Glycosylation of the ENV spike of primate immunodeficiency viruses and antibody neutralization.
Neutralizing antibody titers have been correlated with protection following vaccination against many viral pathogens. The logical target of protective antibody responses elicited by potential HIV vaccines should be the viral Env spike on the surface of the virion. However, the potency and titers of neutralizing antibodies that arise during HIV infection are generally discouragingly low and the antibodies that do arise recognize mainly autologous virus. This is thought to be a result of a combination of immunodominance of hypervariable regions of the Env protein that can easily escape neutralization, antibody reactivity to gp160 "decoy" protein in cell surface debris or monomeric gp120, conformational constraints within the Env trimer that create unfavorable antibody binding conditions and extensive glycosylation of the exposed regions of Env within the trimer. This review will describe current knowledge regarding glycosylation as a mechanism of neutralization resistance and discuss experimental approaches used to overcome this resistance. Part of the strategy toward development of an optimally immunogenic Env spike will likely require modification of Env glycosylation.
Pikora
Cheryl A
CA
Department of Infectious Diseases, Children's Hospital, Boston, MA 02115, USA. cherylpikora@childrens.harvard.edu
D000818:Animals; D000917:Antibody Formation; D022801:Complementarity Determining Regions; D024921:Drug Resistance, Multiple, Viral; D006031:Glycosylation; D015699:HIV Envelope Protein gp120 / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D015497:HIV-1 / Q000737:chemistry / Q000276:immunology; D006801:Humans; D016180:Lentivirus Infections / Q000276:immunology*; D017958:Lentiviruses, Primate / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism*; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D017433:Protein Structure, Secondary; D015302:Simian Immunodeficiency Virus / Q000737:chemistry / Q000276:immunology; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism*; D014771:Virion / Q000276:immunology* / Q000378:metabolism*
D022801:Complementarity Determining Regions; D015699:HIV Envelope Protein gp120; D014759:Viral Envelope Proteins