OR14I1 is a Receptor for the Human Cytomegalovirus Pentameric Complex and Defines Viral Epithelial Cell Tropism

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2019 Mar 22

PMID 30894498

Citations 76

Authors

Xiaofei E

Paul Meraner

Ping Lu

Jill M Perreira

Aaron M Aker

William M McDougall

Ronghua Zhuge

Gary C Chan

Rachel M Gerstein

Patrizia Caposio

Andrew D Yurochko

Abraham L Brass

Timothy F Kowalik

Affiliations

Soon will be listed here.

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.

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