Structural and biochemical studies of HCMV gH/gL/gO and Pentamer reveal mutually exclusive cell entry complexes

Author:

Ciferri Claudio1,Chandramouli Sumana1,Donnarumma Danilo2,Nikitin Pavel A.3,Cianfrocco Michael A.45,Gerrein Rachel1,Feire Adam L.3,Barnett Susan W.1,Lilja Anders E.1,Rappuoli Rino2,Norais Nathalie2,Settembre Ethan C.1,Carfi Andrea1

Affiliation:

1. Novartis Vaccines, Cambridge, MA 02139;

2. Novartis Vaccines, 53100 Siena, Italy;

3. Novartis Institutes for Biomedical Research, Emeryville, CA 94608;

4. Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138; and

5. Department of Cell Biology, Harvard Medical School, Boston, MA 02115

Abstract

Significance Human cytomegalovirus (HCMV) is a major cause of morbidity and mortality in transplant patients and in fetuses after congenital infection. gH/gL/gO and Pentamer are targets for neutralizing antibodies. We show that gO and UL128/UL130/UL131A bind to the same site on gH/gL through formation of a disulfide bond with gL-Cys144. The alternative use of this binding site by either gO or the ULs may provide a mechanism for cell tropism modulation. Our analysis reveals that gH/gL antigenic sites are conserved among gH/gL, gH/gL/gO, and Pentamer, whereas gH/gL/gO- and Pentamer-specific neutralizing antibody-binding sites are located in the gH/gL N terminus protrusion that contains the gO and the UL subunits. These data support the development of vaccines and antibody therapeutics against HCMV.

Publisher

Proceedings of the National Academy of Sciences

Reference45 articles.

1. Epidemiology of Cytomegalovirus Infections

2. Manifestations of human cytomegalovirus infection: Proposed mechanisms of acute and chronic disease;Britt W;Curr Top Microbiol Immunol,2008

3. Vaccine Development to Prevent Cytomegalovirus Disease: Report from the National Vaccine Advisory Committee

4. Cytomegalovirus cell tropism;Sinzger C;Curr Top Microbiol Immunol,2008

5. Entry of herpesviruses into mammalian cells

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.7亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2025 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3