volume is to comprehensively review neutralization and where possible to construct a unifying theory which can be tested by experimentation.
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.