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OR14I1 is a receptor for the human cytomegalovirus pentameric complex and defines viral epithelial cell tropism

Xiaofei E1, Paul Meraner2, Ping Lu2

  • 1Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, MA 01605; xiaofei.e@umassmed.edu timothy.kowalik@umassmed.edu.

Proceedings of the National Academy of Sciences of the United States of America
|March 22, 2019
PubMed

Insights

Human cytomegalovirus (HCMV) uses the olfactory receptor OR14I1 to infect epithelial cells. This discovery reveals new targets for antiviral therapies and vaccines against HCMV infection.

Area of Science:

  • Virology
  • Cell Biology
  • Immunology

Background:

  • Human cytomegalovirus (HCMV) pentameric glycoprotein complex (PC) is crucial for infecting epithelial cells, vital for transmission and disease.
  • Identifying host factors specific to epithelial cell infection is key to understanding HCMV tropism.

Purpose of the Study:

  • To identify host genes specifically required for HCMV infection of epithelial cells.
  • To elucidate the mechanism of HCMV entry into epithelial cells and identify potential therapeutic targets.

Main Methods:

  • Genome-wide CRISPR/Cas9 screens were conducted in parallel across different cell types.
  • HCMV attachment, entry, and infection assays were performed.
  • Signaling pathway analysis involving AKT, adenylate cyclase, and protein kinase A (PKA) was conducted.

Main Results:

  • OR14I1, an olfactory receptor, was identified as a host receptor essential for HCMV infection of epithelial cells.
  • OR14I1 mediates HCMV attachment, entry via endocytosis, and is dependent on the viral PC.
  • HCMV infection was blocked by a synthetic OR14I1 peptide and inhibitors of adenylate cyclase/PKA signaling, highlighting the pathway's role.

Conclusions:

  • OR14I1 is a critical PC-dependent receptor mediating epithelial cell tropism for HCMV.
  • The adenylate cyclase/PKA/AKT signaling pathway is integral to HCMV epithelial cell infection.
  • OR14I1 and the identified signaling pathway represent novel targets for developing HCMV vaccines and antiviral therapies.
Keywords:
CRISPR screenOR14I1human cytomegaloviruspentameric glycoprotein complexvirus receptor

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