Antibody responses to viral infections: a structural perspective across three different enveloped viruses

被引:140
作者
Murin, Charles D. [1 ]
Wilson, Ian A. [1 ,2 ,3 ,4 ]
Ward, Andrew B. [1 ,2 ,3 ]
机构
[1] Scripps Res Inst, Dept Integrat Struct & Computat Biol, La Jolla, CA 92037 USA
[2] Scripps Res Inst, Int AIDS Vaccine Initiat Neutralizing Antibody Ct, Ctr HIV AIDS Vaccine Immunol & Immunogen Discover, La Jolla, CA 92037 USA
[3] Scripps Res Inst, Collaborat AIDS Vaccine Discovery, La Jolla, CA 92037 USA
[4] Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA USA
关键词
BROADLY NEUTRALIZING ANTIBODIES; RECEPTOR-BINDING SITE; INFLUENZA HEMAGGLUTININ STEM; HUMAN MONOCLONAL-ANTIBODIES; GLYCOSYLATED HIV-1 ENV; FC-GAMMA RECEPTORS; CRYO-EM STRUCTURE; NONNEUTRALIZING ANTIBODIES; CRYSTAL-STRUCTURE; FUSION PEPTIDE;
D O I
10.1038/s41564-019-0392-y
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Antibodies serve as critical barriers to viral infection. Humoral immunity to a virus is achieved through the dual role of antibodies in communicating the presence of invading pathogens in infected cells to effector cells, and in interfering with processes essential to the viral life cycle (chiefly entry into the host cell). For individuals that successfully control infection, virus-elicited antibodies can provide lifelong surveillance and protection from future insults. One approach to understand the nature of a successful immune response has been to utilize structural biology to uncover the molecular details of antibodies derived from vaccines or natural infection and how they interact with their cognate microbial antigens. The ability to isolate antigen-specific B-cells and rapidly solve structures of functional, monoclonal antibodies in complex with viral glycoprotein surface antigens has greatly expanded our knowledge of the sites of vulnerability on viruses. In this Review, we compare the adaptive humoral immune responses to human immunodeficiency virus (HIV), influenza and filoviruses, with a particular focus on neutralizing antibodies. The pathogenesis of each of these viruses is quite different, providing an opportunity for comparison of immune responses: HIV causes a persistent, chronic infection; influenza, an acute infection with multiple exposures during a lifetime and annual vaccination; filoviruses, a virulent, acute infection. Neutralizing antibodies that develop under these different constraints are therefore sentinels that can provide insight into the underlying humoral immune responses, as well as important lessons to guide future development of vaccines and immunotherapeutics.
引用
收藏
页码:734 / 747
页数:14
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