UMMS Affiliation

Department of Microbiology and Physiological Systems; Gastroenterology Division, Department of Medicine

Publication Date

2019-04-02

Document Type

Article

Disciplines

Amino Acids, Peptides, and Proteins | Computational Biology | Genetic Phenomena | Immunoprophylaxis and Therapy | Microbiology | Viruses

Abstract

A human cytomegalovirus (HCMV) pentameric glycoprotein complex (PC), gH-gL-UL128-UL130-UL131A, is necessary for viral infection of clinically relevant cell types, including epithelial cells, which are important for interhost transmission and disease. We performed genome-wide CRISPR/Cas9 screens of different cell types in parallel to identify host genes specifically required for HCMV infection of epithelial cells. This effort identified a multipass membrane protein, OR14I1, as a receptor for HCMV infection. This olfactory receptor family member is required for HCMV attachment, entry, and infection of epithelial cells and is dependent on the presence of viral PC. OR14I1 is required for AKT activation and mediates endocytosis entry of HCMV. We further found that HCMV infection of epithelial cells is blocked by a synthetic OR14I1 peptide and inhibitors of adenylate cyclase and protein kinase A (PKA) signaling. Identification of OR14I1 as a PC-dependent HCMV host receptor associated with epithelial tropism and the role of the adenylate cyclase/PKA/AKT-mediated signaling pathway in HCMV infection reveal previously unappreciated targets for the development of vaccines and antiviral therapies.

Keywords

CRISPR screen, OR14I1, human cytomegalovirus, pentameric glycoprotein complex, virus receptor

Rights and Permissions

Copyright © 2019 the Author(s). Published by PNAS. This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND).

DOI of Published Version

10.1073/pnas.1814850116

Source

Proc Natl Acad Sci U S A. 2019 Apr 2;116(14):7043-7052. doi: 10.1073/pnas.1814850116. Epub 2019 Mar 20. Link to article on publisher's site

Journal/Book/Conference Title

Proceedings of the National Academy of Sciences of the United States of America

Related Resources

Link to Article in PubMed

PubMed ID

30894498

Creative Commons License

Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

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